Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis

Introduction Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Methods Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n = 1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n = 15,174; replication population). Results In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p = 0.003), mucoid P. aeruginosa for 31% (p = 0.001), and MRSA for 13% (p = 0.023). The same three pathogens mediated association in the replication population (7%, p < 0.001; 7%, p = 0.002; and 4%, (p = 0.002), respectively). Conclusions Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures.