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Asthma
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Records of the First Lady's Office (Clinton Administration)
Jennifer Klein's Files
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02/27/98
FRI
10:38
FAX
202
456
6210
LOWER PRESS
THE NEW YORK TIMES
NEW
YORK
FRIDAY,
FEBRUARY
27,
1998
A26
NE
Giuliani Withdraws Financing
For Asthma Program in Bronx
By ESTHER B. FEIN
mentation of the program with a
Mayor Rudolph W. Gluliani said
flood of bureaucratic paperwork."
yesterday that the city was with-
Dr. Rediener, who is also the direc-
drawing its money from a multi-
tor of community pediatrics at Mon-
million-dollar asthma education and
tefiore, said the city wanted, for ex-
treatment initlative in the Bronx.
ample, monthly financial account-
saying the organization selected to
ings, approval of treatment plans for
run the program was refusing to
every patient, and weekly schedules
agree to the city's plan for financial
of doctors' hours. The Children's
and program supervision.
Health Fund, he said, had offered
The program, which has been
quarterly reviews of the accounts,
championed by Hillary Rodham
patient charts and schedules.
Clinton, was to have been managed
Dr. Redlener said that he was
by the Children's Health Fund in
stunned by the Mayor's announce-
conjunction with Montefiore Medical
ment yesterday at City Hall that the
Center in the Bronx. In its Il-year
city would no longer help finance the
history, the fund has become a na-
project, adding that he thought his
tional model for providing health
organization and the Health Depart-
care to poor children and its asthma
ment had been making progress.
initiative would have cost $2.3 million
Relations between the city and the
per year for four years. with the city
Children's Health Fund have been
providing $1.5 million annually and
strained almost from the start, with
the state providing the remaining
the two sides arguing over what the
$800,000.
Initiative's focus should be - the city
Asthma is considered the worst
favoring community and physician
chronic health problem affecting
education and the health fund favor-
children, and is particularly preva-
ing direct patient care.
lent among the urban poor because
Yesterday, city officials and Dr.
of the lack of accessible health care
Redlener both promised to carry on
and the high number of allergens in
their asthma Initiatives independent-
the environment. If poorly managed,
ty. Dr. Redlener said that Schering-
asthma can lead to extensive hospi-
Plough, a pharmaceutical company
calization of children and many
based in New Jersey, had pledged
missed days of school
$750,000 a year for two years toward
The president of the Children's
the program.
Health Fund, Dr. Irwin Redlener,
Fred Winters, a spokesman for the
denied that his organization was
city's Health Department, said the
balking at sharing its financial and
city would find another vendor to
patient records with the city, but said
provide asthma services to Bronx
that the requirements being de-
communities. "The money for asth-
manded were SO onerous that "they
ma will not be lost," he said "It will
threatened to strangle the imple-
be redirected."
FEB-27-1998 17:16
DHHS REGION II
212 264 4600
P.02
Friday, February 27, 1998
Rudy kills
2.3M fund
DAILY NEWS
for asthma
By FRANK LOMBARDI and JOE CALDERONE
Daily News Staff Writers
Mayor Giuliani yesterday abruptly canceled fund-
ing for a $2.3 million asthma program that First Lady
Hillary Rodham Clinton had touted in a visit to the
South Bronx last year as a potential national model to
combat the disease.
The mayor pulled the plug
The fund and the City Coun-
after the program's president,
cil last summer devised a four-
Dr. Irwin Redlener, com-
year plan to expand asthma
plained in an interview with
education and medical serv-
the Daily News that the city
ices.
Health Department had been
"Enough is enough," said
dragging its feet on a contract
Council Speaker Peter Val-
to deliver the asthma services,
lone (D-Queens). "We need to
even though the funds had
get this money away from the
been set aside months ago.
bureaucrats and get it deliv-
Giuliani yesterday said
ered to the thousands of chil-
Redlener and the Children's
dren who are suffering"
Health Fund, which runs the
The program called for in-
program, were "unwilling to
creasing staffing for asthma
be accountable for spending."
services at a South Bronx clin-
"He has refused to live by
ic affiliated with Montefiore
the accountability standards
Medical Center and to provide
that we now have in our health
increased services in Wil-
care con-
liamsburg.
tracts of all
Brooklyn.
kinds," the
"Doesn't the
The fund also
mayor said.
planned to
"Therefore,
mayor realize
dispatch two
the Depart-
specially
ment of
that people are
equipped
Health, on
vans
to
the merits,
dying?"
schools and
responsibly
shelters
decided not
MAVELIN MORALES
where asth-
to do busi-
ma rates are
ness with him, and they're not
high.
going to do business with him.
Outside the clinic yesterday.
They are going to have those
asthma sufferers said they were
services provided in other
disappointed with the mayor's
ways."
decision. "Doesn't the mayor
Redlener yesterday said he
realize that people are dying?"
was willing to go along with
said Mavelin Morales, 37,
reasonable standards but ob-
whose 5-year-old son, Benigno,
jected to reporting require-
is treated at the clinic. "They
ments contained in a 14-page
keep putting smokestacks and
rider that was added to the
Dumpsters in this neighbor-
standard city contract.
hood but not asthma clinics."
"They wanted to approve
A White House official called
the purchase of every single
the program's demise "unfortu-
piece of equipment in ad-
nate" but said the First Lady
vance," he said.
would not take sides.
FEB-27-1998 17:17
DHHS REGION 11
COMING SUNDAY
Asthma: A Guide for Life
A special 8-page
Arthur: The Sincerely Epidemic
DAILY NEWS
guide for
A GUIDE
asthmatics and
FOR LIFE
their families,
showing how
to detect
Friday. February 27, 1998
the symptoms,
where to get
help and what to
do in an emergency.
TOTAL P.03
FEB-27-1998 17:16
DHHS REGION II
212 264 4600 P.01
HUMAN SERVICES USA
&
U.S. Department of Health and Human Services
Office of the Regional Director
HEALTH
26 Federal Plaza, Room 3835
Of
New York, New York 10278
DEPARTMENT
FAX TRANSMISSION NOTICE
DATE: 2/27/98
TO: MeLanne Verveer FAX Number: (202) 456-6244
office of First Lady
ORGANIZATION:
FROM: Alison E. Greene, Regional Director
(212) 264-4600 (phone)
(212) 264-3620 (fax)
NUMBER OF PAGES (including this cover) : 2
Please notify us immediately if not received properly. Thank You.
MESSAGE:
This is exactly what I
was concerned about last
December
Alison
TO:
Hillary Rodham Clinton
FROM:
Jennifer Klein
DATE:
11/5/97
RE:
The Vice President's Question on Study Linking Increased Asthma and
Antibiotic Use
You had asked for information about a study that the Vice President mentioned
linking increased asthma and antibiotic use. I have attached two articles discussing a
recent study done in Japan that found that increased rates of childhood asthma are related
to decreased rates of infectious diseases, such as measles and tuberculosis. The study
does not make a direct link between antibiotics and asthma. Instead, it posits that, with
better living standards and immunization programs, children have fewer respiratory
infections. Childhood respiratory infections stimulate a response in the developing
immune system that may protect against asthma. With fewer infections, therefore,
children are at greater risk of suffering from asthma.
Experts from the National Institutes of Health, the American Lung Association,
and the Asthma and Allergy Foundation of America caution that there are questions about
this study. Most research finds that the rise in asthma is related to changes in the
environment and to genetic predisposition.
Jen- This note is from VP Gone
THE WHITE HOUSE
WASHINGTON
Please follow up + time
study
increased
the office time
d child
antibiotic use?
The theses is this:
tree / and biotic use
in childre that
life throath and often
controlled) De
systems ities for
"Fraining and development
and "fine thing." remiting
poly trained immune systems regard
+ that Actions.
TO:
Jennifer Klein
FROM:
Jon Poling
DATE:
November 5, 1997
RE:
Relationship Between the Immune System and
Atopy (Allergic Response) or Asthma in Children
The following studies suggest that increased rates of childhood asthma are related, in
some degree, higher immunization rates and antibiotics use, the diminished exposure to
infections and a less independent immune system. Attached are three articles for your review:
The Inverse Association Between Tuberculin Responses and Atopic Disorder
The study discusses how the increased rates of childhood asthma are
related to the deceased rates of Tuberculosis and other infections. I
believe that this is the study that we have been looking for and seems to
deal with the issue that Vice President Gore had mentioned.
Asthma: An Epidemic in the Absence of Infection
The article is a complementary piece to the previous study. It summarizes
the findings of the previous study and offers an overview with less
medical jargon.
New Clues to Asthma Therapies
The article discusses asthma therapies, but there is another article within
this one entitled Why the Rise in Asthma Cases, that discusses the
relationship between a decrease in infections and an increase in atopy.
Experts who I have talked to from the National Institutes of Health, the American Lung
Association, the Asthma and Allergy Foundation of America and other offices all say that this
study is very new and has not been thoroughly researched. Furthermore, they tell me that this, if
true, is certianly not the only cause for the increase of Asthma cases in developed countries like
the United States. Other articles and studies have been written on the increase of Asthma cases
being related to genetic and environmental reasons.
I have highlighted specific portions of the text that I think you may want to look over. If
you want to read a complete article, I would suggest reading the Asthma: An Epidemic in the
Absence of Infection or Why the Rise in Asthma Cases.
RESEARCH NEWS
project
world's
New Clues to Asthma Therapies
Monju
has
Identification of major players in the inflammatory cascade that damages the lungs in asthma
uterial
offers targets that may produce better treatments for the disease
The
thor-
its
in-
non.
A
rising pollen count means itchy eyes,
Each crisis causes an immediate difficulty in
the inflammatory cascade are a few years away
anging
scratchy throats, and stopped-up sinuses for
breathing, and repeated crises over time lead
from patients' medicine cabinets, two have
Had-
many allergy sufferers, but for those whose
to permanent lung changes that may make
already made it to the shelves. Both drugs,
that
allergies trigger asthma, this means more
the next attack even worse.
which were approved late last year by the U.S.
alying
than just discomfort. For them, exposure to
Current asthma treatments are aimed at
Food and Drug Administration (FDA), got
iplan-
usually harmless pollen or other allergens
the end result. Bronchodilators open the air-
ahead of the crowd for the simple reason that
can set off a life-threatening attack in which
ways, and antihistamines and steroids reduce
their targets, the leukotrienes, were impli-
Na-
the airways leading to the lungs close up-
inflammation. But by dissecting the chain
cated in the cascade nearly 50 years ago.
had
making the sufferers feel, they say, as if they
of command that leads to an attack, re-
Released by activated eosinophils and
gnext
are trying to breathe with a full-grown per-
searchers have identified a whole new set
other immune-system soldiers recruited to
of
son standing on their chest. These frighten-
asthmatic lungs, the leukotrienes have
rule
ing attacks are becoming more and more
Allergen
several effects that contribute to the
common. Since 1980, the prevalence of
Antigen presenting
States. Today, it afflicts more than 14 mil-
lion people in this country alone, and costs
ILLUSTRATION: BUTLIFF
airway constriction and inflammation
asthma has almost doubled in the United
degdritic cell
of asthma. They recruit other inflam-
matory cells, for example. But they
stails
are particularly effective in contract-
scon-
almost 5000 lives each year-with no signs
ing the smooth muscle of the bronchi,
na-
fleveling off.
the tubes carrying air from the trachea
now
Researchers don't have a clear idea of
into the lungs. Molecule for molecule,
what is causing this increase (see sidebar).
says pulmonologist Jeffrey Drazen of
Nor have they worked out what predisposes
H-4
II-5
Brigham and Women's Hospital in
some people to asthma in the first place. But
and others
and others
Boston, the leukotrienes are the most
on one front, they are making real headway.
potent bronchoconstrictors ever de-
They are beginning to pinpoint many of the
scribed-a fact, he adds, "that was not
key biological players that take part in asthma
lost on the drug companies," which
attacks. And that in turn is providing re-
set out to develop inhibitors.
searchers with openings for new ways to treat
The two approved last year are Zi-
asthma, some of which are just entering clini-
IgE
leuton, which blocks a vital enzyme
II-4
II-5
cal use. "There is a story that's coming out,"
needed for leukotriene synthesis and is
says Yale pulmonologist Jack Elias. "It's be-
marketed by Abbott Laboratories in
ginning to hang together."
Chicago, and Zafirleukast, which blocks
The main theme of the story is inflamma-
the lipid's receptors on smooth muscle
tion. Doctors have known for years that
and other cells and is produced by Zeneca
asthma attacks are often triggered by aller-
Pharmaceuticals, based in the United
gens, such as cockroaches, dust-mite feces,
Kingdom. Two more receptor blockers,
Histamines
pollen, or animal hair. Now, researchers are
Leukotrienes
from Merck and from SmithKline Beech-
working out the exact cascade of events that
am, are awaiting FDA approval.
these allergens-and other nonallergen trig-
The drugs have worked miracles in
gers such as cold air, viral infections, and
some hard-to-treat patients, Drazen
exercise-set in motion in the lungs. At the
says. "In some patients it's like manna
top of the cascade is a particular type of im-
from heaven. We treated a veterinar-
mune cell called the T lymphocyte, which
Overzealous warriors. The T lymphocyte helps
ian allergic to dogs and cats who was
responds to the noxious substances by send-
command the immune cells-including mast cells
and eosinophils-that react to pollen, cold, exercise,
just miserable. On this treatment, he is
ing out more than a dozen chemical signals:
and other stimuli to trigger an asthma attack.
a normal person again." But for reasons
so-called cytokines, which attract inflamma-
that are currently unclear, only about
tory cells to the airways of the lungs.
of promising targets for asthma drugs. "The
half of all patients respond to the drugs; in
These warriors, in particular those called
therapy is moving back closer and closer to
the other half, there is almost no change,
the eosinophils, release chemical weapons
the beginning of the inflammation cascade,"
says Sally Wenzel of National Jewish, who
of their own. This second wave of signals,
says Harold Nelson, an allergist and immu-
helped conduct several of the preapproval
including histamine and small, fatty mol-
nologist at the National Jewish Medical and
clinical trials.
ecules called leukotrienes, causes blood ves-
Research Center in Denver. The hope is that
sels to leak and lung tissues to swell, con-
these therapies, because of their improved
Stopping inflammation early
tracts the smooth muscles of the airways-
specificity, will be more effective and less
Patients who receive no relief from the
cutting off the air supply like squeezing a
liable to cause dangerous side effects than
leukotriene inhibitors still have reason to
hose-and encourages mucus production,
current treatments.
hope, however. While the leukotrienes act
further clogging already constricted airways.
Although most of the treatments aimed at
late in the inflammatory cascade, other ef-
www.sciencemag.org
SCIENCE
VOL 276
13 JUNE 1997
1643
forts are aimed at interrupting it before it gets
itself that would bind to the cytokine's re-
no indication of any side effects," Jardieu
established. One development propelling that
ceptor on eosinophils without triggering the
says. Results from a second round of trials,
research is the recognition that a particular
cells, while also preventing the native mol-
which tested the antibody's ability to protect
subset of T lymphocytes seems to be a major
ecule from binding.
400 asthma patients from natural exposures
culprit in asthma and other allergic diseases,
Perhaps closer to pharmacy shelves is an
to allergens, should be published later this
responding with undue vigor to apparently
antibody that blocks IgE itself. After TH2
summer, says Jardieu, and she expects phase
harmless invaders.
signals trigger B-cell production of an IgE
III trials-testing anti-IgE against the best
In work done nearly a decade ago, re-
with a particular specificity, the antibody
available treatment-to begin this fall.
searchers working with T cells from mice
attaches to mast cells, and when it encoun-
found they could divide the cells into two
ters a protein it recognizes as threatening, it
Tipping the balance against asthma
groups based on the cytokines they produce.
triggers the mast cells to unleash their weap-
Another therapeutic strategy currently be-
Members of one set, which they called TH1
ons, including leukotrienes and histamine. If
ing investigated aims to short-circuit mis-
cells, produce a set of signals that orches-
there were some way to block the IgE trigger,
placed TH2 attacks. TH1 and TH2 activities
trate attacks on unfamiliar cells, protecting
researchers reasoned, the whole battle could
are mutually suppressive: Signals from one
the body against bacteria
be avoided.
cell type inhibit the activity of the other. So
and tumor cells. Those in
But disarming IgE
several researchers are attempting to take
the other set-the TH2
has proved to be a
advantage of certain bacteria that induce
cells-produce inflamma-
tricky business. When
vigorous TH1 responses, causing the im-
tory signals normally di-
researchers tried to
mune system to pump out messengers, such
rected against parasitic in-
as interleukin-12 and interferon-y,
vaders. They also encour-
that inhibit TH2 cell activity.
age the antibody-producing
B cells to secrete IgE anti-
STEVE KAGAN
Some, including Steven Holgate
of Southampton University in the
bodies, the hallmark of al-
United Kingdom, Julian Hopkin
lergies, which help trigger
of Oxford University, and Gra-
the inflammatory responses.
ham Rook of University College,
As researchers learned more about these
NPN
London, are working with whole
activity patterns, it became clear that TH2
bacteria. They have just begun a
overactivity is a major factor in asthma. High
series of studies in which they will
levels of IgE, for example, are common in
Terrible trio. House dust mite (top
attempt to protect allergic volun-
asthma patients. And one of the key TH2
left), Alternaria mold (center), and
teers from the perils of allergy sea-
cytokines, called interleukin-5 (II-5 for short),
birch pollen (left) are all common
son by injecting them with a harm-
helps trigger the eosinophils that can wreak
triggers of asthma attacks.
less bacterium of the Mycobacte-
havoc in asthmatic lungs. Although the dis-
rium genus, which-like many bac-
tinction between TH1 and TH2 cells is not as
inactivate it with antibodies, some of their
teria-is a strong TH1 inducer. The hope.
cut-and-dried as many might like-many hu-
efforts turned out to have just the opposite
says Holgate, is that "if we give this to
man T cells seem to produce both TH1 and
effect, even triggering fatal allergic reac-
asthmatic subjects, maybe it can switch off
TH2 signals-Yale's Elias says the concept
tions. "I've accidentally killed animals with
the allergies."
"has opened doors in thinking about asthma"
[the wrong kind of] anti-IgE," says Paula
Immunologists found a few years ago that it
and about potential new therapies.
Jardieu of Genentech, who has led her com-
is particular sequences in the bacterial DNA
Some of those efforts are aimed directly at
pany's efforts to develop the therapy. The
that induce such a strong TH1 response. Those
thwarting the effects of TH2 cytokines. For
problem was that these antibodies attached
sequences play a key role in a therapy under
example, II-5 appears to be a good target. If
to the same part of IgE that binds the aller-
development by immunologists Eyal Raz and
the cytokine's action in mice is blocked, ei-
gen, thus triggering, rather than blocking,
Dennis Carson and allergist David Broide of
ther by inactivating the gene that codes for
IgE's effects on mast cells.
the University of California, San Diego. The
the protein or by giving the animal antibod-
Recently, however, researchers have iden-
team is attempting to devise a more effec-
ies that prevent II-5 from binding to and ac-
tified the specific region of IgE that binds to
tive means of desensitizing people to their
tivating eosinophils, the animal's airways do
the mast cell receptor, enabling them to
allergies, which currently involves repeat-
not react to allergens, says immunologist
produce antibodies that block only that
edly injecting them with small amounts of
David Huston at Baylor College of Medicine
site. Buoyed by promising results in mice,
the allergen, often for years. To bolster this
in Houston. This suggests several possible ap-
they went on to build a human version of
effect, the researchers have designed a small
proaches to asthma treatments.
the mouse antibody. Through DNA ma-
circular piece of DNA, called a plasmid, that
Two pharmaceutical companies, Schering-
nipulation, they were able to transplant
includes both the DNA encoding any of sev-
Plough and SmithKline Beecham, have been
the IgE-binding region of the mouse mol-
eral common allergen proteins and fragments
working on the development of human ver-
ecule onto the base of a human antibody.
of bacterial DNA.
sions of mouse anti-II-5 antibodies, and have
They tested the resulting "humanized" an-
In early tests, the team injected the
been getting promising results in trials with
tibody by giving it to monkeys allergic to
plasmids into mice, whose skin cells took
animals-including primates. In the animal
ragweed and found that it prevented the
up the DNA. There the plasmid started pro-
trials, the anti-II-5 antibodies have pre-
typical skin sensitivity to the pollen.
ducing the antigen protein. "It's like immu-
vented both eosinophil inflammation and
Initial trials, designed to test the safety of
notherapy," says Raz, "but instead of having
airway constriction. Human trials "are immi-
this antibody in humans, have been very
to give it repeatedly, you give it only twice or
nent," Huston says.
positive, says Jardieu. The 40 patients who
three times and it is there permanently." At
In addition, Huston and his colleagues, as
received doses of the antibody suffered only
the same time, the researchers hoped, the
well as a number of industry groups, are work-
mild reactions when the research team blew
bacterial DNA in the plasmids would crank
ing to engineer an inactive version of II-5
allergens into their lungs, with "absolutely
up the suppressive effects of the treatment by
1644
SCIENCE
VOL. 276
13 JUNE 1997
www.sciencemag.org
RESEARCH NEWS
Why the Rise in Asthma Cases?
Asthma is a disease of the industrialized 20th century. First
of Immunology and Allergy in Rome and his colleagues found.
described in the mid-1800s, it may have existed before that time,
that soldiers who tested positive for antibodies to hepatitis A
but was very rare. It is still rare in developing countries. But in the
virus-a sign of more childhood infections in general, say the
developed world in the last 2 decades, asthma rates have skyrock-
authors-had significantly fewer allergies. (The results appeared
eted-doubling in the United States since 1980. "Asthma and
in the April British Medical Journal:)
allergies have become representative of the westernization of our
Researchers have also turned up other hints that early im-
society," says William Busse, an allergist at the University of
munological experience can affect a child's chances of devel-
Wisconsin, Madison.
oping asthma-very early experience, if Jill Warner at the
Researchers do not yet know why. They have come a long way
University at Southampton in the United Kingdom is right.
in dissecting the sequence of events that leads to individual
When she and her colleagues studied immune cells from pre-
asthma attacks: the activation by an allergen or other trigger of
mature and terminated fetuses, they found that cells from fe-
certain immune cells, which in turn marshal other cells that
tuses as young as 22 weeks could multiply when exposed to
mount inflammatory attacks on the lungs (see main text). But
house dust mites and birch pollen-suggesting that they recog-
why some people are predisposed to such attacks-and why their
nized the allergens from a previous exposure. Warner is cur-
numbers are now increasing-remain mysteries, although re-
rently studying whether limiting a mother's exposure to com-
searchers have some clues.
mon allergens can protect her unborn child from later develop-
Increased exposure to environ-
ing allergies and asthma.
16
mental allergens and immune sys-
Still, environmental influences
tem changes due to fewer child-
14
can't be the full answer, because
hood infections may play a role, say
asthma susceptibility is well known
12
some. And geneticists are closing in
to run in families. A number of all-
on a host of genes that have been
urgent, says Busse, because it might
Asthma prevalence
10
out hunts are now under way for
linked to increased asthma suscep-
tibility. The search for a cause is
(in millions)
8
BOURCE: AMERICAN LUNG ASSOCIATION
asthma-susceptibility genes, which
might be interacting with environ-
6
mental factors to drive the rising
point to ways of preventing chil-
4
incidence. So far, only one team—
dren from developing the disease in
at Sequana Therapeutics Inc. in San
the first place. For the moment, he
2
Diego-says it has pinpointed a
says, "we are treating the conse-
0
gene, and team members are keep-
quences of the disease, not prevent-
'82
'83
'84
'85
'86
'87
'88
89
'90
'91
'92
'93
'94
ing details of their find under wraps
ing it from occurring."
(Science, 30 May 1997, p. 1327). But
Asthma ascending. Researchers are struggling to explain
One of the most popular theories
asthma's dramatic increase.
several more public searches are clos-
holds that asthma has increased partly
ing in on genes.
because of greater exposure to aller-
A team led by Carol Ober, a ge-
gens such as house dust mites or cockroaches. Allergist Thomas
neticist at the University of Chicago, reported at the recent
Platts-Mills of the University of Virginia notes that nowadays
American Thoracic Society meeting that its work with the South
children spend more time indoors in front of the television in
Dakota Hutterites, a religious group of 5000 descended from 64
close contact with carpets and upholstered furniture crawling
18th-century ancestors, has linked asthma or asthmalike condi-
with dust mites. Still, Platts-Mills says, this "Annette Funicello"
tions to specific regions on chromosomes 2, 13, and 21. And in a
effect, as he calls it, "can't explain the rise by itself." The asthma
wider study of the general population, the multicenter Collabora-
increase is just too great and has occurred even in dry regions
tive Study on the Genetics of Asthma reported in the April issue
where the dust mite is uncommon.
of Nature Genetics that its researchers have linked asthma in
Another feature of modern life might also be contributing:
various ethnic groups to a half-dozen different chromosome re-
the fall in childhood infections. Early infections, say proponents
gions. Other studies have found linkages to regions on chromo-
of this idea, may stimulate a kind of immune response that
somes 11 and 12 containing genes known to code for important
suppresses later allergic reactions. Earlier this year, Oxford
players in the inflammation that is part of asthma pathology.
pulmonologist Julian Hopkin and colleagues at the Wakayama
The linkages, like all the other clues, are a long way from
Medical Center in Wakayama, Japan, found that children who
solving the asthma riddle, but they are a start. "Everyone knew
onded strongly to a skin test indicating that they had been
[the gene search] was a black hole," says Susan Banks-Schlagel,
exposed to tuberculosis are less likely to suffer from asthma or
manager of asthma research at the National Heart, Lung, and
other allergic diseases (Science, 3 January, p. 77). Similarly, in a
Blood Institute. "They said, 'Oh, you'll never find anything.' But
study of 1600 Italian soldiers, Paolo Matricardi of the Laboratory
some interesting things are starting to happen."
