Etiology and Pathogenesis

Asthma is characterized by the presence of three airway components: inflammation, obstruction, and hyperresponsiveness. Chronic airway inflammation establishes baseline airway edema and obstruction, which sets the stage for acute exacerbations. During acute exacerbations, inciting triggers (Box 38-1) cause inflammation and bronchoconstriction of already hyperresponsive airways. Key cellular components involved in the pathogenesis of asthma include mast cells; eosinophils; and, to some degree, neutrophils, T cells, macrophages, and epithelial cells (Figures 38-1 and 38-2).

Figure 38-1 Steps in the pathogenesis of asthma.

Figure 38-2 Pathology of an acute asthma attack.

Although downstream symptoms are relatively uniform (e.g., respiratory distress, wheezing), upstream predisposing factors are broader in their scope. Asthma is likely the result of interplay among environmental and genetic causes. Environmental factors, such as respiratory pathogens, allergens, and pollutants, can cause airway inflammation and irritation, immune system dysregulation, or both, leading to the development of asthma. Environmental factors can also worsen existing disease. Genetic factors, such as a family history of atopic disease or an altered cytokine profile, can also result in abnormal modulation of the immune system and predispose a patient to developing asthma. For example, a T-helper cell type 2 (Th2)–cytokine profile likely correlates with the development of asthma and allergy. Currently, the genetics of asthma remain complex and multifactorial in nature; in the future, the genetic identification of particular genotypes and phenotypes may allow for the categorization of asthma into distinct subtypes that will aid in tailoring treatment plans.

Clinical Presentation

When providing a patient history, parents of a child with asthma often recall symptoms secondary to episodic airway obstruction. The most common reported symptom is persistent cough, which frequently is the only symptom, and may occur more often while the child is asleep. Nighttime cough caused by asthma, which occurs several hours into sleep, must be differentiated from cough caused by gastroesophageal reflux (GER) or postnasal drip, which occurs soon after a child is recumbent.

Although wheezing is a hallmark symptom of asthma, parents rarely report hearing an audible wheeze. Other symptoms a parent may recall include shortness of breath, chest pain, exercise intolerance, and variable degrees of respiratory distress. Subacute presentations of any of these symptoms, including the presence of chronic cough, are much more commonly encountered than life-threatening episodes of airway obstruction.

A patient or family history of allergy and atopic skin disease may be present. It is important to inquire about the setting(s) in which symptoms occur because a variety of inciting triggers exist (Box 38-1 and Figure 38-3). A patient should also be assessed for comorbid medical conditions, including GER, allergic rhinitis, sinusitis, and obesity, all of which can exacerbate asthma symptoms. For a patient with a previous asthma diagnosis, it is useful to inquire about the frequency of ED visits and hospital admissions, oral steroid use, and any history of severe complications (e.g., endotracheal intubation or admission to the intensive care unit [ICU]).

Figure 38-3 Asthma triggers.

The physical examination of a patient with well-controlled asthma is generally unrevealing. The physical examination of a patient with asthma during an acute exacerbation will most frequently demonstrate heterophonous wheezing (inspiratory, or expiratory, or both). To properly assess for the presence of wheezing, adequate airflow is required; it may be necessary to “squeeze the wheeze” and compress the chest wall to ensure forced exhalation or to ask an older child to exhale forcefully with the mouth wide open. Heterophonous or polyphonic wheezing results from turbulent air flow through multiple obstructed small airways; the different “musical” pitches are a consequence of varying degrees of obstruction. Heterophonous wheezing should be differentiated from homophonous or monophonic wheezing, which typically occurs with obstruction of larger airways.

Additionally, a symptomatic patient with asthma is frequently short of breath and tachypneic. The patient may also have other signs of airway obstruction, including decreased air entry, prolongation of the expiratory : inspiratory ratio, and hyperexpansion of the chest (a widened anteroposterior diameter). Nasal flaring and the use of accessory muscles (e.g., the sternocleidomastoid, intercostal, pectoralis major, and abdominal muscles) are also commonly observed.

Careful attention should be paid to the skin examination for signs of atopic disease, such as eczema or atopic dermatitis, and to the upper respiratory exam for signs of allergic rhinitis, including mucosal swelling, nasal polyps, and rhinorrhea. The presence of nasal polyps should trigger evaluation for cystic fibrosis. Digital clubbing is never a component of uncomplicated asthma and should prompt further evaluation.

Differential Diagnosis

If considering a diagnosis of asthma, the time-worn axiom must be remembered that “all that wheezes is not asthma.” Before a diagnosis of asthma can be confirmed, alternative diagnoses must be considered (Table 38-1). Furthermore, not all wheezes are equal. For example, monophonic wheezing associated with foreign body aspiration is distinct from polyphonic wheezing associated with asthma.

Table 38-1 Differential Diagnosis of Asthma in Children

Adapted from the Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. Washington, DC, U.S. Department of Health and Human Resources, 2007, p 12. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.

Within the respiratory system, upper respiratory infections and allergic rhinitis are the most common causes of recurrent cough and wheezing. Other potential causes include foreign body aspiration, vocal cord dysfunction, tracheal or bronchial compression (by vessels, strictures, or masses), cystic fibrosis, and bronchopulmonary dysplasia (chronic lung disease of prematurity).

Nonrespiratory system causes should be excluded. Cardiac pathology—such as congenital heart disease, pulmonary edema, or vascular abnormalities compressing the respiratory tree—must be considered. GER; aspiration pneumonitis; and less frequently, tracheoesophageal fistula can all cause recurrent wheezing and so mimic asthma.