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OCR for page 19
MAJOR ISSUES IN
UNDERSTANDING AS th ma
I he purpose of this chapter is to provide background infor-
mation helpful to the understanding of the material covered in
the report. It contains a summary of the 1993 Institute of Medi-
cine report Indoor Allergens, which covered some of the same top-
ics examined here. It also addresses some of the major issues in
understanding the medical condition called asthma: the contro-
versy over the definition of the illness; the characteristics of its
clinical presentation in children, adolescents, and adults; and the
concepts of the "development of asthma" and "exacerbations of
asthma." Finally, the chapter presents brief discussions of four
topics addressed in greater detail later in the report: risk factors,
trends in prevalence, pathophysiology, and tools for evaluating
the effectiveness of interventions to reduce asthma.
ORIGIN OF THE STUDY
In 1993, as a result of joint funding between the U.S. Environ-
mental Protection Agency (EPA) Indoor Air Division (IAD) and
several agencies within the Department of Health and Human
Services, the Institute of Medicine (IOM) issued a major report:
Indoor Allergens: Assessing and Controlling Adverse Health Effects
(hereafter called Indoor Allergens). Indoor Allergens received wide
public and press attention and helped to focus public health
19
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20
CLEARING THE AIR
policy on the dramatic increases in asthma, especially in children.
The report also pointed out the role of indoor allergens such as
dust mites, cockroaches, fungi, and pet dander in the etiology of
asthma. At about the same time, IAD and the EPA Office of Re-
search and Development issued a major assessment of the health
impacts of environmental tobacco smoke (ETS), which found a
correlation between exposure to ETS and asthma in children.
EPA's asthma and indoor air initiatives are now the responsi-
bility of the Indoor Environments Division (IED), a part of the
Office of Radiation and Indoor Air. IED has been actively involved
in public outreach efforts on asthma and its relationship to indoor
environmental pollutants. These include educational campaigns
in high-risk communities, the Indoor Air Quality (IA Q) Tools for
Schools Action Kit, and cooperative efforts with other government
agencies.
EPA is currently developing an outreach strategy focused on
reducing asthma-related morbidity and mortality associated with
exposure to indoor environments. To help ensure that such ef-
forts are based on sound science, EPA requested that the National
Academies undertake an assessment of asthma and its relation-
ship to indoor air quality. This report presents the conclusions of
that research effort.
SUMMARY OF THE INDOOR ALLERGENS REPORT
The early 1990s saw an increase in the level of concern about
the potential adverse health effects of indoor air quality. Moti-
vated by this concern, several agencies of the federal government
asked the IOM to undertake an assessment of the public health
significance of indoor allergens. The IOM responded by assem-
bling a committee of experts in such fields as allergy and immu-
nology, epidemiology, mycology, engineering, industrial health,
pulmonology, education, and public policy. The study undertaken
by the committee had three primary objectives:
1. to identify airborne biological and chemical agents found
indoors that can be directly linked to allergic diseases;
2. to assess the health impacts of these allergens; and
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
21
3. to determine the adequacy of the knowledge base that is
currently available on this topic.
That report described what was then known about the ad-
verse human health effects caused by indoor allergens, the mag-
nitude of the problem nationally, the specific causative agents and
their sources, the testing methods used for identifying allergens
and diagnosing related diseases, and associated educational and
research needs. The committee responsible for the study identi-
fied and developed a list of research agenda items and priority
recommendations. The recommendations focused primarily on
the need to improve awareness and education, while the research
agenda focused on the longer-term, more expensive, and more
technical aspects of fundamental research and data collection.
Indoor Allergens details the 1993 study committee's conclu-
sions. Although some of these conclusions address medical con-
ditions and topics outside the scope of the present report, several
address issues related to asthma and the impact of indoor air ex
posures.
