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Abstract：
BACKGROUND: 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.
METHODS: 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 (D LCO) % predicted) and arterial-alveolar oxygen gradient.
RESULTS: 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 (D LCO % 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 (I2=0%). No serious trial-related adverse events were reported.
CONCLUSIONS: 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.
METHODS: 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 (D LCO) % predicted) and arterial-alveolar oxygen gradient.
RESULTS: 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 (D LCO % 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 (I2=0%). No serious trial-related adverse events were reported.
CONCLUSIONS: 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.
摘要：
背景：自身免疫性肺泡蛋白沉积症（aPAP）是巨噬细胞介导的肺泡表面活性脂蛋白清除受损的结果。全肺灌洗一直是一线治疗，但最近的报道表明粒细胞-巨噬细胞集落刺激因子（GM-CSF）的功效。我们旨在回顾雾化GM-CSF在aPAP中的疗效和安全性。
方法：我们进行了系统评价和荟萃分析，CINAHL,MEDLINE和Cochrane协作数据库（1946-2022年4月1日）。研究包括年龄>18岁接受雾化GM-CSF治疗的aPAP患者和一个比较队列。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）进行了前瞻性注册。结果评估为圣乔治呼吸问卷(SGRQ)，6分钟步行试验(6MWT),气体交换（预测的一氧化碳（DLCO）％的肺扩散能力）和动脉-肺泡氧梯度。
结果：确定了六项研究进行综述，三项进行荟萃分析，显示SGRQ评分(平均差-8.09，95%CI-11.88--4.3，p<0.0001)，功能容量（6MWT）（平均差21.72m，95%CI-2.76-46.19m，p=0.08),气体扩散(DLCO%预测)(平均差5.09%，95%CI2.05-8.13%，p=0.001）和动脉-肺泡氧梯度（平均差-4.36mmHg，95%CI-7.19--1.52mmHg，p=0.003）在接受GM-CSF治疗的患者中均有显着改善，具有较小的统计异质性（I2=0％）。未报告与试验相关的严重不良事件。
结论：用吸入GM-CSF治疗的aPAP患者表现出显著的症状改善，呼吸困难评分,肺功能,用不同持续时间的雾化GM-CSF治疗后的气体交换和放射学指标。有一个重要的需要审查的比较有效性和患者的选择在关键临床结果之间的当前标准的护理，全肺灌洗,aPAP中雾化GM-CSF的非侵入性治疗。
方法：我们进行了系统评价和荟萃分析，CINAHL,MEDLINE和Cochrane协作数据库（1946-2022年4月1日）。研究包括年龄>18岁接受雾化GM-CSF治疗的aPAP患者和一个比较队列。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）进行了前瞻性注册。结果评估为圣乔治呼吸问卷(SGRQ)，6分钟步行试验(6MWT),气体交换（预测的一氧化碳（DLCO）％的肺扩散能力）和动脉-肺泡氧梯度。
结果：确定了六项研究进行综述，三项进行荟萃分析，显示SGRQ评分(平均差-8.09，95%CI-11.88--4.3，p<0.0001)，功能容量（6MWT）（平均差21.72m，95%CI-2.76-46.19m，p=0.08),气体扩散(DLCO%预测)(平均差5.09%，95%CI2.05-8.13%，p=0.001）和动脉-肺泡氧梯度（平均差-4.36mmHg，95%CI-7.19--1.52mmHg，p=0.003）在接受GM-CSF治疗的患者中均有显着改善，具有较小的统计异质性（I2=0％）。未报告与试验相关的严重不良事件。
结论：用吸入GM-CSF治疗的aPAP患者表现出显著的症状改善，呼吸困难评分,肺功能,用不同持续时间的雾化GM-CSF治疗后的气体交换和放射学指标。有一个重要的需要审查的比较有效性和患者的选择在关键临床结果之间的当前标准的护理，全肺灌洗,aPAP中雾化GM-CSF的非侵入性治疗。
