The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial
Journal
BMJ Open Respiratory Research
Journal Volume
7
Journal Issue
1
Pages
574
Date Issued
2020
Author(s)
Abstract
Rationale Pulmonary non-tuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Abnormal mucociliary clearance and abnormal nasal nitric oxide (nNO) have been associated with PNTM disease in other patient cohorts. Mucociliary clearance can be affected by NO-cyclic guanosine monophosphate signalling and, therefore, modulation of the pathway may be possible with phosphodiesterase inhibitors such as sildenafil as a novel therapeutic approach. Objective To define ex vivo characteristics of PNTM disease affected by sildenafil. Methods Subjects with PNTM infections were recruited into an open-label dose-escalation trial of sildenafil. Laboratory measurements and mucociliary measurements -ciliary beat frequency, nNO and 24-hour sputum production -were collected throughout the study period. Patients received sildenafil daily during the study period, with escalation from 20 to 40 mg three times per day. Measurements and main results Increased ciliary beat frequency occurred after a single dose of 40 mg sildenafil and after extended dosing of 40 mg sildenafil. The increase ciliary beat frequency was not seen with 20 mg sildenafil dosing. There were no changes in sputum production, nNO production, Quality of Life-Bronchiectasis-NTM module (QOL-B-NTM) questionnaire or the St George's Respiratory Questionnaire during the study period. Conclusion Sildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration. ? Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC.
Subjects
airway epithelium; atypical mycobacterial infection; innate immunity; opportunist lung infections; rare lung diseases; respiratory infection
SDGs
Other Subjects
amikacin; azithromycin; cefoxitin; clarithromycin; clofazimine; cyclic GMP; ethambutol; imipenem; isoniazid; linezolid; meropenem; moxifloxacin; nitric oxide; rifabutin; rifampicin; rifapentine; serum albumin; sildenafil; tigecycline; nitric oxide; phosphodiesterase V inhibitor; sildenafil; adult; aged; airway epithelium cell; albumin blood level; antibiotic therapy; Article; atypical mycobacteriosis; cellular parameters; ciliary beat frequency; ciliary motility; cohort analysis; controlled clinical trial; controlled study; drug dose escalation; drug dose regimen; drug efficacy; drug safety; ex vivo study; female; functional status; headache; human; human cell; hypomagnesemia; in vivo study; infection; intervention study; laboratory test; lung infection; lymphocytopenia; maintenance drug dose; major clinical study; male; mucociliary clearance; nose; nose obstruction; open study; phase 1 clinical trial; phase 2 clinical trial; quality of life; quality of life assessment; Quality of Life Bronchiectasis NTM module Questionnaire; respiratory epithelium; side effect; signal transduction; single drug dose; sputum analysis; St. George Respiratory Questionnaire; thrombocytopenia; atypical mycobacteriosis; atypical Mycobacterium; bronchiectasis; chemistry; cilium; clinical trial; drug effect; health survey; lung disease; microbiology; middle aged; nose mucosa; treatment outcome; very elderly; Aged; Aged, 80 and over; Bronchiectasis; Cilia; Female; Health Surveys; Humans; Lung Diseases; Middle Aged; Mucociliary Clearance; Mycobacterium Infections, Nontuberculous; Nasal Mucosa; Nitric Oxide; Nontuberculous Mycobacteria; Phosphodiesterase 5 Inhibitors; Quality of Life; Sildenafil Citrate; Treatment Outcome
Publisher
BMJ Publishing Group
Type
journal article