Asthma, a chronic inflammatory disease of the airways, is the most common chronic illness in children. It accounts for a large proportion of school days lost to illness and is the most frequent diagnosis for admission in hospitalized children. Between 5% and 15% of all children have asthma at some time during their childhood. In children younger than 10 years, approximately twice as many boys as girls are affected, and by 14 years of age, four times as many boys as girls have asthma. The male predominance begins to decrease after midadolescence, and by early adulthood the incidence among both sexes is approximately equal. Although asthma prevalence rates have stabilized in the United States during the past few years, world-wide prevalence has increased. Risk factors for the devel-opment of childhood asthma, in addition to male sex, include:
Atopy or family history of atopy
Parental history of asthma (especially maternal)
Early viral respiratory infection
Maternal smoking
Prematurity
Passive exposure to tobacco smoke
Maternal age <20 years at the time of birth
Despite recent declines in rates of asthma-related hospitalization and asthma mortality in the United States, racial and ethnic minorities continue to be disproportionately affected with severe asthma. The rates of hospitalization for asthma and asthma-related deaths are three times higher in African Americans than white Americans based on data from The Center for Disease Control in 2005. Known risk factors for fatal asthma include:
Previous nearly fatal episodes of asthma
Hospitalization or care in an emergency department within the previous year
History of psychosocial problems or psychiatric disease
History of poor compliance with asthma medications
Current use of or withdrawal from systemic corticosteroids
Poor access to health care
Exposure to tobacco smoke
The tendency to have asthma is inherited, and the mode of inheritance is polygenic and complex. The risk for the development of asthma in a child with one affected parent is 25%, and the risk increases to approximately 50% if both the parents have asthma. Environmental factors that may be important for the complete expression of the disease in a genetically predisposed child include:
Viral respiratory infections during infancy
Passive exposure to cigarette smoke
Intensive exposure to environmental aeroallergens
PATHOPHYSIOLOGY
Asthma is an inflammatory disorder of the airways in which inflammation contributes to respiratory symptoms, limited airflow, and chronic disease. Immunohistopathology studies of biopsy specimens from the bronchi of asthmatic children reveal an inflammatory process manifested by denudation of the airway epithelium, goblet cell hyperplasia, mucous plugging, deposition of collagen beneath the basement membrane, mast cell activation, and infiltration by inflammatory cells consisting of neutrophils, eosinophils, and T-helper subset 2 (TH2) lymphocytes.
The inflammatory process may be precipitated by one or more triggers (i.e., inhaled allergen, viral infection) that lead to the release of inflammatory mediators from the bronchial mast cells and also from macrophages, T lymphocytes, and epithelial cells. Both stored and newly synthesized mediators are released from the mucosal mast cells following activation. These mediators, which include histamine, leukotrienes C4, D4, and E4, and platelet-activating factor, initiate bronchoconstriction and edema and direct the migration and activation of other inflammatory cells that cause injury (e.g., eosinophils, neutrophils) into the airways. Airway damage is manifested by denudation of the epithelium, hypersecretion of mucus, changes in mucociliary function, bronchospasm, and airway hyperresponsiveness. Bronchial hyperreactivity to viral infection, cold air, exercise, allergens, and environmental irritants is a major feature of asthma, and the level of airway hyperresponsiveness usually correlates with its clinical severity.
CLINICAL PRESENTATION
The clinical manifestations of asthma result from airway obstruction and inflammation. Acute exacerbations are most frequently precipitated by exertion or exposure to inhalant allergens or irritants. Exacerbations caused by viral respiratory infections tend to be slower in onset and worsen gradually. Symptoms of asthma include:
Cough, usually dry but sometimes productive
Wheezing
Dyspnea
Chest pain or tightness
Only one of these symptoms, such as cough, may be present, and patients may be symptom-free between exacerbations.
The physical findings vary depending on the severity and chronicity of disease. Signs that may be present during acute exacerbations include:
Tachypnea
Retractions, use of accessory muscles of respiration
Cyanosis
Pulsus paradoxus
Hyperexpansion of the thorax
On auscultation of the chest, wheezing, crackles, rhonchi, a prolonged expiratory phase of respiration, and diminished breath sounds may be observed, although the chest findings may be completely normal between exacerbations and in children with mild disease. Digital clubbing occurs rarely, even in severe asthma; if present, it suggests a diagnosis of cystic fibrosis or another chronic obstructive lung disease, either alone or in combination with asthma.