-G.V.
eliciting production of interferon-ya other
stance to which they were allergic. Raz and
But the TH2 model that has inspired these
TH2 suppressors.
his colleagues have formed a company,
new treatments may not be a complete an-
Again, initial results are promising. Mice
called Dynavax, and plan to begin human
swer to the asthma puzzle. Viral infections,
receiving the novel immunotherapy have
trials in collaboration with researchers at
for example, have been blamed for 80% of
IgE in their blood, fewer eosinophils in
Johns Hopkins University as soon as they
severe asthma attacks, says Daniel Rotrosen
their lungs, and less evidence of TH2-type
receive FDA approval-expected "within the
of the National Institute of Allergy and In-
cytokines when they are exposed to the sub-
year," says Raz.
fectious Diseases. But viruses have usually
www.sciencemag.org
SCIENCE
VOL. 276
13 JUNE 1997
1645
been considered a trigger of a TH1-type
Those unanswered questions might ex-
many suspect is the case: Asthma is not a
response. Some researchers believe that vi-
plain why new treatments such as the leu-
single disease. Like pneumonia or anemia,
ruses are not the immediate trigger, but
kotriene inhibitors will not work for every-
Brigham and Women's Drazen says, asthma
contribute to asthma susceptibility by at-
one. But the fact that the drugs don't help
is a set of symptoms that has varied causes.
tacking the lining of the lungs, leaving the
some patients may be as important as the
The new treatments, by getting closer to
inner layers more exposed to environmen-
help they do give some people: "That is
those causes, may help doctors divide pa-
tal allergens or other traditional asthma
where it gets really interesting," Drazen says.
tients into subgroups based on how they
triggers-which would then activate TH2
"Up until now, we have graded asthma as
respond to treatments, he adds. That, in
cells and the other responses they orches-
mild, moderate or severe," which is only of
turn, will help researchers determine how to
trate. Others believe the viruses may have
limited help to physicians trying to deter-
treat each patient most effectively-a de-
an inside role, activating certain genes in
mine the best course of treatment.
velopment, certainly, that will help mil-
the nucleus chat exacerbate or trigger the
Patients' different responses to the vari-
lions breathe easier.
inflammatory cascade.
ous drugs may help doctors sort out what
-Gretchen Vogel
IMMUNOLOGY.
New Lead to Safer Marrow Transplants
looked promising: Lymphocytes engineered
with the gene for the enzyme thymidine ki-
Bone-marrow transplants have become a
the top bone-marrow transplant centers, par-
nase died when he doused them with the
mainstay of medicine's battle against blood-
ticularly in patients who relapsed and re-
antiviral drug ganciclovir, which the enzyme
cell cancers, such as leukemias and lym-
quired infusions of donor lymphocytes. Mar-
converts to a deadly poison.
phomas, as well as against certain noncan-
row transplants are needed because the high
After showing that ganciclovir also kills
cerous blood diseases. But in at least half of
doses of chemotherapeutic drugs and radia-
the suicide gene-bearing lymphocytes in mice,
all patients, the donor immune cells turn
tion given to leukemia and lymphoma pa-
Bordignon and colleagues began their pilot
against the recipient's own tissues, triggering
tients in an effort to rid them of all cancer
study in humans. In 1993, they infused donor
a deadly ailment called graft-versus-host dis-
cells also destroy the patients' bone marrow,
lymphocytes bearing the thymidine kinase or
ease (GVHD). Now a team of doctors led by
the vital source of both the red cells and the
suicide gene into 12 patients who, after re-
hematologist Claudio Bordignon at the San
infection-fighting white cells of the blood.
ceiving bone-marrow transplants, had suf-
Raffaele Scientific Institute in Milan, Italy,
But unless the donor is an identical twin,
fered complications such as cancer relapse or
may have found a solution to this problem.
the transplant may turn on a patient, caus-
virus-induced lymphomas. The lymphocytes
On page 1719, the group reports the first
ing GVHD, as the foreign white blood cells
survived in the patients for up to a year, bat-
successful human test of a gene therapy
tling the tumors to achieve complete or par-
designed to halt the attack of the
tial remissions in five of the eight patients for
donated cells on the recipient's tis-
whom results are available.
sues. The researchers genetically en-
Of the three patients who developed
RCH CENTER
gineered the transplanted cells with
GVHD, ganciclovir totally shut down the
a self-destruct button that enables
immune attack in two; in the third, the disease
doctors to kill them selectively with
was attenuated. The success may have been
a drug if they turn mutinous. This
limited in the third patient, Greenberg specu-
allowed the team to wipe out GVHD
lates, because some of the infused lympho-
in two of the three patients who de-
cytes may not have borne the suicide gene.
veloped it, and partially eliminate it
Still, if the new gene-therapy procedure
in the third-without using immuno-
helps two out of every three patients, it will be
suppressive drugs.
an improvement. Researchers caution, how-
That success is a boost for the strug-
Under attack. Multiple lymphocytes are invading the
ever, that tests in many more patients will be
GEORGE SALE/FRED CANCER
gling field of genetic therapy, says im-
epidermis of human skin with graft-versus-host disease.
needed to determine just how effective the
munologist Drew Pardoll of the Johns
therapy is. Toward this end, Bordignon is or-
Hopkins University School of Medicine in
attack essential organs such as the liver,
ganizing a multicenter European trial that he
Baltimore, who calls the work "one of a very
gut, and skin. Clinicians have sought to
hopes will start by the end of 1997. But even
small cohort of examples in which gene
avoid this attack by sifting out all of the
that may not settle the question, says Pardoll,
therapy has been shown to have clinical util-
mature T lymphocytes from the foreign mar-
because transporting the Italian group's tech-
ity." Indeed, if further studies bear out the
row before infusing it. Those are the cells that
nique to other centers may be difficult: "I can
early promise of the technique, it could make
trigger GVHD, but their removal leaves the
count on one hand, with a couple of fingers
bone-marrow transplants much safer and
patient more vulnerable to infections or can-
missing, the number of groups that could do
more effective. Doctors might even start
cer relapse. If infection or cancer does de-
this [gene-transfer procedure] with high effi-
using such transplants more broadly, in pa-
velop, the patient can be infused with the do-
ciency." He adds, however, that developing
tients with less advanced disease. The tech-
nor T cells-again running the risk of GVHD.
simple, reproducible protocols for the proce-
nique is "very exciting," says immunologist
Bordignon, a doctor trained in gene
dure could boost that number.
Philip Greenberg of the Fred Hutchinson
therapy, recalls that he asked himself, "How
One thing is certain. The therapy has al-
Cancer Research Center in Seattle. "It has the
might one take advantage of gene-transfer
ready shown sufficient promise, says Richard
potential to improve substantially the out-
technology to control this problem?" He set
O'Reilly, a marrow-transplant pioneer at
come of [bone-marrow] transplantation."
out in early 1992 to test whether he could
New York City's Memorial Sloan-Kettering
The strategy's seeds were planted in 1990,
introduce a "suicide gene" into these cells,
Cancer Center, to ensure that it "will be
when Bordignon first heard about the prob-
then use the gene to kill the cells if they
looked at by many people."
lems with GVHD
were cropping up in
triggered GVHD. Results with cultured cells
-Ingrid Wickelgren
1
SCIENCE
VOL. 276
13 JUNE 1997
www.sciencemag.org
RESEARCH NEWS
project
world's
New Clues to Asthma Therapies
Monju
ich
has
Identification of major players in the inflammatory cascade that damages the lungs in asthma
naterial
offers targets that may produce better treatments for the disease
The
thor-
ists
in-
non.
A rising pollen count means itchy eyes,
Each crisis causes an immediate difficulty in
the inflammatory cascade are a few years away
anging
scratchy throats, and stopped-up sinuses for
breathing, and repeated crises over time lead
from patients' medicine cabinets, two have
Had-
many allergy sufferers, but for those whose
to permanent lung changes that may make
already made it to the shelves. Both drugs,
that
allergies trigger asthma, this means more
the next attack even worse.
which were approved late last year by the U.S.
adying
than just discomfort. For them, exposure to
Current asthma treatments are aimed at
Food and Drug Administration (FDA), got
iplan-
usually harmless pollen or other allergens
the end result. Bronchodilators open the air-
ahead of the crowd for the simple reason that
trator
can set off a life-threatening attack in which
ways, and antihistamines and steroids reduce
their targets, the leukotrienes, were impli-
Na-
the airways leading to the lungs close up-
inflammation. But by dissecting the chain
cated in the cascade nearly 50 years ago.
had
making the sufferers feel, they say, as if they
of command that leads to an attack, re-
Released by activated eosinophils and
enext
are trying to breathe with a full-grown per-
searchers have identified a whole new set
other immune-system soldiers recruited to
gal
of
son standing on their chest. These frighten-
asthmatic lungs, the leukotrienes have
retule
ing attacks are becoming more and more
Allergen
several effects that contribute to the
common. Since 1980, the prevalence of
Antigen presenting
Japan
asthma has almost doubled in the United
lion people in this country alone, and costs
ILLUSTRATION: SUTLIFF
airway constriction and inflammation
dendritic cell
of asthma. They recruit other inflam-
States. Today, it afflicts more than 14 mil-
matory cells, for example. But they
inails
are particularly effective in contract-
con-
almost 5000 lives each year-with no signs
ing the smooth muscle of the bronchi,
na-
of leveling off.
the tubes carrying air from the trachea
now
Researchers don't have a clear idea of
into the lungs. Molecule for molecule,
hugh
what is causing this increase (see sidebar).
says pulmonologist Jeffrey Drazen of
Nor have they worked out what predisposes
II-4
II-5
Brigham and Women's Hospital in
port
some people to asthma in the first place. But
and others
and others
Boston, the leukotrienes are the most
on one front, they are making real headway.
potent bronchoconstrictors ever de-
They are beginning to pinpoint many of the
scribed-a fact, he adds, "that was not
key biological players that take part in asthma
lost on the drug companies," which
attacks. And that in turn is providing re-
set out to develop inhibitors.
searchers with openings for new ways to treat
The two approved last year are Zi-
for
asthma, some of which are just entering clini-
IgE
leuton, which blocks a vital enzyme
II-4
II-5
cal use. "There is a story that's coming out,"
needed for leukotriene synthesis and is
says Yale pulmonologist Jack Elias. "It's be-
marketed by Abbott Laboratories in
of
ginning to hang together."
Chicago, and Zafirleukast, which blocks
The main theme of the story is inflamma-
the lipid's receptors on smooth muscle
tion. Doctors have known for years that
and other cells and is produced by Zeneca
asthma attacks are often triggered by aller-
Pharmaceuticals, based in the United
gens, such as cockroaches, dust-mite feces,
Kingdom. Two more receptor blockers,
Histamines
pollen, or animal hair. Now, researchers are
Leukotrienes
from Merck and from SmithKline Beech-
working out the exact cascade of events that
am, are awaiting FDA approval.
these allergens-and other nonallergen trig-
The drugs have worked miracles in
gers such as cold air, viral infections, and
some hard-to-treat patients, Drazen
exercise-set in motion in the lungs. At the
says. "In some patients it's like manna
top of the cascade is a particular type of im-
from heaven. We treated a veterinar-
mune cell called the T lymphocyte, which
Overzealous warriors. The T lymphocyte helps
ian allergic to dogs and cats who was
responds to the noxious substances by send-
command the immune cells-including mast cells
and eosinophils-that react to pollen, cold, exercise,
just miserable. On this treatment, he is
ing out more than a dozen chemical signals:
and other stimuli to trigger an asthma attack.
a normal person again." But for reasons
so-called cytokines, which attract inflamma-
that are currently unclear, only about
tory cells to the airways of the lungs.
of promising targets for asthma drugs. "The
half of all patients respond to the drugs; in
These warriors, in particular those called
therapy is moving back closer and closer to
the other half, there is almost no change,
the eosinophils, release chemical weapons
the beginning of the inflammation cascade,"
says Sally Wenzel of National Jewish, who
of their own. This second wave of signals,
says Harold Nelson, an allergist and immu-
helped conduct several of the preapproval
including histamine and small, fatty mol-
nologist at the National Jewish Medical and
clinical trials.
ecules called leukotrienes, causes blood ves-
Research Center in Denver. The hope is that
sels to leak and lung tissues to swell, con-
these therapies, because of their improved
Stopping inflammation early
tracts the smooth muscles of the airways-
specificity, will be more effective and less
Patients who receive no relief from the
cutting off the air supply like squeezing a
liable to cause dangerous side effects than
leukotriene inhibitors still have reason to
hose-and encourages mucus production,
current treatments.
hope, however. While the leukotrienes act
further clogging already constricted airways.
Although most of the treatments aimed at
late in the inflammatory cascade, other ef-
www.sciencemag.org
SCIENCE
VOL. 276
13 JUNE 1997
1643
forts are aimed at interrupting it before it gets
itself that would bind to the cytokine's re-
no indication of any side effects," Jardieu
established. One development propelling that
ceptor on eosinophils-without triggering the
says. Results from a second round of trials,
research is the recognition that a particular
cells, while also preventing the native mol-
which tested the antibody's ability to protect
subset of T lymphocytes seems to be a major
ecule from binding.
400 asthma patients from natural exposures
culprit in asthma and other allergic diseases,
Perhaps closer to pharmacy shelves is an
to allergens, should be published later this
responding with undue vigor to apparently
antibody that blocks lgE itself. After TH2
summer, says Jardieu, and she expects phase
harmless invaders.
signals trigger B-cell production of an IgE
III trials-testing anti-IgE against the best
In work done nearly a decade ago, re-
with a particular specificity, the antibody
available treatment-to begin this fall.
searchers working with T cells from mice
attaches to mast cells, and when it encoun-
found they could divide the cells into two
ters a protein it recognizes as threatening, it
Tipping the balance against asthma
groups based on the cytokines they produce.
triggers the mast cells to unleash their weap-
Another therapeutic strategy currently be-
Members of one set, which they called TH1
ons, including leukotrienes and histamine. If
ing investigated aims to short-circuit mis-
cells, produce a set of signals that orches-
there were some way to block the IgE trigger,
placed TH2 attacks. TH1 and TH2 activities
trate attacks on unfamiliar cells, protecting
researchers reasoned, the whole battle could
are mutually suppressive: Signals from one
the body against bacteria
EFA
be avoided.
cell type inhibit the activity of the other. So
and tumor cells. Those in
But disarming IgE
several researchers are attempting to take
the other set-the TH2
has proved to be a
advantage of certain bacteria that induce
cells-produce inflamma-
tricky business. When
vigorous TH1 responses, causing the im-
tory signals normally di-
researchers tried to
mune system to pump out messengers, such
rected against parasitic in-
as interleukin-12 and interferon-y.
vaders. They also encour-
that inhibit TH2 cell activity.
age the antibody-producing
B cells to secrete IgE anti-
STEVE KAGAN
Some, including Steven Holgate
of Southampton University in the
bodies, the hallmark of al-
United Kingdom, Julian Hopkin
lergies, which help trigger
of Oxford University, and Gra-
the inflammatory responses.
ham Rook of University College,
As researchers learned more about these
NPN
London, are working with whole
activity patterns, it became clear that TH2
bacteria. They have just begun a
overactivity is a major factor in asthma. High
series of studies in which they will
levels of IgE, for example, are common in
Terrible trio. House dust mite (top
attempt to protect allergic volun-
asthma patients. And one of the key TH2
left), Alternaria mold (center), and
teers from the perils of allergy sea-
cytokines, called interleukin-5 (II-5 for short),
birch pollen (left) are all common
son by injecting them with a harm-
helps trigger the eosinophils that can wreak
triggers of asthma attacks.
less bacterium of the Mycobacte-
havoc in asthmatic lungs. Although the dis-
rium genus, which-like many bac-
tinction between TH1 and TH2 cells is not as
inactivate it with antibodies, some of their
teria-is a strong TH1 inducer. The hope,
cut-and-dried as many might like-many hu-
efforts turned out to have just the opposite
says Holgate, is that "if we give this to
man T cells seem to produce both TH1 and
effect, even triggering fatal allergic reac-
asthmatic subjects, maybe it can switch off
TH2 signals-Yale's Elias says the concept
tions. "I've accidentally killed animals with
the allergies."
"has opened doors in thinking about asthma"
[the wrong kind of] anti-IgE," says Paula
Immunologists found a few years ago that it
and about potential new therapies.
Jardieu of Genentech, who has led her com-
is particular sequences in the bacterial DNA
Some of those efforts are aimed directly at
pany's efforts to develop the therapy. The
that induce such a strong TH1 response. Those
thwarting the effects of TH2 cytokines. For
problem was that these antibodies attached
sequences play a key role in a therapy under
example, II-5 appears to be a good target. If
to the same part of IgE that binds the aller-
development by immunologists Eyal Raz and
the cytokine's action in mice is blocked, ei-
gen, thus triggering, rather than blocking,
Dennis Carson and allergist David Broide of
ther by inactivating the gene that codes for
IgE's effects on mast cells.
the University of California, San Diego. The
the protein or by giving the animal antibod-
Recently, however, researchers have iden-
team is attempting to devise a more effec-
ies that prevent II-5 from binding to and ac-
tified the specific region of IgE that binds to
tive means of desensitizing people to their
tivating eosinophils, the animal's airways do
the mast cell receptor, enabling them to
allergies, which currently involves repeat-
not react to allergens, says immunologist
produce antibodies that block only that
edly injecting them with small amounts of
David Huston at Baylor College of Medicine
site. Buoyed by promising results in mice,
the allergen, often for years. To bolster this
in Houston. This suggests several possible ap-
they went on to build a human version of
effect, the researchers have designed a small
proaches to asthma treatments.
the mouse antibody. Through DNA ma-
circular piece of DNA, called a plasmid, that
Two pharmaceutical companies, Schering-
nipulation, they were able to transplant
includes both the DNA encoding any of sev-
Plough and SmithKline Beecham, have been
the IgE-binding region of the mouse mol-
eral common allergen proteins and fragments
working on the development of human ver-
ecule onto the base of a human antibody.
of bacterial DNA.
sions of mouse anti-l1-5 antibodies, and have
They tested the resulting "humanized" an-
In early tests, the team injected the
been getting promising results in trials with
tibody by giving it to monkeys allergic to
plasmids into mice, whose skin cells took
animals-including primates. In the animal
ragweed and found that it prevented the
up the DNA. There the plasmid started pro-
trials, the anti-II-5 antibodies have pre-
typical skin sensitivity to the pollen.
ducing the antigen protein. "It's like immu-
vented both eosinophil inflammation and
Initial trials, designed to test the safety of
notherapy," says Raz, "but instead of having
airway constriction. Human trials "are immi-
this antibody in humans, have been very
to give it repeatedly, you give it only twice or
nent," Huston says.
positive, says Jardieu. The 40 patients who
three times and it is there permanently." At
In addition, Huston and his colleagues, as
received doses of the antibody suffered only
the same time, the researchers hoped, the
well as a number of industry groups, are work-
mild reactions when the research team blew
bacterial DNA in the plasmids would crank
ing to engineer an inactive version of II-5
allergens into their lungs, with "absolutely
up the suppressive effects of the treatment by
1644
SCIENCE
VOL. 276
13 JUNE 1997
www.sciencemag.org
RESEARCH NEWS
Why the Rise in Asthma Cases?
Asthma is a disease of the industrialized 20th century. First
of Immunology and Allergy in Rome and his colleagues found
described in the mid-1800s, it may have existed before that time,
that soldiers who tested positive for antibodies to hepatitis A
but was very rare. It is still rare in developing countries. But in the
virus-a sign of more childhood infections in general, say the
developed world in the last 2 decades, asthma rates have skyrock-
authors-had significantly fewer allergies. (The results appeared
eted-doubling in the United States since 1980. "Asthma and
in the April British Medical Journal.)
allergies have become representative of the westernization of our
Researchers have also turned up other hints that early im-
society," says William Busse, an allergist at the University of
munological experience can affect a child's chances of devel-
Wisconsin, Madison.
oping asthma-very early experience, if Jill Warner at the
Researchers do not yet know why. They have come a long way
University at Southampton in the United Kingdom is right.
in dissecting the sequence of events that leads to individual
When she and her colleagues studied immune cells from pre-
asthma attacks: the activation by an allergen or other trigger of
mature and terminated fetuses, they found that cells from fe-
certain immune cells, which in turn marshal other cells that
tuses as young as 22 weeks could multiply when exposed to
mount inflammatory attacks on the lungs (see main text). But
house dust mites and birch pollen-suggesting that they recog-
why some people are predisposed to such attacks-and why their
nized the allergens from a previous exposure. Warner is cur-
numbers are now increasing-remain mysteries, although re-
rently studying whether limiting a mother's exposure to com-
searchers have some clues.
mon allergens can protect her unborn child from later develop-
Increased exposure to environ-
ing allergies and asthma.
16
mental allergens and immune sys-
Still, environmental influences
tem changes due to fewer child-
14
can't be the full answer, because
hood infections may play a role, say
asthma susceptibility is well known
12
some. And geneticists are closing in
to run in families. A number of all-
on a host of genes that have been
urgent, says Busse, because it might
Asthma prevalence
10
out hunts are now under way for
linked to increased asthma suscep-
tibility. The search for a cause is
(in millions)
8
SOURCE: AMERICAN LUNG ASSOCIATION
asthma-susceptibility genes, which
might be interacting with environ-
6
mental factors to drive the rising
point to ways of preventing chil-
4
incidence. So far, only one team-
dren from developing the disease in
at Sequana Therapeutics Inc. in San
the first place. For the moment, he
2
Diego-says it has pinpointed a
says, "we are treating the conse-
0
gene, and team members are keep-
quences of the disease, not prevent-
'82
'83
'84
'85
'86
'87
'88
89
'90
91
'92
'93
94
ing details of their find under wraps
ing it from occurring."
Asthma ascending. Researchers are struggling to explain
(Science, 30 May 1997, p. 1327). But
One of the most popular theories
asthma's dramatic increase.
several more public searches are clos-
holds that asthma has increased partly.
ing in on genes.
because of greater exposure to aller-
A team led by Carol Ober, a ge-
gens such as house dust mites or cockroaches. Allergist Thomas
neticist at the University of Chicago, reported at the recent
Platts-Mills of the University of Virginia notes that nowadays
American Thoracic Society meeting that its work with the South
children spend more time indoors in front of the television in
Dakota Hutterites, a religious group of 5000 descended from 64
close contact with carpets and upholstered furniture crawling
18th-century ancestors, has linked asthma or asthmalike condi-
with dust mites. Still, Platts-Mills says, this "Annette Funicello"
tions to specific regions on chromosomes 2, 13, and 21. And in a
effect, as he calls it, "can't explain the rise by itself." The asthma
wider study of the general population, the multicenter Collabora-
increase is just too great and has occurred even in dry regions
tive Study on the Genetics of Asthma reported in the April issue
where the dust mite is uncommon.
of Nature Genetics that its researchers have linked asthma in
Another feature of modern life might also be contributing:
various ethnic groups to a half-dozen different chromosome re-
the fall in childhood infections. Early infections, say proponents
gions. Other studies have found linkages to regions on chromo-
of this idea, may stimulate a kind of immune response that
somes 11 and 12 containing genes known to code for important
suppresses later allergic reactions. Earlier this year, Oxford
players in the inflammation that is part of asthma pathology.
pulmonologist Julian Hopkin and colleagues at the Wakayama
The linkages, like all the other clues, are a long way from
Medical Center in Wakayama, Japan, found that children who
solving the asthma riddle, but they:are a start. "Everyone knew
responded strongly to a skin test indicating that they had been
[the gene search] was a black hole," says Susan Banks-Schlagel,
exposed to tuberculosis are less likely to suffer from asthma or
manager of asthma research at the National Heart, Lung, and
other allergic diseases (Science, 3 January, p. 77). Similarly, in a
Blood Institute. "They said, 'Oh, you'll never find anything.' But
study of 1600 Italian soldiers, Paolo Matricardi of the Laboratory
some interesting things are starting to happen."
