Background

Among patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients.

Methods

We analysed data from two European pulmonary hypertension registries, COMPERA (launched in 2007) and ASPIRE (from 2001 onwards), to identify patients diagnosed with IPAH and a lung phenotype defined by a DLCO of less than 45% predicted and a smoking history. We compared patient characteristics, response to therapy, and survival of these patients to patients with classical IPAH (defined by the absence of cardiopulmonary comorbidities and a DLCO of 45% or more predicted) and patients with pulmonary hypertension due to lung disease (group 3 pulmonary hypertension).

Findings

The analysis included 128 (COMPERA) and 185 (ASPIRE) patients with classical IPAH, 268 (COMPERA) and 139 (ASPIRE) patients with IPAH and a lung phenotype, and 910 (COMPERA) and 375 (ASPIRE) patients with pulmonary hypertension due to lung disease. Most patients with IPAH and a lung phenotype had normal or near normal spirometry, a severe reduction in DLCO, with the majority having no or a mild degree of parenchymal lung involvement on chest computed tomography. Patients with IPAH and a lung phenotype (median age, 72 years [IQR 65–78] in COMPERA and 71 years [65–76] in ASPIRE) and patients with group 3 pulmonary hypertension (median age 71 years [65–77] in COMPERA and 69 years [63–74] in ASPIRE) were older than those with classical IPAH (median age, 45 years [32–60] in COMPERA and 52 years [38–64] in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries). While 99 (77%) patients in COMPERA and 133 (72%) patients in ASPIRE with classical IPAH were female, there was a lower proportion of female patients in the IPAH and a lung phenotype cohort (95 [35%] COMPERA; 75 [54%] ASPIRE), which was similar to group 3 pulmonary hypertension (336 [37%] COMPERA; 148 [39%] ASPIRE]). Response to pulmonary arterial hypertension therapies at first follow-up was available from COMPERA. Improvements in WHO functional class were observed in 54% of patients with classical IPAH, 26% of patients with IPAH with a lung phenotype, and 22% of patients with group 3 pulmonary hypertension (p<0·0001 for classical IPAH vs IPAH and a lung phenotype, and p=0·194 for IPAH and a lung phenotype vs group 3 pulmonary hypertension); median improvements in 6 min walking distance were 63 m, 25 m, and 23 m for these cohorts respectively (p=0·0015 for classical IPAH vs IPAH and a lung phenotype, and p=0·64 for IPAH and a lung phenotype vs group 3 pulmonary hypertension), and median reductions in N-terminal-pro-brain-natriuretic-peptide were 58%, 27%, and 16% respectively (p=0·0043 for classical IPAH vs IPAH and a lung phenotype, and p=0·14 for IPAH and a lung phenotype vs group 3 pulmonary hypertension). In both registries, survival of patients with IPAH and a lung phenotype (1 year, 89% in COMPERA and 79% in ASPIRE; 5 years, 31% in COMPERA and 21% in ASPIRE) and group 3 pulmonary hypertension (1 year, 78% in COMPERA and 64% in ASPIRE; 5 years, 26% in COMPERA and 18% in ASPIRE) was worse than survival of patients with classical IPAH (1 year, 95% in COMPERA and 98% in ASPIRE; 5 years, 84% in COMPERA and 80% in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries).

Interpretation

A cohort of patients meeting diagnostic criteria for IPAH with a distinct, presumably smoking-related form of pulmonary hypertension accompanied by a low DLCO, resemble patients with pulmonary hypertension due to lung disease rather than classical IPAH. These observations have pathogenetic, diagnostic, and therapeutic implications, which require further exploration.