DIAGNOSIS
A correct diagnosis of asthma is established by first obtaining a careful medical history and performing a focused physical examination. In children, a history of any of the following strongly suggests a diagnosis of asthma: cough (particularly cough that is worse at night), recurrent wheezing, recurrent difficulty breathing, and recurrent chest tightness. The pattern of symptoms is variable and may be perennial, seasonal, continual, or episodic. Diurnal variations are common, in which symptoms develop or worsen at night and interfere with sleep. Typically, symptoms are precipitated or worsened by one or more of the following factors:
Viral respiratory infection
Exercise
Environmental irritants
Inhalant allergens
Changes in weather
Cold air
Expression of strong emotions (crying, laughing, anger)
Viral upper respiratory infections are the most common precipitants of asthma exacerbations in children <2 years, but as the children become older, sensitivity to aeroallergens increases, and exposure to environmental allergens plays a more important role.
The physical examination focuses on both the upper and lower respiratory tracts and also the skin. Signs of other atopic diseases, such as allergic rhinitis and eczema, are often present, even between asthma exacerbations when the chest examination findings are completely normal.
Pulmonary function tests, particularly spirometry, may be helpful in establishing a diagnosis of asthma by objectively determining the presence of an airflow obstruction and whether it is partially or completely reversible. Spirometry measures the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory flow at 25%, 50%, 75%, and between 25% and 75% of the FVC (FEF25, FEF50, FEF75, and FEF25-75). Some children can perform reproducible spirometric maneuvers at the age of 4 years, and most can do so by 6 years of age. Measurements of lung function should be obtained both before and after bronchodilation, with improvements of 12% in the FEV1 and 25% in the FEF25-75 considered clinically significant.
Although recurrent episodes of cough and wheezing in children are most frequently caused by asthma, other causes of airway obstruction must be considered in the differential diagnosis. A number of other disorders affecting the upper, middle, and lower respiratory tract that can be associated with cough or wheezing are listed in Table 30.1.
MANAGEMENT AND TREATMENT
The long-term goals of asthma therapy, established by the National Asthma Education and Prevention Program (NAEEP), are reduction of impairment and risks associated with asthma.
Reducing the impairment associated with asthma involves:
Prevention of chronic and troublesome symptoms (e.g., coughing, shortness of breath at night, in the early morning, and after exertion)
Infrequent use of inhaled short-acting beta2-agonists for quick relief of symptoms (≦2 days per week)
Maintenance of near “normal” pulmonary function
Maintenance of normal activity levels (including exercise and other physical activity and attendance at work or school)
Meeting patients’ and families’ expectation of and satisfaction with asthma care Reducing the risk associated with asthma includes:
Prevention of recurrent exacerbations and mini miz-ing the need for emergency department visits and hospitalizations
Prevention of progressive loss of lung function; for children, prevention of reduced lung growth
Provision of optimal pharmacotherapy with minimal or no adverse effects
TABLE 30.1 DIFFERENTIAL DIAGNOSIS OF INFANT AND CHILDHOOD ASTHMA
Modified from National Institutes of Health. NAEPP guidelines for the management and diagnosis of asthma.
National Asthma Education and Prevention Program. NIH Pub No 02-5075, Bethesda, MD: 2002, NIH.
Successful implementation of these goals begins with an assessment of the severity of a case of asthma. Whenever possible, evaluation of severity should be performed at the time of diagnosis and before initiation of treatment to determine the type of medication and appropriate dosage for a given patient. When a patient who is being seen for the first time has already initiated therapy, severity may be determined best by the minimum treatment required to maintain control. Asthma may be classified as intermittent, mild persistent, moderate persistent, or severe persistent based on patient’s history, physical examination findings, and pulmonary function results (Tables 30.2, 30.3, and 30.4).
The current 2007 NAEPP guidelines for asthma management recommend initial pharmacologic treatment based on the classification of severity. Assessment of the level of asthma control should be performed on subsequent patient encounters to monitor and adjust therapy. Asthma control is assessed by impairment (daytime and nocturnal symptoms, interference with normal activities, need for rescue inhaled β2-agonists, lung function measured by FEV1 or peak expiratory flow rate, validated control questionnaires) as well as risk (number and severity of exacerbations per year, long-term loss of lung function, and adverse effects of treatment) (Tables 30.5, 30.6, and 30.7).
Therapy should be intensified if asthma is not adequately controlled, and if symptoms remain well controlled for several months, therapy can be stepped down to the least amount of medication needed to maintain control. The specific guidelines for pharmacotherapy used to achieve asthma control vary according to the patient’s age and are shown in Tables 30.8, 30.9, and 30.10.
Pharmacotherapy
Pharmacologic therapy is used to prevent and control the symptoms of asthma, reduce the frequency and severity of exacerbations, and relieve the obstruction to the airflow. Asthma medications can be divided into two general classes: Those used for long-term control, taken daily on an extended basis to achieve and maintain control of persistent asthma, and those used for quick relief, taken to treat acute symptoms and exacerbations.