-G.V.
eliciting production of interferon-yand other
stance to which they were allergic. Raz and
But the TH2 model that has inspired these
TH2 suppressors.
his colleagues have formed a company,
new treatments may not be a complete an-
Again, initial results are promising. Mice
called Dynavax, and plan to begin human
swer to the asthma puzzle. Viral infections,
receiving the novel immunotherapy have
trials in collaboration with researchers at
for example, have been blamed for 80% of
less IgE in their blood, fewer eosinophils in
Johns Hopkins University as soon as they
severe asthma attacks, says Daniel Rotrosen
their lungs, and less evidence of TH2-type
receive FDA approval-expected "within the
of the National Institute of Allergy and In-
cytokines when they are exposed to the sub-
year," says Raz.
fectious Diseases. But viruses have usually
www.sciencemag.org
SCIENCE
VOL. 276
13 JUNE 1997
1645
been considered a trigger of a TH1-type
Those unanswered questions might ex-
many suspect is the case: Asthma is not a
response. Some researchers believe that vi-
plain why new treatments such as the leu-
single disease. Like pneumonia or anemia,
ruses are not the immediate trigger, but
kotriene inhibitors will not work for every-
Brigham and Women's Drazen says, asthma
contribute to asthma susceptibility by at-
one. But the fact that the drugs don't help
is a set of symptoms that has varied causes.
tacking the lining of the lungs, leaving the
some patients may be as important as the
The new treatments, by getting closer to
inner layers more exposed to environmen-
help they do give some people: "That is
those causes, may help doctors divide pa-
tal allergens or other traditional asthma
where it gets really interesting," Drazen says.
tients into subgroups based on how they
triggers-which would then activate TH2
"Up until now, we have graded asthma as
respond to treatments, he adds. That, in
cells and the other responses they orches-
mild, moderate or severe," which is only of
turn, will help researchers determine how to
trate. Others believe the viruses may have
limited help to physicians trying to deter-
treat each patient most effectively-a de-
an inside role, activating certain genes in
mine the best course of treatment.
velopment, certainly, that will help mil-
the nucleus that exacerbate or trigger the
Patients' different responses to the vari-
lions breathe easier.
inflammatory cascade.
ous drugs may help doctors sort out what
-Gretchen Vogel
IMMUNOLOGY
New Lead to Safer Marrow Transplants
looked promising: Lymphocytes engineered
with the gene for the enzyme thymidine ki-
Bone-marrow transplants have become a
the top bone-marrow transplant centers, par-
nase died when he doused them with the
mainstay of medicine's battle against blood-
ticularly in patients who relapsed and re-
antiviral drug ganciclovir, which the enzyme
cell cancers, such as leukemias and lym-
quired infusions of donor lymphocytes. Mar-
converts to a deadly poison.
phomas, as well as against certain noncan-
row transplants are needed because the high
After showing that ganciclovir also kills
cerous blood diseases. But in at least half of
doses of chemotherapeutic drugs and radia-
the suicide gene-bearing lymphocytes in mice,
all patients, the donor immune cells turn
tion given to leukemia and lymphoma pa-
Bordignon and colleagues began their pilot
against the recipient's own tissues, triggering
tients in an effort to rid them of all cancer
study in humans. In 1993, they infused donor
a deadly ailment called graft-versus-host dis-
cells also destroy the patients' bone marrow,
lymphocytes bearing the thymidine kinase or
ease (GVHD). Now a team of doctors led by
the vital source of both the red cells and the
suicide gene into 12 patients who, after re-
hematologist Claudio Bordignon at the San
infection-fighting white cells of the blood.
ceiving bone-marrow transplants, had suf-
Raffaele Scientific Institute in Milan, Italy,
But unless the donor is an identical twin,
fered complications such as cancer relapse or
may have found a solution to this problem.
the transplant may turn on a patient, caus-
virus-induced lymphomas. The lymphocytes
On page 1719, the group reports the first
ing GVHD, as the foreign white blood cells
survived in the patients for up to a year, bat-
successful human test of a gene therapy
tling the tumors to achieve complete or par-
designed to halt the attack of the
tial remissions in five of the eight patients for
donated cells on the recipient's tis-
whom results are available.
sues. The researchers genetically en-
Of the three patients who developed
gineered the transplanted cells with
GVHD, ganciclovir totally shut down the
a self-destruct button that enables
immune attack in two; in the third, the disease
doctors to kill them selectively with
was attenuated. The success may have been
a drug if they turn mutinous. This
limited in the third patient, Greenberg specu-
allowed the team to wipe out GVHD
lates, because some of the infused lympho-
in two of the three patients who de-
cytes may not have borne the suicide gene.
veloped it, and partially eliminate it
Still, if the new gene-therapy procedure
in the third-without using immuno-
helps two out of every three patients, it will be
suppressive drugs.
an improvement. Researchers caution, how-
GEORGE SALE/FRED HUTCHINSON CANCER RESEARCH CENTER
That success is a boost for the strug-
Under attack. Multiple lymphocytes are invading the
ever, that tests in many more patients will be
gling field of genetic therapy, says im-
epidermis of human skin with graft-versus-host disease.
needed to determine just how effective the
munologist Drew Pardoll of the Johns
therapy is. Toward this end, Bordignon is or-
Hopkins University School of Medicine in
attack essential organs such as the liver,
ganizing a multicenter European trial that he
Baltimore, who calls the work "one of a very
gut, and skin. Clinicians have sought to
hopes will start by the end of 1997. But even
small cohort of examples in which gene
avoid this attack by sifting out all of the
that may not settle the question, says Pardoll,
therapy has been shown to have clinical util-
mature T lymphocytes from the foreign mar-
because transporting the Italian group's tech-
ity." Indeed, if further studies bear out the
row before infusing it. Those are the cells that
nique to other centers may be difficult: "I can
early promise of the rechnique, it could make
trigger GVHD, but their removal leaves the
count on one hand, with a couple of fingers
bone-marrow transplants much safer and
patient more vulnerable to infections or can-
missing, the number of groups that could do
more effective. Doctors might even start
cer relapse. If infection or cancer does de-
this [gene-transfer procedure] with high effi-
using such transplants more broadly, in pa-
velop, the patient can be infused with the do-
ciency." He adds, however, that developing
tients with less advanced disease. The tech-
nor T cells-again running the risk of GVHD.
simple, reproducible protocols for the proce-
nique is "very exciting," says immunologist
Bordignon, a doctor trained in gene
dure could boost that number.
Philip Greenberg of the Fred Hutchinson
therapy, recalls that he asked himself, "How
One thing is certain. The therapy has al-
Cancer Research Center in Seattle. "It has the
might one take advantage of gene-transfer
ready shown sufficient promise, says Richard
potential to improve substantially the out-
technology to control this problem?" He set
O'Reilly, a marrow-transplant pioneer at
come of [bone-marrow] transplantation."
out in early 1992 to test whether he could
New York City's Memorial Sloan-Kettering
The strategy's seeds were planted in 1990,
introduce a "suicide gene" into these cells,
Cancer Center, to ensure that it "will be
when Bordignon first heard about the prob-
then use the gene to kill the cells if they
looked at by many people."
lems with GVHD that were cropping up in
triggered GVHD. Results with cultured cells
-Ingrid Wickelgren
1646
SCIENCE
VOL. 276
13 JUNE 1997
www.sciencemag.org
PERSPECTIVES
ing the November 1995 assault on Jaffna.
poration of the rebels into the national army
continue the development of tasks and tools
Cease-fires have been declared in Sudan for
in El Salvador and, recently, in the Philip-
that can serve as instruments of peace.
both polio and dracunculiasis eradication, ex-
pines provides evidence that days of tran-
panding health truces beyond immunization.
quillity can be the first of many steps toward
References
Days of tranquillity permit warring parties
a lasting peace. Polio eradication activities
1. W. Morris, Ed., The American Heritage Dictionary
to disengage and provide a glimpse of peace,
must be conducted amidst current and future
of the English Language (Houghton-Mifflin, Bos-
but also give both sides a common goal to
conflicts around the world. We are confident
ton, 1978), p. 833.
serve as a starting point for future negotia-
that there will be more truces and polio will
2. K. J. Bart et al., WHO 74, 35 (1996).
3. Anonymous, Wkly Epidemiol. Rec. 71, 189 (1995).
tions. The resolution of conflict with incor-
be eradicated. The challenge for science is to
4. H. F. Hull et al., Lancet 343, 1331 (1994).
IMMUNOLOGY
Asthma: An Epidemic in the
den and polluted Poland show the same phe-
nomenon (5). The German investigators also
Absence of Infection?
found that the prevalence of asthma was lower
in the youngest children of large families than
in children high in the birth order (6).
These results suggest that asthma preva-
William O. C. M. Cookson and Miriam F. Moffatt
lence has increased because of something lack-
ing in the modern environment, rather than
through the positive actions of some toxic fac-
7.
tor. Respiratory and other infections are much
Asthma is a chronic and debilitating disease,
Pollution
n
more common in polluted and crowded East-
3-
causing swollen and inflamed airways that are
crowding.
em block countries than in the West, and
prone to constrict suddenly and violently.
Poor sanitation
younger children get more infections from
Asthmatics have attacks of shortness of breath
their siblings than single or older children.
7.
and wheezing that can be life-threatening or
Childhood infections may, therefore, para-
even fatal. The prevalence of asthma in West-
TB
Viral
Helminth
doxically protect against asthma. The study
ernized societies has risen steadily this century,
infection
infection
infection
by Shirakawa et al. on children in Japan
doubling in the last 20 years (1). Asthma now
focuses on tuberculosis as a key in-
affects one child in seven in Great Britain, and
Polyclonal IgE
fection influencing asth-
in the United States it causes one-third of pedi-
ma prevalence (3).
-ve
atric emergency-room visits. Asthma is famil-
Aero allergens
Inflammation is mod-
house dust mite
ial, and genome-wide searches by our group and
pollens
ulated by helper T (TH)
others have shown that many genetic loci pre-
animal danders
lymphocytes. T lympho-
dispose to the disease (2). It is unlikely, how-
cytes may be classified
ever, that the genetic makeup of stable popula-
Delayed cutaneous
Atopy
into TH1 and TH2 types, according to the pat-
tions can change significantly within one cen-
hypersensitivity
(asthma, eczema,
tern of their cytokine production (7). TH1 cells
tury, so the probable cause of the epidemic must
to tuberculin
and rhinitis)
secrete interferon-y interleukin-2 (IL-
lie in the environment. In this issue of Science,
2), and lymphotoxin, whereas TH2 cells secrete
Shirakawa and his colleagues (p. 77) present
Genes
IL-4, IL-5, IL-6, IL-10, and IL-13. TH1 cells
evidence for a novel environmental cause of
An advantage of Infection. Atopy (asthma and
enhance cellular immune responses, and TH2
asthma (3).
other allergic diseases) is reciprocally related to
cells favor the humoral response. Although the
Asthmatic airway inflammation is initi-
immunity to tuberculosis (as measured by de-
TH1/TH2 classification is an oversimplifica-
ated by immunoglobulin E (IgE)-mediated
layed cutaneous hypersensitivity to tuberculin)
tion, cells exhibiting the TH2 phenotype up-
allergy ("atopy") to airborne proteins ("aller-
(3). If an individual has predominantly TH2 T
regulate IgE production and are prominent in
ion
gens"). For asthmatics, the most important
cells, the TH2 phenotype interacts with environ-
mental allergens to produce atopic disease. In-
the pathogenesis of airway inflammation and
oto
source of allergens is the house dust mite.
fections may alter the balance between TH1 and
asthma.
These mites thrive in warm, moist condi-
TH2 phenotypes. The clean living conditions of
As in other modern societies, infection
tions and are ubiquitous in human bedding.
Western society, by reducing the incidence of
with Mycobacterium tuberculosis (Mtb) has
for
There is a dose-response relation between
infection, may tip the balance toward the TH2
declined steadily in Japan during this cen-
exposure to mite antigens and asthma, and a
phenotype and predispose to asthma.
nly
tury. This is in part due to a comprehensive
The
plausible but unproven case can be made for
program of inoculation with attenuated bo-
increasing levels of mite in modern heated
elsewhere in the United States. This suggests
vine tuberculosis vaccine bacillus Calmette-
nu-
for
homes (1). In Japan, asthma has increased
that the innate ability to become allergic can
Guérin (BCG), which is administered at 3
ran-
just as the population has moved away from
readily find alternative antigens.
months of age. Children are tested for de-
dor
the traditional bare and well-ventilated house
Air pollution may aggravate existing
layed hypersensitivity to tuberculin (DHT)
inst
to Western-style buildings. In Arizona, how-
asthma but is not responsible for the asthma
at 6 and 7 years of age and are re-inoculated
93,
ever, the dry heat means that mite allergy is
epidemic (1). Comparisons have been made
with BCG if the skin test is negative. Final
ally
rare, yet asthma is as common in Tucson as
between the prevalence of asthma and al-
skin testing is carried out on all children
vac-
lergy in highly polluted Leipzig in East Ger-
when they are 12. Shirakawa et al. studied
uces
many and clean Munich in the West (4).
867 children after the age of 12 and showed a
The authors are at the University of Oxford, Nuffield De-
kan
Surprisingly, the prevalence of asthma and
clear negative relation between DHT re-
partment of Medicine, John Radcliffe Hospital, Oxford
with
OX3 9DU, UK. E-mail: william.cookson@clinical-
skin tests to common allergens was lower in
sponses and two parameters-the presence
dur-
medicine.ox.ac.uk
the East. Similar comparisons between Swe-
of asthma and the serum IgE concentration.
SCIENCE
VOL. 275
3 JANUARY 1997
41
Children with positive DHT responses to
mans with filariasis, who show TH2-biased
hood tuberculosis infection in Japan is causal
tuberculin had serum cytokine concentra-
cytokine profiles, the ability to respond to Mtb
in the recent asthma epidemic. However, the
tions suggestive of predominant TH1 re-
proteins is not lost (11). Children with eczema,
incidence of other infections may also be
sponses, in contrast to the TH2 profiles seen
another atopic condition, occasionally un-
declining, so the case for tuberculosis re-
in children with negative DHTs.
dergo spontaneous remission after severe bac-
quires further study. Nevertheless, the new
These results are an important extension
terial or viral infections (12), although usually
results emphasize the complexity of the envi-
of observations in the 1960s and 1970s that
temporarily. Both of these observations suggest
ronmental contribution to asthma and re-
there is a reciprocal relation between inflam-
that alterations in the TH2/TH1 balance may
mind us that identification of the relevant
matory and humoral responses to vaccination
become important only in the presence of con-
factors may ultimately resolve this epidemic.
regimes (7, 8). This reciprocal relation has
tinued overwhelming infection.
also been attributed to preferential activation
Also confusing the TH1/TH2 theory of
References
of TH1 or TH2 subsets of T cells and is consis-
asthma are the findings that helminth and
1. A. Seaton et al. Thorax 49, 171 (1994).
tent with the genetic predisposition to TH1 or
other parasite infection may protect against
2. S. E. Daniels and S. Bhattacharyya et al., Nature
TH2 responses of different strains of mice.
allergic diseases, despite up-regulation of
383, 247 (1996).
Central to the relevance of the results is the
TH2 responses. This type of infestation is
3. T. Shirakawa, T. Enomoto, S. Shimazu, J. M.
Hopkin, Science 275, 77 (1996).
hypothesis that the immune system can be
invoked to explain the low prevalence of
4. E. von Mutius et al., Br. Med. J. 305, 1395 (1992).
manipulated to manifest a persistent TH1 or
asthma in rural Africa and the Venezuelan
5. L. Bröböck et al., Clin. Exp. Allergy 24, 826 (1994).
TH2 response. If this is the case, vaccination to
slums (13, 14). Helminth infection produces
6. E. von Mutius et al., Br. Med. J. 308, 692 (1994).
7. A. Kelso, Immunol. Today 16, 374 (1995).
induce TH1 responses may be effective against
high levels of polyclonal IgE that, possibly by
8. C. R. Parish, Transplant. Rev. 13. 35 (1972).
asthma and other allergic disorders (9). In
saturating the number of binding sites for IgE
9. P.G. Holt, Lancet 344, 456 (1994).
mice, overwhelming Schistosoma mansoni in-
on mast and other effector cells of allergy,
10. J. K. Actor et al., Proc. Natl. Acad. Sci. U.S.A. 90,
948 (1993).
fection induces TH2 responses. The infection
prevent activation of these cells by the rela-
11. E. Sartono et al., Eur. J. Immunol. 26, 501 (1996).
concomitantly down-regulates the TH1 re-
tively trivial exposures to allergens.
12. M. Lacour, Dermatology 188, 255 (1994).
sponse to other antigens and delays the clear-
Thus, the results of Shirakawa et al. invite
13. R. C. Godfrey, Clin. Allergy 5, 201 (1975).
14. N.R. Lynch et al., J. Allergy Clin. Immunol. 92. 404
ance of vaccinia virus (10). However, in hu-
the speculation that the decline in child-
(1993).
SIGNAL TRANSDUCTION
(4). But how signaling through GBy is termi-
There Are GAPS and There Are GAPS
nated has not been as clear. A report in Cell
by Gilman and co-workers (5) and two oth-
ers in Nature (6) identifying two members of
Ravi lyengar
the RGS family, GAIP and RGS4, as GAPs
for members of the Gα, family and other
recent papers shed light on this issue.
Members of the RGS family have been
Although their main function is to regulate
and By subunits that exist as a single com-
identified in yeast, Caenorhabditis elegans,
other proteins, guanine nucleotide-binding
plex. Both Gα and GBy can independently
and mammals (7). Sst2p in yeast and EGL-10
proteins (G proteins) are also guanosine tri-
transmit signals (3). Signal termination for
in C. elegans, homologs of RGS, suppress
phosphatases (GTPases), cleaving guanosine
both Gα and GBy subunits likely occurs
signal transmission by acting on the G pro-
triphosphate (GTP) to form guanosine
through GTP hydrolysis. How the GTPase
tein-α subunit (8). Mammalian RGS can
diphosphate (GDP). Because of this activity,
terminates signaling through Gα subunits is
substitute for yeast Sst2p in regulating phero-
they oscillate between GTP- and GDP-bound
easily understood given the observation that
mone signaling (9), which is transmitted
states, and thus regulate diverse processes such
GDP-Gα subunits have much lower affini-
through GBy subunits (10). Taken together,
as protein synthesis, cytoskeleton assembly,
ties for effectors than do GTP-Gα complexes
these data suggest that RGS can regulate
vesicle transport, and signal transduction.
signaling through GBy subunits by modulat-
The superfamily comprises both small mono-
Activated
GTP
ing the activity of the GTPase of the α
meric and large multimeric G proteins, but for
receptor
subunit. How would such regulation
all members, the release of bound GDP and
work? The positive cooperativity
the binding of GTP are highly regulated pro-
GDP
between GBy and GDP inter-
cesses (1). The GTPase activity of small G
action with Gα subunits
proteins, such as EF-Tu and Ras, is stimu-
GDP
lated by associated proteins called GAPs
By
RGS (GAP)
α
GTPase
By
(GTPase activating proteins) (2). But GAPs
+
E
E
Heterotrimeric
Activating
for most large G proteins had not been de-
G protein
Protein
+
GTP
Effector
scribed until recent work identified members
GDP
of the regulators of G protein-signaling
(RGS) family as GAPs for this subfamily.
The large heterotrimeric G proteins in-
volved in signal transduction have α sub-
A four-component heterotrimeric G protein-signaling system. The resting G protein is an aßy
units, which are related to small G proteins,
heterotrimer with GDP bound to it. Activated receptor promotes the release of GDP, the binding of GTP,
and dissociation of GTP-Gα from the GBy complex. GTP-Gα and GBy can now interact with their effec-
tors and propagate the signal. RGS stimulates (+) the GTPase activity of the Ga subunit, resulting in the
The author is in the Department of Pharmacology,
accumulation of GDP-Gα, which re-forms the stable heterotrimer. Free GBy leads to dissociation of GBy
Mount Sinai School of Medicine, New York, NY 10029,
from effector, thus terminating signal propagation. R, receptor; E, effector; αßy, the heterotrimeric G
USA. E-mail: iyengar@msvax. mssm.edu
protein; and RGS (GAP), stimulator of the GTPase of the Gα subunit.
42
SCIENCE
VOL. 275
3 JANUARY 1997
REPORTS
si-
4. M. Itoh et al., J. Cell Biol. 121, 491 (1993); E. Willott et
The Inverse Association Between Tuberculin
he
al., Proc. Natl. Acad. Sci. U.S.A. 90, 7834 (1993).
5. C. P. Ponting and C. Phillips, Trends Biochem. Sci.
nd
20, 102 (1995).
Responses and Atopic Disorder
6. H. C. Kornau, L. T. Schenker, M. B. Kennedy, P. H.
at
Seeburg, Science 269, 1737 (1995).
Taro Shirakawa, Tadao Enomoto, Shin-ichiro Shimazu,
7. E. Kim, M. Niethammer, A. Rothschild, Y. N. Jan, M.
in
Sheng, Nature 378, 85 (1995).
Julian M. Hopkin*
si-
8. J. H. M. Cabral et al., ibid. 382, 649 (1996).
-2
9. D. A. Doyle et al., Cell 85, 1067 (1996).
Human immune responses are heterogeneous and may involve antagonism between T
x-
10. Z. Songyang et al., ibid. 72, 767 (1993).
helper (TH) lymphocyte subsets and their cytokines. Atopy is characterized by immediate
11. A primary peptide library, KNXXXXXXX-COOH,
es-
where X indicates all amino acids except Cys and
immunoglobulin E (IgE)-mediated hypersensitivity to agents such as dust mites and
in
Trp, was first used to screen peptides that bind spe-
pollen, and it underlies the increasingly prevalent disorder asthma. Among Japanese
ni-
cifically to the glutathione-S-transferase (GST)-PDZ
schoolchildren, there was a strong inverse association between delayed hypersensitivity
domains. All the peptides in the library end with free
se
carboxylate, therefore orienting all binding pockets.
to Mycobacterium tuberculosis and atopy. Positive tuberculin responses predicted a
he
The peptides that bound were sequenced as a mix-
lower incidence of asthma, lower serum IgE levels, and cytokine profiles biased toward
lg-
ture, and the selectivities for amino acids at a given
TH1 type. Exposure and response to M. tuberculosis may, by modification of immune
in
position were determined by comparison to the se-
quence of control experiments with GST alone (10).
profiles, inhibit atopic disorder.
or
Arg was not included in the calculation because of
at
buffer contamination during sequencing. A second-
he
ary library, KNXXXXXX(S,T,Y)XX-COOH, where the
-2 position was fixed with Ser, Thr, and Tyr, was
P
used to further define the preference of some PDZ
Atopy is a state of allergic response, me-
according to sibship size and birth order
domains.
diated by IgE, to largely innocuous, com-
(9) also support the possibility that dimin-
he
12. Peptide library synthesis was as described (10).
mon environmental antigens (allergens)
ished exposure to infection might, in some
Individual PDZ domains were expressed and puri-
th
fied as GST fusion proteins: murine hDlg PDZ-1
such as those derived from house dust
way, promote atopic responses. Childhood
le
(186-282), PDZ-2 (281-377), PDZ-3 (428-518),
mites and plant pollens (1); it underlies
respiratory infections that might strongly
lo-
and PDZ-1/2 (281-518); murine PTPbas PDZ-3
the clinical diseases of asthma, hay fever,
modify the developing immune system,
(1351-1445) and PDZ-5 (1758-1848); murine
n-
Tiam-1 PDZ; human LIN-2 PDZ (422-507): human
and eczema (2). Atopy can be recognized
both systemically and within the lung,
nt
erythroid p55 PDZ (1-164); and human AF-6 PDZ
by allergen-specific IgE in serum or by
include measles, whooping cough, and tu-
di-
(983-1102). Glutathione beads (50 to 60 µl) satu-
immediate-type hypersensitivity reactions
berculosis. Some of these infections culti-
rated with GST-PDZ proteins were mixed with the
to
peptide library (1 mg) in 300 µl of TSN buffer [40
to allergens upon intradermal skin testing.
vate a TH1 immunological environment
:C-
mM triethylamine (pH 7.6), 150 mM NaCI, and
Heterogeneous genetic and environmental
with IL-12, interferon-y (IFN-γ), and tu-
nt
0.01% NP-40] containing bovine serum albumin
factors interact in the development of ato-
mor necrosis factor (TNF) as predominant
(BSA, 1 mg/ml) and 1 mM dithiothreitol (DT T). After
ast
45 min of constant shaking at 4°C, the beads were
py (3); a set of cytokines-interleukin-4
cytokines (10); because these cytokines
o-
washed with TSN buffer. The peptides retained
(IL-4), IL-10, and IL-13 derived from the
inhibit TH2 cytokine functions (11), the
at
were eluted with 30% acetic acid, tyophilized, re-
TH2 subset of T lymphocytes-is central
absence of such infections might release
1.
suspended in distilled water, and sequenced on a
Bio-Applied 477A sequencer.
in mediating IgE production and the de-
TH2 immune mechanisms and thus pro-
is
13. Z. Songyang and L. C. Cantley, unpublished data.
velopment of immediate hypersensitivity
mote atopic disorder.
ne
14. T. Sato, S. Irie, S. Kitada, J. C. Reed, Science 268,
(4).
In the case of tuberculosis, an important
n-
411 (1995).
In recent decades there has been an
marker of TH1-mediated acquired immunity
lg,
15. P. Ruff, D. W. Speicher, A. Husain-Chishti, Proc.
Natl. Acad. Sci. U.S.A. 88, 6595 (1991).
increase in severity, and probably in prev-
(not synonymous with protection) is the
th
16. R. Hoskins, A. F. Hajnal, S. A. Harp, S. K. Kim,
alence, of atopic disorders in developed
development of delayed-type hypersensitiv-
IO-
Development 122, 97 (1996); A. Brecher et al., in
countries (5). Studies on migrants from
ity. This can be tested by observing the
2).
preparation.
developing to developed countries support
reaction, after 48 hours, to the intradermal
17. G. G. Habets et al., Cell 77, 537 (1994).
ns
18. R. Prasad et al., Cancer Res. 53, 5624 (1993).
the importance of etiological environmen-
injection of tuberculin protein (12). There
ng
19. G. Payne, S.E. Shoelson, G. D. Gish, T. Pawson, C.
tal changes associated with "Westerniza-
is likely a "J-shaped" relation between the
ns
T. Walsh, Proc. Natl. Acad. Sci. U.S.A. 90, 4902
tion" (6). The nature of these environ-
degree of delayed hypersensitivity and the
In
(1993).
