Table 229.1 lists the infectious agents that have been associated with the clinical entity of bronchiolitis. Viruses, particularly respiratory syncytial virus (RSV), account for most of the pathogens isolated during clinical disease. In reviews of bronchiolitis-associated outpatient and hospital morbidity in Native American and Alaskan Native children, RSV was associated with between 50% and 80% of all cases of bronchiolitis. RSV infection is estimated to be a very common childhood event in all pediatric populations, affecting almost 60% of infants during the first year of life, and it is responsible for over 100,000 hospitalizations annually. The onset of illness varies across the United States, but typically begins in October through December and ends in March to May.

Human metapneumovirus, a paramyxovirus first identified in 2001, has been identified increasingly as being responsible for acute lower tract respiratory infections, including bronchiolitis in all age groups, and severe clinical outcome in very young and/or immunocompromised children. In a retrospective study of over 2,000 healthy U.S. infants followed from 1976 through 2001, human metapneumovirus was identified in 12% of all lower respiratory illnesses and 59% of patients diagnosed with bronchiolitis. In this study, peak viral isolation occurred from December through April. A more recent evaluation of 1,500 Italian infants, children, and their families identified co-isolation of RSV or influenza virus in more than 16% of acute respiratory infections caused by human metapneumovirus.

Influenza viruses cause significant respiratory disease during the winter months, with an attributed 50,000 deaths each year in the United States (1990–1999). Death from influenza is not common in infants. Modeling data estimate about 92 deaths in U.S. children younger than 5 years of age occurred during the 1990s. Estimates for influenza-related hospitalizations were 114,000 per year in the United States during the 1990s. In a Canadian cohort of 182 infants hospitalized for influenza from 1999 through 2002, 27% were admitted with a diagnosis of LRTIs (not bronchiolitis) and 15% with asthma/bronchiolitis diagnoses.

Other viral agents (adenovirus, parainfluenza, mumps) have been reported in the literature in association with bronchiolitis. Seasonal patterns of isolation overlap for many of the listed viral agents (Table 229.1). Adenovirus isolation is unique, when compared with the other listed viral agents, in its more marked nasopharyngeal isolation during non-winter months. Like metapnuemovirus, adenovirus isolation may occur year round. Although Mycoplasma pneumoniae has been associated with lower respiratory tract disease and episodes of wheezing occasionally in infants and more commonly in older children, no bacterial agents have been implicated as inciting the wheezing.

The sites of inflammation in bronchiolitis are the small bronchi and bronchioles; the alveolar spaces are spared. Pathologic changes include necrosis and sloughing of respiratory epithelium, with destruction of ciliated cells, lymphocytic infiltration of epithelium, and intrabronchiolar plugs of fibrin and mucus
and edema causing either complete or partial obstruction. Usually, 1 to 2 weeks are required before the respiratory epithelium is restored completely.

Airway obstruction from fibrinous debris and mucus plugs, combined with the abnormal mechanics of respiration in bronchiolitis, increases substantially the work of breathing for affected infants and also leads to mismatching of pulmonary ventilation and perfusion. Not surprising, arterial hypoxemia can be documented frequently during clinical disease. A retention of carbon dioxide is not a common problem, but, when it is present, it can result in acute respiratory acidosis and the need for prompt ventilatory assistance. Blood pH level abnormalities can be documented and may reflect contraction alkalosis related to the dehydration associated with poor oral intake and the contraction of extracellular spaces.

An investigation of immunologic responses at the site of injury after viral infection and bronchiolitis have occurred has led to speculation regarding the long-term complications and sequelae of bouts of bronchiolitis, including subsequent reactive airway disease. For most children, no such clinical correlation can be documented. However, in subpopulations of infants with elevated serum IgE levels and likely genetic predisposition to atopic disease, early onset of wheezing with bronchiolitis has been associated with documented pulmonary function changes consistent with asthma in their early school years.

Traditionally, inflammatory responses after viral infection are thought to be cell-mediated, with lymphocytic infiltration followed by the recruitment of macrophages to clear debris. In children with RSV-associated bronchiolitis, an evaluation of nasal and bronchial washings shows that the normal immune cytokine response is aberrant, with a shift towards a T helper cell type 2 (Th2) inflammatory response and poor or absent Th1 cytotoxic response. This shift in cytokine response likely is responsible for ineffective viral clearance and the production of proinflammatory cytokines that result in a continued inflammatory response. Therapeutic and/or preventive intervention for bronchiolitis will be defined better as more information on the immune response of bronchiolitis-associated pathogens and host response is determined.

Most often, bronchiolitis affects children between ages 2 and 12 months. The clinical presentation of bronchiolitis is that of a lower respiratory tract viral illness: fever [usually 38.3°C (101°F) or less], cough, dyspnea, and rhinitis. Hypoxia with cyanosis and increased work of breathing precipitates most hospitalizations for infants with bronchiolitis, but hypoxia frequently can be documented even without clinical evidence of desaturation (i.e., cyanosis or poor peripheral perfusion). On physical examination, tachypnea with chest retractions and wheezing with rhonchi are common findings, and mild conjunctivitis and otitis are not uncommon. Often, increased respiratory effort, fever, and cough lead to poor feeding and vomiting. Lethargy and dehydration often are observed.

Usually, radiographic abnormalities are nonspecific and may include air trapping, atelectasis, and peribronchial thickening and consolidation (Fig. 229.1). A diffuse interstitial infiltration pattern also has been reported, adding to the spectrum of chest radiographic abnormalities in this disease.

Children with significant cardiopulmonary disease or immunodeficiency are at much greater risk of having serious sequelae from bronchiolitis. Atelectasis, apnea, and respiratory failure are the most important acute complications of bronchiolitis. Immature ventilatory control and respiratory muscle fatigue lead to apnea and respiratory failure in the youngest patients with bronchiolitis. Once they are intubated and mechanically ventilated, infants with bronchiolitis are at risk for developing pneumothorax and pneumomediastinum. Intubated patients should be monitored for changes in the amount of tracheal secretions and for secondary fever, which may indicate superinfection and the need for antibiotic therapy. Infants with chronic lung disease and who have been weaned from oxygen therapy may require supplemental oxygen at the time of discharge from the hospital after a bout of bronchiolitis.