肺动脉非结核分枝杆菌病患者中西地那非对纤毛频率的影响：I/II 期试验。
The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial.
机构信息
Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA.
出版信息
BMJ Open Respir Res. 2020 Mar;7(1). doi: 10.1136/bmjresp-2020-000574.
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.
理由
在过去几十年中，肺部非结核分枝杆菌（PNTM）疾病有所增加，尤其是老年女性。在其他患者群体中，异常的黏液纤毛清除功能和异常的鼻内一氧化氮（nNO）与 PNTM 疾病有关。NO-环磷酸鸟苷信号转导可以影响黏液纤毛清除功能，因此，磷酸二酯酶抑制剂（如西地那非）可能通过调节该途径成为一种新的治疗方法。
目的
定义西地那非对 PNTM 疾病的体外特征。
方法
招募患有 PNTM 感染的受试者参加西地那非的开放性剂量递增试验。在整个研究期间收集实验室测量值和黏液纤毛测量值-纤毛摆动频率、nNO 和 24 小时痰液产生量。在研究期间，患者每天接受西地那非治疗，剂量从 20 毫克增加到每天 3 次，每次 40 毫克。
测量和主要结果
单次 40 毫克西地那非剂量后和延长 40 毫克西地那非剂量后，纤毛摆动频率增加。20 毫克西地那非剂量给药后没有观察到纤毛摆动频率增加。在研究期间，痰液产生量、nNO 产生量、生活质量-支气管扩张-NTM 模块（QOL-B-NTM）问卷或圣乔治呼吸问卷没有变化。
结论
西地那非 40 毫克可急性增加纤毛摆动频率，也可延长给药时间增加纤毛摆动频率。
Zotero 插件