Department of Respiratory Medicine, Alfred Health, Melbourne, Australia.
Department of Respiratory and Sleep Medicine, Austin Health, Melbourne, Australia.
Eur Respir Rev. 2023 Nov 22;32(170). doi: 10.1183/16000617.0080-2023. Print 2023 Dec 31.
Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP.
We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide ( ) % predicted) and arterial-alveolar oxygen gradient.
Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion ( % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I=0%). No serious trial-related adverse events were reported.
Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.
自身免疫性肺泡蛋白沉积症（aPAP）是由肺泡表面活性脂蛋白的巨噬细胞清除功能受损引起的。全肺灌洗一直是一线治疗方法，但最近的报告表明粒细胞-巨噬细胞集落刺激因子（GM-CSF）的疗效。我们旨在综述 GM-CSF 雾化在 aPAP 中的疗效和安全性。
我们进行了系统评价和荟萃分析，检索了 Embase、CINAHL、MEDLINE 和 Cochrane 协作数据库（1946 年-2022 年 4 月 1 日）。纳入研究为年龄＞18 岁的接受 GM-CSF 雾化治疗的 aPAP 患者和对照组队列。排除标准包括继发性或先天性肺泡蛋白沉积症、GM-CSF 过敏、活动性感染或其他严重疾病。该方案在 PROSPERO（CRD42021231328）中进行了前瞻性注册。评估的结局包括圣乔治呼吸问卷（SGRQ）、6 分钟步行试验（6MWT）、气体交换（一氧化碳弥散量占预计值的百分比（ ）%）和肺泡动脉氧梯度。
共确定了 6 项研究进行综述，3 项研究进行荟萃分析，结果显示 SGRQ 评分（平均差异-8.09，95%CI-11.88-4.3，p＜0.0001）、功能能力（6MWT）（平均差异 21.72m，95%CI-2.76-46.19m，p=0.08）、气体扩散（ ）%）（平均差异 5.09%，95%CI 2.05-8.13%，p=0.001）和肺泡动脉氧梯度（平均差异-4.36mmHg，95%CI-7.19-1.52mmHg，p=0.003）在 GM-CSF 治疗的患者中均显著改善，且存在较小的统计学异质性（I=0%）。未报告与试验相关的严重不良事件。
接受 GM-CSF 雾化吸入治疗的 aPAP 患者，在接受不同时间的 GM-CSF 雾化治疗后，其症状、呼吸困难评分、肺功能、气体交换和影像学指标均显著改善。在全肺灌洗作为目前的标准治疗方法的基础上，有必要对关键临床结局（如患者选择）进行比较有效性和评估，以评估非侵入性治疗 GM-CSF 雾化吸入在 aPAP 中的应用。
