SynthesisBMC pulmonary medicine2026
Efficacy of recombinant human GM-CSF compared to placebo for autoimmune pulmonary alveolar proteinosis: a systematic review and meta-analysis.
Synthesis in BMC pulmonary medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
backgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease characterized by surfactant accumulation within alveoli due to impaired clearance or GM-CSF signaling defect. Whole lung lavage (WLL) removes accumulated surfactant but is invasive and does not correct macrophages dysfunction. Recombinant GM-CSF (molgramostim or sargramostim) aims to restore macrophage activity¸ enhance gas exchange and reduce dependence on WLL.
objectiveThis systematic review and meta-analysis evaluated the efficacy of recombinant human GM-CSF (molgramostim or sargramostim) compared with placebo in patients with aPAP.
methodFollowing PRISMA guidelines, PubMed, Cochrane CENTRAL, and Scopus were searched for randomized controlled trials in adults with aPAP receiving molgramostim or sargramostim versus placebo. Primary outcomes included changes in alveolar–arterial oxygen gradient (A-aDO₂) and diffusing capacity of the lung for carbon monoxide (DLCO). Secondary outcomes included St. George’s Respiratory Questionnaire (SGRQ) scores, radiologic ground-glass opacity (GGO) scores, vital capacity, six-minute walk distance, serum biomarkers (CEA and KL-6), and GM-CSF autoantibody levels. Data were analyzed using a random-effects model RevMan 5.4.1, and risk of bias with ROB 2.0.
resultFour RCTs involving 338 participants (190 interventions,148 control) were included. Recombinant GM-CSF significantly improved gas exchange, with decreased A-aDO₂ MD of -4.67 (95% CI: -8.49 to -1.42, p = 0.006) and increased DLCO (% predicted) with a mean difference of 6.13 (95% CI: 3.36 to 8.89). Significant improvements were also observed in SGRQ-T scores (MD = –6.60; p < 0.00001) and GGO scores (MD = –1.98; p = 0.0007). No significant differences were found for six-minute walk distance, vital capacity, or serum biomarkers. Most included trials showed low to moderate risk of bias with a few high risk. Egger’s test (p = 0.37) showed no publication bias and overall certainty of evidence ranged from moderate to high.
conclusionRecombinant GM-CSF (molgramostim and sargramostim) is an effective, disease targeted therapy for aPAP. It improves pulmonary function gas exchange and radiological outcomes while reducing reliance on whole lung lavage.
trial registrationPROSPERO reference number CRD420251165258.
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