The Well-Known Gene HHIP and Novel Gene MECR Are Implicated in Small Airway Obstruction

Small airway obstruction is an important phenotype of chronic obstructive pulmonary disease (COPD), which can be induced by a genetic predisposition and/or environmental factors, such as cigarette smoke and occupational exposures (1). Multiple genome-wide association studies have identified genes associated with COPD and predominantly large airway obstruction (FEV₁, FEV₁/FVC). So far, only one genome-wide association study was performed specifically on a spirometric measurement of small airway obstruction. Variants in, among others, IL6R, NID2, and SYT10 were associated with forced expiratory flow at 25–75% of forced vital capacity (FEF_25–75), analyzed as percentage predicted, FEF_25–75%predicted/FVC, or change over time (2). In addition, we previously showed that occupational exposures affect small airway obstruction, even independent of large airway obstruction (3). Therefore, we hypothesized that specific genes may underlie small airway obstruction, also independent of large airway obstruction or cigarette smoke exposure.