Acute bronchiolitis is predominantly a viral disease. RSV is responsible for >50% of cases(Chapter 252). Other agents include parainfluenza (Chapter 251), adenovirus, and Mycoplasma. Emerging pathogens include human metapneumovirus (Chapter 253) and human bocavirus, which may be a primary cause of viral respiratory infection or occur as a co-infection with RSV. There is no evidence of a bacterial cause for bronchiolitis, although bacterial pneumonia is sometimes confused clinically with bronchiolitis, but bronchiolitis is rarely followed by bacterial superinfection. Concurrent infection with viral bronchiolitis and pertussis has been described.

Approximately 75,000-125,000 children <1 yr old are hospitalized annually in the United States due to RSV infection. Increasing rates of hospitalization might reflect increased attendance of infants in daycare centers, changes in criteria for hospital admission, and/or improved survival of premature infants and others at risk for severe RSV-associated disease.

Bronchiolitis is more common in boys, in those who have not been breast-fed, and in those who live in crowded conditions. Risk is higher for infants with young mothers or mothers who smoked during pregnancy. Older family members are a common source of infection; they might only experience minor upper respiratory symptoms (colds). The clinical manifestations of lower respiratory tract illness (LRTI) seen in young infants may be minimal in older patients, in whom bronchiolar edema is better tolerated.

Not all infected infants develop LRTI. Host anatomic and immunologic factors play a significant role in the severity of the clinical syndrome, as does the nature of the viral pathogen. Infants with pre-existent smaller airways and diminished lung function have a more-severe course. In addition, RSV infection incites a complex immune response. Eosinophils degranulate and release eosinophil cationic protein, which is cytotoxic to airway epithelium. Innate immunity plays a significant role and can depend on polymorphisms in toll-like receptor (TLR), interferon (IF), interleukins (IL), and nuclear factor κB (NFκB). Chemokines and cytokines such as tumor necrosis factor α (TNF-α) may be differentially expressed depending on the inciting virus. Co-infection with >1 virus can also alter the clinical manifestations and/or severity of presentation.

Acute bronchiolitis is characterized by bronchiolar obstruction with edema, mucus, and cellular debris. Even minor bronchiolar wall thickening significantly affects airflow because resistance is inversely proportional to the 4th power of the radius of the bronchiolar passage. Resistance in the small air passages is increased during both inspiration and exhalation, but because the radius of an airway is smaller during expiration, the resultant respiratory obstruction leads to early air trapping and overinflation. If obstruction becomes complete, trapped distal air will be resorbed and the child will develop atelectasis.

Hypoxemia is a consequence of ventilation-perfusion mismatch early in the course. With severe obstructive disease and tiring of respiratory effort, hypercapnia can develop.

Chronic infectious causes of wheezing should be considered in infants who seem to fall out of the range of a normal clinical course. Cystic fibrosis is one such entity; suspicion increases in a patient with persistent respiratory symptoms, digital clubbing, malabsorption, failure to thrive, electrolyte abnormalities, or a resistance to bronchodilator treatment(Chapter 395).

Allergy and asthma are important causes of wheezing and probably generate the most questions by the parents of a wheezing infant. Asthma is characterized by airway inflammation, bronchial hyperreactivity, and reversibility of obstruction(Chapter 138). Three identified patterns of infant wheezing are the transient early wheezer, the persistent wheezer, and the late-onset wheezer. Transient early wheezers constituted 19.9% of the general population, and they had wheezing at least once with a lower respiratory infection before the age of 3 yr but never wheezed again. The persistent wheezer constituted 13.7% of the general population, had wheezing episodes before age 3 yr, and were still wheezing at 6 yr of age. The late-onset wheezer constituted 15% of the general population, had no wheezing by 3 yr, but was wheezing by 6 yr. The other of the children had never wheezed by 6 yr. Of all the infants who wheezed before 3 yr old, almost 60% stopped wheezing by 6 yr.

Multiple studies have tried to predict which early wheezers will go on to have asthma in later life. Risk factors for persistent wheezing include parental history of asthma and allergies, maternal smoking, persistent rhinitis (apart from acute upper respiratory tract infections), eczema at <1 yr of age, and frequent episodes of wheezing during infancy.

Other Causes

Congenital malformations of the respiratory tract cause wheezing in early infancy. These findings can be diffuse or focal and can be from an external compression or an intrinsic abnormality. External vascular compression includes a vascular ring, in which the trachea and esophagus are surrounded completely by vascular structures, or a vascular sling, in which the trachea and esophagus are not completely encircled(Chapter 426). Cardiovascular causes of wheezing include dilated chambers of the heart including massive cardiomegaly, left atrial enlargement, and dilated pulmonary arteries. Pulmonary edema caused by heart failure can also cause wheezing by lymphatic and bronchial vessel engorgement that leads to obstruction and edema of the bronchioles and further obstruction (Chapter 436).

Foreign body aspiration (Chapter 379) can cause acute or chronic wheezing. It is estimated that 78% of those who die from foreign body aspiration are between 2 mo and 4 yr old. Even in young infants, a foreign body can be ingested if given to the infant by another person such as an older sibling. Infants who have atypical histories or misleading clinical and radiologic findings can receive a misdiagnosis of asthma or another obstructive disorder as inflammation and granulation develop around the foreign body. Esophageal foreign body can transmit pressure to the membranous trachea, causing compromise of the airway lumen.

Gastroesophageal reflux (Chapter 315.1) can cause wheezing with or without direct aspiration into the tracheobronchial tree. Without aspiration, the reflux is thought to trigger a vagal or neural reflex, causing increased airway resistance and airway reactivity. Aspiration from gastroesophageal reflux or from the direct aspiration from oral liquids can also cause wheezing.

Trauma and tumors are much rarer causes of wheezing in infants. Trauma of any type to the tracheobronchial tree can cause an obstruction to airflow. Accidental or nonaccidental aspirations, burns, or scalds of the tracheobronchial tree can cause inflammation of the airways and subsequent wheezing. Any space-occupying lesion either in the lung itself or extrinsic to the lung can cause tracheobronchial compression and obstruction to airflow.