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Background::Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with “emphysema phenotype.” The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.Methods::Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. n In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n n = 10 for each group). We also evaluated airway IgA from rats.n Results::Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15±1.53 n vs. 6.03±0.85; 1.94±0.66 n vs. 1.67±0.04; 41.69±21.02 n vs. 28.44±9.45, all n P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89±24.81 n vs. 31.49±9.28, n P=0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (n r=0.45, n P=0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, n P>0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, alln P < 0.01) were only observed between control rats and those exposed for 30 days. However, in the group exposed for 15 days, although the VV airway was higher than that in normal rats (27.61±2.26 n vs. 20.39±1.99, n P0.05).n Conclusion::Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with “emphysema phenotype” preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.