Lung Function and Gene Expression of Pathogen Recognition Pathway Receptors: the Cardia Lung Study

Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV₁), Forced Vital Capacity (FVC) and FEV₁/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study. Spirometry testing was used to measure lung function and gene expression levels were measured using the Nanostring platform. Multivariate linear regression models were used to study the association between lung function measured at year 30, 10-year decline from year 20 to year 30, and gene expression levels (highest quartile divided into two levels – 75th to 95th and>95th to 100th percentile) adjusting for center, smoking and BMI, measured at year 25. Year 30 FEV₁ and FVC were lower in the highest level of TLR5 compared to the lowest quartile with difference of 4.00% (p for trend: 0.04) and 3.90% (p for trend: 0.05), respectively. The 10-year decline of FEV₁ was faster in the highest level of CCR1 as compared to the lowest quartile with a difference of 1.69% (p for trend: 0.01). There was no association between gene expression and FEV₁/FVC. Higher gene expression levels in TLR5 and CCR1 are associated with lower lung function and faster decline in FEV₁ over 10 years, in a threshold manner, providing new insights into the role of inflammation in lung function.