Heterogeneity of airway macrophage in different clinical phenotypes of COPD patients with frequent or infrequent exacerbations

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To compare the clinical features and the heterogeneity of macrophages in different clinical phenotypes of chronic obstructive pulmonary disease (COPD) patients with frequent or infrequent exacerbations. Methods: Clinical characteristics of eighty COPD patients with chronic bronchitis (CB), emphysema (EM) or asthma-COPD overlap (ACO) phenotypes suffered from acute exacerbation were analyzed. The expressions of CCL3 and CD163 in sputum macrophages were detected by flow cytometry. The expressions of HIF-1α and Cav-1 in sputum macrophages were detected by quantitative PCR (qPCR). Results: The age, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), sputum bacteria positive rate, COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) score between the patients with FE and iFE were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower (P<0.01), while CD163 was significantly increased (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with CB phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P<0.05), while CD163 was significantly raised (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, duration of disease, FEV1/FVC, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with EM phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P>0.05), while CD163 was slightly raised (P>0.05). Meanwhile, HIF-1α levels were slightly elevated (P>0.05), while Cav-1 expression was significantly increased (P<0.01). There were no significant differences in all clinical features between FE and iFE patients with ACO phenotype. The fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower than that in iFE patients (P<0.01); there was no significant difference in CD163 (P>0.05). At the same time, the expression of HIF-1α (P<0.01) and Cav-1(P<0.05) also increased significantly. There was a significant negative correlation between CCL3 and HIF-1α or Cav-1 in all FE and FE patients with CB phenotype. CD163 was only positively correlated with HIF-1α in those patients and FE patients with EM phenotype. There was a significant negative correlation between CCL3 and HIF-1α in FE patients with ACO phenotype, while CD163 was significantly positively correlated with HIF-1α. Conclusion: The clinical features of FE or iFE patients with CB, EM or ACO phenotype are different, and M2 in induced sputum from FE patients are dominant. HIF-1α may play a key role in the polarization process.