RT Journal Article
SR Electronic
T1 Inhaled sargramostim and whole lung lavage (WLL) as therapy of autoimmune pulmonary alveolar proteinosis (aPAP)
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA3870
DO 10.1183/13993003.congress-2016.PA3870
VO 48
IS suppl 60
A1 Ilaria Campo
A1 Francesca Mariani
A1 Elena Paracchini
A1 Zamir Kadija
A1 Michele Zorzetto
A1 Carmine Tinelli
A1 Giuseppe Rodi
A1 Federica Meloni
A1 Matthias Griese
A1 Bruce Trapnell
A1 Gerhard Scheuch
A1 Bernhard Muellinger
A1 Maurizio Luisetti
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/PA3870.abstract
AB Background: aPAP is a rare disease characterized by neutralizing GM-CSF autoantibodies and alveolar surfactant accumulation. WLL is the standard therapy but results in complete resolution only in 30% of patients. We hypothesized that the combination WLL and inhaled hGM-CSF (Sargramostim) is more effective than WLL alone.Methods: We conducted a phase II clinical trial:aPAP patients were randomized to receive either WLL alone (group A) or WLL followed by inhaled sargramostim (250 mcg/day every other week for 12 weeks followed by 250 mcg/day on 2 consecutive days every 2 weeks for 6 months) (group B). GM-CSF was administered by the Akita 2 nebulizer (Vectura). Here, we report interim results obtained 30 months after WLL.Results: 18 aPAP patients (7 females/11 males) were randomized (equally) into each group. 7 in the initial group A required re-randomization because of recurrence while only 1 in the initial group B required re-randomization. Compared to the group A, the group B had significant improvement in pulmonary function including increases in mean (95% CI) DLCO%(15.7, 10.0-21.4), FVC%(11.8, 7.4-16.3), TLC%(10, 6.4-13.8), FEV1%(9.6, 5.5-13.7) (P<0.001 for all). The mean difference in PaO2 and alveolar-arterial oxygen gradient between B and A groups were both improved (13.7 (9.4-18.0) mmHg) and (-13.5 (-17.9 - -9.1) mmHg), respectively (P<0.001).In the group B we also found a significant decrease in serum biomarkers: KL6 (P=0.03), LDH (P<0.001), CYFRA (P=0.022), CEA (P=0.001).Conclusion: Interim results demonstrate that inhaled sargramostim was well tolerated and effective in aPAP and that combination therapy is more effective than WLL alone.Funding: AIFA(FARM7MCPK4).