Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

Background Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Methods Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. Results A total of 8,345 participants had clinical and CT scanning data available. A 5% absolute increase in interstitial changes was associated with an absolute decrease in FVC % predicted of 2.47% (P <.001) and a 1.36-point higher St. George's Respiratory Questionnaire score (P <.001). Among the 6,827 participants with mortality data, a 5% increase in interstitial changes was associated with a 29% increased risk of death (P <.001). These associations were present in a subgroup without visually defined interstitial lung abnormalities, as well as in those with normal spirometric test results, and in those without chronic respiratory symptoms. In non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter polymorphism, there was a 0.64% (P <.001) absolute increase in the percentage of lung with interstitial changes. Conclusions Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures.