Childhood Asthma

Etiology

Although the cause of childhood asthma has not been determined, a combination of environmental exposures and inherent biologic and genetic susceptibilities has been implicated ( Fig. 169.1 ). In the susceptible host, immune responses to common airways exposures (e.g., respiratory viruses, allergens, tobacco smoke, air pollutants) can stimulate prolonged, pathogenic inflammation and aberrant repair of injured airways tissues ( Fig. 169.2 ). Lung dysfunction (AHR, reduced airflow) and airway remodeling develop. These pathogenic processes in the growing lung during early life adversely affect airways growth and differentiation, leading to altered airways at mature ages. Once asthma has developed, ongoing inflammatory exposures appear to worsen it, driving disease persistence and increasing the risk of severe exacerbations.

Epidemiology

Asthma is a common chronic disease, causing considerable morbidity. In 2011, >10 million children (14% of U.S. children) had ever been diagnosed with asthma, with 70% of this group reporting current asthma. Male gender and living in poverty are demographic risk factors for having childhood asthma in the United States. About 15% of boys vs 13% of girls have had asthma; and 18% of all children living in poor families (income <$25,000/yr), vs 12% of children in families not classified as poor, have had asthma.

Childhood asthma is among the most common causes of childhood emergency department visits, hospitalizations, and missed school days. In the United States in 2006, childhood asthma accounted for 593,000 emergency department (ED) visits, 155,000 hospitalizations, and 167 deaths. A disparity in asthma outcomes links high rates of asthma hospitalization and death with poverty, ethnic minorities, and urban living. In the past 2 decades, black children have had 2-7 times more ED visits, hospitalizations, and deaths as a result of asthma than nonblack children. Although current asthma prevalence is higher in black than in nonblack U.S. children (in 2011, 16.5% vs 8.1% for white and 9.8% for Latino children), prevalence differences cannot fully account for this disparity in asthma outcomes.

Worldwide, childhood asthma appears to be increasing in prevalence, despite considerable improvements in our management and pharmacopeia to treat asthma. Although childhood asthma may have plateaued in the United States after 2008, numerous studies conducted in other countries have reported an increase in asthma prevalence of approximately 50% per decade. Globally, childhood asthma prevalence varies widely in different locales. A study of childhood asthma prevalence in 233 centers in 97 countries (International Study of Asthma and Allergies in Childhood, Phase 3) found a wide range in the prevalence of current wheeze in 6-7 yr (2.4–37.6%) and 13-14 yr old children (0.8–32.6%). Asthma prevalence correlated well with reported allergic rhinoconjunctivitis and atopic eczema prevalence. Childhood asthma seems more prevalent in modern metropolitan locales and more affluent nations, and is strongly linked with other allergic conditions. In contrast, children living in rural areas of developing countries and farming communities with domestic animals are less likely to experience asthma and allergy.

Approximately 80% of all asthmatic patients report disease onset prior to 6 yr of age. However, of all young children who experience recurrent wheezing, only a minority go on to have persistent asthma in later childhood. Early childhood risk factors for persistent asthma have been identified ( Table 169.1 ) and have been described as major (parent asthma, eczema, inhalant allergen sensitization) and minor (allergic rhinitis, wheezing apart from colds, ≥4% peripheral blood eosinophils, food allergen sensitization) risk factors. Allergy in young children with recurrent cough and/or wheeze is the strongest identifiable factor for the persistence of childhood asthma.

Pathogenesis

Airflow obstruction in asthma is the result of numerous pathologic processes. In the small airways, airflow is regulated by smooth muscle encircling the airway lumen; bronchoconstriction of these bronchiolar muscular bands restricts or blocks airflow. A cellular inflammatory infiltrate and exudates distinguished by eosinophils, but also including other inflammatory cell types (neutrophils, monocytes, lymphocytes, mast cells, basophils), can fill and obstruct the airways and induce epithelial damage and desquamation into the airways lumen. Helper T lymphocytes and other immune cells that produce proallergic, proinflammatory cytokines (interleukin [IL]-4, IL-5, IL-13), and chemokines (eotaxins) mediate this inflammatory process (see Fig. 169.2 ). Pathogenic immune responses and inflammation may also result from a breach in normal immune regulatory processes (e.g., regulatory T lymphocytes that produce IL-10 and transforming growth factor-β) that dampen effector immunity and inflammation when they are no longer needed. Hypersensitivity or susceptibility to a variety of provocative exposures or triggers ( Table 169.3 ) can lead to airways inflammation, AHR, edema, basement membrane thickening, subepithelial collagen deposition, smooth muscle and mucous gland hypertrophy, and mucus hypersecretion—all processes that contribute to airflow obstruction.

Clinical Manifestations and Diagnosis

Intermittent dry coughing and expiratory wheezing are the most common chronic symptoms of asthma. Older children and adults report associated shortness of breath and chest congestion and tightness; younger children are more likely to report intermittent, nonfocal chest pain. Respiratory symptoms can be worse at night, associated with sleep, especially during prolonged exacerbations triggered by respiratory infections or inhalant allergens. Daytime symptoms, often linked with physical activities (exercise-induced) or play, are reported with greatest frequency in children. Other asthma symptoms in children can be subtle and nonspecific, including self-imposed limitation of physical activities, general fatigue (possibly resulting from sleep disturbance), and difficulty keeping up with peers in physical activities. Asking about previous experience with asthma medications (bronchodilators) may provide a history of symptomatic improvement with treatment that supports the diagnosis of asthma. Lack of improvement with bronchodilator and corticosteroid therapy is inconsistent with underlying asthma and should prompt more vigorous consideration of asthma-masquerading conditions.