The Indoor Allergens committee recommended that steps be
taken to improve estimates of allergenic disease incidence and
prevalence, and to establish effective mechanisms for medical
professionals to acquire assessments of potential exposure to in-
door allergens in residential environments. It called for improve-
ments in heating, ventilating, and air-conditioning (HVAC) equip-
ment in order to minimize allergen reservoirs and amplifiers, and
for the development of consensus standards for controlling mois-
ture in buildings to help control microbial and arthropod
aeroallergens and allergen reservoirs. The committee also recom-
mended several educational initiatives including the develop-
ment of focused intervention programs for allergic populations
with different socioeconomic and educational characteristics. It
called for efforts to inform architects, engineers, contractors,
building maintenance personnel, and others responsible for the
design and maintenance of indoor environments about the mag-
nitude and severity of diseases caused by indoor allergens and
the health implications of the design, construction, and operation
of buildings.
Among the report's research agenda items were calls to
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22
CLEARING THE AIR
· better characterize rates of initial asthma sensitization, in-
cidence, prevalence, and morbidity, and clarify the relation be-
tween these and socioeconomic status, race, and other factors;
· identify, characterize, and determine the health impact of
indoor allergens, specifically suggesting research on allergenic
chemicals, arthropods, dust mites, fungi, and indoor animals and
plants;
· conduct dose-response studies in humans to determine
both the relationship between allergen concentration and immu-
nologic response and the threshold environmental exposure con-
centration for sensitization; and
· evaluate the effectiveness and cost-effectiveness of a broad
variety of environmental control measures on patient symptoms,
and determine whether long-term allergen avoidance has a posi-
tive effect on quality of life.
DEFINITIONS OF ASTHMA
Although patients of all ages are routinely diagnosed with
asthma, finding a widely accepted definition for this disease has
proven to be problematic (Samet, 1987; Toelle et al., 1992, 1997~.
One commonly used definition of asthma (Murphy, 1997) states:
Asthma is a chronic inflammatory disorder of the airways in which
many cells and cellular elements play a role, in particular, mast cells,
eosinophils, T lymphocytes, macrophages, neutrophils, and epithe-
lial cells. In susceptible individuals, this inflammation causes re-
current episodes of wheezing, breathlessness, chest tightness, and
coughing, particularly at night or in the early morning. These epi-
sodes are usually associated with widespread but variable airflow
obstruction that is often reversible either spontaneously or with
treatment. The inflammation also causes an associated increase in
the existing bronchial hyper-responsiveness to a variety of stimuli.
(Murphy, 1997)
There are two important concerns with this definition: (1) the
definition implies that asthma is a single disease entity, although
much of the contemporary evidence suggests that asthma is a syn-
drome caused by several different mechanisms (Borish, 1999~; and
(2) many interpret this definition to mean that asthma results from
an aberration or variation of the immune system leading to
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
23
chronic inflammation. There is general agreement that asthma is
always associated with inflammation within the lungs, and the
intensity of the inflammation is related to the severity of respira-
tory symptoms and the degree of bronchial hyperresponsiveness
(slough and Dow, 1987; Ingram, 1991; Pattemore and Holgate,
1993~. (Hyperresponsiveness refers to the abnormally large re-
sponse of the lungs to the inhalation of minor irritants such as
cold air.) There is also consensus that inflammation is the cause of
hyperresponsiveness (Ingram, 1991; Jeffrey et al., 1989; Richmond
et al., 1996; Woolley et al., 1996~. Discovering the origin or origins
of the inflammatory response, however, remains a critical unan-
swered question for researchers.
The absence of a universally accepted definition of asthma
makes it especially difficult to arrive at a consistent operational
definition for epidemiologic studies. One of the most commonly
used definitions of asthma in epidemiology is a "physician's di-
agnosis" (Barbee et al., 1985; Dodge et al., 1986; Samet, 1987;
Yunginger et al., 1992~. This term is imprecise since there is little
information about the reasoning and consistency used by physi-
cians when making this diagnosis. A variety of definitions, based
on questions about symptoms, have been proposed. The validity
of these symptom-based definitions has rarely been rigorously
evaluated (Toelle et al., 1997~.
