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Abstract：
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.
To define ex vivo characteristics of PNTM disease affected by sildenafil.
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.
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.
Sildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration.
To define ex vivo characteristics of PNTM disease affected by sildenafil.
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.
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.
Sildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration.
摘要：
肺非结核分枝杆菌（PNTM）疾病在过去几十年中有所增加，尤其是老年妇女。在其他患者队列中，异常的粘膜纤毛清除和异常的鼻一氧化氮（nNO）与PNTM疾病相关。粘液纤毛清除可受NO-环磷酸鸟苷信号的影响，因此,作为一种新的治疗方法,磷酸二酯酶抑制剂如西地那非可能对该途径进行调节.
定义西地那非影响的PNTM疾病的离体特征。
患有PNTM感染的受试者被招募到西地那非的开放标签剂量递增试验中。实验室测量和粘膜纤毛测量-纤毛搏动频率，在整个研究期间收集nNO和24小时痰液产量。在研究期间，患者每天接受西地那非治疗，每天三次从20毫克增加到40毫克。
单剂量40mg西地那非和延长剂量40mg西地那非后，纤毛搏动频率增加。服用20mg西地那非未观察到纤毛搏动频率的增加。痰液产量没有变化，nNO生产，研究期间的生活质量-支气管扩张-NTM模块（QOL-B-NTM）问卷或圣乔治呼吸问卷。
西地那非,40毫克，纤毛搏动频率急剧增加以及延长给药时间。
定义西地那非影响的PNTM疾病的离体特征。
患有PNTM感染的受试者被招募到西地那非的开放标签剂量递增试验中。实验室测量和粘膜纤毛测量-纤毛搏动频率，在整个研究期间收集nNO和24小时痰液产量。在研究期间，患者每天接受西地那非治疗，每天三次从20毫克增加到40毫克。
单剂量40mg西地那非和延长剂量40mg西地那非后，纤毛搏动频率增加。服用20mg西地那非未观察到纤毛搏动频率的增加。痰液产量没有变化，nNO生产，研究期间的生活质量-支气管扩张-NTM模块（QOL-B-NTM）问卷或圣乔治呼吸问卷。
西地那非,40毫克，纤毛搏动频率急剧增加以及延长给药时间。
