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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
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 5/65 0.19 [0.00–0.37] 0.047
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 5/75 0.10 [−0.03–0.23] 0.13
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 4/38 0.09 [−0.08–0.26] 0.293
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 4/24 0.19 [−0.06–0.43] 0.136
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 4/39 0.16 [−0.03–0.35] 0.098
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 3/18 0.27[−0.02–0.56] 0.066
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 3/19 0.16[−0.15–0.46] 0.312
Subgroup PaO2, mmHg P[A-a]O2, mmHg
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 4/62 19.63 [5.82–33.45] 0.005
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 4/68 24.56 [15.41–33.72] < 0.001
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 3/30 18.23 [−0.14–36.59] 0.052
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 4/42 18.40 [5.10–31.69] 0.007
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 4/35 33.59 [14.54–52.64] 0.001
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
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 2/15 48.88(− 12.16–109.92) 0.117
  1. 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