支气管肺泡灌洗淋巴细胞增多对特发性非特异性间质性肺炎、特发性胸膜肺弹力纤维增生症和未分类特发性间质性肺炎抗炎治疗效果的影响。
Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia.
机构信息
Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
出版信息
Respir Res. 2021 Apr 20;22(1):115. doi: 10.1186/s12931-021-01726-8.
BACKGROUND
Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP.
METHODS
Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis.
RESULTS
Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11-0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13-0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value.
CONCLUSIONS
BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.
背景
特发性非特异性间质性肺炎（iNSIP）、特发性胸膜肺弹力纤维增生症（iPPFE）和不能分类的特发性间质性肺炎（IIP）是具有慢性纤维化表型的 IIP，与特发性肺纤维化不同，它们通常使用抗炎药物治疗，包括皮质类固醇和免疫抑制剂。然而，支气管肺泡灌洗（BAL）淋巴细胞增多对抗炎治疗效果的影响从未被评估过。本研究旨在阐明 BAL 淋巴细胞增多是否可用于预测 iNSIP、iPPFE 和不能分类的 IIP 的抗炎药物疗效。
方法
使用全国性登记处，通过多学科讨论确定被诊断为 iNSIP、iPPFE 和不能分类的 IIP 的日本患者。将符合条件的患者分为 BAL 淋巴细胞增多和无 BAL 淋巴细胞增多且接受抗炎治疗的四组，以比较总生存率（OS）和肺功能变化。BAL 淋巴细胞增多定义为淋巴细胞分类计数>15%，并通过生存分类和回归树分析验证该截断值。
结果
共分析了 186 例患者（37 例 iNSIP、16 例 iPPFE 和 133 例不能分类的 IIP）。仅限于接受抗炎药物治疗的患者（n=123），BAL 淋巴细胞增多的患者具有更好的预后[风险比（HR），0.26；95%置信区间（CI），0.11-0.63；P=0.003]、2 年内用力肺活量（FVC）%预计值的斜率更高，OS 更长（对数秩检验，P=0.012），而无 BAL 淋巴细胞增多的患者则无上述情况。多变量分析显示，BAL 淋巴细胞增多（HR 0.31；95%CI 0.13-0.75；P=0.009）是 OS 的预后因素，与年龄和 FVC %预计值相关。相反，对于未接受抗炎治疗的患者（n=63），BAL 淋巴细胞增多的存在与否对预后无价值。
结论
BAL 淋巴细胞增多与接受抗炎药物治疗的患者的良好结局相关，但在未使用抗炎药物时无预后价值。BAL 淋巴细胞增多可能为识别可能从抗炎药物中获益的 iNSIP、iPPFE 和不能分类的 IIP 患者提供预测生物标志物。
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