Search

Introduction Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA. Methods Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities. Results Plasma survivin levels were lower in OSA in the evening (27.6 ± 89.9 vs. 108.3 ± 161.2 pg/ml, p < 0.01) and in the morning (17.4 ± 48.6 vs. 36.4 ± 69.2 pg/ml, p = 0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea-hypopnoea index (r = - 0.45) or oxygen desaturation index (r = - 0.40, both p < 0.01); however, when adjusting to BMI, these became insignificant (p > 0.05). Low plasma survivin concentrations were associated with high BMI (r = - 0.35), high CRP (r = - 0.31), low HDL cholesterol (r = 0.24) and high triglyceride levels (r = - 0.24, all p < 0.05). Conclusion Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail., Author(s): Laszlo Kunos [sup.1] , Peter Horvath [sup.1] , Adrian Kis [sup.1] , David Laszlo Tarnoki [sup.2] , Adam Domonkos Tarnoki [sup.2] , Zsofia Lazar [sup.1] , Andras Bikov [sup.1] [...]

The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an in vitro model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca 2+ -activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression of MUC5AC , TGF-β1 , and MMP-9 mRNAs was measured before and after losartan treatment. In vitro , CS exposure of HBECs caused a significant increase in mRNA expression of MUC5AC and TGF-β1 and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease in MUC5AC expression and mucus concentrations, partially by inhibiting TGF-β signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels of MUC5AC , TGF-β1 , and MMP-9 in the upper airways after 2 months of losartan treatment. Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases., Competing Interests: Conflict of interest: M.D. Kim reports grants from the National Institutes of Health (NIH), Cystic Fibrosis Foundation, Flight Attendant Medical Research Institute, and James and Esther King Florida Biomedical Research Program, during the conduct of the study. Conflict of interest: N. Baumlin reports grants from the NIH, Cystic Fibrosis Foundation, Flight Attendant Medical Research Institute, and James and Esther King Florida Biomedical Research Program, during the conduct of the study. Conflict of interest: J.S. Dennis has nothing to disclose. Conflict of interest: M. Yoshida has nothing to disclose. Conflict of interest: A. Kis has nothing to disclose. Conflict of interest: C. Aguiar has nothing to disclose. Conflict of interest: A. Schmid has nothing to disclose. Conflict of interest: E. Mendes reports grants from the Florida Department of Health during the conduct of the study and outside the submitted work. Conflict of interest: M. Salathe reports grants and personal fees for grant review from the NIH and the Flight Attendant Medical Research Institute; grants from the James and Esther King Florida Biomedical Research Program; grants, and personal fees for grant review and committee work from the Cystic Fibrosis Foundation; and grants from the COPD Foundation, all during the conduct of the study; and grants and personal fees from Arrowhead Pharmaceuticals outside the submitted work., (Copyright ©ERS 2021.)