Additionally, it was shown that airway β-defensin-1 levels were significantly elevated in the sputum of COPD patients (88) whereas secretory IgA (sIgA) levels were markedly reduced due to altered epithelial cell differentiation in the airways of COPD patients (89) Following exposure to cigarette smoke, pollutants, and microbes, alarmins such as TSLP, IL-33, and IL-25 are released from the epithelium. This evidence concerns the gene IL33 and chronic obstructive pulmonary disease.