20. H. T. Yu et al., Cell 76, 933 (1994).
mental changes is obscure, but speculation
risk of tuberculous disease, in which people
H-
21. z. Songyang et al., data not shown.
has focused on increased air pollution or
with moderate hypersensitivity are at least
an
22. J.S. Simske, S. M. Kaech, S. A. Harp, S. K. Kim, Cell
other toxins in the environment, in-
risk (13).
he
85, 195 (1996).
creased indoor exposure to dust mite an-
To test for clinical evidence of antag-
23. S. M. Marfatia et al., J. Biol. Chem., in press.
to
24. V. Hata, S. Butz, T. Sudhof, J. Neurosci. 16, 2488
tigens in less ventilated modern homes,
onism between delayed hypersensitivity to
lo-
(1996).
and dietary changes (7). One factor tem-
tuberculin and immediate atopic respons-
ifs
25. J.E. Brenman et al., Cell 84, 757 (1996).
porally associated with the rise of atopy is
es, we conducted an epidemiologic survey
dr-
26. B. Lipinska, M. Zylicz, C. Georgopoulos, J. Bacteriol.
the decline of many infectious diseases in
in a county of the Wakayama prefecture in
172, 1791 (1990).
m-
27. S. V. Shestakov et al., J. Biol. Chem. 269, 19354
developed countries as the result of im-
southern Honshu, Japan, where there has
ey
(1994).
proved living standards and immunization
been a long-established program of tuber-
ti-
28. We thank M. Berne for peptide synthesis and se-
programs (8). Data on the risk of atopy
culin testing and immunization with at-
quencing, R. Mackinnon for structural coordinates of
tenuated bovine M. tuberculosis vaccine
PSD-95-3, W. Boll and A. Nguyen for technical as-
sistance, A. Couvillon for antibodies to GST, M. Oishi
T. Shirakawa and J. M. Hopkin, Lung Research Labora-
[bacillus Calmette-Guérin (BCG)] after
and T. Woodford-Thomas for the PTPbas cDNA,
tory, Osler Chest Unit, Churchill Hospital, Oxford OX3
7LJ, UK.
birth and at 6 and 12 years of age (14).
and A. Brecher for human LIN-2 PDZ. C.F. is a Lucille
T. Enomoto, Department of Otolaryngology, Japanese
From a population of approximately 1000
237
Markey Fellow. Supported by grants from American
Cancer Society and Lucille P. Markey Charitable
Red Cross Society, Wakayama Medical Center,
12- to 13-year-old schoolchildren attend-
91);
Trust (L.C.C.), NIH grants CA66263 and DK34989
Wakayama, Japan.
S. Shimazu, Department of Pediatrics, National Waka-
ing the 18 junior high schools of the coun-
(J.M.A. and A.S.F), Pew Scholars Program (A.C.C.),
29
yama Hospital, Wakayama, Japan.
ty in 1995, we studied 867 children with
and NIH grant CA66263 (A.H.C. and S.M.M.).
20,
*To whom correspondence should be addressed. E-mail:
complete retrospective records of their tu-
22 July 1996; accepted 23 October 1996
[email protected]
berculin responses. We administered a
SCIENCE
VOL. 275
3 JANUARY 1997
77
questionnaire documenting atopic symp-
strong inverse association was found be-
were one-half to one-third as likely in
toms and social and environmental vari-
tween positive tuberculin responses at
positive tuberculin responders as in nega-
ables, and we also measured IgE serum
both 6 and 12 years of age and a range of
tive responders (Table 2). Moreover, re-
levels and TH1 and TH2 cytokine profiles
atopic characteristics, including symptoms
mission of atopic symptoms between 7 and
(15); these data were analyzed in relation
at any age and IgE levels and TH2 cyto-
12 years of age was six to nine times as
to the record of tuberculin responses.
kine profiles assayed at 12 years of age
likely in positive tuberculin responders.
There was a bimodal distribution of
(Fig. 1B and Tables 1 and 2). In positive
Serum IgE levels, both total and allergen-
delayed-type hypersensitivity responses to
tuberculin responders, the rate of current
specific, were also lower in the positive
tuberculin upon skin testing (Fig. 1A).
atopic symptoms was one-third the rate in
tuberculin responders. The geometric
Positive tuberculin tests (>10 mm skin
negative responders. Asthmatic symptoms
mean for total serum IgE level was 112
induration) correspond to response to M.
tuberculosis; negative tests include fully
negative reactions as well as intermediate
Table 1. History of infectious diseases, atopic symptoms, IgE levels, and cytokine profiles in subjects
grouped by tuberculin reactivity. ASE, allergen-specific IgE; UD, undetectable.
reactions (5 to 9 mm) that generally re-
flect responses to nontuberculous environ-
Group 1
Group 2
Group 3
Group
4
mental mycobacteria or to BCG (16). Pos-
Measurement
(n
=
290)
(n = 289)
(n = 213)
Total (n = 867)
(n
=
75)
itive tuberculin responses were recorded in
3% of the children at 3 months of age, in
Tuberculin response
33.2% at 6 years, and in 58.0% at 12 years.
At 6 years
-
-
+
+
In many children, the tuberculin status
At 12 years
-
+
+
-
Positive antiviral immunity (%)
changed, to either positive or negative,
Measles (history + vaccine)
83.4
87.2
84.5
81.3
84.3
between the ages of 6 and 12 years (Table
Chicken pox (history + vaccine)
86.9
82.3
82.2
82.7
83.9
1, groups 2 and 4). None of the children
Mumps (history + vaccine)
62.8
60.9
60.1
57.3
61.0
suffered clinical tuberculous disease at any
Number with IgE to Ascaris
2
2
2
1
7
stage, including 24 with florid tuberculin
Symptoms (%)
responses (>40 mm skin induration) who
Atopy (past + present)
46.8
33.9#
25.8##
38.7
36.6
Atopy (present)
32.1
7.9##
9.8##
30.7
18.5
underwent full clinical and radiographic
Asthma (past + present)
13.4
4.1#
3.7#
6.8
7.4
assessment for the disease.
Rhinitis (past + present)
16.2
4.8#
8.6
14.6
10.4
Of all the children studied, 36% man-
Eczema (past + present)
22.7
12.8##
12.2#
16.0
16.2
ifested atopic symptoms at some time. A
Geometric mean IgE (IU/ml)
208
149**
98***
178
154
Positive ASE (%)
55.8
43.9#
41.8#
53.3
48.2
Atopic (high IgE or positive
65.5
54.0#
49.2#
61.3
57.3
A 15
ASE) (%)
Median cytokine level (pg/ml)
IL-4
1.88
0.96t
0.92t
1.66
1.22 (10.2-UD)§
IL-13
18.3
10.2ttt
7.8ttt
19.1
14.2 (45.6-UD)
Frequency (%)
10
IL-10
5.9
3.1tt
2.9tt
5.9
3.9 (10.2-UD)
IL-12
UD
UD
UD
UD
UD
IFN-γ
7.8
11.0tt
13.2+t
6.4
10.5 (23.2-UD)
5
Positive family history within
54.1
49.8
49.8
48.0
51.0
three generations (%)
Mean BMI
21.1
22.0
21.9
21.2
21.6
0
"P < 0.01, ***P < 0.001 on the basis of Student's test.
tp < 0.05, ttp < 0.01, tttp < 0.001 on the basis of a
10
20
30
median test. #P < 0.05, # < 0.01, ##P < 0.001 on the basis of x² against group 1, respectively.
Maximum-
minimum values.
DHT (mm)
B
4
Table 2. Odds ratios for atopy and for occurrence and remission of atopic symptoms in positive
versus negative tuberculin responders by age. Multiple logistic analysis was conducted with the
SPSSX package, version 2.2. In all models, allowance was made for dichotomized variables including
3
o
sex, life-style, nutritional status, environmental factors, and family history. Only significant values are
serum IgE)
shown.
8
2
o
Odds ratio
8°
8
Tuberculin response
Atopic symptoms
1
Atopy
8
Occurrence
Remission
00
0
Conversion to
0.50
Asthma: 0.31
Asthma: 8.2
0
20
40
60
60
positive up to 6
(0.29 to 0.83)*
(0.22 to 0.45)*
(6.0 to 9.8)**
years of age
Eczema: 0.50
Eczema: 1.6
DHT (mm)
(0.33 to 0.91)*
(1.0 to 2.2)*
Fig. 1. Delayed hypersensitivity to tuberculin
Conversion to
0.43
Asthma: 0.42
Asthma: 6.0
(DHT, in millimeters) and relation to serum IgE. (A)
positive between
(0.25 to 0.83)**
(0.24 to 0.56)*
(2.8 to 10.3)'
Histogram showing bimodal distribution of re-
6 and 12 years of age
Eczema: 6.7
sponses to tuberculin, assayed as DHT at 12
(4.8 to 11.4)*
years of age in 867 Japanese schoolchildren. (B)
Rhinitis: 9.0
Plot of log(total serum IgE) versus DHT in the same
(6.2 to 14.2)*
children (r = -0.492, P < 0.001).
*P < 0.05, **P < 0.01, ""P 0.005.
78
SCIENCE
VOL. 275
3 JANUARY 1997
REPORTS
IU/ml for children who had a positive
in the rate of positive atopic skin tests
ration after 48 hours), intermediate (5 to 9 mm), or
tuberculin response at any time, whereas it
(20). In our study, we found no relation
negative. At each of these ages, negative respond-
ers were immunized with 10⁶ colony-forming units
was 194 IU/ml for children whose respons-
between a history of measles infection and
(CFU) of attenuated bovine M. tuberculosis (BCG,
es were always negative. A plot of the
atopy. However, there are important pop-
Tokyo 172 strain, Japan BCG Laboratory). At 3
logarithm of total serum IgE against the
ulation and environmental differences be-
months of age, 97 to 98% of the children (groups 1 to
4 in Table 1) were tuberculin-negative and received
diameter of tuberculin response shows an
tween Wakayama and Guinea-Bissau;
BCG.
inverse linear relation, T = -0.492 (Fig.
also, the Wakayama region has had an
15. T. Shirakawa and K. Morimoto, Allergy 48, 177
1B). Positive tuberculin responders had
established program of measles immuniza-
(1993); T. Shirakawa et al., Eur. J. Epidemiol., in
significantly lower levels of TH2 cytokines
tion, with an uptake of 60% or more, and
press. The sample consisted of 867 12- to 13-year-
old students (454 boys and 413 girls) at the 18
(IL-4, IL-10, and IL-13) and higher levels
there had been no measles epidemic rele-
junior high schools in the southern county of
of the TH1 cytokine IFN-γ.
vant to our study. It is likely that a set of
Wakayama prefecture who responded to a ques-
In tests for confounding variables (15),
specific infections that strongly promote
tionnaire and donated blood for serology. The
questionnaire included details on personal and fa-
we found no differences in life-style, en-
TH1 immunity has the potential to inhibit
milial atopic disorders, life-style and environmental
vironmental factors, or nutritional status
atopic disorder by the repression of TH2
characteristics, weight and height, and history of
between the positive and negative tuber-
immunity. We believe that the role of
public health immunizations. Nutritional status was
assessed as BMI (body mass index), calculated by
culin responders; estimated allergen expo-
such an infection in repressing atopy de-
weight and height. Concentrations of nitrogen di-
sure was similar among the groups with
pends on a number of factors, including its
oxide and sulfur dioxide in ambient air have been
respect to pet animal exposure, character
timing, anatomical site, dose, and pro-
<0.02 parts per million for the last 30 years in this
district. Personal records for skin test responses to
and ventilation of homes, and residence in
tractedness; exposure to other infections;
tuberculin and BCG inoculation, documented by
a rural area. Exposure to helminths, which
and host characteristics such as genetic
school doctors, were available from each school's
can promote high IgE levels, was minimal
variables and nutritional status (21). Pro-
filed records. Diagnoses of asthma, eczema, and
rhinitis were made by school doctors on the basis
in the population; only 7 of the 867 chil-
spective and experimental studies are
of international criteria. Specific IgE to five airborne
dren showed IgE to Ascaris lumbricoides.
needed to investigate the action of M.
allergens and total serum IgE were assayed by
Similar numbers of positive and negative
tuberculosis and other microorganisms,
Lumiward immunoassay (Shinogi); IgE to Ascaris
tuberculin responders reported atopy in
through natural infection or immunization
lumbricoides was assayed (Arastat; DPC, Tokyo,
Japan). A positive altergen-specific IgE was >0.35
any sib, parent, or grandparent (~50%) or
schedules, in deviating immunity away
IU/liter. An elevated total serum IgE was taken to be
had chest radiograph reports of tuberculo-
from atopy.
>1 SD above the geometric mean (200 IU/liter).
sis in the same relatives at any time
Atopy was defined as one or more positive aller-
gen-specific IgE, a raised total IgE, or both. Serum
(~13%).
REFERENCES AND NOTES
cytokine levels were immunoassayed in the Mit-
Several lines of evidence suggest that a
subishi Kagaku BCL laboratories (Tokyo) by means
causal link between tuberculin response
1. R. Ishizaka, Clin. Allergy 1, 9 (1971).
of commercial kits; the minimum detectable levels
and atopy is more likely than fixed deter-
2. B. Burrows, F. D. Martinez, M. Halonen, R. A. Bar-
were 0.50 pg/ml for IL-4 and IL-10, 3.1 pg/ml for
bee, M. G. Cline, N. Engl. J. Med. 320, 271 (1989).
IL-13, 5 pg/ml for IFN-γ, and 7.8 pg/ml for IL-12
mination of both atopy and diminished
3. J. M. Hopkin, Pediatr. Allergy Immunol. 6, 139
heterodimer. Serum IgE levels were correlated with
tuberculin responses by a genetic factor or
(1995).
TH2 cytokine levels (IL-4, correlation coefficient r =
0.356; IL-13, r = 0.565; IL-10, r = 0.558; P <
factors. Our data show that tuberculin
4. I. Aebischer and B. M. Stadler, Adv. Immunol. 61,
0.001) and were inversely correlated with levels of
responses change, from positive to nega-
341 (1996); J. M. Carballido, N. Carballido-Perrig, G.
Terres, C. H. Heusser, K. Blaser, Eur. J. Immunol.
the TH1 cytokine IFN-y V = -0.567; P = 0.001).
tive and vice versa, in many children be-
22, 1357 (1992).
16. N. S. Galbraith, A. Hanson, R. Shoulman, D. W.
tween 6 and 12 years of age (groups 2 and
5. I. N. Bruce, R. W. Harland, N. A. McBride, J. Mac-
Andres, D. B. Lee, Br. Med. J. 1, 647 (1972); T.
Mahon, Q. J. Med. 86, 425 (1993); F. Schultz-
Oettinger, A. Holm, I. M. Mtoni, A. B. Andersen, K.
4 in Table 1). A marked decline in the
Larsen, Monogr. Allergy 31, 9 (1993); E. von Mutius,
Hasloov, Infect. Immun. 63, 4613 (1995). As a rule,
incidence of positive tuberculin responses
C. Fritsch, S. K. Weiland, G. Roell, H. Magnussen,
positive tuberculin responses are caused by infec-
in the Wakayama region over a very short
tion with M. tuberculosis, whereas intermediate re-
Br. Med. J. 305, 1395 (1992).
sponses are caused by exposure to nontuberculous
genetic interval-95% in 1965, 85% in
6. D. A. Waite, E. F. Eyles, S. L. Tonkin, T. V. O'Donnell,
mycobacteria or immunization with BCG. We cannot
1975, 60% in 1985, and 58% in our
Clin. Allergy 10, 71 (1980); J. Morrison-Smith and S.
exclude the possibility that some of the conversions
Cooper, Postgrad. Med. J. 57, 774 (1981).
survey-was accompanied by a decline
to tuberculin positivity after 6 years of age might be
7. H. E. Wickmann, Clin. Exp. Allergy 26, 621 (1996).
attributable to a second immunization with BCG,
in infectious clinical cases of tuberculosis
8. V. H. Springett, J. H. Darbyshire, A. J. Nunn; I. Suth-
especially because the Tokyo 172 BCG used is
from 154.4 per 100,000 in 1974 to 52.1 per
erland, J. Epidemiol. Community Health 42, 370
strongly immunogenic, having retained the gene for
(1988); R. Doll, Am. J. Public Health 82, 933 (1992);
100,000 in 1994 (17). Experimental ani-
the major antigen, MPT 64; nor do we know what
M. Burnet and D. O. White, Natural History of Infec-
role environmental mycobacteria may have played in
mal data show antigen-independent, re-
tious Disease (Cambridge Univ. Press, Cambridge,
this semirural environment.
ciprocal inhibition of either TH1 or TH2
1972).
17. Japanese Ministry of Health and Welfare, Trends of
immunity by infectious agents that strong-
9. E. von Mutius et al., Br. Med. J. 308, 692 (1994).
Health and Welfare in Japan, 1994 (Ministry of Health
10. D. T. Fearon and R. M. Locksley, Science 272, 50
ly promote TH1 responses [such as myco-
and Welfare, Tokyo, 1995).
(1996); S. H. E. Kaufmann, Annu. Rev. Immunol. 11,
18. G. B. Mackaness, P. H. Lagrange, T. Ishibashi, J.
bacteria (18)] or TH2 responses [such as
129 (1993).
Exp. Med. 139, 1540 (1974).
schistosomes (19)]. The data support the
11. A. M. Cooper et al., Immunology 84, 423 (1995); V.
19. E. J. Pearce, P. Caspar, J.-M. Grzych, F.A. Lewis, A.
Donckier et al., J. Immunol. 153, 2361 (1994); L. Xu
hypothesis that a decline in infection, in
Sher, ibid. 173, 159 (1991).
and P. Rothman, Int. Immunol. 6, 515 (1994).
this instance tuberculosis, is a factor
20. S. O. Shaheen et al., Lancet 347, 1792 (1996).
12. G. P. Youmans, Am. Rev. Respir. Dis. 111, 109
21. R. W. Baker, A. Zumla, G. A. W. Rook, Q. J. Med. 89,
underlying the rising severity and preva-
(1975).
387 (1996); J. M. Grange, ibid., p. 323; P. G. Holt,
lence of atopic disorders in recent decades
13. P.E. Fine, J. A. Steme, J. M. Ponnighaus, R. J. Rees,
Toxicol. Lett. 86, 205 (1996).
Lancet 344, 1245 (1994).
in developed countries. These data are
22. We thank the school doctors of Hidaka Medical As-
14. The regimen in Japan for prevention of tuberculosis
also consistent with the idea that atopic
sociation for help with sample collections, and T.
to 12 years of age by the Ministry of Health and
Yamashita and F. Kurimoto (Mitsubishi), T. Onishi
responses are limited by TH1 immune
Welfare was administered as follows. Mantoux skin
(Shinogi), and K. Kato (DPC Japan) for help with
testing-after single-needle intradermal injection of
mechanisms.
purified protein derivative (2.5 tuberculin units) of M.
serological assays. We thank the students for partic-
Epidemiological data from Guinea-Bis-
ipating and their teachers and school nurses for their
tuberculosis (Aoyama B strain, Japan BCG Labora-
assistance. Supported in part by Mitsubishi Chemi-
sau show that a history of childhood mea-
tory, Tokyo)-was performed in all children within 3
cal Company (Tokyo).
sles infection around the time of an epi-
months of birth, at 6 years of age, and at 12 years of
age. Delayed hypersensitivity to tuberculin was cat-
demic was associated with a 50% decrease
egorized as positive mm diameter of skin indu-
23 August 1996; accepted 21 October 1996
SCIENCE
VOL. 275
3 JANUARY 1997
79
TO:
Jennifer Klein
FROM:
Jon Poling
DATE:
10-9-97
RE:
Wall Street Journal Article on EPA and Asthma Inhalers
As of 1996, the Clean Air Act banned all production of CFCs (chlorofluorocarbons ) in
accordance with the Montreal Protocol, an international agreement to protect the ozone layer.
However, the United States successfully argued for an "essential use exemption" that allows for
enough domestic production of CFCs to meet the needs of American asthmatics. These
exemptions last until 1999 and cover all Metered Dose Inhalers (MDIs) that are CFC based.
There is one CFC-free inhaler on the market, but it is not an adequate substitute for the
CFC based inhalers. The International Pharmaceutical Aerosol Consortium estimates that 11
new CFC-free inhalers will be on the market by the year 2000. Until that time, the EPA will
keep the CFC based inhalers exempt from the Montreal Protocol Ban.
Jon' see Check If this to happened info
Gather on what
EPA to Asthmatic Kids: Hold Your Breath
are
doing
we
to fight
By ROBERT M. GOLDBERG
gies and Infectious Diseases found in
emitting fire extinguishers even though
Today, the Clinton administration will
1995 that failure to comply with treat-
the EPA found some alternatives are ai-
asthma.
issue a proposal that could take away
ment explains the 300% increase in
ready on the market and in use. The
asthma inhalers from inner-city children
asthma-related deaths among children
EPA's Ms. Browner apparently believes
Jen
to protect the Earth's ozone layer.
between 1980 and 1993.
that preservation sprays and coaxial ca-
This is not a sick joke. or the product of
-Why would the EPA want to hasten the
ble are more important than medicine for
an overheated conservative imagination.
elimination of a medicine that's essential
asthmatic children.
Rather. the Environmental Protection
to keeping kids alive? The Montreal proto-
This is what we have come to expect
Agency wants to announce a ban on chlo-
col doesn't require it. And a large number
from the Clinton administration: Chil-
rofluorocarbon-powered inhalers in Mon-
of member countries are opposed to such a
dren are shamelessly invoked as a justi-
treal at the international meeting on ozone
quick phase-out.
fication, even for policies that hurt chil-
protection as a shining symbol of Amer-
Yet the EPA wants America to be the
dren. When it comes to their inhalers-
ica's international environmental stew-
first country to develop a solution for the
well, what's a few innocent lives, partic-
ardship. Never mind that such a ban would
elimination of CFC-powered inhalers. So,
ularly of children in the inner city,
increase the cost and difficulty of treating
despite resistance from doctors, the EPA
compared to President Clinton's goal of
childhood asthma. and that inner-city chil-
has pushed the Food and Drug Adminis-
showing international leadership on envi-
dren are already six times more likely
tration for tougher regulations. Under the
ronmental protection? If children lose ac.
than other children to the because of mad
proposed new FDA rules, If one CRC-free
COSS to inhalers, they'll just have to hold
equate asthma care. Even though such in-
inhaler hits the market. any CFC-powered
their breath until the ozone layer is re-
halers account for less than 1.5% of total
inhaler delivering the same medicine
paired.
CFC emissions world-wide, the EPA is
would have to go. In this way, all those who
likely to get its wish.
use CFC inhalers-about 95% of asthma in-
Mr. Goldberg is a senior research fellow
Under the Montreal protocol on ozone-
haler users-will be deprived of the oppor-
at the Center for Neuroscience, Medical
depleting substances. 155 countries have
tunity to use the inhaler that works best for
Progress and Society, George Washington
agreed to phase out production of CFCs
them.
University.
me other ozone-depleting substances. An
Dozens of medical groups and him-
amendment to the protocol introduced by
dreds of allergists have urged the FDA not
the U.S. in 1990 accelerated the interna-
to go ahead with its planned termination.
tional phase-out. However, that amend-
pleading that a change in medicine will
ment left one important feature of the pro-
compromise children's health. The Joint
tocol intact. It still allows each member
Council of Allergy. Asthma and Immunol-
country to exempt from the ban certain
ogy has told both the FDA and the EPA
CFC-containing products deemed "essen-
that their proposal will unfairly punish
tial." Since the treaty was ratified. asthma
poor children and the elderly. who have
inhalers have been exempt because of
the highest risk of asthma-related sick-
their public health importance. And each
ness and death. Even the FDA panel that
year, the EPA nominates other products
made this proposal expressed concerns
for exemption. This time around. however,
about the impact on such children of wip-
the EPA wants to tell the world it will no
ing out a whole class of CFC-powered in-
longer ask to exempt inhalers.
halers.
EPA Administrator Carol Browner says
The question is why the EPA is willing
that the goal of the ban. like her many
to invite those consequences. In a letter to
other environmental initiatives. is to en-
the FDA. the EPA claimed that the U.S. is
sure that U.S. children are protected from
forced under the terms of the Montreal
environmental health risks. Ms. Browner
protocol to limit exemptions to cases
claims that more environmental regula-
where no non-CFC substitutes are avail-
tions will protect asthmatic children most
able. Since CFC-free devices do exist. the
of all. since they are among the most vul-
EPA argues. the ban must apply. The EPA
nerable to environmental threats. Hence,
objects to the FDA's intention to weigh the
taking asthma inhalers away from chil-
benefits of reducing CFC emissions com-
dren is being done in the name of chil-
pared to the negative effects for asthmat-
dren's health.
ics. Incredibly. the EPA wrote to the FDA
It's true that non-CFC asthma prod-
that domestic assessments of impact can-
ucts do exist, and that some work better
not be considered in the FDA's decisions if
than those containing CFCs. But differ-
they conflict with U.S. treaty obligations.
ent patients' asthma symptoms respond
In other words, the FDA cannot consider
differently to each of the available med
the health impact of a ban on CM powered
iemes, and specialists are opposed to ru-
inhalers on U.S. children because it is at
ducing that range of products simply for
odds with the EPA's desire to demonstrate
the sake of environmental correctness.