Funding

COMPERA is funded by unrestricted grants from Acceleron, Bayer, GlaxoSmithKline, Janssen, and OMT. The ASPIRE Registry is supported by Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

中文翻译：

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特发性肺动脉高压的表型：登记分析

背景

在符合特发性肺动脉高压（IPAH）诊断标准的患者中，出现了一种新出现的肺部表型，其特征是一氧化碳（DLCO）扩散能力低和有吸烟史。本研究旨在详细描述这些患者的特征。

方法

我们分析了两个欧洲肺动脉高压登记处 COMPERA（2007 年启动）和 ASPIRE（2001 年起）的数据，以确定诊断为 IPAH 且肺表型由 DLCO 低于预测值 45% 和吸烟史定义的患者。我们将这些患者的特征、对治疗的反应以及生存率与经典 IPAH 患者（定义为不存在心肺合并症且 DLCO 预测为 45% 或更高）和因肺部疾病引起的肺动脉高压患者（第 3 组肺动脉高压患者）进行了比较。高血压）。

发现

该分析包括 128 名 (COMPERA) 和 185 名 (ASPIRE) 患有经典 IPAH 的患者，268 名 (COMPERA) 和 139 名 (ASPIRE) 患有 IPAH 和肺表型的患者，以及 910 名 (COMPERA) 和 375 名 (ASPIRE) 因肺动脉高压而患有肺动脉高压的患者。肺部疾病。大多数具有肺表型的 IPAH 患者肺活量正常或接近正常，DLCO 严重减少，大多数胸部计算机断层扫描显示无或轻度肺实质受累。患有IPAH和肺表型的患者（COMPERA中的中位年龄为72岁[IQR 65-78]，ASPIRE中的中位年龄为71岁[65-76]）和第3组肺动脉高压患者（中位年龄为71岁[65-77]） COMPERA 和 ASPIRE 中的 69 岁 [63–74]）比经典 IPAH 患者年龄大（中位年龄，COMPERA 中为 45 岁 [32–60]，ASPIRE 中为 52 岁 [38–64]；IPAH 的 p<0·0001两个登记处均具有肺表型与经典 IPAH）。虽然 COMPERA 中的 99 名（77%）患者和 ASPIRE 中的 133 名（72%）患有经典 IPAH 的患者是女性，但 IPAH 和肺表型队列中女性患者的比例较低（95 [35%] COMPERA；75 [1] 54%] ASPIRE），与第 3 组肺动脉高压相似（336 [37%] COMPERA；148 [39%] ASPIRE]）。COMPERA 提供了首次随访时对肺动脉高压治疗的反应。在 54% 的经典 IPAH 患者、26% 具有肺表型的 IPAH 患者以及 22% 的第 3 组肺动脉高压患者中观察到 WHO 功能分级改善（经典 IPAH 与 IPAH 相比，p<0·0001，a 组 IPAH 的 p<0·0001 ）。肺表型，IPAH 和肺表型与第 3 组肺动脉高压相比，p=0·194）；这些队列的 6 分钟步行距离的中位改善分别为 63 m、25 m 和 23 m（对于经典 IPAH与IPAH 和肺表型，p=0·0015；对于IPAH和肺表型与肺表型，p=0·64第 3 组肺动脉高压），N 端脑钠尿肽前体的中位减少分别为 58%、27% 和 16%（经典 IPAH与IPAH 和肺表型相比，p=0·0043，p=0·0043）对于 IPAH 和肺表型与第 3 组肺动脉高压，=0·14）。在两个登记处，具有肺表型的 IPAH 患者的生存率（1 年，COMPERA 中为 89%，ASPIRE 中为 79%；5 年，COMPERA 中为 31%，ASPIRE 中为 21%）和第 3 组肺动脉高压患者（1 年，78 %（COMPERA 中的 %，ASPIRE 中的 64%；5 年，COMPERA 中的 26%，ASPIRE 中的 18%）比经典 IPAH 患者的生存率更差（1 年，COMPERA 中的 95%，ASPIRE 中的 98%；5 年，84%在 COMPERA 中为 80%，在 ASPIRE 中为 80%；在两个登记处，肺表型 IPAH 与经典 IPAH相比， p<0·0001）。

解释

一组符合 IPAH 诊断标准、具有独特的、可能与吸烟相关的肺动脉高压并伴有低 DLCO 的患者队列，类似于因肺部疾病而不是典型的 IPAH 导致的肺动脉高压患者。这些观察结果具有发病、诊断和治疗的意义，需要进一步探索。

资金

COMPERA 的资金来自 Acceleron、拜耳、葛兰素史克、杨森和 OMT 的无限制资助。ASPIRE 登记处由英国谢菲尔德谢菲尔德教学医院 NHS 基金会信托基金支持。