For the purposes of this report, asthma is understood to be a
chronic disease of the airways characterized by an inflammatory
response involving many cell types. Both genetic and environ-
mental factors appear to play important roles in the initiation and
continuation of the inflammation. Although the inflammatory re-
sponse may vary from one patient to another, the symptoms are
often episodic and usually include wheezing, breathlessness,
chest tightness, and coughing. Symptoms may occur at any time
of the day but are more commonly seen at night. These symp-
toms are associated with widespread airflow obstruction that is
at least partially reversible with pharmacologic agents or time.
Many persons with asthma also have varying degrees of bron-
chial hyperresponsiveness (Britton, 1992; Ingram, 1991~. Research
has shown that after long periods of time this inflammation may
cause a gradual alteration or remodeling of the architecture of the
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24
CLEARING THE AIR
lungs that cannot be reversed with therapy Jeffrey et al., 1989;
Kamm and Drazen, 1992; Murphy, 1997; Richmond et al., 1996~.
CLINICAL PRESENTATION OF ASTHMA
.
Asthma may present at any age, but most studies suggest that
in the majority of patients, asthma will present before puberty
(Barbee et al., 1985; Martinez et al., 1995~. Discussing the presen-
tation of asthma is complicated by a lack of consensus on criteria
for defining the onset of asthma. Many children who are sick with
respiratory infections will experience asthma-like symptoms. In
some children the symptoms will diminish, whereas in others the
symptoms will persist (Brooke et al., 1995; Dodge et al., 1996;
Martinez et al., 1995; Ross et al., 1995; Williams and McNicol,
1969~. A diagnosis of asthma is dependent upon the recurring na-
ture of these symptoms over a period of time. It appears that the
more frequently these episodes occur, the more likely the child is
to have asthma (Dodge et al., 1996; Martin et al., 1982; Martinez et
al., 1995; Williams and McNicol, 1969~. Unfortunately, no clear
criteria mark the transition from recurrent wheezing with infec-
tions to asthma, and there are no tests capable of confirming a
diagnosis (Brooke et al., 1995; Dodge et al., 1996~. Tests of pulmo-
nary function are very helpful in the diagnosis of asthma in ado-
lescents and adults, but testing the lung function of children ages
1-6 is very difficult and possible only in a small number of re-
search settings. This means that defining the onset of asthma de-
pends on the variable skills and criteria applied by different phy
. .
slclans.
In most children, asthma begins as episodes of prolonged
coughing, with or without wheezing, within the first few years of
life. In young children, these symptomatic episodes are almost
always associated with infections of the respiratory tract. The
agents most often associated with these respiratory infections are
common viral respiratory pathogens (Busse, 1989,1995; Folkerts
and Nijkamp, 1995; Martinez, 1995; Pattemore et al., 1992) . The
potential roles of other infectious agents including mycoplasma
and chlamydia have been questioned but not defined (Hahn et
al., 1991, 1998; von Hertzen et al., 1999~. In the majority of chil-
dren these symptomatic episodes resolve with time. For others,
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
25
the episodes will continue and will gradually begin to occur with-
out the concomitant presence of infection (Brooke et al., 1995;
Martinez et al., 1995~. The frequency and severity of these epi-
sodes appear to increase with exposure to tobacco smoke and
other forms of airborne pollutants (Arlian et al., 1993; Gidding
and SchydIower, 1994; Menon et al., 1991~. A family history of
asthma and allergy and a personal atopic predisposition increase
the likelihood that asthma will develop (Brooke et al., 1995;
Martinez et al., 1995; Williams and McNicol, 1969~.
