37 Bronchiolitis and Wheezing

Wheezing is a high-pitched musical sound produced by air flowing through narrowed airways. Wheezes are heard mostly during the expiratory phase. They are usually a sign of increased airway resistance resulting from obstruction in the intrathoracic airways. The predominance of wheezing during expiration is explained by the normal tendency of the intrathoracic airways to narrow when the intrapleural pressure exceeds intraluminal pressure during this phase of respiration. Narrowing of the intrathoracic airways is accentuated when the expiratory intrapleural pressure becomes positive during forced exhalation or in the setting of small airways obstruction. When obstruction occurs in the extrathoracic airways, it manifests with a distinct harsh inspiratory noise that is referred to as stridor.

Wheezing is heterophonous or polyphonic in nature when there is diffuse narrowing of the airways. This widespread involvement of the airways produces a mixture of sounds associated with various degrees of obstruction to airflow. Multiple varied degrees of obstruction typically occur in the presence of bronchospasm, edema, or intraluminal secretions. The most common causes of heterophonous wheezing in the pediatric population are viral bronchiolitis and asthma (see Chapter 38). Conversely, homophonous wheezing refers to a single set of pitches that originates in the larger airways but that can be transmitted widely. Common causes of homophonous wheezing include tracheomalacia, bronchomalacia, foreign body aspiration, and anatomic compression of the airways (Figure 37-1).

Figure 37-1 Homophonous and heterophonous wheezing.

Etiology and Pathogenesis

The majority of wheezing in infants is caused by viral bronchiolitis or asthma, but many other entities can also cause wheezing at this age (Box 37-1).

Box 37-1 Differential Diagnosis of Wheezing in Infants and Young Children

I Infection

• Respiratory syncytial virus

• Human metapneumovirus

• Parainfluenza virus 3

• Parainfluenza virus 1

• Parainfluenza virus 2

• Adenovirus

• Influenza virus (A or B)

• Rhinovirus

• Mycoplasma pneumoniae

• Bacterial bronchitis (e.g., Haemophilus influenzae, Moraxella catarrhalis)

II Asthma

III Aspiration Syndromes

• Gastroesophageal reflux

• Swallowing dysfunction

• Tracheoesophageal fistula or laryngeal cleft

IV Mucociliary Clearance Disorders

• Cystic fibrosis

• Primary ciliary dyskinesia

V Anatomic Abnormalities

• Tracheomalacia or bronchomalacia

• Vascular ring or sling

• Compressing lymphadenopathy or tumor

• Airway hemangioma

• Cystic adenomatoid malformation

• Bronchial or lung cyst

• Congenital lobar emphysema

• Pulmonary sequestration

• Foreign body aspiration

VI Immunodeficiency

• HIV infection

• Congenital cellular or humoral immunodeficiency

VII Other Causes

• Interstitial lung disease (e.g., surfactant protein C deficiency)

• Bronchiolitis obliterans

• Pulmonary edema

• Toxic inhalation

Bronchiolitis

Bronchiolitis commonly refers to an acute episode of obstructive lower airway disease caused by a viral infection in infants younger than 24 months of age. The peak incidence of severe disease occurs between 2 and 6 months of age. Approximately 1% of infants in the first 12 months of life are hospitalized with bronchiolitis, accounting for more than 125,000 annual hospitalizations in the United States. Hospitalization rates are five times higher in high-risk groups, including premature infants with bronchopulmonary dysplasia and patients with congenital heart disease.

The infectious cause of acute bronchiolitis typically includes viruses with specific tropism for bronchiolar epithelium. Respiratory syncytial virus (RSV) is responsible for more than 50% of cases, but other viruses are increasingly recognized as causes of this clinical entity. Viral infection of the lower airways can induce severe changes in the epithelial cell and mucosal surfaces of the human respiratory tract. Bronchiolar epithelial cell necrosis, ciliary disruption, and peribronchiolar lymphocytic infiltration are the earliest lesions. Edema of the small airways and mucus secretion, mixed with denudated epithelial cells, elicits obstruction and narrowing of the airways (see Figure 37-2). The generation of atelectasis is often associated with ventilation/perfusion mismatch and consequent hypoxemia. Heterogeneous ventilation and dynamic collapse of the airways during exhalation can lead to air trapping and pulmonary hyperinflation (see Figure 37-2). With severe obstructive lung disease and respiratory muscle fatigue, hypercapnia can also arise.

Figure 37-2 Pathogenesis of bronchiolitis.

Many infants with RSV infection do not develop bronchiolitis. Approximately 60% to 70% of RSV-infected infants will have disease confined to the upper respiratory tract. The severity of the clinical syndrome is largely determined by host immunologic and anatomic factors. The presence of immunoglobulin G antibodies to the F (fusion) protein of RSV (whether transplacentally acquired or administered postnatally) attenuates the severity of the RSV infection. Conversely, premature infants are particularly prone to developing significant lower respiratory symptoms. The lungs of newborns with bronchopulmonary dysplasia have alveolar simplification and thus decreased small airways diameter because of lower elastic recoil. Because airflow resistance is inversely related to the radius of the airway to the fourth power, airflow in infants with bronchopulmonary dysplasia can be compromised with minimal changes in the bronchiolar lumen. Bronchiolitis is also more common in boys, in those who have not been breastfed, and in those who live in crowded conditions.

Asthma

Asthma is another important cause of wheezing in infants and children (see Chapter 38). This clinical entity is characterized by recurrent episodes of airway obstruction that are at least partially reversible with bronchodilators. Another pathogenic feature of the disease is chronic inflammation of the airways. Whereas extensive bronchiolar epithelial cell necrosis and T-helper cell type 1 (Th1) cytokines like interferon-γ are present in viral bronchiolitis, inflammation in asthma is often driven by allergic (Th2) cytokines such as interleukin-13 (IL-13), IL-4, and IL-5. Other abnormalities of the asthmatic airway include constriction and hypertrophy of the airway smooth muscle, mucosal edema, hypertrophic mucous glands, and sometimes eosinophilic infiltration.

Viral infections are the most common causes of exacerbations in infantile asthma. As opposed to bronchiolitis, lower respiratory symptoms in asthma tend to recur during exposure to other triggers, such as exercise, allergens, or cold air. Depending on the clinical course of their wheezing, infants may be early transient wheezers with at least one episode before the age of 3 years but complete resolution by school age; persistent wheezers with episodes before 3 years that are still present at 6 years of age; or late-onset wheezers with no history of wheezing by 3 years but with wheezing by 6 years. Approximately 60% of infants who wheeze will outgrow wheezing by 6 years of age. Risk factors for persistent wheezing include a maternal history of asthma, maternal smoking, elevated immunoglobulin E (IgE) level, and eczema at younger than 1 year of age. In addition, early respiratory viral infections, particularly RSV and rhinovirus, are associated with the presence of subsequent recurrent wheezing and asthma.

Whether bronchiolitis modifies the immune response or airway biology to evoke asthma later in life is still unclear. Experimental studies primarily based on animal models have reported that early RSV infection can upregulate neurokinin-mediated neurogenic inflammation, potentially leading to airway hyperreactivity. Other proasthmatic mechanisms postulated include a viral-induced bias of the host toward allergic Th2 immune responses during early infancy and the production of virus-specific IgE antibodies. Notwithstanding these hypotheses, infants with bronchiolitis may be a select group of patients with an inherent predisposition to asthma that is simply unmasked by an episode of viral respiratory infection. The relationship between early respiratory viral infections and subsequent wheezing and asthma remains a topic of intense investigation and controversy.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Join