Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study
Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study
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DOI：
10.1016/s2213-2600(13)70191-7
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发表时间：
2013-11-01
影响因子：
76.2
通讯作者：
Raghu, Ganesh
中科院分区：
文献类型：
--
作者：
Morell, Ferran;Villar, Ana;Raghu, Ganesh
背景 特发性肺纤维化（IPF）和慢性过敏性肺炎的临床特征可能难以区分；在诊断评估过程中，显然需要消除已知会导致疑似 IPF 患者肺纤维化的隐匿环境因素。我们的目的是使用常规测试之外的测试来调查诊断为 IPF 的患者环境中隐匿的推定原因。 方法 在这项病例队列研究中，根据 2000 年美国胸科学会 (ATS) 和欧洲呼吸学会 (ERS) 标准诊断为 IPF 的连续 60 名患者在 2004 年 1 月 1 日至 2009 年 12 月 31 日期间每 4 个月进行一次前瞻性随访，为期 6 年。对这 60 名患者进行了统一问卷调查，以确定已知可引起过敏性肺炎的隐匿性抗原暴露。患者接受了特异性 IgG 测定、支气管肺泡灌洗、可疑抗原的支气管激发试验，并对现有和随后获得的手术肺活检样本和肺外植体的组织病理学特征进行了重新审查。从患者环境的可疑来源获得的样本在微生物实验室进行培养。这些临床数据以及熟悉 IPF 的肺科医师和放射科医师之间的讨论用于根据 2011 年 ATS、ERS、日本呼吸学会和拉丁美洲胸科协会指南确认诊断；根据 2011 年指南，60 名患者中有 46 名患有 IPF，我们在本研究中的分析集中于这 46 名患者。结果显示，根据 2011 年指南，46 名 IPF 患者（43%，95% CI 29-58）中，有 20 名患者随后被诊断为慢性过敏性肺炎：9 名患者支气管激发试验呈阳性（其中 8 名患者也是 IgG 阳性，其中 6 名患者为慢性过敏性肺炎）还进行了外科肺活检，显示与慢性过敏性肺炎一致的模式）； 7 例为 IgG 阳性，且手术肺活检的组织病理学结果与过敏性肺炎一致；一种是 IgG 阳性且支气管肺泡灌洗液中淋巴细胞大于 20%；其中 3 例的手术肺活检结果与亚急性过敏性肺炎（且 IgG 阳性）一致。总共，在研究期间，符合 2011 年标准的 46 名诊断为 IPF 的患者中，有 29 名具有可用于组织病理学的肺组织（28 名患者进行了手术肺活检，2 名患者进行了移植肺，其中一名患者还进行了手术活检），而 20 名慢性过敏性肺炎患者中，16 名的手术肺活检的组织病理学特征与该诊断一致。 46 名患者中，有 26 名仍被诊断为 IPF。 解释 根据 2011 年标准诊断为 IPF 的患者中，几乎一半随后被诊断为慢性过敏性肺炎，其中大多数病例是由于暴露于常用羽毛床上用品中的隐匿性禽类抗原所致。我们的结果反映了一个在慢性过敏性肺炎方面具有公认专业知识的中心的发现，并且有必要在其他中心进行进一步的研究。
Background The clinical features of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis can be indistinguishable; the need to eliminate occult environmental factors known to cause pulmonary fibrosis in patients suspected to have IPF during diagnostic evaluation is evident. We aimed to investigate occult, putative causes in the environments of patients diagnosed with IPF using tests beyond those conventionally used.Methods In this case-cohort study, 60 consecutive patients diagnosed with IPF on the basis of the 2000 American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria were prospectively followed up every 4 months for 6 years between Jan 1, 2004, and Dec 31, 2009. At each visit a uniformly applied questionnaire was administered to these 60 patients to identify occult antigen exposure known to cause hypersensitivity pneumonitis. Patients underwent specific IgG determination, bronchoalveolar lavage, bronchial challenge testing with suspected antigens, and re-review of histopathological features in existing and subsequently obtained surgical lung biopsy samples and from lung explants. Specimens obtained from suspected sources from the patient's environment were subjected to cultures in microbiology laboratory. These clinical data and discussions among pulmonologists and radiologists familiar with IPF were used to confirm the diagnosis in accordance with 2011 ATS, ERS, Japanese Respiratory Society, and Latin American Thoracic Association guidelines; 46 of the 60 patients had IPF according to the 2011 guidelines, and our analyses in this study were focused on these 46 patients.Findings 20 of the 46 (43%, 95% CI 29-58) patients with IPF according to 2011 guidelines had a subsequent diagnosis of chronic hypersensitivity pneumonitis: nine patients had positive bronchial challenge testing (eight of whom were also IgG positive and six of these patients also had surgical lung biopsy showing a pattern consistent with chronic hypersensitivity pneumonitis); seven were IgG positive plus had histopathology on surgical lung biopsy that was consistent with hypersensitivity pneumonitis; one was IgG positive plus had greater than 20% lymphocytes in bronchoalveolar lavage fluid; and three had findings on surgical lung biopsy that were consistent with subacute hypersensitivity pneumonitis (and IgG positive). Altogether, 29 of 46 patients diagnosed with IPF who had met the 2011 criteria had lung tissue available for histopathology (surgical lung biopsy in 28 patients and explanted lung in two patients, one of whom also had surgical biopsy) during the study period, and 16 of the 20 patients with chronic hypersensitivity pneumonitis had histo pathological features on surgical lung biopsy that were consistent with this diagnosis. 26 of the 46 patients remained with a diagnosis of IPF.Interpretation Almost half of patients diagnosed with IPF on the basis of 2011 criteria were subsequently diagnosed with chronic hypersensitivity pneumonitis, and most of these cases were attributed to exposure of occult avian antigens from commonly used feather bedding. Our results reflect findings in one centre with recognised expertise in chronic hypersensitivity pneumonitis, and further research and studies at other centres are warranted.