Medications used for long-term control include anti-inflammatory agents, long-acting bronchodilators, and leukotriene modifiers. The most effective medications for long-term control are those that attenuate inflammation. Medications used for quick relief include short-acting β2-agonists and anticholinergics. Inhaled short-acting β2-agonists are the drugs of choice for treating acute symptoms of asthma and preventing exercise-induced bronchospasm. Despite their delayed onset of action, systemic corti-costeroids are important in treating moderate to severe exacerbations because they help prevent the progression of symptoms, speed up recovery, and prevent early relapses.
TABLE 30.2 CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN YOUTHS ≧12 YEARS OF AGE AND ADULTS
Assessing severity and initiating treatment for patients who are not currently taking long-term control medications
Classification of Asthma Severity ≧12 years of age
Persistent
Components of Severity
Intermittent
Mild
Moderate
Severe
Impairment
Normal FEV1/FVC:
8-19 yr 85%
20-39 yr 80%
40-59 yr 75%
60-80 yr 70%
Symptoms
≦2 days/week
>2 days/week but not daily
Daily
Throughout the day
Nighttime awakenings
≦2×/month
3-4×/month
>1×/week but not nightly
Often 7×/week
Short-acting beta2-agonist use for symptom control (not prevention of EIB)
≦2 days/week
>2 days/week but not daily, and not more than 1× on any day
Consider severity and interval since last exacerbation. corticosteroids Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Treatment (See Table 30.8 for treatment steps.)
Step 1
Step 2
Step 3
Step 4 or 5
and consider short course of oral systemic corticosteroids
In 2-6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly.
Key: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care unit.
Notes:
The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient needs.
Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of previous 2-4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≧2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
The information in Table 30.2 is directly abstracted from the National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, National Heart, Lung, and Blood Institute. August 2007. NIH publication 08-4051.
Corticosteroids
Corticosteroids are the most potent and consistently effective medications for the long-term control of asthma. They interfere with the inflammatory response by numerous mechanisms and clinically they have been shown to reduce the severity of symptoms, prevent exacerbations, improve lung function, decrease airway hyperresponsiveness, and may possibly prevent progression of airway remodeling.
Inhaled corticosteroids are the most effective long-term therapy for persistent asthma and in general are safe and well tolerated at recommended doses. Systemic effects can occur, especially at high doses, and occasionally at lower doses in individual patients. Recent studies have not shown any significant effect on the long-term linear growth in children receiving long-term therapy with inhaled corticosteroids at low to medium doses. Rinsing the mouth and spitting following inhalation and using a spacer, significantly decreases local side effects and systemic absorption. Oral corticosteroids are occasionally indicated for long-term therapy in patients with severe persistent asthma who remain poorly controlled despite optimal medical management and pharmacotherapy. Alternate-day dosing with the lowest dose of oral corticosteroid that controls disease is recommended to minimize both short- and long-term side effects.
TABLE 30.3 CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN CHILDREN 5-11 YEARS OF AGE
Assessing severity and initiating therapy in children who are not currently taking long-term control medication
Classification of Asthma Severity (5-11 years of age)
Persistent
Components of Severity
Intermittent
Mild
Moderate
Severe
Impairment
Symptoms
≦2 days/week
>2 days/week but not daily
Daily
Throughout the day
Nighttime awakenings
≦2×/month
3-4×/month
>1×/week but not nightly
Often 7×/week
Short-acting beta2-agonist use for symptom control (not prevention of EIB)
≦2 days/week
>2 days/week but not daily
Daily
Several times per day
Interference with normal activity
None
Minor limitation
Some limitation
Extremely limited
Lung function
Normal FEV1 between exacerbations
FEV1 >80% predicted
FEV1/FVC >85%
FEV1 = >80% predicted
FEV1/FVC >80%
FEV1 = >60-80% predicted
FEV1/FVC = 75-80%
FEV1 <60% predicted
FEV1/FVC <75%
Risk
Exacerbations requiring oral
0-1/year (see note)
≧2/year (see note)
systematic corticosteroids
Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Therapy (See Table 30.9 for treatment steps.)
Step 1
Step 2
Step 3 medium-dose ICS option
Step 3, medium-dose ICS option, or step 4
and consider short course of oral systemic corticosteroids
In 2-6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly.
The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient needs.
Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of the previous 2-4 weeks and spirometry. Assign severity to the most severe category in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≧2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
The information in Table 30.3 is directly abstracted from the National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, National Heart, Lung, and Blood Institute. August 2007. NIH publication 08-4051.
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Consider severity and interval since last exacerbation. 
corticosteroids Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
Consider severity and interval since last exacerbation. 
Frequency and severity may fluctuate over time for patients in any severity category. Relative annual risk of exacerbations may be related to FEV1.
