Bronchiolitis

The most common cause is respiratory syncytial virus (RSV). One meta-analysis of studies examining respiratory viruses found in children under 2 years of age with bronchiolitis confirmed that RSV predominated (59.2%, 95% CI 54.7 to 63.6), while rhinovirus was second most common (19.3%, 95% CI 16.7 to 22.0). Human bocavirus accounted for 8.2% (95% CI 5.7 to 11.2), adenovirus was found in 6.1% (95% CI 4.4 to 8.0), human metapneumovirus occurred in 5.4% (95% CI 4.4 to 6.4), parainfluenza was detected in 5.4% (95% CI 3.8 to 7.3), influenza in 3.2% (95% CI 2.2 to 4.3), coronavirus in 2.9% (95% CI 2.0 to 4.0), and enterovirus in 2.9% (95% CI 1.6 to 4.5). In those babies with multiple viruses detected, RSV was most commonly found with rhinovirus or human bocavirus.[14][15]

Bronchiolitis caused by RSV and other respiratory viruses begins as an upper respiratory tract infection, which then spreads to the lower respiratory tract in 1 to 3 days.

RSV infection occurs in almost all infants by 3 years of age, but only a minority develop bronchiolitis. This observation has led to the hypothesis that host and possibly environmental factors play a role in disease pathogenesis.[16] Birth cohort studies have shown that diminished lung function at birth is a risk factor for wheezing in early infancy, but this mechanism cannot completely explain the variability of clinical manifestations of RSV infection.[17][18]

Environmental tobacco smoke exposure may contribute to disease severity.[19][20][21] Similarly, environmental pollutants are linked to more severe RSV disease. A time-series study from northwestern Italy reported an association between the concentration of 10-micron airborne particulate matter (PM10) with rates of RSV hospitalisation in infants under 1 year of age; PM10 concentrations in the 2 weeks preceding hospital admission were strongly associated with an increased risk of RSV hospitalisation.[22] The authors speculated that environmental factors such as air pollution could affect an infant's immune system and limit responses to viral illnesses.

Another area of focus has been the role of the host immune response in determining the effects of RSV infection.

The virus infects the respiratory epithelial cells of the small airways, leading to necrosis, inflammation, oedema, and mucus secretion. Neutrophils are the predominant inflammatory cells that invade the airways in severe respiratory syncytial virus (RSV) disease. The combination of cellular destruction and inflammation leads to obstruction of the small airways. The physiological and clinical results consist of hyperinflation, atelectasis, and wheezing. In severe cases, interstitial inflammation and alveolar infiltrates also develop. Re-growth of the epithelial cell layer does not occur until approximately 2 weeks after infection, with complete recovery requiring 4 to 8 weeks.

Early studies reported that RSV infection was associated with mediators typically produced by type-2 helper T cells (TH2 cells).[23][24][25][26] However, subsequent clinical studies have suggested that the severity of RSV infection and the likelihood of wheezing with any respiratory viral infection probably reflects alterations in the infant's innate and adaptive immune responses to infection.[27][28][29][30][31] Additionally, RSV may inhibit the lung antioxidant system and promote the development of reactive oxygen species, resulting in increased lung oxidative damage.[32]

Wheezing with non-RSV infections, such as rhinovirus, may reflect an early sign of asthma because these infants are more likely to have wheezing later in life.[9]

Clinical entities of bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis

Viral bronchiolitis caused by RSV

Non-RSV bronchiolitis

Viral bronchiolitis cases in which RSV has not been detected

Pathophysiology

Classification

Clinical entities of bronchiolitis