America's commitment to environmental
In addition, poorer children are espe-
vigilance.
cially reliant on generic inhalers with
Worse, even as the EPA is hell-bent on
CFC propellants. which can cost one-
snatching asthma inhalers away from
eighth the price of newer brand-name
children and the elderly. it had no prob-
THE WALL STREET JOURNAL FRIDAY, SEPTEMBER 19, 1997
products without CFCs. Ultimately. these
lem exempting other products that have
two factors contribute to the fact that
nothing to do with children's health.
only half of all children are following the
Among the other CFC-laden products the
inhalation schedule necessary to keep
EPA has decided not to ban: document-
their asthma under control. An expert
preservation sprays and foam insulation
panel of the National Institute for Aller-
for coaxial câble. It has also spared CFC-
Background on the Montreal Protocol Ban on CFCs
Metered Dose Inhalers (MDIs) are medical devices used to treat asthma. Most MDIs now
use chlorofluorocarbons (CFCs) to propel the medication in the inhaler. In 1996, the Clean
Air Act banned production of CFCs, pursuant to the Montreal Protocol, an international
agreement to protect the ozone layer.
EPA did not announce a ban on CFC-based MDIs at the Meeting of the Parties to the
Montreal Protocol held September 8 -19 1997. By contrast, the U.S. successfully argued for
"essential use exemptions" from the ban in 1996, 1997, 1998 and 1999, in order to allow for
domestic production of enough CFCs to meet the needs of American asthmatics.
While a CFC-free inhaler is currently on the market, it does not adequately substitute for the
many different types MDIs now in use. The International Pharmaceutical Aerosol
Consortium estimates that 11 new CFC-free inhalers will be available by the year 2000, and
as many as 35 by 2005. EPA will continue to ask for necessary exemptions from the
Montreal Protocol ban on CFC production until a transition from CFC-based to CFC-free
inhalers occurs in the U.S.
Progress in protecting the ozone layer will not come at the expense of other important public
health concerns, like asthma. EPA has worked closely with the FDA to craft a transition
process that ensures health protection of all MDI users. Over time, the availability of
substitutes will provide several options for American asthmatics while protecting public
health and the ozone layer.
EPA Actions to Fight Asthma in Children
In July 1997, EPA Administrator Carol M. Browner signed updated air quality standards for
ozone and particulate matter to better protect American children from the harmful effects of
air pollution These new standards will provide new health protections to 35 million children,
by helping to prevent 15,000 premature deaths, about 350,000 cases of aggravated asthma
and nearly a million cases of decreased lung function.
Working in partnership with the National Parent Teachers Association, the National
Education Association, the American Federation of Teachers and the American Lung
Association, EPA has developed the Indoor Air Quality Tools for Schools Action Kir, an
easy-to-use guide which describes simple, low-cost methods for schools to improve their
indoor air quality and, thereby, reduce environmental asthma risks to children.
By integrating the American Lung Association's "Open Airways" children's asthma
management curricula and EPA's Indoor Air Quality Tools for Schools program, the "Open
Airways for Schools" program focuses on developing asthma management skills for high-
risk, inner city minority children who have a higher than average asthma death rate.
2/2
PAGE
ID:202 260 3684
OCT-09-97 16:43 FROM OF ADMIN /OCEPA
and
163!
THE
Children's
Health
FUND
A decade of caring for kids
1987 1997
THE NEW YORK CHILDHOOD ASTHMA INITIATIVE
Revised Preliminary Scope of Work
This city wide initiative is designed to address a growing health crisis with respect to childhood
asthma. Organized as a partnership between the office of Councilman Ken Fisher and The
Children's Health Fund (CHF), with strong collaboration with the New York City Department of
Health, the program will have the following goals and program components.
I.
GOALS
1.
Increase in public awareness and knowledge of pediatric asthma
2.
Development of innovative primary care programs with a special asthma focus
3.
Development of a broad, system-based model that integrates community, medical,
educational and other interventions to address the childhood asthma epidemic
4.
Development of sustainable public policies and programs that will contribute to the
ongoing reduction of childhood asthma morbidity and the elimination of childhood
deaths due to asthma
II.
PROGRAM DEVELOPMENT PROCESS
The program will be developed through a process that will a) give program attention to specific
communities with high asthma prevalence and to special populations with high asthma prevalence,
and b) ensure coordination with and be complementary to current asthma-related activities of the
NYC DOH, as well as asthma-related activities of other institutions, agencies and organizations, and
c) consult and collaborate with community organizations in targeted, high prevalence communities
on program development, implementation and potential for sustainability.
An initial collaborative planning meeting will be scheduled with representatives from Councilman
Fisher's office, the Children's Health Fund and the NYC DOH, chaired by Councilman Fisher and
Irwin Redlener, MD, to discuss program design, implementation and potential community linkages.
Specific topics will include a) the development of criteria for the identification of high prevalence
communities / special populations as well as the site selection process, and b) the coordination of
New York Childhood Asthma Initiative program components with current DOH activities, especially
those in the Hunts Point area. The discussion of overall program design for the Childhood Asthma
Initiative will also include contributions of the experience of the NYC DOH in Hunts Point, as well
as the experience of other asthma programs and population-based models, both in NYC and
elsewhere.
NYCAI: Goals and Program Components: Draft 8/1/97
1
The Children's Health Fund
317 East 64th Street
New York NY 10021
Telephone (212) 535-9400
Fax (212) 535-7488
III.
PROGRAM COMPONENTS
A.
Establishment of a Childhood Asthma Task Force
Co-chaired by Councilman Fisher and CHF President Irwin Redlener, MD, the task force will be
composed of representatives of NYC agencies, organizations, unions, and individuals with relevant
experience in a wide range of service sectors. The Task Force may appoint subcommittees as
needed.
Potential Tasks:
1.
Participation in the development of a major asthma awareness campaign focused on
the epidemic of childhood asthma in NYC
2.
Development of appropriate public policy responses to the epidemic of childhood
asthma
B.
Childhood Asthma Awareness Campaign
This campaign is designed to call significant public attention to the new crisis in pediatric asthma.
Its purpose will be to inform the public, provide essential information to parents of children with
asthma, educate children with asthma about their disease and offer state-of-the-art information on
asthma diagnosis and treatment to primary care providers who deal with this condition. It will be
designed to develop effective asthma educational models to train a wide range of service providers,
agencies and community organizations that interact with children. An important anticipated
outcome of the Childhood Asthma Initiative will be the development of successful models of health
education around asthma that may also be applied to other health conditions.
Possible Campaign Components:
1.
Public Information Initiative: This component will include the development of
asthma awareness and knowledge surveys, the development of an ad campaign,
public service announcements, the development of media coverage and appropriate
materials for general distribution. These materials might include Asthma
Information Kits for children and parents, community organizations such as churches
and other religious institutions, tenants associations, block associations, local
businesses and community service organizations; Asthma Fact Sheets for distribution
at health fairs, local businesses and community events as well as other asthma
information materials. The targeted audience for the public information initiative
would include parents and caretakers of children with asthma, children and
adolescents with asthma, community organizations, residents of high-risk
communities, special populations with high asthma prevalence rates such as
homeless children, and the general population. The public campaign would also
NYCAI: Goals and Program Components: Draft 8/4/97
2
The Children's Health Fund 317 East 64th Street - New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
publicize the "asthma information hotline" and other aspects of this program.
Development of the public information initiative will be in coordination with the
health promotion activities of the NYC DOH and other asthma education efforts in
the NYC area.
2.
Asthma Information Hotline: This component will be directed at provision of state-
of-the-art information on asthma for parents, teachers, community organizations,
agencies and others as well as enhancing the participation of parents in the
management of asthma for their children. Information will be linguistically and
culturally appropriate. The hotline will have an 800 number available 5-7 days a
week. It will offer general information about asthma, prevention of asthma attacks
and advice on how and where to secure a primary care provider with appropriate
expertise in asthma management.
3.
Provider Education: In New York City currently, provider knowledge with respect
to asthma diagnosis and management is variable and inconsistent. The recent release
of the revised Guidelines for the Diagnosis and Management of Asthma (National
Asthma Education and Prevention Program, NHLBI) offers an opportunity to
develop provider education strategies that reflect state-of-the-art asthma care. Under
this component of the program, an effort will be undertaken to educate physicians,
as well as other primary care providers such as nurses and physician assistants.
Other professionals that interact regularly with asthmatic children and their parents
will also be targeted, including clerks at health facilities, pharmacists and social
service providers. A particular focus will be those providers who provide services
in high risk communities and those serving high risk special populations. The
provider education programs will be coordinated with existing efforts that target
provider education under the auspices of DOH and other organizations in the city.
Provider education strategies will identify effective approaches and will be designed
to complement current programs, such as the Greater New York Asthma Initiative
Provider Education Conference scheduled for Spring, 1998. It may also include:
the organization of a city-wide conference on childhood asthma
development of targeted teaching programs and educational materials for
physicians
a physician's newsletter
the development of special training programs for nurses, pharmacists, social
service workers and clerical staff
The provider education programs will include information on the diagnosis of
asthma, identification of asthma symptoms, identification of asthma triggers,
identification of risk factors for fatal asthma, current treatment options, prevention
strategies, development of patient-provider asthma management plans, and
NYCAI: Goals and Program Components: Draft 8/4/97
3
The Children's Health Fund 317 East 64th Street - New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
appropriate use of asthma management devices such as peak flow meters and spacers.
4.
Enhanced School and Day Care Programs: This component will focus on educating
school-age children and adolescents with asthma about asthma triggers, asthma
management, asthma medications, strategies for maximal asthma control, asthma and
athletics and reduction in activity limitation due to asthma. It will also focus on
educational programs for teachers, administrators and other school staff. It will build
on school-based programs already existing in the city and will be targeted towards
high-risk school districts.
The Day Care program would provide education to both day care staff and parents
in the recognition of asthma symptoms, use of asthma medications, identification of
asthma triggers, general asthma management strategies and identification of primary
care resources. It will also include specific early childhood development programs
such as Head Start.
C.
Clinical Program: Primary Care and Asthma Centers
Possible Program Components:
1.
Establishment and/or enhancement of primary care programs with a special asthma
focus: Primary Care and Asthma Centers will be organized in two communities
where asthma is particularly problematic. Locations will include the Hunts Point
Peninsula community where The Children's Health Fund's affiliated project, the
South Bronx Children's Health Center, is already working closely with the New
York City Department of Health. This program will be structured to complement
existing asthma initiatives in the Hunts Point community. An additional Primary
Care and Asthma Center site will be established in collaboration with institutions that
currently provide primary health care services in Brooklyn. On-going development
of this program component will be closely coordinated with the Department of
Health and local community partners such as The Point. The Primary Care and
Asthma Centers will provide needed state-of-the-art asthma care in these two high-
risk communities and will also serve as demonstration sites for the development and
evaluation of a range of clinical, educational and community programs and materials
targeted at childhood asthma for broader implementation and dissemination.
Neighborhood Asthma Specialists: A critical component of the childhood asthma
initiative will be the integration of increased public awareness of asthma with the
provision of enhanced clinical care. As part of this effort, nurses would be trained
to become neighborhood-based specialists in asthma management and education.
They would be initially based in the Primary Care and Asthma Centers described
below and would provide asthma education, training and outreach across a wide
range of sites within a specific geographic area, linking medical facilities to schools,
NYCAI: Goals and Program Components: Draft 8/4/97
4
The Children's Health Fund 317 East 64th Street - New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
housing, community organizations, churches, tenant associations, day care centers,
multi service centers, block associations, local social service organizations, local
pharmacies, local businesses and others providing community services. The
Neighborhood Asthma Specialists would thus serve a key role in integrating and
linking asthma education and services within high-risk geographic locations and in
developing a sustainable focus on childhood asthma within those communities. A
particular component of their community education activities would be the
identification and training of key neighborhood residents to become Neighborhood
Asthma Educators. This program component will be initially developed as part of
the Primary Care and Asthma Centers; additional Neighborhood Asthma Specialists
may also be based in other high risk communities. In Hunts Point, the Neighborhood
Asthma Specialists will coordinate with ongoing activities of the NYC DOH.
2.
High prevalence special population emphasis: This program component will focus
on special population subgroups with high asthma prevalence rates, including
homeless children, children under detention, street youth, immigrant children and
high-risk age groups such as infants, very young children, and teen parents.
3.
Other clinical enhancement programs and asthma interventions: Interventions that
could be developed and evaluated in high-risk communities, either as pilot programs
or smaller-scale components of the main program, include the development of
generalizable models for short-term intensive asthma interventions, the use of
mobile units to supplement fixed site programs in additional sites for clinical or
educational purposes and the development of interventions to reduce environmental
and psychosocial risk factors for asthma attacks.
IV.
EVALUATION
A specific evaluation plan will be developed for each program component to assess its effectiveness,
generalizability, and potential for sustainability and expansion. The program -specific evaluation
plans will be developed in consultation with other asthma-related programs in NYC that have similar
program components to ensure effective linking of evaluation results across programs. In particular,
evaluation of program components that are situated in the Hunts Point community will be
coordinated with existing programs of the NYC DOH. As part of an evaluation baseline assessment,
a targeted assessment of childhood asthma prevalence and incidence in NYC could be undertaken.
This could include the identification of communities, age groups and special populations with high
asthma prevalence rates, assessment of indicators of asthma morbidity (e.g. hospitalizations,
emergency department use, primary care visits, days missed from school because of asthma), and
surveillance / investigation of near-fatal asthma attacks and asthma deaths. Surveillance efforts will
be coordinated with and will collaborate with other surveillance efforts, in particular those of the
NYC DOH and others around emergency department asthma surveillance. The evaluation plan will
also serve to identify new directions for the New York Childhood Asthma Initiative and suggest
modifications of the existing program.
NYCAI: Goals and Program Components: Draft 8/4/97
5
The Children's Health Fund 317 East 64th Street - New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
09/15/97 MON 16:36 FAX 212 535 7488
CHF
003
THE Children's
DRAFT 091597 11:58
Health FUND
THE PROPOSED PLAN TO ANNOUNCE THE NEW YORK CITY
CHILDHOOD ASTHMA INITIATIVE
WHAT: A press conference for The Children's Health Fund to announce a major public health Initiative, The
New York City Childhood Asthma Initiative, and plans to develop a primary care and asthma center.
This is an opportunity to unveil the program components, to talk with principals involved, and dignitaries
who support the initiative as an effort to fight against the epidemic of asthma. This comprehensive plan is
designed to be a model for programs that can be executed throughout the United States.
WHO: An exceptional coalition of:
FEDERAL INTERESTS: The White House, Ms. Hillary Rodham Clinton;
LOCAL GOVERNMENT: The City Council of New York, led by Councilman Kenneth Fisher;
PUBLIC HEALTH ADMINISTRATION: the New York City Department of Health, represented by
Benjamin Mojica, Acting Commissioner;
THE CHILDREN'S HEALTH FUND: spearheaded by Irwin Redlener, MD;
ACADEMIC HEALTH CENTER: Montefiore Medical Center, represented by Spencer Forman, MD,
Chief Executive Officer;
WHY: The New York City Childhood Asthma Initiative addresses the epidemic proportions of asthma in New
York City, where incidence of the disease is among the highest in the nation. The press conference is to
advise the community, via the press, of the diverse efforts that the Initiative will introduce, and to introduce
the plan as a national model.
WHEN:
Monday, September 22, 1997
1:00 pm
Time frame: approximately 20 minutes to one-half hour;
Post-conterence: visit to nearby day care center.
WHERE:
South Bronx Children's Health Center
911 Longwood Avenue
The Bronx, New York.
OTHER:
1.0 Speakers
11
Irwin Redlener, MD, President, The Children's Health Fund;
1.2
Kenneth Fisher, Councilman. Borough of Brooklyn;
1.3
Benjamin Mojica, MD, Acting Commissioner, NYC Department of Health:
1.4
Spencer Forman, MD, President, Chief Executive Officer,
Montefiore Medical Center;
1.5
Hillary Rodham Clinton, Esq., First Lady of the United States.
The Children's Health Fund, 317 East 64th Street, New York NY 10021, Telephone (212) 535-9400, Fax (212) 535-7488
09/15/97 MON 16:36 FAX 212 535 7488
CHF
4
004
New York City Childhood Asthma
Initiative announcement, page 2.
2.0
Other invited, nonspeaking guests to be acknowledged, including New York City Council
President Peter Vallone, Bronx Borough President Frederic Ferrer, U.S. Representative Jose Serrano,
Bronx Assemblyman Jeffiey Klein, private sector major donation from the President of Schering
Laboratories (full list to follow.)
3.0 Tentative Agenda
1:00
Scheduled start time
1:00
Irwin Redlener, MD opens the floor, introduces Mrs. Clinton, introduces other
speakers, invites Ken Fisher to speak.
1:01
Kenneth Fisher discusses the genesis of the budget allocation for the
New York City Childhood Asthma Initiative.
1.05
Irwin Rediener speaks of the problems of underserved children, asthma and the
need for a children's agenda in New York City.
1:09
Benjamin Mojica, Acting Commissioner of Health, presents the
Department's perspectives on the program.
1:13
Spencer Forman, Montefiore Medical Center, speaks of the initiative from
the perspective of the incidence of asthma in the Bronx, and Montefiore's long-
term commitment to children's health.
1:17
Hillary Rodham Clinton speaks. (CHF to be advised of her point of view.)
1:21
Conclusion.
1:22
Questions and answers.
20.70 uninsured
65% Medicard
Call re Speakers
15070 Third party
Insurance
2 perces.
I
Ulinical services
65% Hispanic
Public Awareness
30-35070 Af- Am.
1
eligible for
Many Medicard,
but not
enrolled
CC: Sanjay Gupta
was
9/22
THE WHITE HOUSE
WASHINGTON
ic Davids
OFFICE OF THE FIRST LADY
57234
TO
Patti Solis - Doyle
FROM
Jen
FAX #
6- 5340
PHONE #
# OF PAGES (including cover)
COMMENTS
As I said, the event could
include:
,
A visit to the clinic in Hunt's
Point ( which has the highest
asthma rate in the country);
and
2
4 visit to a child care
center in Hunt's Point where
they will be training child
care providers about asthma.
Irwin has all commitments ($) 187
place for this project (except for
contribution from Schering- Plough which
they expect soon). This event would
be the launch of the initiative.
Jen
100
12:10 26/60/60
THE Children's
Health
FUND
A decade of caring for kids
1987 I997
THE NEW YORK CHILDHOOD ASTHMA INITIATIVE
Revised Preliminary Scope of Work
This city wide initiative is designed to address a growing health crisis with respect to childhood
asthma. Organized as a partnership between the office of Councilman Ken Fisher and The
Children's Health Fund (CHF), with strong collaboration with the New York City Department of
Health, the program will have the following goals and program components.
I.
GOALS
1.
Increase in public awareness and knowledge of pediatric asthma
2.
Development of innovative primary care programs with a special asthma focus
3.
Development of a broad, system-based model that integrates community, medical,
educational and other interventions to address the childhood asthma epidemic
4.
Development of sustainable public policies and programs that will contribute to the
ongoing reduction of childhood asthma morbidity and the elimination of childhood
deaths due to asthma
II.
PROGRAM DEVELOPMENT PROCESS
The program will be developed through a process that will a) give program attention to specific
communities with high asthma prevalence and to special populations with high asthma prevalence,
and b) ensure coordination with and be complementary to current asthma-related activities of the
NYC DOH, as well as asthma-related activities of other institutions, agencies and organizations, and
c) consult and collaborate with community organizations in targeted, high prevalence communities
on program development, implementation and potential for sustainability.
An initial collaborative planning meeting will be scheduled with representatives from Councilman
Fisher's office, the Children's Health Fund and the NYC DOH, chaired by Councilman Fisher and
Irwin Redlener, MD, to discuss program design, implementation and potential community linkages.
Specific topics will include a) the development of critcria for the identification of high prevalence
communities / special populations as well as the site selection process, and b) the coordination of
New York Childhood Asthma Initiative program components with current DOH activities, especially
those in the Hunts Point area. The discussion of overall program design for the Childhood Asthma
Initiative will also include contributions of the experience of the NYC DOH in Hunts Point, as well
as the experience of other asthma programs and population-based models, both in NYC and
elsewhere.
NYCAI: Goals and Program Components: Draft 8/1/97
1
The Children's Health Fund . 317 East 64th Street New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
0222
D
12:11
26/60/60
III.
PROGRAM COMPONENTS
A.
Establishment of a Childhood Asthma Task Force
Co-chaired by Councilman Fisher and CHF President Irwin Redlener, MD, the task force will be
composed of representatives of NYC agencies, organizations; unions, and individuals with relevant
experience in a wide range of service sectors. The Task Force may appoint subcommittees as
needed.
Potential Tasks:
1.
Participation in the development of a major asthma awareness campaign focused on
the epidemic of childhood asthma in NYC
2.
Development of appropriate public policy responses to the epidemic of childhood
asthma
B.
Childhood Asthma Awareness Campaign
This campaign is designed to call significant public attention to the new crisis in pediatric asthma.
Its purpose will be to inform the public, provide essential information to parents of children with
asthma, educate children with asthma about their disease and offer state-of-the-art information on
asthma diagnosis and treatment to primary care providers who deal with this condition. It will be
designed to develop effective asthma educational models to train a wide range of service providers,
agencies and community organizations that interact with children. An important anticipated
outcome of the Childhood Asthma Initiative will be the development of successful models of health
education around asthma that may also be applied to other health conditions.
Possible Campaign Components:
1.
Public Information Initiative: This component will include the development of
asthma awareness and knowledge surveys, the development of an ad campaign,
public service announcements, the development of media coverage and appropriate
materials for general distribution. These materials might include Asthma
Information Kits for children and parents, community organizations such as churches
and other religious institutions, tenants associations, block associations, local
businesses and community service organizations; Asthma Fact Sheets for distribution
at health fairs, local businesscs and community events as well as other asthma
information materials. The targeted audience for the public information initiative
would include parents and caretakers of children with asthma, children and
adolescents with asthma, community organizations, residents of high-risk
communities, special populations with high asthma prevalence rates such as
homeless children, and the general population. The public campaign would also
NYCAI: Goals and Program Components: Draft 8/4/97
2
The Children's Health Fund 317 East 64th Street - New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
803
11:11
26/60/60
publicize the "asthma information hotline" and other aspects of this program.
Development of the public information initiative will be in coordination with the
health promotion activities of the NYC DOH and other asthma education efforts in
the NYC area.
2.
Asthma Information Hotline: This component will be directed at provision of state-
of-the-art information on asthma for parents, teachers, community organizations,
agencies and others as well as enhancing the participation of parents in the
management of asthma for their children. Information will be linguistically and
culturally appropriate. The hotline will have an 800 number available 5-7 days a
week. It will offer general information about asthma, prevention of asthma attacks
and advice on how and where to secure a primary care provider with appropriate
expertise in asthma management.
3.
Provider Education: In New York City currently, provider knowledge with respect
to asthma diagnosis and management is variable and inconsistent. The recent releasc
of the revised Guidelines for the Diagnosis and Management of Asthma (National
Asthma Education and Prevention Program, NHLBI) offers an opportunity to
develop provider education strategies that reflect state-of-the-art asthma care. Under
this component of the program, an effort will be undertaken to educate physicians,
as well as other primary care providers such as nurses and physician assistants.
Other professionals that interact regularly with asthmatic children and their parents
will also bc targeted, including clerks at health facilities, pharmacists and social
service providers. A particular focus will be those providers who provide services
in high risk communities and those serving high risk special populations. The
provider education programs will be coordinated with existing efforts that target
provider education under the auspices of DOH and other organizations in the city.
Provider education strategies will identify effective approaches and will be designed
to complement current programs, such as the Greater New York Asthma Initiative
Provider Education Conference scheduled for Spring, 1998. It may also include:
the organization of a city-wide conference on childhood asthma
development of targeted teaching programs and educational materials for
physicians
a physician's newsletter
the development of special training programs for nurscs, pharmacists, social
service workers and clerical staff
The provider education programs will include information on the diagnosis of
asthma, identification of asthma symptoms, identification of asthma triggers,
identification of risk factors for fatal asthma, current treatment options, prevention
strategies, development of patient-provider asthma management plans, and
NYCAI: Goals and Program Components: Draft 8/4/97
3
The Children's Health Fund 317 East 64th Street New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
004
12:12
26/60/60
appropriate use of asthma management devices such as peak flow meters and spacers.
4.
Enhanced School and Day Care Programs: This component will focus on educating
school-age children and adolescents with asthma about asthma triggers, asthma
management, asthma medications, strategies for maximal asthma control, asthma and
athletics and reduction in activity limitation due to asthma. It will also focus on
educational programs for teachers, administrators and other school staff. It will build
on school-based programs already existing in the city and will be targeted towards
high-risk school districts.
The Day Care program would provide education to both day care staff and parents
in the recognition of asthma symptoms, use of asthma medications, identification of
asthma triggers, general asthma management strategies and identification of primary
care resources. It will also include specific early childhood development programs
such as Ilead Start.
C.
Clinical Program: Primary Care and Asthma Centers
Possible Program Components:
1.
