1 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
2 Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Ann Am Thorac Soc. 2018 Jul;15(7):854-863. doi: 10.1513/AnnalsATS.201801-067OC.
Accurate diagnosis of interstitial lung disease is necessary to identify the most appropriate management strategy and to inform prognosis. Many patients cannot be provided a confident diagnosis, despite an exhaustive search for potential etiologies and review in a multidisciplinary conference, and are consequently labeled with unclassifiable interstitial lung disease.
To systematically review and meta-analyze previous studies reporting on the diagnostic criteria, prevalence, clinical features, and outcome of unclassifiable interstitial lung disease.
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were systematically searched for all studies related to unclassifiable interstitial lung disease published before September 1, 2017. Two authors independently screened each citation for eligibility criteria, serially reviewing the title, abstract, and full-text manuscript, and then abstracted data pertaining to the study objectives from eligible studies. Articles were stratified by risk of selection bias, whether the publication stated that patients were reviewed in a multidisciplinary discussion, and by the frequency of surgical lung biopsy. Meta-analyses and meta-regression were performed to calculate the pooled prevalence of unclassifiable interstitial lung disease within an interstitial lung disease population and within specific subgroups to identify reasons for across-study heterogeneity.
The search identified 10,130 unique citations, 313 articles underwent full-text review, and eligibility criteria were met in 88 articles. Twenty-two studies were deemed low risk of selection bias, including 1,060 patients with unclassifiable interstitial lung disease from a total of 10,174 patients with interstitial lung disease. The terminology and definition of unclassifiable interstitial lung disease varied substantially across publications, with inconsistent diagnostic criteria and evaluation processes. The prevalence of unclassifiable interstitial lung disease was 11.9% (95% confidence interval, 8.5-15.6%), with lower prevalence in centers that reported use of a formal multidisciplinary discussion of cases (9.5% vs. 14.5%). Four articles reported survival of unclassifiable interstitial lung disease, with 1-year, 2-year, and 5-year survival of 84% to 89%, 70% to 76%, and 46% to 70%, respectively.
This systematic review and meta-analysis shows that unclassifiable interstitial lung disease is common but has substantial heterogeneity and inconsistent definitions across interstitial lung disease cohorts. These findings highlight important limitations in multicenter studies of fibrotic interstitial lung disease and the need for a standardized approach to interstitial lung disease diagnostic classification.
准确诊断间质性肺疾病对于确定最合适的管理策略和告知预后至关重要。尽管对潜在病因进行了详尽的搜索，并在多学科会议上进行了审查，但仍有许多患者无法做出明确的诊断，因此被归类为无法分类的间质性肺疾病。
系统回顾和荟萃分析既往关于无法分类的间质性肺疾病的诊断标准、患病率、临床特征和结局的研究。
系统检索了 MEDLINE、Embase 和 Cochrane 对照试验中心注册库，以获取截至 2017 年 9 月 1 日之前发表的所有关于无法分类的间质性肺疾病的研究。两名作者独立筛选了每篇引文的入选标准，通过标题、摘要和全文进行连续审查，然后从符合入选标准的研究中提取与研究目标相关的数据。文章按选择偏倚风险、出版物中是否表明患者在多学科讨论中进行了审查以及肺活检的频率进行分层。进行荟萃分析和荟萃回归，以计算在间质性肺疾病人群内和特定亚组内无法分类的间质性肺疾病的总患病率，以确定研究间异质性的原因。
检索共确定了 10130 个独特的引文，对 313 篇文章进行了全文审查，有 88 篇符合入选标准。22 项研究被认为选择偏倚风险较低，包括来自 10174 例间质性肺疾病患者的 1060 例无法分类的间质性肺疾病患者。无法分类的间质性肺疾病的术语和定义在不同的出版物中有很大差异，诊断标准和评估过程不一致。无法分类的间质性肺疾病的患病率为 11.9%（95%置信区间，8.5%-15.6%），在报告使用病例多学科讨论的中心患病率较低（9.5%比 14.5%）。有 4 篇文章报告了无法分类的间质性肺疾病的生存情况，1 年、2 年和 5 年的生存率分别为 84%-89%、70%-76%和 46%-70%。
本系统回顾和荟萃分析表明，无法分类的间质性肺疾病很常见，但在间质性肺疾病队列中存在很大的异质性和不一致的定义。这些发现突出了纤维化间质性肺疾病多中心研究中的重要局限性，以及对间质性肺疾病诊断分类采用标准化方法的必要性。
