An Open-Label Trial of Granulocyte Macrophage Colony Stimulating Factor Therapy for Moderate Symptomatic Pulmonary Alveolar Proteinosis: Conclusion
The other factor that would argue in favor of a treatment effect for the observed clinical response is that many of these patients required frequent WLL for symptom relief before enrolling in our study, suggesting that they did not have many quiescent periods in their disease activity.
GM-CSF therapy was well tolerated, with minor side effects such as local skin reactions. The mean duration of follow-up was 39 months, and we did not see toxicity such as pulmonary fibrosis or bone marrow suppression with this therapy. The duration of follow-up may not be adequate to rule out longterm pulmonary or hematologic toxicity. Long-term follow-up of PAP patients treated with GM-CSF is ongoing.
All patients in our study had pretreatment anti-GM-CSF antibody, indicating an important diagnostic role for this antibody in the noninvasive diagnosis of PAP. In a study conducted at our institution, all adult patients (n = 40) with idiopathic PAP were found to have systemic and localized antibodies against GM-CSF, and the autoantibody response was specific for GM-CSF. The lowest serum end-titer for the PAP population was 1:400, and the highest titer was > 1:25,600. None of the healthy control subjects had end-titers > 1:10, and two of other pulmonary disease control subjects (beryllium lung disease) had end-titers at 1:100. The sensitivity of the serum anti-GM-CSF assay was 100%, and the specificity improved to 100% (using a cut-off end-titer of 1:400).