Lacedonia Donato, Correale Michele, Tricarico Lucia, Scioscia Giulia, Stornelli Silvia Romana, Simone Filomena, Casparrini Massimo, Brunetti Natale Daniele, Foschino Barbaro Maria Pia
Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Cardiology Department, Policlinico Riuniti University Hospital, Foggia, Italy.
Intern Emerg Med. 2022 Apr;17(3):815-822. doi: 10.1007/s11739-021-02883-w. Epub 2021 Nov 16.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause that leads to respiratory failure and death within few years of diagnosis. Pulmonary hypertension (PH) is a common complication in IPF, where it is strongly associated with increased morbidity and mortality. Patients with IPF and PH have particularly poor prognosis, despite current best medical therapies and the anti-fibrotic therapy with pirfenidone or nintedanib. The aim of our study was to assess the clinical and prognostic impact of PH in patients affected by IPF, already treated with pirfenidone or nintedanib. Seventy-four consecutive outpatients with a diagnosis of IPF, in therapy with pirfenidone or nintedanib, were prospectively enrolled in the study. All patients underwent pulmonary and cardiology assessment by clinical exam, spirometry, DLCO test, chest CT, 6MWT and echocardiography performed by a cardiologist experienced in PH in an ambulatory setting under resting conditions. GAP index has been determinate for all patients. During follow-up, all patients were evaluated every 6 months, or less if necessary. Data about mortality were then collected in a 3-year follow-up. Of the seventy-four patients enrolled, 38 were treated with pirfenidone and 36 with nintedanib. The two groups were comparable for age, gender, FVC, DLCO and PAPS. The patients were also divided in four groups, based on presence of mild/moderate/severe PH by echocardiography at baseline. Significant differences were found for DLCO and the GAP index. Severity of PH was significantly associated with a reduction of DLCO and with an increased GAP index. Survival was directly correlated with 6MWT (R = 0.48), DLCO (R = 0.29, p < 0.01), and reversely with tGAP index (- 0.31, p < 0.01 in all cases), while no significant correlation was found with PAsP. 36-month survival analysis showed an HR of 4.05 (95% CI 1.07-7.34, p = 0.02) for DLCO < 50% and of 1.56 (95% CI 1.02-2.39, p = 0.03) for GAP index. The development and progression of PH in patients affected by IPF reduce the survival and the severity of PH is associated with a reduction of DLCO value and an increase of the GAP index. Echocardiographic stratification based on PAsP values may be useful in stratifying prognosis in IPF patients and deciding specific PAH drugs.
特发性肺纤维化(IPF)是一种病因不明的慢性、进行性、纤维化间质性肺炎的特殊形式,在诊断后的几年内会导致呼吸衰竭和死亡。肺动脉高压(PH)是IPF的常见并发症,与发病率和死亡率的增加密切相关。尽管有目前最佳的药物治疗以及吡非尼酮或尼达尼布的抗纤维化治疗,但IPF合并PH的患者预后特别差。我们研究的目的是评估PH对已接受吡非尼酮或尼达尼布治疗的IPF患者的临床和预后影响。74例连续诊断为IPF且正在接受吡非尼酮或尼达尼布治疗的门诊患者被前瞻性纳入研究。所有患者均在静息状态下,由一位在PH方面经验丰富的心脏病专家在门诊环境中通过临床检查、肺功能测定、一氧化碳弥散量(DLCO)测试、胸部CT、6分钟步行试验(6MWT)和超声心动图进行肺部和心脏评估。为所有患者确定了GAP指数。在随访期间,所有患者每6个月评估一次,必要时可缩短评估间隔。然后收集3年随访期内的死亡数据。在纳入的74例患者中,38例接受吡非尼酮治疗,36例接受尼达尼布治疗。两组在年龄、性别、用力肺活量(FVC)、DLCO和肺动脉收缩压(PAPS)方面具有可比性。根据基线超声心动图显示的轻度/中度/重度PH的存在情况,患者也被分为四组。在DLCO和GAP指数方面发现了显著差异。PH的严重程度与DLCO的降低和GAP指数的增加显著相关。生存率与6MWT(R = 0.48)、DLCO(R = 0.29,p < 0.01)直接相关,与tGAP指数呈负相关(所有情况下R = - 0.31,p < 0.01),而与PAsP无显著相关性。36个月生存分析显示,DLCO < 50%时的风险比(HR)为4.05(95%置信区间[CI] 1.07 - 7.34,p = 0.02),GAP指数为1.56(95% CI 1.02 - 2.39,p = 0.03)。IPF患者中PH的发生和进展会降低生存率,PH的严重程度与DLCO值的降低和GAP指数的增加相关。基于PAsP值的超声心动图分层可能有助于对IPF患者的预后进行分层,并决定是否使用特定的肺动脉高压药物。