Notably, COL9A2 , a chondrogenic cough-associated gene, showed a trend toward downregulation across both comparisons (log 2 FC = −0.65, P = 0.0456; log 2 FC = −0.69, P = 0.0175), suggesting a potential role in structural changes to the extracellular matrix contributing to chronic cough through altered airway mechanics or fibrosis.
In particular, when we compared LC only versus LC-ILD, the gene HCAR3 , which encodes a G-protein–coupled receptor involved in regulation of energy metabolism and fatty acid oxidation ( 9 ), crossed significance thresholds, whereas other genes trended close to significance, suggesting that a larger sample size may increase power to detect additional specific expression differences (Figure E1C and Excel file 8).