A retrospective cohort study on infant respiratory tract infection hospitalizations and recurrent wheeze and asthma risk: impact of respiratory syncytial virus.

AIM Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections. METHODS We performed a retrospective cohort study using Danish national hospital discharge registers. Infants under 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, non-pathogen coded lower respiratory tract infections (LRTI), pertussis, or non-specific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5 minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF). RESULTS We included 68130 infants, of whom 20920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR: 2.69; 95% CI: 2.48-2.92), AURTI (1.48; 1.34-1.58), or pertussis (2.32; 1.85-2.91), similar to pneumonia and other respiratory pathogens (1.15; 0.99-1.34) and LRTI (0.79; 0.60-1.04), but lower than non-specific respiratory infections (0.79; 0.73-0.87).Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI: 2.08-2.70) for 0 to <1 year to 1.23 (0.88-1.73) for 6 to <10 years for term-born children, and from 1.48 (1.09-2.00) to 0.60 (0.25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors. CONCLUSIONS Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly in preschool age. If causal, RSV-prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma.