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Overview of chronic childhood asthma I: Definition; Epidemiology;

Pathophysiology
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Sep 17, 1998
Susan M Brugman, MD
Leland L Fan, MD

UpToDate performs a continuous review of over 270 journals and other resources. Updates are
added as important new information is published. The literature review for version 9.2 is current
through April 2001; this topic was last changed on September 17, 1998.

Asthma is a chronic, inflammatory lung disease characterized by [1]:

• Airway narrowing that is partially or completely reversible


• Symptoms of cough, wheezing, dyspnea, and chest tightness which occur in paroxysms and
are usually related to specific triggering events
• Increased airways responsiveness to a variety of stimuli

The symptoms of asthma are due to airflow obstruction. This results from the cumulative effects
of smooth muscle constriction of the small and large airways, airway wall edema, intraluminal
mucus accumulation, inflammatory cell infiltration of the submucosa, and basement membrane
thickening (show figure 1).

Attacks of asthma are typically slowly progressive but may occur suddenly with catastrophic
consequences. Although the symptoms and pulmonary function abnormalities of asthma are
completely reversible in most cases, alterations in airflow may be persistent or become
permanent [2-4].

This card will provide an overview of the epidemiology and pathophysiology of chronic childhood
asthma. An overview of the evaluation and treatment of chronic childhood asthma is provided
elsewhere. (See "Overview of chronic childhood asthma II: Evaluation and principles of
treatment").

EPIDEMIOLOGY – Asthma is the most common chronic disease in childhood, affecting


approximately three million children in the United States [5,6]. Between 5 and 12 percent of the
pediatric population develop the disease [7,8].

A number of factors are associated with an increased risk of developing asthma, including:

Gender – Boys are more commonly affected than girls (6 versus 3.7 percent) until puberty, when
the incidence begins to equalize [7].

Locale – Urban dwellers are more likely than rural inhabitants to have asthma (7.1 versus 5.7
percent) [9]. Asthma is more prevalent in the southern United States than the Midwest (11.8
versus 8.3 percent) [7].

Race – Differences in the prevalence of asthma have been noted across various racial and
ethnic groups, including African-Americans (13.4 percent), native Americans: (12.3 percent),
Mexican-Americans (2.7 percent), and American whites (9.7 percent) [7,10,11].

Socioeconomic status – Poor and disadvantaged children are more severely affected than
affluent children [12]. These differences are most pronounced in urban settings.

Recent trends – Data from the Centers for Disease Control have shown that the prevalence of
asthma has increased in the United States [13]. During the period from 1982 to 1992, the overall
annual age-adjusted prevalence rate of self-reported asthma increased by 42 percent, from 34.7
to 49.4 per 1000. For the younger age group five to 34 years, where the diagnosis of asthma is
thought to be more accurate, the rate increased from 34.6 to 52.6 per 1000, an increase of 52
percent (show figure 2). The largest increase in prevalence was seen in persons under 18 years
of age (show figure 3) [14-19]. (See "Definition; diagnostic criteria; and prevalence of asthma").

During this same period, the annual death rate from asthma also increased, with consistently
higher rates for blacks than for whites (show figure 4). This difference in death rates is thought to
be due both to socioeconomic factors and to differences in access to medical care [20].

Several hypotheses have been proposed to explain the increased frequency of asthma in all age
groups, including:

• Increased indoor air pollution brought on by energy efficient building construction and
recycled air, increased nitrogen dioxide and other irritant gases, cigarette smoke, and/or
increased allergens (especially cockroach, cat, dust mite, molds)

• Increased incidence of early-onset respiratory viral infections

• Enhanced host susceptibility (eg, more premature infants surviving with chronic lung disease)

• Congenitally small lungs due to maternal cigarette smoking [21]

• Increased awareness and recognition of asthma by patients and physicians

Social costs – The vast economic and social toll which asthma cumulatively exacts is illustrated
by the following data:

• Two-thirds of the children with this disease suffer noticeable disability.


• Ten million school days are missed each year due to the disease.
• Childhood asthma is a major cause of parental work absenteeism [22].
• An estimated $1.6 billion/yr (excluding medication costs) is spent to care for children with
asthma [2-12,23].