With asthma symptoms ranging from clearly episodic to
nearly continuous, from mild to severe, and from an isolated
cough to a loud wheeze, diagnosing patients accurately can prove
to be very difficult. In some children, asthma presents as distinct
episodes of wheezing and difficulty breathing, whereas in others,
cough may be the only complaint. When episodes are distinct
events and wheezing is a prominent symptom, a diagnosis of
asthma is relatively easy to make. However, when symptoms are
less episodic and when wheezing is minimal or absent, asthma
can be misdiagnosed or missed altogether. In many children the
episodes of symptoms are diagnosed as recurrent bronchitis,
bronchiolitis, or pneumonia (Brooke et al., 1995; Dodge et al., 1996;
Sherman et al., 1990~. When treated with antibiotics, these ill-
nesses seemingly "resolve." If these episodes occur only a few
times each year, the true asthma diagnosis may be missed for
years (Davis, 1976; Martin et al., 1982; Schwartz et al., 1990~. Phy-
sician recognition of asthma symptoms is further complicated by
the parents' and child's perceptions, expectations, and abilities to
describe the symptoms. When a diagnosis of asthma has been
made, many parents of asthmatic children often state that the
symptoms they now recognize as coming from asthma were
present months or years before a diagnosis was made.
These variations in the presentation of asthma lead to confu-
sion between the concepts of the "development of asthma" and
the "exacerbations of asthma." The concept of developing asthma
is that the lungs of a normal individual go through a process in
which they develop characteristic, chronic, eosinophilic inflam-
mation. The eosinophilic inflammation is associated with symp-
toms, such as cough and wheezing, that are recognized as asthma.
Because there is no distinct finding or test that allows precise iden
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26
CLEARING THE AIR
tification of these changes, it is usually impossible to pinpoint
when asthma actually begins or develops. The term asthma exac-
erbation is used when referring to the sudden onset of symptoms
in someone who already has developed asthma. In older children
and some adults, the onset of asthma can be defined by the first
exacerbation that brought the patient to medical attention. How-
ever, even in these individuals there was presumably a gradual
process that took days, weeks, or months before the exacerbation
appeared. There is essentially no information concerning whether
changes in lung function or immune process in the lung can be
detected prior to or during the development of asthma.
Another important but difficult concept is referred to as
"growing out of asthma," which originated from the experiences
of many parents and physicians. As already mentioned, many in-
fants and young children wheeze in association with viral respi-
ratory infections (Brooke et al., 1995; Martinez et al., 1995; Ross et
al., 1995~. As these infants grow older they cease to wheeze with
this type of infection. If the child had been diagnosed as having
asthma, he or she has now "outgrown" that asthma. There are
also children who have recurrent episodes of wheezing during
childhood and are diagnosed as having asthma, but cease to
wheeze during adolescence, often during the years of puberty.
The probability that the symptoms of asthma will remit appears
to be higher if the child has little evidence of allergic disease
(Martinez et al., 1995; Ross et al., 1995; Williams and McNicol,
1969~. Some of the children whose asthma has remitted will rede-
velop asthma symptoms in adulthood. Because of the length of
time required, there have been few prospective studies of the risk
of asthma recurring once remission has occurred; hence there is
no information about risk factors for redeveloping asthma.
As children move into adolescence and adulthood, respira-
tory infections remain a common cause of symptomatic episodes
(Busse, 1995; Martinez, 1995~. Additionally, symptoms may occur
"spontaneously" or with exercise. Spontaneous symptoms are of-
ten discovered to be the result of exposure to either an allergen or
a potent airborne irritant. When symptoms of coughing and
wheezing are associated only with exercise, it is often difficult to
distinguish whether these are new symptoms or unrecognized
symptoms that have been present for years. Symptoms associ
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
27
ated with exercise are more easily recognized in older children
because they typically have a higher level of physical activity and
have developed the verbal means to describe their symptoms. In
some adolescents and adults, symptoms are perceived more as
chest tightness or chest pain than as difficulty breathing. People
who experience these symptoms may not recognize them as com-
ing from the chest and complain instead of chronic fatigue or of
becoming fatigued rapidly during the day (Brooke et al., 1995;
Dodge et al., 1993~.
