Kishaba Tomoo, Hozumi Hironao, Fujisawa Tomoyuki, Nei Yuichiro, Enomoto Noriyuki, Sugiura Hiroaki, Kitani Masashi, Suda Takafumi
Department of Respiratory Medicine, Okinawa Chubu Hospital, Okinawa, Japan.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Respir Investig. 2020 May;58(3):177-184. doi: 10.1016/j.resinv.2020.02.004. Epub 2020 Mar 20.
Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.
We investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion. This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan-Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.
In this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).
FF and %DL were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.
急性加重（AE）是特发性肺纤维化（IPF）患者死亡的主要原因。目前关于AE-IPF的证据主要基于临床分析，而非病理分析。
我们使用多学科讨论诊断为IPF的患者的临床、放射学和病理数据，调查AE发生率及其预测因素。本研究是对先前研究的二次分析，纳入了155例行外科肺活检（SLB）的IPF患者。采用Kaplan-Meier法评估累积AE发生率。使用Fine-Gray亚分布风险模型分析AE-IPF的预测因素。采用倾向评分匹配分析进行亚组分析。
在该队列中，患者的中位年龄为66岁，预测的用力肺活量中位数百分比为82.8%。SLB后30天和1年的累积AE发生率分别为1.9%和7.6%。多变量分析显示，较低的预测肺一氧化碳弥散量百分比（%DL）（每增加1%，风险比为0.98，P = 0.02）和成纤维细胞灶（FF）存在（与不存在相比；风险比为3.01，P = 0.04）与较高的AE发生率独立相关。在对年龄、性别和%DL进行调整的倾向评分匹配分析中，FF存在亚组的累积AE发生率显著高于FF不存在亚组（1年发生率分别为10.5%和0%；Gray检验，P = 0.04）。
FF和%DL是经活检证实的IPF患者AE的独立预测因素。FF可能与AE-IPF的发病机制有关。
