Pneumonia in Infancy and Risk for Asthma: The Role of Familial Confounding and Pneumococcal Vaccination

Abstract

Background: Studies have reported an increased risk for asthma following lower respiratory tract infections, but few studies have specifically assessed this risk in children diagnosed with pneumonia in infancy. Furthermore, it is not fully understood whether this association is indicative of a causal relationship or if certain children have a predisposition for both diseases.

Research question: Are children diagnosed with pneumonia in infancy at increased risk for asthma, and what is the role of familial confounding and pneumococcal conjugate vaccine immunization on the association?

Study design and methods: This study was a nationwide register-based cohort analysis of > 900,000 Swedish children to assess the association between pneumonia in infancy and prevalent asthma at 4 years. A secondary aim was to assess if the association has changed after the introduction of nationwide pneumococcal conjugate vaccine (PCV) immunization as this has led to a shift in pneumonia etiology. The study controlled for important confounders, including shared environmental and familial confounding, by using sibling analyses.

Results: There was a strong association between pneumonia diagnosis in infancy and prevalent asthma at 4 years (adjusted OR, 3.38; 95% CI, 3.26-3.51), as well as in the full sibling analyses (adjusted OR, 2.81; 95% CI, 2.58-3.06). The risk for asthma following pneumonia diagnosis in infancy was slightly higher for those born in the PCV period compared with the pre-PCV period (adjusted OR, 3.80 [95% CI, 3.41-4.24] vs 3.28 [95% CI, 3.15-3.42]) when the proportion of viral pneumonia etiology was also higher (14.5% vs 10.7%, respectively) and the overall asthma prevalence was lower (5.3% vs 6.6%).

Interpretation: Children diagnosed with pneumonia in infancy have a highly increased risk for prevalent asthma at 4 years, which might have implications for future asthma preventive measures and needs to be considered when assessing the morbidity that can be attributed to pneumonia.

Keywords: asthma; children; epidemiology; family design; pneumonia.

Graphical abstract

Figure 1

A-B, Timeline and overview of data sources. A, Overview of study cohorts and registers used. In the full cohort (children born between July 2001 and December 2010), data from SPDR were available for all children from the age of 4 years, whereas the restricted cohort used in the sensitivity analysis was limited to children with complete data from all registers for the whole study period (children born between July 2005 and December 2008). B, Overview of PCV immunization according to county. For each county, the study period was classified as occurring in the pre-PCV (the period preceding 3 months prior to the introduction date), washout (3 months prior to until 9 months following the introduction date) and PCV period (9 months following the introduction date until end of the study period). LISA = Longitudinal Integration Database for Labour Market Studies; MBR = Medical Birth Register; NPR = National Patient Register; PCV = pneumococcal conjugate vaccine; SPDR = Swedish Prescribed Drug Register.

Figure 2

Flowchart and overview of the different cohorts used in the study.

Figure 3

Association between pneumonia in infancy and prevalent asthma at 4 years. Point estimates expressed as ORs and 95% CIs assessed in the full cohort as well as in sibling and half-sibling analyses. ^aAdjusted for sex, prematurity, cesarean section, small for gestational age, maternal smoking during pregnancy, parity, educational level of parents, birth country of parents, and parental asthma. ^bAdjusted for sex, prematurity, cesarean section, and small for gestational age.