An interesting change that takes place between childhood and
adulthood is in the ratio of males to females with asthma. In child-
hood, boys with asthma outnumber girls by 1.5-2 to 1. By 20-30
years of age, women with asthma outnumber men by 1.5-2 to 1, a
complete reversal of the childhood ratio (Barbee et al., 1985;
Clough, 1993~. Although it is tempting to speculate that this
change, which occurs over the years of sexual maturation, results
from hormonal changes, little is known about the actual cause.
Although asthma can develop anytime, there are times in a
person's life when it can be especially troublesome. For some
women, asthma first appears or markedly increases during preg-
nancy. Because poorly managed asthma is associated with an in-
creased risk of maternal and fetal complications, the prompt rec-
ognition and appropriate treatment of asthma during pregnancy
are important. During pregnancy, the onset of asthma and
changes in the severity of preexisting asthma are presumed to be
related to the major hormonal changes that occur, but the exact
cause is unknown.
Occupational asthma is another complex problem (Cartier,
1994; Park et al., 1986~. In some individuals, asthma symptoms
first develop as a result of an occupation-related exposure. In most
cases the agent responsible for the onset is an allergen to which
the worker has become sensitized. In other cases the agent is a
strong respiratory irritant. Occupational problems are beyond the
scope of this report, however, and are therefore not discussed in
detail.
A final important concern about the progression of asthma
throughout life is the relationship between asthma and chronic
obstructive pulmonary disease. As mentioned earlier, the chronic
inflammatory process of asthma appears to ultimately result in
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28
CLEARING THE AIR
irreversible obstructive changes in the lungs. The progression
from a largely reversible airway obstruction, asthma, to an essen-
tially irreversible state, chronic obstructive lung disease, appears
to be highly variable and dependent upon a variety of factors such
as smoking. The contribution of indoor sources of allergens and
irritants to respiratory disease is important because chronic ob-
structive pulmonary disease is an important cause of increased
morbidity and mortality among adults.
RISK FACTORS FOR ASTHMA
As early as the 1920s, studies demonstrated that a familial
predisposition to asthma existed, suggesting that genetics may
play a role in asthma development. This genetic influence has
remained constant in subsequent studies; however it explains
only 30-80% of the asthma risk. The remaining risk appears to be
related to environmental exposure. The recently noted increase in
the prevalence of asthma suggests a change in some environmen-
tal influence since it is hard to imagine a significant change in
human genetics in such a short time (Borish, 1999~.
Major studies have been conducted to better define the genes
related to the development of asthma. These studies reveal com-
plex relationships between genes and asthma (Borish, 1999~. It
appears that asthma results from the effects of multiple genes, not
a single gene. Further complicating the association between ge-
netics and asthma has been the discovery that genes closely linked
to asthma in one population may not be significantly linked in
another population. Some of these discrepancies appear to be ra-
cial, and some appear to be related to the peculiarities of rela-
tively isolated and therefore somewhat inbred populations. These
findings raise the question of whether asthma is best thought of
as a single disease entity, a syndrome, or a final common manifes-
tation of several different disease processes (Borish, 1999~.
Many different environmental variables have been evaluated
in relationship to asthma. Some of these are nonspecific such as
an increase in global pollution, a decrease in exercise or outdoor
play because of television and computer games, fewer childhood
infections because of immunizations, more childhood respiratory
infections because of day care, alterations in microbial flora be
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
29
cause of the frequent use of antibiotics, or changes in indoor envi-
ronments. Alternatively, there are relatively specific factors, such
as increased exposure to dust mite allergens, that are discussed in
more detail in Chapters 5-8.
TRENDS IN THE PREVALENCE OF ASTHMAS
Many studies have shown that the prevalence of asthma has
been increasing in the United States for the past 30 years. Al-
though this subject is explored further in Chapter 3, it is impor-
tant to summarize some of the most important aspects of asthma
trends to provide a better understanding of the problem of asthma
in the United States today.
