Management of Cough in Patients with Chronic Obstructive Pulmonary Disease: Results of the Multicenter Randomized Placebo-Controlled Clinical Trial.

BACKGROUND: Chronic cough declines quality of life and increases risk of complications in patients with chronic obstructive pulmonary disease (COPD). Reducing cough severity and associated negative effects is important therapeutic goal in COPD. Rengalin with anti- and protussive activity is based on technologically processed antibodies to bradykinin, histamine and morphine. AIM: To evaluate efficacy and safety of Rengalin in treatment of cough in patients with COPD. METHODS: Patients (n=238, mean age 64.3±8.2 years) with stable COPD and persistent cough despite maintenance therapy (anticholinergics, beta-2-adrenergic agonists, inhaled corticosteroids) were included and randomized in the study. The severity of cough assessment (according to the "Cough Severity Score"), COPD impact on patient's life (COPD Assessment Test, CAT), and spirometry were performed at screening. Patients took Rengalin or Placebo 2 tablets 2 times daily for 4 weeks. The endpoints were proportion of patients who responded to treatment, dynamics of cough severity, and severity of COPD symptoms. Intention-to-treat (per protocol) analysis was performed. RESULTS: Positive response to Rengalin was recorded in 83.6 [85.7]% (vs 72.6 [72.7]% in Placebo group, p=0.0422 [p=0.0163]). Double decrease of cough severity was reported in 42.2 [43.8]% in Rengalin group (versus 32.7 [32.7]% in Placebo; p=0.1373 [p=0.0907]). The total CAT score decreased by 3.3±4.2 [3.6±3.9] points (versus 2.5±4.1 [2.5±4.2] in Placebo group); the difference between groups was 0.79±4.16 [1.04±4.02] points (p=0.0870 [p=0.0416]). The number of patients with adverse events (AEs) in Rengalin (n=13) and Placebo (n=12) groups did not have significant differences (p=1.00). No AEs with certain relationship with study drug were registered. CONCLUSION: Rengalin is an effective and safe drug in patients with stable COPD and persistent cough, despite stable doses of maintenance therapy according to the GOLD guidelines. Four-week therapy decreases severity of cough by two times in more than 40% of patients. TRIAL REGISTRATION: ClinicalTrials.gov (id: NCT03159091).

Common intronic D variant of ACE gene is associated with endothelial dysfunction in COPD.

BACKGROUND: Pathogenesis of chronic obstructive lung disease (COPD) includes primary inflammatory events, multiple vascular reactions, remodeling of bronchial and vascular walls. OBJECTIVE: The aim of present single-center study was to assess relations between angiotensin-converting enzyme (ACE) gene and prevalence of clinical symptoms characteristic to COPD. METHODS: The study involved sixty-three male patients with COPD (44-86 years old, a mean of 60.4 years). COPD diagnostics was performed according to common criteria, including evaluation of systolic pressure in pulmonary artery (SPPA) and endothelial disfunction (ED). Genotyping of ACE I/D was performed by means of gene-specific PCR. RESULTS: 1. Allele distribution of studied gene alleles among COPD patients did not differ from control age-matched group. 2. Detectable endothelial dysfunction in COPD patients was shown to correlate with high-producer D allele of ACE gene, at an odds ratio of 6.632 (CI = 1.67-26.31; chi2 = 8.39, p = 0.004). Moreover, detectable ED correlated with numbers of COPD exacerbations per year. CONCLUSIONS: These findings suggest possible association of the functional ACE D allele with altered vascular responses that may modulate development of distinct COPD symptoms. The results are obtained in a limited clinical cohort, and deserve repeated trials in other groups of COPD patients.