Cyclophilin D Contributes to Airway Epithelial Mitochondrial Damage in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Airway epithelial mitochondrial injury is an important pathogenesis of chronic obstructive pulmonary disease (COPD). Cyclophilin D (CypD) is a component of mitochondrial permeability transition pore and related to mitochondrial damage. However, the role of CypD in airway epithelial mitochondrial injury and COPD pathogenesis remains unclear. METHODS: CypD expression in human airway epithelium was determined by immunohistochemistry, and mitochondrial structure of airway epithelial cell was observed under the transmission electron microscopy. The expression of CypD signaling pathway in cigarette smoke extract (CSE)-treated airway epithelial cells was measured by real-time PCR and Western-blot. CSE-induced damage of airway epithelial cell and mitochondria was further studied. RESULTS: Immunohistochemistry and transmission electron microscopy analysis revealed that CypD expression in airway epithelium was significantly increased associated with notable airway epithelial mitochondrial structure damage in the patients with COPD. The mRNA and protein expression of CypD was significantly increased in concentration- and time-dependent manners when airway epithelial cells were treated with CSE. CypD siRNA pretreatment significantly suppressed the increases of CypD and Bax expression, and reduced the decline of Bcl-2 expression in 7.5% CSE-treated airway epithelial cells. Furthermore, CypD silencing significantly attenuated mitochondrial damage and cell apoptosis, and increased cell viability when airway epithelial cells were stimulated with 7.5% CSE. CONCLUSION: These data suggest that CypD signaling pathway is involved in the pathogenesis of COPD and provide a potential therapeutic target for COPD.

FVC/DLCO identifies pulmonary hypertension and predicts 5-year all-cause mortality in patients with COPD.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). However, it is unknown whether the ratio of forced vital capacity (FVC) to diffusing lung capacity for carbon monoxide (DLCO) can identify PH in the patients with COPD and predict its prognosis. METHODS: The study population I included 937 COPD patients who were admitted to inpatient treatments from 2010 to 2017, and finally 750 patients were available to follow-up the 5-year all-cause mortality (study population II). Clinical characteristics of the study population were recorded. RESULTS: COPD patients with PH had a higher FVC/DLCO value compared with the patients without PH. The threshold for FVC/DLCO to identify PH in COPD patients was 0.44 l/mmol/min/kPa. Multivariate logistic regression analysis showed that FVC/DLCO was a significant predictor for PH in the patients with COPD. The study population II showed that the 5-year all-cause mortality of COPD patients was significantly higher in combined with PH group than without PH group. Compared with the survivor group, FVC/DLCO value was significantly increased in non-survivor group. The threshold for FVC/DLCO to predict 5-year all-cause mortality was 0.41 l/mmol/min/kPa. Kaplan-Meier survival curves showed that 5-year cumulative survival rate for COPD patients were significantly decreased when the value of FVC/DLCO was ≥ 0.41 l/mmol/min/kPa. Multivariate cox regression analysis showed that FVC/DLCO was an independent prognostic factor for 5-year all-cause mortality in COPD patients. CONCLUSION: FVC/DLCO could identify PH in the patients with COPD and was an independent predictor for 5-year all-cause mortality of COPD.