In 1998, the Centers for Disease Control and Prevention (CDC)
published a study concerning the change in the prevalence of
asthma across the United States from 1960 to 1995 (Manning et
al., 1998~. That report combined information from several sources
to produce a broad picture of the changes in asthma prevalence.
Population estimates were based on the 1960,1970,1980, and 1990
censuses and the 1996 intercensal estimate. Each data set was
stratified by region, sex, race, and age group. Self-reported asthma
data came from the National Health Interview Survey, which is
conducted annually. Data on visits to physicians' offices for
asthma have been collected since 1975 by the National Center for
Health Statistics (NCHS). The data have been gathered on five
different occasions within the study interval, and each time ap-
proximately 2,000 physician offices or about 30,000-60,000 patient
encounters, were evaluated. Also since 1992, NCHS has gathered
annual data on hospital emergency and outpatient department
visits. Hospitalizations attributable to asthma were estimated
from 1979 to 1994 from the National Hospital Discharge Survey.
Only cases with a primary discharge diagnosis of asthma were
included. Finally, mortality was estimated from the Underlying
Cause of Death data set from NCHS for 1960 through 1995 to
identify all deaths in which asthma was selected as the underly-
~ng cause.
The results of this study show an increase in the prevalence of
asthma and death rates from asthma over 15 years both nation-
ally and regionally. Regional differences were found for some end
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30
CLEARING THE AIR
points such as hospitalization but not for others such as preva-
lence. The self-reported prevalence of asthma increased by 75%
from 1980 to 1994. In 1993-1994, an estimated 13.7 million resi-
dents of the United States reported asthma during the preceding
12 months. A significant increase in asthma was found for all
races, both sexes, and for all age groups. The increase was most
prominent among children 0-4 years (160%) and 5-14 years (74%~.
During 1993-1994, the self-reported prevalence of asthma was
slightly higher among children <14 years of age than among per-
sons 215 years of age. In this same year, prevalence rates were
similar in all four regions of the country.
When office visits for asthma are considered, the estimated
annual number of visits increased from 4.6 million to 10.4 million
between 1975 and 1993-1994. Again, the increasing rates were
found for all race strata, both sexes, and all age groups. During
1993-1994, the rate of office visits for asthma was lowest for the
15-34 year age group.
Data on emergency room (ER) visits for asthma were avail-
able only from 1992-1995, and during this interval there was no
significant change. In 1995, there were in excess of 1.8 million ER
visits for asthma. African Americans had consistently higher rates
of ER visits than whites. The rate of ER visits decreased with in-
creas~ng age.
From 1979-1980 to 1993-1994, the estimated number of
asthma-related hospitalizations increased, but the rate of hospi-
talization did not change over this interval. Hospitalization rates
were consistently higher among African Americans than among
whites. In 1993-1994, the age-adjusted asthma hospitalization
rates were higher in the Northeast than in the West. In each time
interval examined, the hospitalization rates were highest among
children 0-4 years, lowest among persons aged 15-34 years, and
intermediate for those 235.
Mortality rates from asthma are confused by the changes in
the International Classification of Diseases (ICD) coding criteria.
Asthma death rates declined from 1960-1962 to 1975-1978, and
then began to rise again by 1993-1994. The 1960-1962 death rate
was 28.2 per 100,000 in contrast to a rate of 17.9 per 100,000 in
1993-1994. The lowest death rate was in 1975-1978 at 8.2 per
100,000 or less than half the rate of 1993-1994.