Establishment and/or enhancement of primary care programs with a special asthma
focus: Primary Care and Asthma Centers will be organized in two communities
where asthma is particularly problematic. Locations will include the Hunts Point
Peninsula community where The Children's Health Fund's affiliated project, the
South Bronx Children's Health Center, is already working closely with the New
York City Department of Health. This program will be structured to complement
existing asthma initiatives in the Hunts Point community. An additional Primary
Care and Asthma Center site will be established in collaboration with institutions that
currently provide primary health care services in Brooklyn. On-going development
of this program component will be closely coordinated with the Department of
Health and local community partners such as The Point. The Primary Care and
Asthma Centers will provide needed state-of-the-art asthma care in these two high-
risk communities and will also serve as demonstration sites for the development and
evaluation of a range of clinical, educational and community programs and materials
targeted at childhood asthma for broader implementation and dissemination.
Neighborhood Asthma Specialists: A critical component of the childhood asthma
initiative will be the integration of increased public awareness of asthma with the
provision of enhanced clinical care. As part of this effort, nurses would be trained
to become neighborhood-based specialists in asthma management and education.
They would be initially based in the Primary Care and Asthma Centers described
below and would provide asthma education, training and outreach across a wide
range of sites within a specific gcographic area, linking medical facilities to schools,
NYCAI: Goals and Program Components: Draft 8/4/97
4
The Children's Health Fund 317 East 64th Street New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
900
12:13
26/60/60
housing, community organizations, churches, tenant associations, day care centers,
multi service centers, block associations, local social service organizations, local
pharmacies, local businesses and others providing community services. The
Neighborhood Asthma Specialists would thus serve a key role in integrating and
linking asthma education and services within high-risk geographic locations and in
developing a sustainable focus on childhood asthma within those communities. A
particular component of their community education activities would be the
identification and training of key neighborhood residents to become Neighborhood
Asthma Educators. This program component will be initially developed as part of
the Primary Care and Asthma Centers; additional Neighborhood Asthma Specialists
may also be based in other high risk communities. In Hunts Point, the Neighborhood
Asthma Specialists will coordinate with ongoing activities of the NYC DOH.
2.
High prevalence special population emphasis: This program component will focus
on special population subgroups with high asthma prevalence rates, including
homeless children, children under detention, street youth, immigrant children and
high-risk age groups such as infants, very young children, and teen parents.
3.
Other clinical enhancement programs and asthma interventions: Interventions that
could be developed and evaluated in high-risk communities, either as pilot programs
or smaller-scale components of the main program, include the development of
generalizable models for short-term intensive asthma interventions, the use of
mobile units to supplement fixed site programs in additional sites for clinical or
educational purposes and the development of interventions to reduce environmental
and psychosocial risk factors for asthma attacks.
IV.
EVALUATION
A specific evaluation plan will be developed for each program component to assess its effectiveness,
generalizability, and potential for sustainability and expansion. The program -specific evaluation
plans will be developed in consultation with other asthma-related programs in NYC that have similar
program components to ensure effective linking of evaluation results across programs. In particular,
evaluation of program components that are situated in the Hunts Point community will be
coordinated with existing programs of the NYC DOH. As part of an evaluation baseline assessment,
a targeted assessment of childhood asthma prevalence and incidence in NYC could be undertaken.
This could include the identification of communities, age groups and special populations with high
asthma prevalence rates, assessment of indicators of asthma morbidity (e.g. hospitalizations,
emergency department use, primary care visits, days missed from school because of asthma), and
surveillance / investigation of near-fatal asthma attacks and asthma deaths. Surveillance efforts will
be coordinated with and will collaborate with other surveillance efforts, in particular those of the
NYC DOH and others around emergency department asthma surveillance. The evaluation plan will
also serve to identify new directions for the New York Childhood Asthma Initiative and suggest
modifications of the existing program.
NYCAI: Goals and Program Components: Drall 8/4/97
5
The Children's Health Fund 317 East 64th Street New York NY 10021 Telephone (212) 535-9400 Fax (212) 535-7488
900
12:14
26/60/60
MEMORANDUM FOR THE FIRST LADY
Sep 10, 1997
FROM:
Domestic Policy Staff
SUBJECT:
Child Asthma Initiative
IMPACT
Asthma is a chronic inflammatory disease of the airways. In the United States, asthma affects 14 to 15
million persons. It is the most common chronic disease of childhood, affecting an estimated 4.8 million
children with the direct and indirect cost estimated at $6.2 billion dollars in 1993. Over 3800 children and
young adults under 25 died from asthma nationwide during the period 1980-1993. 342 children died from
asthma in 1993 alone. Asthma is associated with the loss of 28 million activity days annually and 2.2 million
pediatrician visits. It is the leading cause of school absenteeism. It has been estimated that among children 5-
17 years old, asthma accounted for approximately 10 million missed school days at a cost of $726.1 million
in caretakers' time lost from work.
TRENDS
The burden of asthma on the US population is increasing. Through the 1980's, the prevalence of asthma
increased 29%, hospitalization rates increased 6% and mortality rates increased as well. The most notable
increases were for children and young adults. Hospitalization rates for children less than five years old have
increased 57% since 1980. These rates increased at a time when total hospitalization rates for children
decreased. Overall, the annual age-specific asthma death rate increased 118% (from 1.7 to 3.7 per million)
between 1980 and 1993 for persons aged 0-24. Explanations for rising prevalence, morbidity and mortality
are varied. Investigators have attributed increased hospitalization to improved diagnosis, untoward effects of
treatment, environmental factors, improvements in vital statistic reporting, and increased tendencies for
asthmatic patients to use hospital emergency departments as primary sources of care.
VULNERABLE POPULATIONS
Childhood asthma has become more prevalent and more severe in the last decade, and disproportionately
affects minority populations. In 1993, among children aged 5-14 years, blacks were four times more likely
than whites to die from asthma.. In the 0-4 age group, blacks were six times more likely to die from asthma
than whites. Hospitalization rates are consistently highest among blacks. In 1993, among persons aged 0-24
years, blacks were 3.4 times more likely than whites to be hospitalized for asthma..
Children living in the inner city are particularly vulnerable. New York City has the highest rate of
hospitalization and mortality for childhood asthma of any area in the United States. As of 1993, New York
City children were hospitalized for asthma at four times the national rate. Within the city, these rates are
three to five times higher for African Americans and Latinos than for the rest of the population. Areas in New
York City with the highest asthma hospitalization rates include the South Bronx, Upper Manhattan, Central
and North Brooklyn. Nationally, asthma rates are highest in New york, Chicago, Fresno, and Maricopa
County, Arizona.
The exact relationship between generally known risk factors and the increase in asthma-related morbidity and
mortality among minority inner city children has not been determined. Poverty undoubtedly impacts upon the
health of inner-city populations. Poverty has been linked to underdiagnosis and subsequent reduced
preventive asthma care. Defined risk factors such as passive and active cigarette smoking and air pollution
may be greater for minority, inner-city children. Also, infestation with pests such as roaches, mites, rodents
and mosquitoes are greater problems among the poor than the more affluent. Finally, socio-economic status
has been directly linked to overall compliance and medical follow-up.
PATHOGENESIS AND MANAGEMENT
Asthma results from complex interactions among inflammatory cells, mediators and the cells and tissues
resident in the airway. Atopy, the genetic predisposition for the development of a mediated response to
common aeroallergens, is the strongest identifiable predisposing factor for developing asthma. In susceptible
individuals, this chronic inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness
2
and cough, particularly at night and in early morning. The episodes are usually associated with widespread
but variable airflow obstruction that is reversible either spontaneously or with treatment. This inflammation
does cause an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.
The effective treatment of asthma is dependent on four components: 1) correct diagnosis of asthma 2)
reducing factors contributing to asthma severity 3) pharmacological therapy 4) self-management education.
The goals of asthma therapy are to: 1) prevent chronic and troublesome symptoms 2)maintain normal
pulmonary function 3) maintain normal activity levels 4)prevent recurrent exacerbations 5) provide optimal
pharmacotherapy with minimal side-effects and 6) meet patients' and families' expectations of satisfaction
with asthma care.
NEW YORK CHILDHOOD ASTHMA INITIATIVE
This initiative is organized as a partnership between the office of Councilman Ken Fisher and The Children's
Health Fund, with strong collaboration from the New York City Department of Health. The goals of the
program are to increase public awareness and knowledge of pediatric asthma and develop programs, models,
and policies that will serve to reduce childhood asthma morbidity and eliminate childhood deaths due to
asthma. The initiative will give attention to specific communities with high asthma prevalence.
The program components will include a Childhood Asthma Task Force. This task force will be representative
of NYC service sector agencies and will be co-chaired by Councilman Fisher and Children's Health Fund
President Irwin Redlener MD. Other program components are Childhood Asthma Awareness Campaign and
Clinical Programs. These components will include a public information initiative, asthma information hotline
and provider education. In addition, the establishment and/or enhancement of primary care programs with
special asthma focus will be organized in two communities where asthma is particularly problematic, Hunt's
Point and Brooklyn. Existing care centers will provide needed state-of-the-art asthma care in these two high
risk communities and will serve as demonstration sites for a range of clinical and educational programs
targeted at childhood asthma.
3
TO:
Tom Freedman
FROM:
Neera Tanden
RE:
Asthma
The Problem:
There has been a huge increase in asthma over the last decade. It is a particular problem for
children. While there has been a great deal of speculation as to the cause of the dramatic
increase, no one can figure out why it is happening. The speculation runs the gamut from
environmental pollution to tobacco to urban violence.
Asthma is actually a problem throughout the developed world; people are suffering asthmatic
reactions to a range of allergens that once caused little trouble. And basically, although scientists
are learning more about asthma, the explosion is still largely a mystery.
The Facts
Asthma now afflicts about 14.6 million Americans.[Newsweek, 5/26/97] This is twice
the number it was 25 years ago. [Life, 5/97]
The number of American asthmatics grew by 6.2 million between 1984 and 1994 -- an
astonishing 74% increase. [San Francisco Chronicle, 7/3/96]
There are now more than 5 million children afflicted with asthma - 1 in 13 children in
1993, which is 79% more than in 1982.[LA Times, 10/27/96]
Asthma costs $ 6.2 billion a year in missed work and school, in medications and hospital
visits. [Life, 5/97]
Asthma has become the most common chronic disease of childhood, the No. 1 cause of
hospitalization and absenteeism. [Life, 5/97]
Asthma is especially severe in the inner city, where rates of asthma emergency room
visits and deaths can be eight times the national average.
The United States has an overall asthma rate of about 5 percent. But the rate is 8.4
percent in New York City, and it can reach 25 percent among kids in the poorest urban
neighborhoods.
The Interest:
The dramatic rise in asthma has been called an "epidemic," "pandemic," and "crisis" in recent
media stories.
1. Newsweek, "The Scary Spread of Asthma" (Cover Story), 5/26/97
2. Good Morning America
3. The Today Show
4. Life Magazine, "An Epidemic of Sneezing and Wheezing," 5/97
5. Front page: LA Times, San Francisco Chronicle, NY Daily News
The Tie-In
Asthma is related to three policy proposals the Administration is currently pushing. Generating
interest in fighting asthma will only help increase support for these proposals.
1. New EPA regulations --
We have used asthma as a major justification for our plan to increase environmental regulations.
In fact, during the briefing on the new standards, Katie McGinty said:
"[T]he President is strengthening current smog standards that we know seriously exacerbate
asthma conditions and other lung ailments, and that particularly affect children. Asthma is one
of the leading causes of children's hospitatlization and, following from that, a leading cause of
children missing out on school days. So the step -- the decision the President made today
advances our commitment to clean air in this country and allows ust ot take important gains on a
pullutant that we konw causes premature death and other pullutants that we know dramatically
exacerbate lung conditions and particularly asthma."
We are and should continue to highlight the fact that we are proposing these regulations simply
to lower the number of children who suffer from asthma.
2. Expanding Health Care for Children
Because asthma is the number one chronic disease in children and the number one cause of
hospitalization, it is a big reason why we need to insure these children whose parents are working
but cannot afford health care. If asthmatic children have regular access to medical care, their
asthma can be regulated and controlled, thereby lessening the number of emergency room visits.
3. Tobacco
Smoking - especially by parents near their children - can cause asthma. And of course,
asthmatics suffer greatly from those who smoke around them because their smoke can often
trigger an attack.
The Proposals
1. Researching the Causes of Asthma. We basically do not know why rates of asthma are
climbing - but we should. As we did with breast cancer, we can marshall federal resources to
study the causes of asthma as well as new treatments. Our funding of breast cancer research was
popular with a certain constituency; in a like manner, parents may similarly support an effort to
find the causes of asthma.
2. Launching a National Education Campaign on Asthma. A national education campaign
would do some good here. Asthma is one disease in which educating parents about the
symptoms and some of the instigators of attacks would alleviate some of the problem. In fact,
New York City is already experimenting with ways to educate parents of asthmatic children by
simply explaining to them that they need to get rid of rugs, stuffed animals, etc.
3. Grants to schools for medical equipment for asthma management that will be available for use
in school nurses' offices. Arizona is starting such a program.
09/15/97 MON 16:36 FAX 212 535 7488
CHF
4
002
MEMO TO:
Jennifer Klein
THE Children's
Health FUND
FROM:
Melissa Ziriakus
DATE:
September 15, 1997
SUBJECT:
Children's Health Fund press event
Irwin Redlener and I have been in discussions to develop and provide you with a proposed outline for the New York
City Asthma Initiative press conference on September 22 involving Ms. Hillary Clinton.
HRC seen this
before
I've attached that for your review, and invite you to call if you have any questions.
1 TV evew
or couple of
reporters
DS to Speaking Program, HRC to tour
monil unit
No Q3A
Fina parent of child w/ asinma
what needs to be done to Uinic
CC: Irwin Redlener, MD
Review pieces of initiative
Message
1
Asthmu epiaemic
all children
HHS, EPA Accomp.
high risk neighborhoods
Other states doing anything
Sanjay to tain to Irwin ve Hunt's Point up Rate]
2.
Connect to underserved children - Hes into kid's health
impl. B children's health fund work on
7
$ 314 M to from Astnma Schering Plow - - Public Partnership Partnership
HRC to
me ntion
The Children's Health Fund, 317 East 64th Street, New York NY 10021, Telephone (212) 535-9400, Fax (212) 535-7488
4
Montejiore committed to building (nildren's Health System for
South Bronx
Griwide program - HRC shld stress - - not just S.Bronx
Sanjay Gupta
12/10/97 07:33:03 PM
Record Type:
Record
To:
Brenda B. Costello/WHO/EOP
CC:
Jennifer L. Klein/OPD/EOP
Subject: Final points
FOOD SAFETY
President Clinton asked for and received 43 million dollars in FY 98
budget to fund an early-warning system for food-borne illness, increased
seafood inspections and expanded food-safety research.
Last year, President signed the Safe Drinking Water Act of 1996, which
includes regulatory improvements to help states and water utility managers
to prevent drinking-water contamination problems. Resources are
provided for thr first time for drinking water infrastructure that will help
hundreds of communities protect residents from harmful contaminants.
done
Sanjay Gupta
12/10/97 06:48:23 PM
Record Type:
Record
To:
Jennifer L. Klein/OPD/EOP
CC:
Brenda B. Costello/WHO/EOP
Subject: Asthma
ASTHMA
The congressional report from HHS that I received states there are no
recent bills directly addressed to asthma. I did find a few things that could
be included in the briefing book for asthma. I'll try to be brief.
NHLBI (National Heart Lung and Blood Institute)
NIAID (National Institute of Allergy and Infectious Diseases)
NAEPP(National Asthma Education and Prevention Program)
1) Childhood Asthma Management Program -- examines and compares
the long-term effects of asthma on lung growth and develpment
2) National Cooperative Inner City AsthmaStudy -- supports seven centers
to design, implement, and evaluate a comprehensive intervention program
to reduce recurrent asthma episodes among inner-city children
3) NAEPP has convened two expert panels to prepare guidelines for the
diagnosis and management of asthma. The first in 1989 and the most recent
in 5-97
AHCPR( Agency for Health Care Policy and Research)
1) Pediatric Asthma Patient Outcome Research Team (PORT II) -- will test
the cost-effectiveness of the NHLBI (described above) and evaluate new
educational and organizational approaches to deliver pediatric asthma
care in
managed settings
CLEAN AIR
Administrator Browner signed the new standards for smog and soot
on July 16, 1997. These standards will prevent approx 350,000 cases
of aggravated asthma. These standards are expected to prevent 15,000
premature deaths and 1 million cases of decreased lung function
In September 1996, Browner issued the National Agenda to protect
Children's Health from Environmental threats. This agenda called on the
EPA to address the special vulnerabilities of children - like susceptibility
to air pollution ans asthma.
In May, 1997, Browner created the Office of Children's Health Protection to
ensure implementation of the Agency's National Agenda
President Clinton signed the Executive Order on the Protection of Children
from Environmental Health and Safety Risks (EO #13045) on April 21, 1997.
This execuitve order stated that eachfederal agency must address
environmental health threats to children in its regulations and programs.
The executive order also created the Task Force on Environmental Health
and Safety Risks which is chaired by Browner and Shalala.
FOOD SAFETY
Statement by the President Aug 3, 1996
Signed into law H.R. 1627 -- the "Food Quality Protection Act of 1996"
Replaces conflicting and outdated pesticide residue standards
with a single, rigorous, health-based standards for all food. All pesticides
will be required to meet the new standard. It will also provide for the swift
approval of safe, new pesticide alternatives for farmers.
Most importantly, HR 1627 contains special new provisions to protect
America's infants and children from pesticide risks.
Demonstrates how Congress and the Administration can
work together to help both farmers and consumers.
TOXIC WASTE
Administration has strengthened and improved Superfund clean-ups.
In first three years, 197 sites were cleaned up. This is more than in the
previous 12 years of other administartion. This administration is cleaning
sites three times more a year than were done before.
12/10/97 18:16 FAX
CHILDREN'S HEALTH FUND
002
CONTACT:
THE CHILDREN'S HEALTH FUND
SCHERING PLOUGH CORPORATION
Melissa Ziriakus (212) 535-9400
William O'Donnell (973) 822-7476
COMMUNICATIONS STRATEGIES
Laurie Smith (973) 635-6669
THE CHILDREN'S HEALTH FUND, SCHERING-PLOUGH CORPORATION,
THE NEW YORK CITY COUNCIL, AND NYC DEPARTMENT OF HEALTH LAUNCH
MAJOR INITIATIVE TO FIGHT ASTHMA
BRONX, N.Y., December 11, 1997 - Tackling the urgent need to treat childhood asthma,
The New York City Childhood Asthma Initiative today launched a nationwide effort to fight
asthma in inner-city communities.
First Lady Hillary Rodham Clinton, speaking at a press conference at the South Bronx Children's
Health Center, headed adist of dignitaries praising this innovative community-based effort that
teams the public and private sectors to deliver asthma prevention and treatment services to
neighborhoods with the greatest need. The multi-year, multimillion dollar prograin is a
partnership of The Children's Health Fund (CHF), Schering-Plough Corporation, Montefiore
Medical Center, and the New York City Council.
The New York City Childhood Asthma Initiative, brainchild of New York City Councilman
Kenneth Fisher and CHF President Dr. Irwin Redlener, is designed to be a comprehensive
treatment, prevention and education model to serve as a prototype for urban areas throughout the
country. The New York City Council, under the leadership of Speaker Peter Vallone and
Councilman Fisher, has provided $1.5 million in funding for the New York project.
-more-
12/10/97 18:17 FAX
CHILDREN'S HEALTH FUND
003
The Childhood Asthma Initiative/page 2
Schering-Plough Corporation and Schering-Plough Foundation have provided funds
estimated at more than $1 million to establish a primary care and asthma center in the South
Bronx. Primary medical care and asthma speciality services will be provided by Montefiore
Medical Center in the Bronx. Community education and outreach will be coordinated with other
special asthma programs in New York City.
"Asthma is a serious illness, complicating many aspects of a child's life and becoming a chronic
lifelong problem if left unmanaged," said Irwin Redlener, MD, president and co-founder of The
Children's Health Fund. "Yet today, unlike just a few years ago, we know that there are ways to
prevent the occurrence of asthma attacks and there are treatments available that can dramatically
lessen its effccts. Every day, we see the effect of asthma on children's lives, and we are excited
to be able to implement a program that can have a significant, positive impact on the health of
young children."
"What is sadly ironic about asthma is that so much emergency effort is spent to treat patients and
we still lose too many children unnecessarily," said Richard W. Zahn, president of Schering
Laboratories. "Given the many scientific advances in asthma treatment and prevention, it is
unconscionable that this disease remains such as menacing problem. Children's lives can be
saved and cnhanced, if proper steps are taken."
An estimated 12- to 14 million Americans suffer from asthma; 5-6 million are children. These
numbers are growing rapidly. Since 1980, there has been a 57 percent increase in asthma
hospitalization rates for children less than 5 years old. Approximately 5,000 U.S. deaths are
attributed to asthma annually. New York is particularly hard hit it has the highest rate of
asthma per capita in the nation. Asthma now ranks as the No. 1 health concern in many New
York City schools, mainly elementary schools in poor areas and in minority communities.
-more-
12/10/97 18:17 FAX
CHILDREN'S HEALTH FUND
004
The Childhood Asthma Initiative/page 3
"Asthina is at its worst in cities such as New York, where children are hospitalized for asthma at
nearly twice the national rate," said Dr. Redlener. "Inner-city areas present a host of agents that
can aggravate asthma, including outdoor allergens such as dust, mold and other indoor allergens
including cockroach droppings and crowded conditions that can breed respiratory infections.
Stress and tobacco smoke arc also contributing factors."
"We have the opportunity to improve the quality of life for 120,000 children in New York. We
can keep these children in schools, keep their parents at work and reduce health care costs by
recognizing the tragic consequences of asthma and making it a public policy," said Fisher.
"The New York City Council is proud to be part of this partnership to tackle asthma in
New York," said Speaker Vallone. "All children in this city deserve the opportunity to lead
healthy, productive lives, and this initiative can help make that happen."
"As a nation, we must declare war on childhood asthma and allergies." said Zahn. "Today, The
Children's Health Fund, Schering- Plough Corporation, Montefiore Medical Center and The
New York City Council are dedicating ourselves to helping underprivileged children who suffer
from these respiratory diseases."
The Children's Health Fund initiates and supports pediatric programs designed to meet the
complex health care needs of medically underserved, homeless and indigent children. Now in its
tenth year of operation, The Children's Health Fund was established by pediatrician Redlener
and singer/composer Paul Simon.
-more-
12/10/97 18:17 FAX
CHILDREN'S HEALTH FUND
1.
005
The Childhood Asthma Initiative/page 4
In addition to the contribution to The New York City asthma initiative, a separate contribution
from the Schering-Plough Foundation will fund the purchase of a dedicated CHF mobile medical
unit for use in helping children in Newark and Elizabeth, N.J. and in the surrounding Union
County area.
Schering-Plough Corporation is a research-based pharmaceutical and health care products
company headquartered in Madison, N.J. Schering laboratories is the U.S. pharmaceutical
business unit and Schering-Plough Foundation is the philanthropic arm of the parent company.
Today, company scientists continue to pursue new and more effective agents to prevent or block
the effects of the body's allergic and immunological responses. In the disease management area,
the company has developed comprehensive intervention programs to manage the coverage,
quality and costs of disease treatments in asthma, rhinitis, angina, hepatitis and prostate cancer.
###
12/10/97 WED 19:00 FAX 212 535 7488
CHF
001
FAX TRANSMITTAL
THE Children's
COVER SHEET
Health FUND
To:
Jennifer Klein
Via Fax #:
202 456 2878
From:
Dennis Jahnson
Date:
12/10
The number of pages in this fax (including this cover page): 5
If there is a problem with this fax transmission, please call (212) 535-9400 Ext.
Message:
Jennifer,
Attached IS the correspendence
about CHF / Dept. of Health
agreement. Please call me if you
need additional info.
Dennis
The Children's Health Fund
317 East 64th Street
New York, New York 10021
212/535-9400
1002
12/10/97 WED 19:00 FAX 212 535 7488
CHF
TEL 212-788-4920
Dec 10'97 17:08 No. 012 P.02
EHS/ADMINISTRATION
THE CITY OF NEW YORK
DEPARTMENT OF HEALTH
OFFICE OF THE COMMISSIONER
on
BENJAMIN MOJICA, M.D., M.P.H.
ACTING COMMISSIONER
125 WORTH STREET
TEL (212) 788-5261
NEW YORK, NY 10013
FAX (212) 964-0472
December 10, 1997
Kenneth K. Fisher
Council Member, 33rd District
16 Court Street - Room 1505
Brooklyn, NY 11241
Dear Council Member Fisher:
I have reviewed your memo of December 9, 1997 regarding the Asthma Initiative and the
development of an agreement with the Children's Health Fund. I am pleased that this memo
contains many of the suggestions we recently provided to you and Dr. Redlener. There are.
however, a number of issues that require further clarification. I have noted below our comments
on each of the items listed in your memo:
1.
Any agreement for payment must be subject to an actual registered contract not just an
agreed upon scope of service.
2.
This is agreeable subject to legality and a review of the reasonableness of amount sought.
as well as the factors cited in your memo. As stated several times in the past, we will be
as llexible as is reasonable in this reyard.
3.
Agreed.
4.
Agreed, but with the understanding that the partnership relationship extends to the
planning and execution of all activities, including public relations activities surrounding
the initiative.
5.
Agreed.
6.
