Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses

Sheng, Gaohong; Chen, Peng; Wei, Yanqiu; Chu, Jiaojiao; Cao, Xiaolei; Zhang, Hui-Lan

doi:10.1186/s12931-018-0862-4

Table 2 Subgroup analysis of the effects of GM-CSF therapy on patients with aPAP

From: Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses

Subgroup	Response rate				Relapse rate
Subgroup	Studies/patients, n/N	Response rate [95% CI]	p value	p value for interaction	Studies/patients, n/N	Relapse rate [95% CI]	p value	p value for interaction
Route of GM-CSF
Subcutaneous	5/50	0.71 [0.46–0.96]	< 0.001	0.023	5/50	0.24 [−0.08–0.55]	0.14	0.262
Inhaled	5/65	0.89 [0.71–1.06]	< 0.001	0.023	5/65	0.19 [0.00–0.37]	0.047	0.262
Age, years
< 45	5/40	0.83 [0.61–1.04]	< 0.001	0.18	5/40	0.33 [0.01–0.64]	0.04	0.006
≥ 45	5/75	0.79 [0.57–1.01]	< 0.001	0.18	5/75	0.10 [−0.03–0.23]	0.13	0.006
Gender, men %
< 70	6/77	0.81 [0.62–1.01]	< 0.001	0.543	6/77	0.32 [0.05–0.60]	0.02	0.349
≥ 70	4/38	0.80 [0.51–1.09]	< 0.001	0.543	4/38	0.09 [−0.08–0.26]	0.293	0.349
Smoker, %
< 60	4/84	0.63 [0.40–0.86]	< 0.001	0.002	4/84	0.37 [0.01–0.72]	0.041	0.84
≥ 60	4/24	0.93 [0.80–1.07]	< 0.001	0.002	4/24	0.19 [−0.06–0.43]	0.136	0.84
Combined therapy with WLL, %
< 80	6/76	0.77 [0.59–0.96]	< 0.001	0.962	6/76	0.27 [0.00–0.53]	0.047	0.965
≥ 80	4/39	0.86 [0.57–1.15]	< 0.001	0.962	4/39	0.16 [−0.03–0.35]	0.098	0.965
Anti GM-CSF antibody titer
< 40μg/ml	3/50	0.86[0.58–1.14]	< 0.001	0.051	3/50	0.06[−0.06–0.19]	0.313	0.045
≥ 40μg/ml	3/18	0.95[0.80–1.10]	< 0.001	0.051	3/18	0.27[−0.02–0.56]	0.066	0.045
Initial dose of GM-CSF
≤ 250μg/d	7/96	0.74[0.55–0.93]	< 0.001	0.005	7/96	0.25[0.04–0.47]	0.022	0.751
> 250μg/d	3/19	0.95[0.80–1.10]	< 0.001	0.005	3/19	0.16[−0.15–0.46]	0.312	0.751
Subgroup	PaO₂, mmHg				P[A-a]O₂, mmHg
Subgroup	Studies/patients, n/N	WMD [95% CI]	p value	p value for interaction	Studies/patients, n/N	WMD [95% CI]	p value	p value for interaction
Route of GM-CSF
Subcutaneous	3/38	8.28 [6.3–10.26]	< 0.001	< 0.001	3/38	9.15 [7.53–10.78]	< 0.001	< 0.001
Inhaled	2/17	21.02 [15.41–26.62]	< 0.001	< 0.001	4/62	19.63 [5.82–33.45]	0.005	< 0.001
Age, years
< 45	3/29	12.11 [3.65–20.57]	0.005	0.614	4/35	14.14 [6.85–21.44]	< 0.001	0.725
≥ 45	2/26	15.88 [1.96–29.80]	0.025	0.614	4/68	24.56 [15.41–33.72]	< 0.001	0.725
Gender, men %
< 70	2/25	11.32 [1.19–21.46]	0.029	0.712	4/70	11.36 [7.27–15.45]	< 0.001	0.186
≥ 70	3/30	16.00 [4.31–27.69]	0.007	0.712	3/30	18.23 [−0.14–36.59]	0.052	0.186
Smoker, %
< 60	1/13	6.77 [3.87–9.67]	< 0.001	< 0.001	3/58	8.53 [6.87–10.18]	< 0.001	< 0.001
≥ 60	4/42	16.27[7.16–25.37]	< 0.001	< 0.001	4/42	18.40 [5.10–31.69]	0.007	< 0.001
Combined therapy with WLL, %
< 80	3/29	12.11 [3.65–20.57]	0.005	0.614	4/68	10.64 [6.87–14.4]	< 0.001	0.006
≥ 80	2/26	15.88 [1.96–29.80]	0.025	0.614	4/35	33.59 [14.54–52.64]	0.001	0.006
Anti GM-CSF antibody titer
< 40μg/ml	1/5	23.16(18.36–27.96)	< 0.001	-^*	3/50	20.11(1.48–38.74)	0.034	0.516
≥ 40μg/ml	1/12	17.20(9.37–25.03)	< 0.001	-^*	2/15	48.88(−12.16–109.92)	0.117	0.516
Initial dose of GM-CSF
≤ 250μg/d	4/43	13.02(6.36–19.67)	< 0.001	0.715	6/88	14.53(8.85–20.20)	< 0.001	0.466
> 250μg/d	1/12	17.20(9.37–25.03)	< 0.001	0.715	2/15	48.88(− 12.16–109.92)	0.117	0.466

GM-CSF granulocyte macrophage colony stimulating factor, aPAP autoimmune pulmonary alveolar proteinosis, PaO₂ alveolar oxygen partial pressure, P[A-a]O₂ alveolar-arterial oxygen gradient, WMD Weighted Mean Difference; ^* only one study included in each subgroup, p value for interaction not available

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