Alqarni Abdullah A, Alghamdi Sara A, Aldhahir Abdulelah M, Alqahtani Jaber S, Siraj Rayan A, Alasimi Ahmed H, Bintalib Heba M, AlGarni Abdulkareem A, Majrshi Mansour, Alshabasy Adel M, AlBahrani Salma, Alwafi Hassan
Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Respiratory Therapy Unit, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Front Pharmacol. 2025 Sep 5;16:1641932. doi: 10.3389/fphar.2025.1641932. eCollection 2025.
Pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is categorized as group 3 PH and is associated with increased mortality and morbidity. Currently, there are no approved therapies for those who have PH secondary to COPD due to conflicting evidence. Therefore, this systematic review aims to summarize the current evidence on the effectiveness of drugs targeting the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway on clinical outcomes among patients with COPD-associated PH.
We conducted a comprehensive search of electronic databases, including Embase, Medline, Cochrane, and Scopus, from inception to 1 February 2024. Studies investigating the efficacy of drugs targeting the NO-sGC-cGMP pathway on clinical outcomes in patients with COPD-associated PH were included. Exclusion criteria encompassed case reports, systematic reviews, review articles, conference abstracts with no full text, non-full-text articles, non-English manuscripts, opinion articles, and book chapters. Two distinct Cochrane risk-of-bias tools designed for randomized and non-randomized clinical trials were used to evaluate the risk of bias within the selected studies for inclusion.
Fourteen studies, comprising a total of 567 adult patients diagnosed with PH secondary to COPD, met the inclusion criteria and were included in this systematic review. Among these, nine studies reported significant improvements in clinical parameters related to pulmonary hemodynamics. Improvement in exercise capacity was observed in four out of seven studies. Three studies evaluated dyspnea severity and quality of life following treatment with agents targeting the NO-sGC-cGMP pathway. Of these, three demonstrated improvement in dyspnea severity while two reported enhancements in health-related quality of life. Substantial heterogeneity was evident regarding the potential of pharmacological agents targeting the NO-sGC-cGMP pathway to enhance gas exchange, lung function, and arterial oxygenation in COPD patients with concurrent PH.
The short-term use of oral drugs targeting the NO-sGC-cGMP pathway, particularly sildenafil, demonstrates promising potential for enhancing pulmonary hemodynamics, exercise capacity, dyspnea severity, and health-related quality of life but not lung function and oxygenation status in adult patients with COPD-associated PH. Further double-blind, randomized, placebo-controlled trials are needed to assess the therapeutic benefits of agents targeting the NO-sGC-cGMP pathway, particularly inhaled therapies for managing PH due to COPD.
https://www.crd.york.ac.uk/prospero/#recordDetails, CRD42023453503.
慢性阻塞性肺疾病（COPD）所致的肺动脉高压（PH）被归类为3组PH，与死亡率和发病率增加相关。目前，由于证据相互矛盾，尚无针对COPD继发PH患者的获批治疗方法。因此，本系统评价旨在总结目前关于靶向一氧化氮（NO）-可溶性鸟苷酸环化酶（sGC）-环磷酸鸟苷（cGMP）途径的药物对COPD相关性PH患者临床结局有效性的证据。
我们对电子数据库进行了全面检索，包括Embase、Medline、Cochrane和Scopus，检索时间从建库至2024年2月1日。纳入研究靶向NO-sGC-cGMP途径的药物对COPD相关性PH患者临床结局疗效的研究。排除标准包括病例报告、系统评价、综述文章、无全文的会议摘要、非全文文章、非英文手稿、观点文章和书籍章节。使用两种专为随机和非随机临床试验设计的不同Cochrane偏倚风险工具来评估纳入的选定研究中的偏倚风险。
14项研究共纳入567例诊断为COPD继发PH的成年患者，符合纳入标准并纳入本系统评价。其中，9项研究报告了与肺血流动力学相关的临床参数有显著改善。7项研究中有4项观察到运动能力有所改善。3项研究评估了使用靶向NO-sGC-cGMP途径的药物治疗后的呼吸困难严重程度和生活质量。其中，3项研究显示呼吸困难严重程度有所改善，2项研究报告健康相关生活质量有所提高。在靶向NO-sGC-cGMP途径的药物增强合并PH的COPD患者气体交换、肺功能和动脉氧合的潜力方面，存在明显的异质性。
短期使用靶向NO-sGC-cGMP途径的口服药物，尤其是西地那非，在改善COPD相关性PH成年患者的肺血流动力学、运动能力、呼吸困难严重程度和健康相关生活质量方面显示出有前景的潜力，但对肺功能和氧合状态无改善作用。需要进一步开展双盲、随机、安慰剂对照试验，以评估靶向NO-sGC-cGMP途径药物的治疗益处，尤其是用于治疗COPD所致PH的吸入疗法。
https://www.crd.york.ac.uk/prospero/#recordDetails，CRD42023453503。