The support is not limited to the Peninsula as the Hunts Point program extends over both
zip codes 10474 and 10459. In addition, the DON would be most comfortable if the
support were to be provided out of the South Bronx Children's Health Center or, in the
alternative, another location in the Hunts Point program area.
003
12/10/97 WED 19:00 FAX 212 535 7488
CHF
Dec 10'97
17:08 Nu. 012 P.03
EHS/ADMINISTRATION
TEL 212-788-4920
Kenneth K. Fisher
Council Member, 33rd District, cont.
7.
Agreed.
8.
Agreed. Guidelines and comments have already been provided.
9.
We are unclear as to the intent of the phrase "work within" and do not feel il adds
anything of substance to the discussion and may, in fact, limit collaboration.
10.
Agreed.
1 trust that you will find these comments helpful in reaching a quick resolution of outstanding
issues. 1 have instructed my staff to contact Dr. Redlener to schedule a meeting as soon as
possible to work on the contract. Finally, concerning the press conference, 1 have been advised
that it is not appropriate to hold a press conference with Dr. Redlener announcing the citywide
asthma initiative until a contract is in place. Therefore, 1 regret that I will not be attending the
press conference.
Sincerely,
Benjamin Mojica MD. MPH
12/10/97 WED 19:00 FAX 212 535 7488
CHF
004
DEC-09-1997 16:29 FROM CM KENNETH K. FISHER-33CD
TO
12125357488
P.02
CHAIR
LANDMARKS, PUBLIC SITING
THE COUNCIL
AND MARITIME USES
THE CITY OF NEW YORK
KENNETH K. FISHER
CITY HALL
COMMITTEE ASSIGNMENTS:
COUNCIL MEMBER 33RD DISTRICT
NEW YORK, NY 10007
ECONOMIC DEVEI SIPMENT
BROOKLYN
GOVERNMENT CONTRACTS
LAND USE
PARKS. RECREATION, CULTURAL AFFAIRS AND
INTERNATIONAL INTERGROUP RELATIONS
TO:
Benjamin Mojica, Acting Commissioner
NYC Department of Health
Irwin Redlener, MD
The Children's Health Fund
FROM:
Kenneth K. Fisher
DATE:
December 9, 1997
RE:
Asthma Initiative
CC:
Andrew Goodman, MD
James Capoziello
Karen Redlener
Dianne McLean, PhD
John Talmage
Mia Kozicharow
I want to thank both of you for your efforts to this point. In the interest of
moving forward I have memorialized the agreement as I understand it, with a further
understanding that the following points will be incorporated in a formal contract.
1.
The Department of Health agrees to provide The Children's Health Fund with
$1.122 million dollars for the first year of the agreement, pending a mutually agreed
upon scope of services.
2.
The Department of Health agrees to make retroactive payments to The
Children's Health Fund for expenses incurred since July 1, 1997 for the initiation,
planning and development of the Initiative, assuming the expenses are relevant to the
final agreement, within the scope of services, and The Department of Health has the
authority to make such payments.
3.
The Children's Health Fund agrees that the legal relationship between itself and
The Department of Health will be that of purchaser/vendor.
He
The Department of Health agrees that the programmatic and public relationship
between itself, The Children's Health Fund and The New York City Council will be that
of partners.
5.
The Children's Health Fund agrees to commit to a series of activities, including
the development of a primary care and asthma center for children, a provider education
program, and a mobile-based primary care and asthma program for homeless children
CITY HALL: 250 BROADWAY, 22ND FLOOR
NEW YORK, NY 10007
212-788-6981
FAX: 212-788-7052.
DISTRICT OFFICE: 16 COURT STREET (ROOM 1505) BROOKLYN, NY 11241
718-875-5200
FAX. 718-643-0620
12/10/97 WED 19:01 FAX 212 535 7488
CHF
4.
005
P.00
Memorandum
December 9, 1997
page - 2-
6.
The Children's Health Fund agrees to provide primary-care-based asthma
education services, including an health educator, social worker, nurse asthma specialist
and asthma intervention medical supplies for approximately 250 children, to the Hunts
Point Peninsula community in partnership with existing Department of Health
programs at that site. "These education services may operate out of The Children's
Health Fund's South Bronx Children's Health Center and/or a new primary care and
asthma center.
7.
The Department of Health agrees that The Children's Health Fund will operate a
primary care and asthma center as part of the contract which may be implemented in
another South Bronx community.
8.
The Children's Health Fund agrees that the contract is predicated on a mutually
agreedupon scope of services of sufficient detail which The Children's Health Fund will
provide to The Department of Health The Department of Health agrees to provide
guidelines to and work collaboratively with The Children's Health Fund so that they can
draft an appropriate scope of work.
9.
The Department of Health agrees that all personnel paid for by The Children's
Health Fund's portion of the funds will work within and report to The Children's Health
Fund.
10.
All parties agree that the remaining program will be finalized with The
Department of Health within a reasonable period of time.
Again, I want to thank you for your cooperation and I look forward to
participating in Thursday's press conference with you and putting a contract in place as
soon as possible.
Georg
Speech
FAX COVER SHEET
Thursday, December 11, 1997 09:14:31 AM
To: Neera Tanden
Fax #: 12024562878
From:
Fax: 3 pages and a cover page.
MEMORANDUM
December 10, 1997
To: Ilillary Clinton
From: Emily Jenkins, Tucson/Almaty HealthCare Goalition
Re: Synopsis of current issues regarding asthma from the perspectives of clinical
treatment, research, and community efforts in education and prevention
Introduction
Since our brief conversation in Almaty, I have been interviewing various experts regarding
asthma as a health problem in the U.S., especially among children, and have assembled
materials which I hope will be helpful to you in gaining an understanding of the problem and
what has and needs to be done about it. For the sake of brevity, I will send a list of the
specialists and background data under separate cover as an attachment to this document.
Because of the in-migration of asthmatics to Tucson, the medical community and the University
of Arizona College of Medicine have conducted long term research studies which have put
Tucson in the forefront in clinical knowledge and expertise in research, especially in
epidemiology, the analysis of the mechanisms of the disease, and the role of indoor air quality
and environmental factors in the development of the discasc.
Asthma is a significant and growing health problem, despite advances in understanding
and treating the disease
For a quick description of the clinical aspects of the disease and the medications used to treat
it, see pages 3-4 in Tackling Asthma in Arizona. This document also summarizes the key issues
regarding the impact of the disease, since asthma is the chronic condition which causes the most
hospital admissions for children and accounts for the most absentccism from school. In the last
20 years, the death rate from asthma in the U.S. has increased 50 per cent. This increase has
occurred in spite of advances in the clinical diagnosis and treatment of the disease and the
reduction of particulates in the air in the environment. Much of the current research is aimed
at these questions.
For children, there are some significant areas of concern:
Children of lower socio-economic groups have more severe asthma than children of
higher economic groups
Black and Puerto Rican children have more asthma than children of other ethnic
groups, including children of Mexican-American descent
The development of the disease in children is not easily understood, and prevention
and treatment issues are multi-faceted
Guidelines for the diagnosis and treatment of asthma have been developed by the NIH
and adopted by WHO for global application
In April 1997, the National Heart, Lung and Blood Institute of the National Institutes for
Health issued updated Clinical Practice Guidelines for the Diagnosis and Management of
Asthma (copy sent under separate cover). These NIH guidelines have been modified and
adopted by WHO (Global Initiative for Asthma sent under scparate cover). Rescarch in Tucson
and other places has established that adherence to the guidelines results in improved outcomes
for patients. Theseaguidelines incorporate the new drugseand therapies and also the diagnostic
tools available tophysicians and patients to monitor the disease. The barriers to the
successful implementation of the guidelines appears to be the need to educate
physicians who treat children, including pediatricians, family practice specialists, and
physicians in urgent care and emergency departments. Nurses and paramedic personnel
also need to be included. A model project is the Tucson Alliance for Pediatric Asthma
Care, which provides cducational programs to physicians, nurscs, school nurscs, daycarc
providers, athletic coaches and other persons who regularly have custodial relationships with
children. The programs include families and trains health care volunteers and staff as patient
and family educators.
The role of the patients and the families are critical in this process. Even very young
children can learn to use a peak flow meter to monitor their airway status, and parents must
monitor the usc of the medication and bc ccrtain that there is continuous treatment of the
disease. Parents also need to create an environment in the home which reduces triggers for the
disease, such as cigarette smoke, dust mites, cockroach and rodent urine, dog and cat dander,
formaldehyde-impregnated carpets and furnishings, and other regional allergens such as mold
and mildew.
This need for parents to be proactive may be one of the reasons why children of lower
socio-economic status have more asthma and more severe disease. Parcnts of children at
risk for asthma or with asthma must have access to a quality health system and seek out care
early on, not only for asthma but also for respiratory infections that can lead to the
development of the asthma. Seeking medical care only when the child is having a severe
attack is not effective in preventing or managing the disease. The ability to change the
home environment may also be beyond the capability of these parents. The Inner City
Asthma Project currently being funded by NIH will study the impact of effective treatment and
home environmental and patient/family education programs on populations in several regions of
the country, including Tucson. This five year program should provide the data needed to
support changes in services and environmental conditions by physicians, managed care plans,
state and local health agencies and providers, and other organizations, such as schools, day care
providers and housing authorities. Managed care plans and Medicaid providers must be
convinced of the need for early intervention in diagnosis and treatment of children with asthma,
including patient and family education, allergen testing, and easy access to health providers for
these children.
What needs to be done to prevent the development of asthma and to limit its impact on
the health of children?
1. Community wide programs such as the Tucson Alliance for Pediatric Asthma need to be
conducted to implement what is already known and established in the areas of clinical
diagnosis and treatment, education for patients, families, and care providers, and control
of indoor air quality in homes, schools, day care centers, and other places where children
spend their time.
2. Managed care/plans and other insurance programs such as Mcdicaid need to provide
accessible health care services to asthmatic children of children at risk for asthma,
including educational programs and case management services to support the families to
assure compliance.
3. Public attention needs to be directed to this problem, with special attention to primary
prevention efforts, which include elimination of smoking during pregnancy, protection of
infants and small children from indoor air pollutants, and early treatment of respiratory
infections which can lead to the development of the disease.
4. Research needs to be continued in the areas of the development and treatment of the
disease, the regional (geographic) variances in environmental factors, genetic factors, and
varianccs in incidence in socio-cconomic groups.
Asthma in the Elderly Population
The longer people live, the more likely it is that they will develop asthma, especially if
they have a history of smoking or respiratory discase or infections. As the population ages,
the incidence of asthma will increase. Research indicates that children may appear to
"outgrow" their asthma, but actually it smolders and often reappears in later life. When asthma
occurs along with other diseases of the elderly, such as congestive heart failure, it can be
difficult to diagnose and treat. An aging population will require diagnostic and treatment
services, and environmental conditions in nursing homes must be addressed.
Gaining a comprehensive understanding of the problem of asthma and what needs to
be donc
If you would like to increase your understanding of the issues surrounding asthma and what is
known and can he implemented to prevent and limit the impact of the disease, I invite you to
Tucson. I will organize a program which will include:
1. discussions with national and international experts in clinical and research areas
2. discussions with physicians regarding patient care issues
3. a briefing on the Inner City Asthma Project, including a tour of the El Rio Community
Health Center, which will be the research site
4. briefing on the Tucson Alliance for Asthma Care which operates under the auspices of the
Tucson chapter of the American Lung Association
5. meeting with families and children regarding their experiences in learning about and
monitoring their asthma and the impact which it hasion their lives.
6. discussion of the present and future role of managed care plans in providing coverage and
prevention programs (Arizona has a managed care alternative Medicaid program)
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TUCSON/ALMATY HEALTHCARE COALITION
TEL: 520-324-1784
FAX: 520-795-5689
Tucson Medical Center, Arizona Building, 2nd floor, 5301 East Grant Road, Tucson, Arizona 85712
FAX COVER SHEET:
Brenda
D
DATE: 12/9/97
TOTAL PGS:
TO: Nera Tanden
Tel:
Fax:
FROM: Emily Jenhis
Tel:
Almatly Project
Fax: 795-5689
RE: 202 456 2878
Good summery of issues- -
Arizona +US,
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Tackling Asthma in Arizona
A Report by the Arizona
Asthma Coalition
August 1997
DEC-09-1997
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ARIZONA ASTHMA COALITION
The Arizona Asthma Coalition, a prevention partnership, was formed in 1996 with five objectives.
OBJECTIVES
Collaborate and build partnerships to improve asthma management
Increase awareness of asthma management
Share data and information
Evaluate the effectiveness of interventions
Advocate for public health priorities and activities
It is our hope that appropriate legislative, administrative and medical bodies will act upon the
recommendations contained in this report.
The Coalition membership includes the following groups:
Academy of Family Physicians, Arizona Chapter
Glaxo Wellcome, Inc.
Academy of Pediatrics, Arizona Chapter
Health Services Advisory Group
ADHS/Arizona Center for Minority Health
Health Partners Health Plan
ADHS/Health Planning, Evaluation & Statistics
Humana Inc.
ADHS/Community & Family Health
Intel Corporation
ADHS/Women & Children's Health
Intergroup of Arizona, Inc.
ADHS/Public Health Policy & Practice
Kid Radio KHITS
ADHS/Chronic Disease Prevention
Merck and Company, Inc.
ADHS/Chronic Disease Epidemiology
Maricopa County Department of Health
Arizona Disease Control Research Commission
Maricopa Managed Care Systems
Aetna US Healthcare
Mercy Care Plan
AHCCCS
Mohave County Department of Health
American Lung Association of Arizona
Murphy Elementary, School District 21
Arizona Asthma and Allergy Institute
PCS Health Systems
Arizona Physicians, Inc.
Phoenix Children's Hospital
Arizona HMO Association
Phoenix Pediatrics
Arizona Public Health Association
Samaritan Prime Care Network
Asthma Information Resources
Scottsdale Memorial Home Health Care
BlueCross BlueShield
Scottsdale Memorial Hospital North
Cathy Graeff, Inc.
Signature Homecare
CIGNA Healthcare
St. Joseph's Children's Hospital
Coconino County Health Department
University of AZ College of Pharmacy
Faculty from the U of A, Health Sciences Center
Your Family Physicians
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WHAT IS ASTHMA?
Asthma, once thought of as a "simple" hypersensitive reaction, is now known to be a complex
condition with a spectrum of causes and contributing factors, with airway inflammation as its central
attribute.
Asthma is a reversible obstructive lung disease, caused by an increased reaction of the airways to
various stimuli. It is a chronic condition with acute exacerbations. Asthma can be a life-threatening
disease if not properly managed.
Asthmatics have bronchial tubes that are virtually continuously inflamed and hyperactive, sent into
suffocating spasms by a broad range of provocations that may vary from one individual to another.
Some of the substances and circumstances that may trigger attacks are: smoke, airborne molds,
pollens, dust, animal dander, exercise, cold air, many household and industrial products, air pollutants,
scents, and simple stress. An episode finds the victim gasping for breath as the airways become
constricted, the passages inflamed and clogged with thick, sticky secretions. The narrowed airway is
responsible for the difficulty in breathing with the familiar "wheeze."
3
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WHAT IS THE TREATMENT?
Those who suffer from asthma must typically take a variety of medications, usually on a regular basis.
They include bronchodilators, corticosteroids, and other reducers of inflammation. With the recent
recognition of the major role played by continuing inflammation, regular use of inhaled steroids is
increasingly advised. Complying with these often complex treatment regimens can prove particularly
difficult for children.
Two classes of medications are used to treat asthma--bronchodilators and anti-inflammatory agents.
Bronchodilators act principally to dilate the airways by relaxing bronchial muscle. They include
beta-adrenergic agonists, methylxanthines, and anticholinergics.
Anti-inflammatory agents interrupt the development of bronchial inflammation and have a
prophylactic or preventive action. They may also modulate or terminate ongoing inflammatory
reactions in the airways. These agents include corticosteroids, cromolyn sodium or cromolyn-like
compounds, and other anti-inflammatory compounds.
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ASTHMA PREVALENCE IN ARIZONA
According to the Arizona Department of Health Services, an estimated 210,000
asthmatics reside in Arizona.
Hospital discharge rates for pediatric asthma in Arizona are highest among African-
Americans (see graph #1), approximately 4 times that of Hispanics and Whites.
Hospital discharge rates for asthma in 1995 were highest in Yuma County followed by
Maricopa County (see graph #2).
The asthma death rate in Arizona in 1995 was 2.8 per 100,000 while the death rate in the
United States was 2.1 (see graph #3).
According to the Arizona Department of Health Services, Maricopa County had the third
highest death rate from asthma compared with other counties in the United States.
Asthma hospitalizations in 1995 were highest in the last quarter of the year, the time of year
with the highest levels of airborne particulate matter in Arizona (see graph #4).
5
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ASTHMA PREVALENCE NATIONWIDE
Asthma affects 14 to 15 million persons, including 4.8 million children under the age of 18.
Between 1982 and 1992, the prevalence rate--the rate per thousand persons--of pediatric asthma
rose from 40.1 to 63.4, an increase of 58 percent.
Some of this increase in prevalence may be due to "diagnostic exchange," the tendency for
physicians to label patients with asthma instead of an alternative diagnosis, but this only
accounts for part of the increase in prevalence.
The number of deaths attributed to asthma has increased by 98.9 percent since 1979, from
2,598 in 1979 to 5,167 in 1993.
For persons under age 25, the annual age specific asthma death rate increased 118% between
1980-1993.
Annual hospitalization rates among persons age 25 and under increased 28% from 1980- 1993.
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ASTHMA IN CHILDREN
Asthma is the leading serious chronic illness among children. Most children have mild
problems, and their illness can be controlled by treatment at home or in the doctor's office. For
some children the illness becomes a formidable problem causing many visits to the hospital
emergency room and multiple hospitalizations.
Asthma accounts for 10 million lost school days annually. It is the leading cause of school
absenteeism attributed to chronic conditions.
Asthma is the third-ranking cause of hospitalization among children under the age of 15; it is
the first-ranking cause among chronic conditions.
Secondhand smoke can cause serious harm to children. An estimated 200,000 to one million
asthmatic children have their condition worsened by exposure to secondhand smoke.
Children are more vulnerable than adults to air pollution because they breathe more rapidly and
inhale more pollutants per ratio of body weight than adults.
Only about a quarter of the children with asthma outgrow the condition; for the rest, the
condition is a lifelong ordeal. The condition persists in 85 percent of women and in 72 percent
of men who had the disease as children.
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COSTS
Hospital charges for treating children with asthma amounted to $12 million in Arizona in 1995.
Addition uncounted costs include emergency room visits, physician costs, lost work days, and
missed school.
The annual direct health care cost of asthma nationwide is approximately $9.8 billion; indirect
costs (e.g., lost work days) add another $2.8 billion, for a total of $12.6 billion. The largest
single direct cost may be emergency room use estimated to account for 43% of the direct costs.
Asthma also accounts for an estimated 10.1 million missed days from school and 200,000
hospitalizations per year in children less than 18.
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WHO GETS ASTHMA?
Recent studies suggest that children of smokers are twice as likely to develop asthma as
children of nonsmokers.
Women who smoke during pregnancy have babies with abnormally narrowed airways that
predispose them to asthma.
Although African-Americans represent approximately 12 percent of the U.S. population, they
account for 21 percent of deaths due to asthma. The reason for this discrepancy is unknown.
In 1982, the prevalence rate of asthma among African-Americans was 13.3 percent higher
than the rate among whites; in 1992, the rates for both races were up--but the rate among
blacks was 15.4 percent higher than that for whites.
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COALITION RECOMMENDATIONS
Based on the asthma prevalence and mortality compared to other states, the Arizona Asthma Coalition
recommends:
Work in conjunction with managed care organizations to implement the guidelines from the
National Institutes of Health on diagnosing and managing asthma. Because over 80% of
Arizonans covered by health insurance receive care through HMO's, these systems provide the
most effective route to implement "best practices." Some HMO's in Arizona are already
providing leadership in asthma care.
Train providers such as physicians, nurse practitioners and nurses in up-to-date asthma
prevention and treatment protocols. Establish a certification process for primary caregivers,
especially in the area of pediatric asthma management.
Provide self-care education and resources for patients and families with asthmatic children.
Target improved asthma management services to communities with disproportionally high rates
of hospitalization from asthma.
Improve funding and equipment for school-based health care providers and ensure that each
school has a full-time certified asthma care provider. Asthma is the number one cause of school
absences. School-based providers can play a vital role in treating and educating children with
asthma and in preventing emergency room visits from uncontrolled asthma episodes.
Implement clean indoor air laws around the state, including a ban on smoking in the workplace.
Research shows a link between passive smoking and increased exacerbations of asthma.
Implement control measures to reduce airborne particulates in order to help us achieve the
federal Environmental Protection Administration (EPA) health standard for particulate
pollution. Research shows a link between poor outdoor air quality and higher morbidity rates.
The relationship is most apparent with particulate pollution. By December 1997 Arizona must
submit a plan to reduce particulates to EPA.
10
1995 Arizona Asthma Hospital Discharges*
By Race/Ethnicity-Specifio Rates
1
Among Children Age 2-20
Race/Ethnicity
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Black
M-305
827.6
Hispanic
n=542
198.5
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Nat Am*
51.6 (n=41)
Asian
38.3 (n=6)
0
200
400
600
800
1,000
12024562878 P.12
Discharges Rate/100,000 Population
Arizona hospital discharges from non-federal facilities (Does not include IHS facilities)
Tote: Rate based on Arizona 1990 Census Population
1995 Asthma Hospital Discharge Rate
2
By County For Children Age 2-20
County of Residence
DEC-09-1997 14:39
Yuma
323.5
Maricopa
213.7
FROM
Pinal
192.2
Pima
175
Mohave
151.4
La Paz
138.2
Santa Cruz
111.1
Coconino
107.7
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104.7
Graham
91
Yavapai
75.7
TO
Navajo
62
Gila
37.7
Apache
30.8
Greenlee
30.6
O
50
100
150
200
250
300
350
Discharges/100,000 Population
12024562878 P.13
Arizona hospital discharges from non-federal facilities (Does not include IHS facilities)
bie: Rate based on ADES 1995 Population Projections
Asthma Death Rate*
3
Arizona and United States, 1991-1995
Arizona
United States
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n=116
FROM
2.5
n=94
n=87
CO 7791
90
2
Rate
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1
TO
0.5
0
1991
1992
1993
1994
1995
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Year
Number of Deaths per 100,000 population
ource: Arizona Department of Health Services; Office of Planning, Evaluation, and Statistics
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Hospital Asthma Charges
Among Children in Arizona During 1995
($12,614,344)*
HMO
3.84
Payor Type
Care
AHCCCS/Medicaid
3
AHCCCS HCG
1.96
other
PPO
1.65
395
Indemity
Indemity
1.17
AHCCCS
Other
0.56
Self/Charity
0.45
0
1
2
3
4
5
Charges (Millions $)
Other includes CHAMPUS, Child Rehab, Work Comp, IHS, Foreign Nation
*All discharges from non-federal facilities among children age 2-20
Asthma Hospital Discharges*
Among Children Age 2-20
4
During 1995 (2,346 Discharges)
250
* Emergency - Urgent - Elective
232
204
200
Discharges
150
112
118
126
110
131
123
100
86
74
96
63
49
50
33
35
$
7
8
4
1
6
3
3
9
14
11
10
0
Jan Feb M3r ACT May Jun Jul Aug Sep Oct Nov Dec
Month of Admission
"Discharges From All Non-federal facilities
asthma
Page 1
MEMORANDUM TO
JENNIFER KLEIN
FROM
SANJAY GUPTA
RE
PEDIATRIC ASTHMA
ASTHMA IN CHILDREN
KEY FACTS
What is asthma?
Asthma is a chronic inflammatory disorder of the airways. In
susceptible individuals, this inflammation causes recurrent
episodes of wheezing, breathlessness, chest tightness and
coughing, particularly at night or in the early morning. These
episodes, or "asthma attacks", are usually associated with airflow
obstruction that is often reversible, either spontaneously or with
treatment.
Asthma can vary in severity and is categorized as either: mild
intermittent, mild persistent, moderate persistent or severe
persistent.
Asthma often begins in childhood and can start as early as the
first year of life: 70% of all people with asthma developed asthma
before age seven.
Asthma is frequently found in association with what is referred to
as "atopy", the susceptibility to produce antibodies toward
common allergens such as animals, cockroaches, house-dust
mites, indoor molds and outdoor allergens.
asthma
Page 2
Other factors that can precipitate or trigger asthma attacks
include: tobacco smoke, indoor/outdoor pollution, viral respiratory
infections, trauma and other stressors, exercise, drugs, emotions,
cold air, aspirin and sulfite sensitivity.
Who has asthma?
As of 1994, approximately 4.8 million children under the age of
18 have asthma, according to the National Institute for Allergy
and Infectious Diseases, for a prevalence rate of 4.3%.
Nationally, asthma rates are highest in New York, Chicago,
Fresno, California and Maricopa County, Arizona. Asthma
prevalence and mortality rates are continuing to rise nationwide.
In 1994, in high risk areas of New York City the asthma
prevalence rate for children reached between 8.6% and 14%. In
1996, it reached 25% for the population of homeless children
cared for by The Children's Health Fund.
As of 1993, New York City children were hospitalized for asthma
at more than four times the national rate and the hospitalization
rate is continuing to rise. Within New York City, African
Americans and Latinos have three to five-and-and a- half times
the hospitalization rates of whites. Among New York City
children 14 and younger, those living in a zip code in the lowest
20th percentile of median income had four times the
hospitalization rate of those living in the highest 20th percentile
of median income. Areas in New York City with highest asthma
hospitalization rates include the South Bronx, Upper Manhattan,
Central and North Brooklyn.
