Abstract Rationale Pulmonary alveolar proteinosis (PAP) is a rare syndrome of surfactant accumulation that may result in hypoxemic respiratory failure. Among all PAP patients, autoimmune PAP (aPAP) accounts for 90% of cases and is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies (GMAb). Other genetic and acquired conditions make up the other 10% of cases. Serum GMAb testing is reported to be 100% sensitive and specific for the diagnosis of aPAP. No therapy in aPAP is approved in the US or Europe and, currently, patients are treated by whole lung lavage (WLL) and/or off-label pharmacotherapies. Methods The US National PAP Registry comprises patient-reported and medical record-derived information regarding medical history, diagnosis, and therapy. This update reports on aPAP patients. Continuous and categorical data are mean±SEM or percentage of registrants, respectively. Results aPAP registrants (n = 127) presented at 41±1.4 years of age with dyspnea (98%), fatigue (80%), cough (69%), sputum production (59%), chest tightness (52%), and/or chest pain (46%); 50% had a history of smoking. Accurate diagnosis occurred 1.2±0.3 years after symptom onset and was frequently preceded by misdiagnosis as pneumonia (41%) or asthma (13%). Among patients misdiagnosed as pneumonia, they received 2.8±0.6 courses of antibiotics before the diagnosis was reconsidered. Among 100 aPAP patients with complete medical records available, 69% had a lung biopsy during evaluation including surgical (42%), transbronchial (46.4%), or both (11.6%). Lung biopsies were not diagnostic of aPAP and failed to identify PAP histologically in 10.4% of cases. aPAP was diagnosed in 127 (100%) of patients by serum GMAb testing; the median (interquartile range) GMAb was 94.6 (54.6-169.7) mcg/ml. Among aPAP patients, most (86%) received therapy for aPAP including WLL (78%), GM-CSF augmentation (38%), corticosteroids (26%), or rituximab (8.9%). Among WLL recipients, 25.3% received 1 procedure, 50.5% received 2-5 procedures, and 24.2% received 5 procedures and, overall, 69% of patients reported a “good” response. Among GM-CSF recipients, the route included inhaled (49%), subcutaneous (32%) or both (13%) and, overall, 56% reported a “good” response. Among corticosteroid recipients, overall, 68% reported a “poor” response. Among rituximab recipients, overall, 73% reported a “good” response. Conclusions Among aPAP patients in the US National PAP Registry, dyspnea was the most common presenting symptom, serum GMAb was diagnostic in all, lung biopsies were non-diagnostic of aPAP and failed to identify PAP in some. Most patients reported a positive treatment response to WLL, GM-CSF, and rituximab, and a poor response to corticosteroids (which are not recommended). This abstract is funded by: U54HL127672; R01FD007604
Carey et al. (Fri,) studied this question.