Cullivan Sarah, Genecand Leon, El-Merhie Natalia, MacKenzie Alison, Lichtblau Mona
National Pulmonary Hypertension Unit, Dublin, Ireland.
Service de pneumologie, Département de médecine, Hôpitaux universitaires de Genève, Geneva, Switzerland.
Breathe (Sheff). 2025 Mar 18;21(1):240242. doi: 10.1183/20734735.0242-2024. eCollection 2025 Jan.
Group 3 pulmonary hypertension (PH) associated with lung disease is a common cause of PH and is associated with substantial morbidity and mortality. Multiple studies of pulmonary arterial hypertension (PAH) therapies in this population have demonstrated conflicting results regarding their safety and efficacy, and therefore the optimum treatment for this group is unknown. The INCREASE and PERFECT randomised, double-blind, placebo-controlled trials attempted to address this unmet need by exploring the role of inhaled treprostinil (iTRE) in PH associated with interstitial lung disease (PH-ILD) and PH associated with COPD (PH-COPD), respectively. In the INCREASE and PERFECT studies individuals were randomised to placebo or iTRE, which was administered an ultrasonic, pulsed-delivery nebuliser to a maximum dose of 72 μg, four times a day. The INCREASE study randomised 326 subjects with PH-ILD over a 16-week period and met its primary endpoint of change in 6-min walk distance, with a treatment effect of +31.12 m (p<0.001). Reduced disease progression events and increased forced vital capacity were also reported in the treatment arm in a analysis. By contrast, the PERFECT study was stopped prematurely by the data and safety monitoring committee due to evidence that iTRE increased serious adverse events in subjects with PH-COPD. This journal club provides an overview of these important trials and highlights pertinent unanswered questions in this field.
3型与肺部疾病相关的肺动脉高压（PH）是PH的常见病因，与较高的发病率和死亡率相关。针对该人群的肺动脉高压（PAH）治疗的多项研究在安全性和有效性方面显示出相互矛盾的结果，因此该组的最佳治疗方法尚不清楚。INCREASE和PERFECT随机、双盲、安慰剂对照试验分别试图通过探索吸入性曲前列尼尔（iTRE）在与间质性肺疾病相关的PH（PH-ILD）和与慢性阻塞性肺疾病相关的PH（PH-COPD）中的作用来满足这一未满足的需求。在INCREASE和PERFECT研究中，个体被随机分配到安慰剂组或iTRE组，使用超声脉冲递送雾化器给药，最大剂量为72μg，每日4次。INCREASE研究在16周内将326名PH-ILD受试者随机分组，达到了其6分钟步行距离变化的主要终点，治疗效果为+31.12m（p<0.001）。在一项分析中，治疗组还报告了疾病进展事件减少和用力肺活量增加。相比之下，由于有证据表明iTRE增加了PH-COPD受试者的严重不良事件，PERFECT研究被数据和安全监测委员会提前终止。本期刊俱乐部概述了这些重要试验，并突出了该领域相关的未解决问题。