Thus, improving the quality of life for children with asthma and reducing the economic burden of
the disease for their families should be a concern of every health care provider. Strategies for
accomplishing these goals include improved asthma education, individualized asthma action
plans, and regular follow-up care in the office, with telephone calls, or with home visits to
maximize patients' understanding and compliance with their medical regimen. (See "NAEPP
Expert Panel Report II: (2) Introduction")

PATHOLOGY – Patients with fatal asthma exhibit pronounced pathologic changes in the
segmental and subsegmental bronchi, with involvement of the small airways down to, but usually
sparing, the respiratory bronchioles [24]. Salient abnormalities include:

• Thickening of the basement membrane due to type IV collagen deposition


• Desquamation of the epithelial lining with loss of ciliated cells and partial regeneration by
goblet and squamous cells
• Mucosal edema
• Airway smooth muscle thickening, with hyperplasia and hypertrophy of myocytes
• Luminal plugging with inflammatory cells (eosinophils, lymphocytes, mast cells, neutrophils),
sloughed epithelial cells, tenacious mucus, and plasma proteins
• Submucosal infiltration by inflammatory cells, with deposition of submucosal connective tissue

Similar but less extensive changes can be seen in the airways of asthmatics with less severe
disease (show histology 1) [25-28].

Many of these pathologic changes are reflected in the sputum (show picture 1). As examples,
Charcot-Leyden crystals (eosinophil remnants), Curschmann's spirals (airway lumen casts of
exudate), and Creola bodies (clumps of sloughed epithelial cells) can be found in the sputum of
asthmatics [29]. However, sputum analysis is rarely useful in children because most children
swallow their sputum.

PHYSIOLOGY – The physiologic consequences of asthma follow from the reduction in airway
luminal diameter that is appreciated pathologically. The three defining components of asthmatic
airflow obstruction are reversible bronchoconstriction, airway inflammation, and increased
airways hyperresponsiveness to a variety of stimuli [30]. The cascade of events leading to
clinically recognizable asthma is complicated and not yet fully understood. (See "Pathogenesis of
asthma" and see "NAEPP Expert Panel Report II: (3) Pathogenesis and definition").

Reversible airflow obstruction and lung volumes – The physiologic hallmark of asthma is
reduced expiratory airflow (measured either with a peak flow meter or a spirometer) which
normalizes following the administration of a bronchodilator. (See "Use of pulmonary function
testing in the diagnosis of asthma"). Lung volumes, particularly the residual volume and total lung
capacity, may also decrease significantly post-bronchodilator due to the reduction of gas trapping
distal to narrowed airways (show figure 5). This phenomenon is called "volume shifting" and may
occur in the absence of improvement in measured flow rates that are uncorrected for volume.
However, when post-bronchodilator flow rates are corrected for lung volume, they are
significantly better. Relief of gas trapping may explain the subjective improvement reported by
some patients after bronchodilator administration despite an absence of spirometric improvement
[31,32].

Conversely, the obstruction to airflow in some asthmatics occurs at the level of very small
alveolar ducts. This results in restriction which reverses (ie, lung volumes increase toward
normal) following bronchodilator administration (show figure 6) [33].

Airways hyperresponsiveness – Airways hyperresponsiveness is a hallmark of asthma and


one measure of its severity. Airways responsiveness is defined as the degree to which airways
narrow in response to a nonspecific stimulus such as methacholine or histamine [34]. Asthmatic
airways are hyperresponsive, such that less methacholine is needed to induce airflow obstruction
(show figure 7). (See "Bronchoprovocation testing")

The degree of increased airways responsiveness correlates with asthma severity in adults and
children [35,36]. However, there is wide variability in airways responsiveness in individuals with
all categories of asthma, and the judgment of severity is more accurately based upon symptoms
and medication need. Stimuli that increase airways responsiveness include viral respiratory tract
infections, allergens, air pollutants, and occupational agents. (See "Trigger control to enhance
asthma management", see "Viral-induced wheezing and asthma", and see "Occupational
asthma").

Nonspecific airways hyperresponsiveness (by criteria used for adults and older children) occurs
in normal infants and lessens with age as the airways grow and increase in size [37,38]. Induced
bronchoconstriction in babies is reproducible, reversible, and inhibited by pretreatment with beta
agonists [39].

Nonspecific airways hyperresponsiveness compared to age-matched controls has been


demonstrated in infants with a family history of asthma, following bronchiolitis (even in the
absence of recurrent wheezing), in infants with passive smoke exposure, and in those with cystic
fibrosis. Surprisingly, recurrently wheezing infants do not have increased airways
responsiveness, but do have lower baseline lung function [39]. The relationship between airways
responsiveness, airway size, and the development of asthma in young children is not yet fully
delineated. (See "Risk factors for asthma").

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