The number of children hospitalized for asthma nationwide has
increased fivefold over the past 20 years. In 1993, asthma
accounted for nearly 200,000 hospitalizations among people less
than 25 years old.
asthma
Page 3
Hospitalization rates for children less than five years old have
increased by 57% since 1980.
Compared with white children, African American children are four
to six times more likely to die from asthma and three times more
likely to be hospitalized for asthma.
Poor children with asthma reported 40% fewer physician visits,
yet were 40% more likely to be hospitalized than children with
more economic resources.
What are the consequences of asthma for children?
Nationwide, asthma is associated with the loss of 28 million
activity days annually and 2.2 million pediatrician visits. It is the
leading cause of school absenteeism. It has been estimated that
among children 5-17 years old, asthma accounted for
approximately 10 million missed school days, at a cost of $726.1
million in caretaker's time lost from work.
Asthma can be fatal. Over 3,800 children and young adults
under 25 died from asthma nationwide during the period of
1980-1993. In 1993 alone, 342 children and young adults under
25 died from asthma.
What are the costs of asthma?
In 1993, the total direct and indirect annual costs of asthma were
estimated to be over $6.2 billion in 1990 dollars, not including
the economic impact of this disease on affected patients and
families.
Non-monetary costs for children with asthma include decreased
asthma
Page 4
quality of life, mental distress for patients and families, social
labeling associated with a chronic disease and complications from
medication use.
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CLASSIFICATION
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002
DRAFT 12/9/97
FIRST LADY HILLARY RODHAM CLINTON
STATEMENT FOR NEW YORK CITY CHILDREN'S ASTHMA INITIATIVE
SOUTH BRONX CHILDREN'S HEALTH CENTER
DECEMBER 11, 1997
I
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Acknowledgments. From advance
Today we take another step in our comprehensive effort to protect the health
of America's youth a step that will meet head on the most common chronic
medical problem children face today: asthma. And like all important steps, it is one
we are taking together: doctors, nurses, health care providers, community leaders,
government, citizens, and parents.
Asthma affects nearly 5 million American children. Over the past decade, it
has led to more than 4000 deaths. Worse, these numbers are on the rise. In the last
20 years, the number of children hospitalized for asthma has increased five-fold; the
number of deaths has more than doubled.
We also know asthma hits hardest the children of our inner cities. New York
City children, for example, are hospitalized at four times the national rate.
Moreover, the hardest hit of the hardest hit are minorities - African Americans and
Latinos.
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Here in Now York, the asthma rates for African American and Latino children are
three to five times higher than rates for other populations. An African American
child is four to six times more likely to die from asthma than a white child.
Behind these statistics, there are human stories. Children who cannot step
outside the front door without a pocketful of inhalers. Children who cannot walk a
block or ride a bike without grasping for air. Children who miss out on education,
friendship, and community because of their condition. Asthma is the leading cause
of school absenteeism. Last year, it was the cause of more than 10 million missed
school days. To a parent, there are few things more frightening than sceing the look
he or che is struck hv asthma To
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These resources will go toward providing health care coverage for children who are
currently uninsured. Up to 10 percent of these funds can be used for on-the-ground
services -- like those we see here today.
Earlier this year, the President announced a plan to see to it that parents and
doctors know exactly what and how much medicine to give children. Right now, the
vast majority of medications -- including asthma drugs -- are not tested for kids. The
President's Pediatric Labeling Initiative will change all that. No parent should have
to guess how much medicine to give a sick child.
During the course of his administration, my husband has taken a series of
other important steps to safeguard the health of our children: from protecting and
defending Medicaid to signing cutting-edge legislation like the Family and Medical
Leave and Kennedy-Kassebaum Acts to shielding our young people from tobacco
and drugs to seeing to it that our children get the immunizations they necd.
5
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He has also made a special effort to see to it that the air our children breathe,
the water they drink, and the 1000 шсу cal
public health standards for smog and soot that will prevent 350,000 cases of
aggravated asthma. He has cleaned up a record number of toxic waste sites and
expanded community right to know laws SO that families know exactly what
substances are being released into the world around them. Under this administration,
we have strengthened and revolutionized food safety laws for meat, seafood, and
poultry for the first time in a generation -- and we have toughened regulations to
keep harmful pesticides off our children's food.
All these efforts work toward a single dream: Better health and safer lives for
our children. With today's initiative -- and with your work and commitment -- we
are one step closer toward making that dream a reality.
Thank you.
6
DAVID SHIPLEY
12/09/97 01:51:38 PM
Record Type:
Record
To:
Jennifer L. Klein/OPD/EOP, Sanjay Gupta/WHO/EOP, OMARY_M @ A1 @ CD @ LNGTWY
CC:
Subject: edit of asthma speech. as you can see, there are some questions. thanks, di
DRAFT 12/9/97
FIRST LADY HILLARY RODHAM CLINTON
STATEMENT FOR NEW YORK CITY CHILDREN'S ASTHMA INITIATIVE
SOUTH BRONX CHILDREN'S HEALTH CENTER
DECEMBER 11, 1997
Acknowledgments. From advance
Today we take another step in our comprehensive effort to protect the health of
America's youth -- a step that will meet head on the most common chronic medical problem
children face today: asthma. And like all important steps, it is one we are taking together:
doctors, nurses, health care providers, community leaders, government, citizens, and parents.
Asthma affects nearly 5 million American children. Over the past decade, it has led to
more than 4000 deaths. Worse, these numbers are on the rise. In the last 20 years, the number
of children hospitalized for asthma has increased five-fold; the number of deaths has more than
doubled.
We also know asthma hits hardest the children of our inner cities. New York City
children, for example, are hospitalized at four times the national rate. Moreover, the hardest
hit of the hardest hit are minorities -- African Americans and Latinos. Here in New York, the
asthma rates for African American and Latino children are three to five times higher than rates
for other populations. An African American child is four to six times more likely to die from
asthma than a white child.
Behind these statistics, there are human stories. Children who cannot step outside the
front door without a pocketful of inhalers. Children who cannot walk a block or ride a bike
without grasping for air. Children who miss out on education, friendship, and community
because of their condition. Asthma is the leading cause of school absenteeism. Last year, it
was the cause of more than 10 million missed school days. To a parent, there are few things
more frightening than seeing the look of confusion and then fear on your child's face as he or
she is struck by asthma. To a child, I cannot imagine anything more terrifying than not being
able to breathe -- no matter how hard you try.
That is why I am so gratified by the action you are taking today. The Children's Health
Fund, the Montefiore [Monta-fee-or] Medical Center, and [what level of govt? Are we
involved?] have come together to create an innovative public-private partnership to lower the
UNITED is 3
rates of childhood asthma. This initiative will increase public awareness of pediatric asthma
through programs, models and policies [can we be more specific about this? Will teach parents
to take their kids for checkups? Get away from cockroaches? What?]. Mobile medical units
and primary care centers will provide treatment to homeless children and those at particular
dvan
risk. [need one more specific here. What does it do for real people?] If there is any disease
that illustrates that an ounce of prevention is worth a pound of intensive care, asthma is it.
care and teachersion prof.
This is part of the President's [are we involved? Is there govt support? If so, say above
wrt people coming in pub-priv partnership. If not, trans should be, "what you are doing here
fits with the president's efforts to build a ] overall commitment to building a strong
foundation for the health of all our children. This summer, the President signed into law a
balanced budget that will help extend health insurance to up to 5 million children.
During the course of his administration, my husband has taken a series of important
steps to safeguard the health of our children: from protecting and defending Medicaid
to
signing cutting-edge legislation like the Family and Medical Leave and Kennedy-Kassebaum
Acts to shielding our young people from tobacco and drugs to seeing to it that our children
get the immunizations they need.
He has made a special effort to see to it that the air our children breathe, the water they
drink, and the food they eat are safe. The President issued tough new public health standards
for smog and soot that will prevent 350,000 cases of aggravated asthma. He has cleaned up a
record number of toxic waste sites and expanded community right to know laws so that
families know exactly what substances are being released into the world around them. Under
this administration, we have strengthened and revolutionized food safety laws for meat,
seafood, and poultry for the first time in a generation -- and we have toughened regulations to
keep harmful pesticides off our children's food.
All these efforts work toward a single dream: Better health for our children. With
today's initiative -- and with your help and commitment -- we are one step closer toward
making that dream a reality.
Thank you.
12/02/97 18:07 FAX
CHILDREN'S HEALTH FUND
001
THE Children's
Health FUND
FAX TRANSMITTAL
COVER SHEET
To:
Jennifer Klein
Via Fax #:
(202) 456-2878
From:
Melissa Ziriakus
Date:
September 16, 1997
The number of pages in this fax (including this cover page): 6
If there is a problem with this fax transmission, please call (212) 535-9400
Proposed outline for December 11, 1997 Children's Health Fund press event. I look forward to
speaking with you about details and can be reached at (212) 535-9400, ext. 280.
12/02/97 18:07 FAX
CHILDREN'S HEALTH FUND
002
THE Children's
Health
FUND
Memo to:
Jcnnifer Klein
From:
Melissa Ziriakus
Date:
December 2, 1997
Subject:
Children's Health Fund press event
Irwin Redlener and I have been in discussions to develop and provide you with a proposed
outline for the New York City Asthma Initiative press conference on December 11 at 11:00 AM
involving Ms. Hillary Clinton.
I've attached that for your review, and invite you to call if you have any questions.
Separately, I also sent to Sanjay Gupta, via FedEx today for tomorrow morning delivery, a copy
of the childhood Asthma Briefing Book, along with some other program orientation pieces.
CC: Irwin Redlener, MD
The Children's Health Fund . 317 East 64th Street New York NY 10021 Telephone (212) 535-9400 . Fax (212) 535-7488
12/02/97 18:07 FAX
CHILDREN'S HEALTH FUND
120297 15:20
DRAFT
DRAFT
DRAFT
DRAFT
The Proposed Plan
to Announce
The New York City Childhood Asthma Initiative
WHAT:
A press conference for The Children's Health Fund to announce a major public health initiative,
The New York City Childhood Asthma Initiative, and plans to develop a primary care and
asthma center, This is an opportunity to unveil the program components, to talk with principals
involved, and dignitaries who support the initiative as an effort to fight against the epidemic of
asthma. This comprehensive plan is designed to be a model for programs that can be executed
throughout the United States.
WHO:
An exceptional coalition of:
FEDERAL INTERESTS: The White House, Ms. Hillary Rodham Clinton;
LOCAL GOVERNMENT: The City Council of New York, led by Councilman
Kenneth Fisher;
PUBLIC HEALTH ADMINISTRATION: the New York City Department of Health,
represented by Benjamin Mojica, Acting Commissioner;
THE CHILDREN'S HEALTH FUND and MONTEFIORE MEDICAL CENTER:
spearheaded by Irwin Redlener, MD:
PRIVATE SECTOR: Schering Laboratories, represented by Richard W. Zahn,
president.
WHAT:
The New York City Childhood Asthma Initiative addresses the epidemic proportions of asthma in
New York City, where incidence of the disease is among the highest in the nation. The press
conference is to advise the community, via the press, of the diverse efforts that the Initiative will
introduce, and to introduce the plan as a national model.
WHEN:
Thursday, December 11, 1997
11:00 am
Time frame: approximately 20 minutes to one-half hour;
WHERE:
South Bronx Children's Health Center
911 Longwood Avenue
The Bronx, New York.
OTHER:
Speakers
Irwin Redlener, MD, President. The Children's Health Fund; Vice President for the
Children's Medical Center. Montefiore Medical Center;
Kenneth Fisher, Councilman, Borough of Brooklyn;
Benjamin Mojica, MD, Acting Commissioner, NYC Department of Health;
Richard W. Zahn, President, Schering Laboratories;
Hillary Rodham Clinton, Esq., First Lady of the United States.
Other invited, nonspeaking guests to be acknowledged, include New York City Council President Peter Vallone, Bronx
Borough President Frederic Ferrer, U.S. Representative Jose Serrano, Bronx Assemblyman Jeffrey Klein.
12/02/97 18:08 FAX
CHILDREN`S HEALTH FUND
4.
004
New York Childhood Asthma
Initiative Announcement, page 2.
Tentative Agenda
11:00
Scheduled start time
11:00
Irwin Rediener, MD opens the floor, introduces Mrs. Clinton, introduces other
speakers, invites Ken Fisher to speak.
11:01
Kenneth Fisher discusses the genesis of the budget allocation for the
New York City Childhood Asthma Initiative.
11:05
Irwin Redlener speaks of the problems of underserved children, asthma and the
need for a children's agenda in New York City.
11:09
Benjamin Mojica, Acting Commissioner of Health, presents the
Department's perspectives on the program.
11:13
Richard Zahn, president of Schering Laboratories, speaks of the initiative from
the perspective of the advances in asthma treatment, and the need to deliver these
treatments.
11:16
Irwin Redlener speaks of bringing the effort to the attention of Hillary
Rodham Clinton, and her interest in it.
11:17
Hillary Rodham Clinton speaks. (CHF to be advised of her point of view.)
11:21
Conclusion.
11:22
Questions and answers.
###
12/02/97 18:08 FAX
CHILDREN'S HEALTH FUND
005
New York Childhood Asthma
Inititive Announcement, page 3.
Other considerations
1.
Will there be limitations to the number of persons allowed within the restricted area? If so, how many
people?
2.
How far in advance do you need lists of invitees? Do you need both date of birth and social security
number? Separate from invitees, presumably employees of the South Bronx Children's Health Center will
also need to be cleared, correct? (The Center will be used as an indoor holding station before the event.)
What about the days' patients?
3.
Who takes care of street permits (the street will need to be blocked off), WE or The White House?
4.
What is the general size of a restricted area? (See below)
5.
We are intending to set up a large enclosed heated tent for the press conference since it will be outside in
the Bronx and it will likely be cold. May we do so re security? The size tent we have in mind is 20 x 60 (to
fit approx 100 people and including a stage as shown in att. drawing.)
6.
Are credentials issued at the time of the event?
7.
What is the protocol for inviting local politicians? Is that done by The White House or by The Children's
Health Fund?
006
D
ASTHMA MOBILE MEDICAL
UNIT
16*12*12
H HEWITT PLACE
20x80
STAGE
TENT-
APARTMENT
WITH
CLEAR
BLDGS.
SIDES
CHILDREN`S HEALTH FUND
SEATING
APARTMENT
BUILDING
SIDEWALK
STANDING
(PROJECTS)
ROOM
SIDEWALK
SOUTH
PRESS
BRONX
TABLE
-
CHILDREN'S
HEALTH
CENTER
# Receipt
A
OPEN-ENDED
ROAD
BLACKS
LONGWOOD AVENUE
12/02/97 18:08 FAX
LAYOUT (PROPOSED) FOR 12.11.97 (11:00 AM)
PRESS CONFERENCE
MEMORANDUM FOR THE FIRST LADY
Nov 25, 1997
FROM:
Domestic Policy Staff
SUBJECT:
Child Asthma Initiative
IMPACT
Asthma is a chronic inflammatory disease of the airways. In the United States, asthma affects 14 to 15
million persons. It is the most common chronic disease of childhood, affecting an estimated 4.8 million
children with the direct and indirect cost estimated at $6.2 billion dollars in 1993. Over 3800 children and
young adults under 25 died from asthma nationwide during the period 1980-1993. 342 children died from
asthma in 1993 alone. Asthma is associated with the loss of 28 million activity days annually and 2.2
million pediatrician visits. It is the leading cause of school absenteeism. It has been estimated that among
children 5-17 years old, asthma accounted for approximately 10 million missed school days at a cost of
$726.1 million in caretakers' time lost from work.
TRENDS
The burden of asthma on the US population is increasing. Through the 1980's, the prevalence of asthma
increased 29%, hospitalization rates increased 6% and mortality rates increased as well. The most notable
increases were for children and young adults. Hospitalization rates for children less than five years old
have increased 57% since 1980. These rates increased at a time when total hospitalization rates for
children decreased. Overall, the annual age-specific asthma death rate increased 118% (from 1.7 to 3.7
per million) between 1980 and 1993 for persons aged 0-24. Explanations for rising prevalence, morbidity
and mortality are varied. Investigators have attributed increased hospitalization to improved diagnosis,
untoward effects of treatment, environmental factors, improvements in vital statistic reporting, and
increased tendencies for asthmatic patients to use hospital emergency departments as primary sources of
care.
VULNERABLE POPULATIONS
Childhood asthma has become more prevalent and more severe in the last decade, and disproportionately
affects minority populations. In 1993, among children aged 5-14 years, blacks were four times more
likely than whites to die from asthma.. In the 0-4 age group, blacks were six times more likely to die from
asthma than whites. Hospitalization rates are consistently highest among blacks. In 1993, among persons
aged 0-24 years, blacks were 3.4 times more likely than whites to be hospitalized for asthma..
Children living in the inner city are particularly vulnerable. New York City has the highest rate of
hospitalization and mortality for childhood asthma of any area in the United States. As of 1993, New
York City children were hospitalized for asthma at four times the national rate. Within the city, these
rates are three to five times higher for African Americans and Latinos than for the rest of the population.
Areas in New York City with the highest asthma hospitalization rates include the South Bronx, Upper
Manhattan, Central and North Brooklyn. Nationally, asthma rates are highest in New york, Chicago,
Fresno, and Maricopa County, Arizona.
The exact relationship between generally known risk factors and the increase in asthma-related morbidity
and mortality among minority inner city children has not been determined. Poverty undoubtedly impacts
upon the health of inner-city populations. Poverty has been linked to underdiagnosis and subsequent
reduced preventive asthma care. Defined risk factors such as passive and active cigarette smoking and air
pollution may be greater for minority, inner-city children. Also, infestation with pests such as roaches,
mites, rodents and mosquitoes are greater problems among the poor than the more affluent. Finally,
socio-economic status has been directly linked to overall compliance and medical follow-up.
PATHOGENESIS AND MANAGEMENT
Asthma results from complex interactions among inflammatory cells, mediators and the cells and tissues
resident in the airway. Atopy, the genetic predisposition for the development of a mediated response to
common aeroallergens, is the strongest identifiable predisposing factor for developing asthma. In
2
susceptible individuals, this chronic inflammation causes recurrent episodes of wheezing, breathlessness,
chest tightness and cough, particularly at night and in early morning. The episodes are usually associated
with widespread but variable airflow obstruction that is reversible either spontaneously or with treatment.
This inflammation does cause an associated increase in the existing bronchial hyperresponsiveness to a
variety of stimuli.
The effective treatment of asthma is dependent on four components: 1) correct diagnosis of asthma 2)
reducing factors contributing to asthma severity 3) pharmacological therapy 4) self-management
education.
The goals of asthma therapy are to: 1) prevent chronic and troublesome symptoms 2)maintain normal
pulmonary function 3) maintain normal activity levels 4)prevent recurrent exacerbations 5) provide
optimal pharmacotherapy with minimal side-effects and 6) meet patients' and families' expectations of
satisfaction with asthma care.
NEW YORK CHILDHOOD ASTHMA INITIATIVE
This initiative is organized as a partnership between the office of Councilman Ken Fisher and The
Children's Health Fund, with strong collaboration from the New York City Department of Health. The
goals of the program are to increase public awareness and knowledge of pediatric asthma and develop
programs, models, and policies that will serve to reduce childhood asthma morbidity and eliminate
childhood deaths due to asthma. The initiative will give attention to specific communities with high
asthma prevalence.
The program components will include a Childhood Asthma Task Force. This task force will be
representative of NYC service sector agencies and will be co-chaired by Councilman Fisher and
Children's Health Fund President Irwin Redlener MD. Other program components are Childhood Asthma
Awareness Campaign and Clinical Programs. These components will include a public information
initiative, asthma information hotline and provider education. In addition, the establishment and/or
enhancement of primary care programs with special asthma focus will be organized in two communities
where asthma is particularly problematic, Hunt's Point and Brooklyn. Existing care centers will provide
3
needed state-of-the-art asthma care in these two high risk communities and will serve as demonstration
sites for a range of clinical and educational programs targeted at childhood asthma.
4
DEC-04-1997 12:56
FROM
TMC PLANNING/MARKET
TO
12024562878
P.01
TUCSON/ALMATY HEALTHCARE COALITION
520-324-1784
FAX 520-795-5689
Tucson Medical Center, Arizona Bldg, 2nd floor, 5301 East Grant Road, Tucson, Arizona 85712
FAX COVER SHEET:
Date: 12/4/97
Number of Pages:
To:
Jennifer Klein
202-456-2878
Assistant to the First Lady
From: Emily Jenkins, Project Director
520-795-5689
Re:
Asthma Information and Invitation
to Speak at Greater Issues Series
Jennifer:
Thank you for your call. Attached is a copy of Dr. Thorpe's invitation to Mrs. Clinton to
speak at the Greater Issues Series. We would like to combine this visit with an
informational program for Mrs. Clinton on asthma from clinical, research and community
perspectives.
I will FedEx a package of information to you next week regarding asthma as a health
problem in the U.S., with information on these different areas of the problem.
Emily Jenkins
DEC-04-1997 12:56
FROM
TMC PLANNING/MARKET
TO
12024562878
P.02
TMC HealthCare
December 3. 1997
Mrs. Hillary Rodham Clinton
1600 Pennsylvania Avenue
Washington, DC 20500-0001
Dear Mrs. Clinton:
As an influential advocate for a better world, we ask that you consider sharing your
views on social reform - both nationally and globally - in our widely acclaimed speakers
program held annually in Tucson, Arizona. Our program, which is sponsored by the
TMC Foundation, is 14 years old. Known as the Greater Issues Series (GIS), the
program features prominent national and international figures.
Tucson Medical Center (TMC), a community hospital, is the largest medical facility in
Southern Arizona. Through relationships with health care providers throughout Southern
Arizona and Northern Mexico, we strive to improve the quality of life within our sphere of
influence. TMC has a large pediatrics department. More than 4,500 babies are born
each year in TMC's Labor & Delivery department. We do extensive work in the area of
respiratory ailments, especially pediatric asthma.
We excel in a wide range of health care services, and assure that our services are
provided to all, including the uninsured and underinsured. One of TMC's primary
missions is to help create a healthier community, and that includes relationships beyond
Tucson - and even Mexico.
TMC is the lead hospital in the Almaty, Kazakhstan, health care program, which you
visited recently. Almaty Program Director Emily Jenkins is housed in our TMC facilities
and is a member of our Communications Team.
We want to thank you for your kind remarks about Tucson during media interviews, and
for the interest you expressed to Emily about our asthma projects in Tucson. The
University of Arizona has one of the leading programs in respiratory disease. We would
arrange a briefing for you regarding the research being done in the respiratory program
as part of a GIS visit.
Currently, we are developing an early learning and elder care program for employees
and the community, with specific attention being given to welfare-to-work participants.
The State of Arizona considers this a model program for other Arizona organizations to
emulate. We are hopeful that TMC's work in this area can impact some of the family
needs you address in your book It Takes a Village.
Communications Team
5301 E. Grant Road
Tucson, AZ 85712
(520) 324-2018
Fax: (520) 324-2127
DEC-04-1997 12:56 FROM
TMC PLANNING/MARKET
TO
12024562878 P.03
Mrs. Hillary Rodham Clinton
December 3, 1997
Page 2
The TMC Foundation, which has sponsored GIS since 1983, has attracted distinguished
speakers who have had an impact on our community. We would greatly appreciate the
opportunity to include your name in that register of eminent speakers: James (Scotty)
Reston, Helmut Schmidt, Edward Heath, Henry Kissinger, Jeanne Kirkpatrick, Abba
Eban, Peter Ueberroth, Tip O'Neill, Casper Weinberger, Eric Sevareid, Mario Cuomo,
George Will, Carl Sagan, Zbigniew Brzezinski, Peter Arnett, William Bennett, Richard
Cheney, Elizabeth Dole, Richard Lamm and Shimon Peres.
The GIS format focuses on a single guest speaker, who addresses an audience of
approximately 2,000. Before and after the speech, there are receptions/discussions
with smaller groups. There also is a brief meeting with the media.
Normally, we set ground rules for the media so that the focus of questions is on the
topics addressed during the GIS program. Given your prominence and the news
coverage that would be generated by your appearance in Tucson, we would work with
your press secretary to manage the media briefing.
GIS speakers who were in office or a spouse of someone in office when they spoke
in our program include: Mario Cuomo, governor of New York at the time; Zbigniew
Brzezinski, who was a member of the President's Foreign Intelligence Advisory Board;
and Elizabeth Dole, whose husband, Bob, was in Senate leadership.
Enclosed is our recent report to the community, which provides a brief overview of the
work we do at TMC.
If you need more information, please have someone on your staff contact us. If you
decide to participate in our GIS program, we would hope that it could be during the first
quarter of 1998. We are more than willing to work around your schedule and help with
any special arrangements that you need.
We look forward to hearing from you.
Sincerely,
Danece P Thoye
Darrell P. Thorpe, M.D.
President and Chief Executive Officer
TMC HealthCare
CC:
Patti Solis-Doyle, Director of Scheduling
Mona Pasqael, Western Political Director
Emily Jenkins, Almaty Program Director
Enclosures
Communications Team
5301 E. Grant Road Tucson, AZ 85712
(520) 324-2018
Fax: (520) 324-2127