Is Childhood Pneumonia Associated With Future Disease Susceptibility? An Investigation Into the Early Origins of Chronic Obstructive Pulmonary Disease

Abstract

BACKGROUND Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for COPD in adult smokers and that genome wide analysis studies (GWAS) will identify genetic loci associated with development of pneumonia.

METHODS Smokers between 45–80 years old from the US COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Childhood and lifetime pneumonia GWAS were performed separately in non-Hispanic whites (NHW) and African Americans (AA) and the results combined in meta-analysis.

RESULTS Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95%CI 1.17-1.66), decreased lung function, and increased airway wall thickness on CT, without significant difference in emphysema.

Case-control GWAS meta-analysis of childhood pneumonia identified variants of interest in NGR1 (p=6.32E-08) and PAK6 (p=3.277E-07). Meta-analysis of GWAS results in the lifetime pneumonia group identified variants of interest in PRR27 (p=4.341E-07) and near MCPH (p=2.705E-07).

CONCLUSIONS Children with pneumonia are at increased risk for future smoking-related respiratory disease including COPD and decreased lung function. The variability in prevalence of childhood pneumonia and the association with increased risk for future disease suggest an underlying genetic susceptibility. We have identified potential genes associated with risk of pneumonia. Further research will be required to determine whether these genes confer risk for childhood pneumonia, lifetime pneumonia and COPD.