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
31
These national statistics are consistent with many local and
regional reports showing an increase in the prevalence of asthma
predominantly in children (Gergen et al., 1988; Gerstman et al.,
1993; Vollmer et al., 1998; Yunginger et al., 1992~. This problem
has been found in all regions of the United States and affects all
races. Even though all races are affected, most studies have con-
sistently shown a greater impact of asthma in African Americans
in comparison to whites (Cunningham et al., 1996; Gergen, 1996;
Gergen et al., 1988; Gerstman et al., 1993~. Similar trends have
been observed in most developed countries. This increase in the
prevalence of asthma over the relatively short interval of approxi-
mately 30 years strongly suggests that some as yet unidentified
environmental or behavioral change is responsible.
MECHANISMS OF ASTHMA
Details of the pathophysiology of asthma are presented in
Chapter 4; thus, only the major concepts are discussed here. Fig-
ure 1-1 attempts to illustrate these major concepts in a schematic
form. Asthma appears to present in two different forms, allergic
and nonallergic asthma, illustrated on the left and right sides of
the figure, respectively. The critical difference is that in persons
with allergic asthma, inhalation of allergens initiates an inflam-
matory response that leads to hyperreactivity of the airways and
symptoms of asthma. In persons with nonallergic asthma, the in-
flammatory process and airway hyperreactivity appear the same
as in individuals with allergic asthma, but allergic responses, de-
fined by the presence of immunoglobulin E (IgE) antibodies spe-
cific for allergens, cannot be demonstrated. As shown in the fig-
ure, allergic asthma is the result of allergen exposure leading to
allergic sensitization of a genetically predisposed individual. The
development of allergic sensitization during allergen exposure
may be influenced by other environmental effects such as the fre-
quency and type of respiratory infections, passive exposure to to-
bacco smoke, or intensity of allergen exposure. Airway hyperre-
activity may be a direct result of allergic airway inflammation or
may result from one or more genes. Once asthma is present, a
variety of exposures may result in acute or chronic asthma symp-
toms. In addition to allergen exposure, the exposures capable of
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32
Genetic Predisposition
Allergen ~ I
Exposure
Respiratory,' Allergic *~~~~----
lnfections .' Sensitization
. . _ ,,
, ,
~ ~ ,-
lnflammation Airway
in the Lungs + Hyperreactivity
Allergic Asthma
\
CLEARING THE AIR
Genetic Predisposition
~ \
,' \ Respiratory
~ , ~ ~
Factors ~~~~~~~~,~~----~\,, ' Infections
i ~
-~- Environmental
Exercise-_
\: Pollutants- _ am/
Allergen
Exposure ~ \* --Temperature Changes ./
\~ Infections ~ /
\ Emotions - - - - ~ ~ ~ ~ +/
Asthma Symptoms
Inflammation Airway
in the Lungs + Hyperreactivity
""' 1
'1
Nonallergic Asthma
FIGURE 1-1 Development of asthma symptoms. This figure attempts to il-
lustrate schematically the interrelationships of a number of factors thought
to be important in the development of both allergic and nonallergic asthma.
The weight of the lines attempts to provide some information about the
strength of the evidence for the relationships: bold lines where there is ample
evidence for a relationship and regular lines where the relationships have
been demonstrated or at least strongly suggested. Dashed lines illustrate
relationships that are likely to exist but for which there is little direct evi-
dence at present. The phrase "genetic predisposition" is used to convey all
of the genes in the human genome that are likely to be directly related to the
outcome.
causing symptoms include airborne irritants, infections, and ex-
ercise.
The development of nonallergic asthma is somewhat harder
to explain, although there are suggestions that chronic infections
may be related to asthma in some nonallergic individuals (von
Hertzen et al., 1999~. As in the case of allergic asthma, inflamma-
tion occurs in the lungs and is typically accompanied by airway
Hyperreactivity A variety of exposures may lead to wheezing in
the nonallergic asthmatic; however, the origin of the inflamma-
tion cannot be directly identified. It is probable that various ge-
netic influences on the immune system lead to inflammation in
the lungs following some as yet undefined environmental expo
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
33
sure. It is possible that nonallergic asthma is the result of an uni-
dentified allergen, but for many reasons this appears unlikely.
