Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients

BACKGROUND: T helper (Th) cell cytokine imbalances have been associated with the pathophysiology of chronic obstructive pulmonary disease (COPD), including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Clarifying cytokine profiles during COPD acute exacerbation (AE) and their relationships with clinical manifestations would help in understanding the pathogenesis of disease and improve clinical management. MATERIALS AND METHODS: Eighty seven patients admitted to the hospital with AEs of COPD were included in this study, and follow-up was conducted after discharge (every 30 days, for a total of 120 days). Sputum samples of patients at different time points (including at admission, discharge, and follow-up) were collected, and sputum cytokine profiling (12 cytokines in total) was performed using a Luminex assay. RESULTS: According to the cytokine profiles at admission, patients were divided into three clusters by a k-means clustering algorithm, namely, Th1(high) Th17(high) (n=26), Th1(low)Th17(low) (n=56), and Th1(high) Th17(low) (n=5), which revealed distinct clinical characteristics. Patients with Th1(high) Th17(low) profile had a significantly longer length of non-invasive ventilation time and length of hospital stay than patients with Th1(high) Th17(high) profile (7 vs 0 days, 22 vs 11 days, respectively, p < 0.05), and had the highest AE frequency. Sputum levels of Th17 cytokines (IL-17A, IL-22, and IL-23) during AE were negatively correlated with AE frequency in the last 12 months (r = −0.258, −0.289 and −0.216, respectively, p < 0.05). Moreover, decreased sputum IL-17A levels were independently associated with increased AE frequency, with an OR (95% CI) of 0.975 (0.958–0.993) and p = 0.006. CONCLUSION: Th1/Th17 imbalance during AE is associated with the severity of COPD. Decreased Th17 cytokine expression is correlated with increased AE frequency. The Th1/Th17 balance may be a specific target for the therapeutic manipulation of COPD.