Asthma symptoms can be triggered by numerous common events or exposures: physical exertion and hyperventilation (laughing), cold or dry air, and airways irritants (see Table 169.3 ). Exposures that induce airways inflammation, such as infections with common respiratory pathogens (rhinovirus, RSV, metapneumovirus, parainfluenza virus, influenza virus, adenovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae ) , and inhaled allergens in sensitized children, also increase AHR to dry, cold air and irritant exposures. An environmental history is essential for optimal asthma management.

The presence of risk factors, such as a history of other allergic conditions (allergic rhinitis, allergic conjunctivitis, atopic dermatitis, food allergies), parental asthma, and/or symptoms apart from colds, supports the diagnosis of asthma. During routine clinic visits, children with asthma typically present without abnormal signs, emphasizing the importance of the medical history in diagnosing asthma. Some may exhibit a dry, persistent cough. The chest findings are often normal. Deeper breaths can sometimes elicit otherwise undetectable wheezing. In clinic, quick resolution (within 10 min) or convincing improvement in symptoms and signs of asthma with administration of an inhaled short-acting β-agonist ( SABA ; e.g., albuterol) is supportive of the diagnosis of asthma.

Asthma exacerbations can be classified by their severity based on symptoms, signs, and functional impairment ( Table 169.4 ). Expiratory wheezing and a prolonged exhalation phase can usually be appreciated by auscultation. Decreased breath sounds in some of the lung fields, commonly the right lower posterior lung field, are consistent with regional hypoventilation caused by airways obstruction. Rhonchi and crackles (or rales ) can sometimes be heard, resulting from excess mucus production and inflammatory exudate in the airways. The combination of segmental crackles and poor breath sounds can indicate lung segmental atelectasis that is difficult to distinguish from bronchial pneumonia and can complicate acute asthma management. In severe exacerbations the greater extent of airways obstruction causes labored breathing and respiratory distress, which manifests as inspiratory and expiratory wheezing, increased prolongation of exhalation, poor air entry, suprasternal and intercostal retractions, nasal flaring, and accessory respiratory muscle use. In extremis, airflow may be so limited that wheezing cannot be heard ( silent chest ).

Differential Diagnosis

Many childhood respiratory conditions can present with symptoms and signs similar to those of asthma ( Table 169.5 ). Besides asthma, other common causes of chronic, intermittent coughing include gastroesophageal reflux (GER) and rhinosinusitis. Both GER and chronic sinusitis can be challenging to diagnose in children. Often, GER is clinically silent in children, and children with chronic sinusitis do not report sinusitis-specific symptoms, such as localized sinus pressure and tenderness. In addition, both GER and rhinosinusitis are often comorbid with childhood asthma and, if not specifically treated, may make asthma difficult to manage.

In early life, chronic coughing and wheezing can indicate recurrent aspiration, tracheobronchomalacia (congenital anatomic abnormality of airways), foreign body aspiration, cystic fibrosis, or bronchopulmonary dysplasia.

In older children and adolescents, vocal cord dysfunction (VCD) can manifest as intermittent daytime wheezing. The vocal cords involuntarily close inappropriately during inspiration and sometimes exhalation, producing shortness of breath, coughing, throat tightness, and often audible laryngeal wheezing and/or stridor. In most cases of VCD, spirometric lung function testing reveals truncated and inconsistent inspiratory and expiratory flow-volume loops, a pattern that differs from the reproducible pattern of airflow limitation in asthma that improves with bronchodilators. VCD can coexist with asthma. Hypercarbia and severe hypoxia are uncommon in VCD. Flexible rhinolaryngoscopy in the patient with symptomatic VCD can reveal paradoxical vocal cord movements with anatomically normal vocal cords. Prior to the diagnosis, patients with VCD are often treated unsuccessfully with multiple different classes of asthma medications. This condition can be well managed with specialized speech therapy training in the relaxation and control of vocal cord movement. Furthermore, treatment of underlying causes of vocal cord irritability (e.g., high GER/aspiration, allergic rhinitis, rhinosinusitis, asthma) can improve VCD. During acute VCD exacerbations, relaxation breathing techniques in conjunction with inhalation of heliox (a mixture of 70% helium and 30% oxygen) can relieve vocal cord spasm and VCD symptoms.

In some locales, hypersensitivity pneumonitis (farming communities, homes of bird owners), pulmonary parasitic infestations (rural areas of developing countries), or tuberculosis may be common causes of chronic coughing and/or wheezing. Rare mimics of asthma in childhood are noted in Table 169.5 . Chronic pulmonary diseases often produce clubbing, but clubbing is a very unusual finding in childhood asthma.

Laboratory Findings

Lung function tests can help to confirm the diagnosis of asthma and to determine disease severity.