Considering previous studies have showed ILA was a risk factor for acute exacerbation and ultimately may affect COPD mortality, moreover, ILA was proved to be associated with an increased rate of dying from pulmonary fibrosis (2, 9, 23), ILA may represent a precursor of pulmonary fibrosis development in COPD patients. The gene discussed is TNFRSF9; the disease is pulmonary fibrosis.