In stratified analyses of LHS-2, genotype at SNP rs111720447 was significantly associated with rate of FEV<sub>1</sub> decline in patients taking ICS (C allele β 56.36 mL·year<sup>-1</sup>, 95% CI 29.96-82.76 mL·year<sup>-1</sup>) and in patients who were assigned to placebo, although the relationship was weaker and in the opposite direction to that in the ICS group (C allele β -27.57 mL·year<sup>-1</sup>, 95% CI -53.27- -1.87 mL·year<sup>-1</sup>).The study uncovered genetic factors associated with FEV<sub>1</sub> changes related to ICS in COPD patients, which may provide new insight on the potential biology of steroid responsiveness in COPD.