Estimates suggest that approximately 80% of asthma in chil-
dren is allergic asthma. In adults, the percentage of those with
allergic asthma is lower, in the 30-50% range depending on the
population studied (Burr, 1993; Eriksson, 1990; von Mutius, 1996;
Wever and Wever-Hess, 1993~. The lower prevalence of allergic
asthma in adults may arise in many different ways. The preva-
lence of allergic sensitivity is lower in adults than in children. It is
possible that the inflammatory response that started as an allergic
response in a child may become self-perpetuating by adulthood
even as the allergic sensitization is lost. It is also possible that
these are two different disease processes that merely have similar
clinical appearances.
EVALUATING THE EFFECTIVENESS OF
INTERVENTIONS TO REDUCE ASTHMA
Before an asthma intervention can be evaluated, the goals of
the intervention must be defined. The goal of asthma therapy is
ultimately to prevent a patient's asthma from altering or unduly
influencing their life. Specific goals proposed in the Guidelinesfor
the Diagnosis and Management of Asthma include (1) prevention of
chronic and troublesome symptoms; (2) maintenance of "normal"
pulmonary function; (3) prevention of recurrent exacerbations of
asthma and minimization of the need for emergency department
visits or hospitalizations; (4) provision of optimal pharmaco-
therapy with minimal or no adverse effects; and (5) meeting pa-
tients' and families' expectations and satisfaction with asthma
care (Murphy, 1997~.
Once goals are agreed upon, tools must be selected to evalu-
ate how close the intervention comes to achieving all of the goals.
In a typical clinical practice, the physician simply asks patients
how they are doing. This is imprecise, and responses can vary
depending upon how well the person can perceive his or
her symptoms. Since many patients perceive their symptoms
poorly, other tools are necessary to assess the adequacy of asthma
control.
Pulmonary function tests, primarily spirometry, are essential
OCR for page 34
34
CLEARING THE AIR
tools for evaluating a patient with asthma. Good control of asthma
is reflected in normal or near-normal spirometry. Sequential
i]
spirometry allows the physician to follow the course of disease
and judge the adequacy of therapy. In children old enough to per-
form spirometry, lung growth can be monitored and assessed
more easily.
There has been increasing recognition that control of asthma
evolves more than the absence of symptoms and the normality
of lung function tests. Important aspects of asthma management
involve the total impact of the disease on a person's life. How
much does it affect what a person tries to accomplish? How does
it affect daily activities? Do people avoid certain situations for
fear of an attack? These diverse aspects have been grouped under
the term "quality of life," and questionnaires have been devel-
oped that attempt to capture and estimate these aspects of dis-
ease control Quniper et al., 1993; Rowe and Oxman, 1993~.
Other methods for evaluating asthma are constantly being
developed and evaluated. One of the most important areas in
need of an adequate means of testing is the intensity of Jung in-
flammation. In research settings it is possible to directly sample
the linings of the airways and the numbers of inflammatory cells
within the lungs, but these techniques are very expensive and
involve some risk to the patient. Techniques are needed that could
estimate Jung inflammation accurately and yet be simple and in-
expensive enough for use on a routine clinical basis.
The present state of the art in assessing any form of interven-
tion for the control of asthma typically involves four components:
(1) patient symptom scores or checklists, (2) physician assess-
ments, (3) spirometry (often supplemented with home peak flow
monitoring), and (4) completion of quality-of-life questionnaires.
Given the lack of precision of these instruments, it is usually nec-
essary to apply them with a relatively large number of persons
for weeks or months before the effect of the intervention can be
estimated adequately. In some cases, other measurements can be
used to supplement the components listed above. These measures
could include some attempt at estimating Jung inflammation, de-
termining allergen-specific IgE levels in serum, or assessing exer
cise tolerance.
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MAJOR ISSUES IN UNDERSTANDING ASTHMA
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Representative terms from entire chapter:
american journal
