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Autoimmune Pulmonary Alveolar Proteinosis: Presentation, Clinical Manifestations and Current Therapeutic Approaches
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A3117 - Autoimmune Pulmonary Alveolar Proteinosis: Presentation, Clinical Manifestations and Current Therapeutic Approaches
Author Block: B. C. Carey1, C. McCarthy1, M. Nowell-Bostic1, M. Rieman-Klingler1, C. Chalk1, A. Toth1, H. Lee2, M. Brelsford2, T. S. Wang3, J. Krischer2, B. C. Trapnell1; 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2University of South Florida, Tampa, FL, United States, 3UCLA Dept of Pulm / Crit Care, Los Angeles, CA, United States.
Rationale: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disorder of surfactant accumulation resulting in hypoxemic respiratory failure. It is caused by antibody-mediated disruption of granulocyte/macrophage-colony stimulating factor (GM-CSF) signalling and accounts for 85-90% of all PAP patients and anti-GM-CSF autoantibodies are 100% sensitive and specific for diagnosis. While there is no FDA-approved therapy, a variety of therapeutic approaches, including several off-label pharmacotherapies are currently used. The aim of this study was to determine the presentation and treatments presently employed in aPAP patients.
Methods: The National PAP Registry includes patients with all types of PAP syndrome. Data from patients with confirmed aPAP who had completed a detailed questionnaire were included to define the clinical features and current treatment patterns.
Results: Among National PAP Registry participants, aPAP was the PAP-causing disease in 88%, and 35 aPAP patients for whom complete data were available were studied further. The mean age of aPAP patients was 44.03+/-1.5 years and 51.4% of patients had a history of smoking. The median time to diagnosis of aPAP from initial symptoms was 1.5yrs (IQR 1.5-2.25yrs, range 0.5-13.5yrs) and presenting symptoms included dyspnea (97%), fatigue (85.7%), persistent cough (68%), sputum production (62.8%) and chest tightness (60%). The median shortness of breath questionnaire scores (SOBQ:range=0-120) was 36.5 (IQR 17-72.5, range 0-95) at registration. Less common symptoms/signs included peripheral cyanosis (20%), hemoptysis (14.3%) and fever (14.3%). In the period just prior to diagnosis of PAP 28.5% of patients had been treated for a presumed pneumonia which failed to improve with antibiotic therapy. Of note, 5.7% of aPAP patients had a history of opportunistic infections of the central nervous system and in 2.8%, this was noted at initial presentation. Whole lung lavage (WLL) had been performed at least once in 77% of patients (n=27/35), the mean time between WLLs was 10.2 months (±5.5 months). There was high variation in treatment frequency (coefficient of variation 54.55%) across patients; 1 WLL (26%), 2-5 WLL (55%) and >5 WLL (18%). Other experimental therapies included GM-CSF therapy (28.5%), rituximab (17.1%), corticosteroids (8.6%) and mycophenolate mofetil (2.8%).
Conclusion: Dyspnea was the most common presenting symptom of PAP and 90% of patients report progression over time. The majority of aPAP patients receiving WLL required this on a recurrent basis, and the frequency was highly variable among individuals. Further studies are needed to better define the safety and efficacy of pharmacotherapies of aPAP.
Author Block: B. C. Carey1, C. McCarthy1, M. Nowell-Bostic1, M. Rieman-Klingler1, C. Chalk1, A. Toth1, H. Lee2, M. Brelsford2, T. S. Wang3, J. Krischer2, B. C. Trapnell1; 1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2University of South Florida, Tampa, FL, United States, 3UCLA Dept of Pulm / Crit Care, Los Angeles, CA, United States.
Rationale: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disorder of surfactant accumulation resulting in hypoxemic respiratory failure. It is caused by antibody-mediated disruption of granulocyte/macrophage-colony stimulating factor (GM-CSF) signalling and accounts for 85-90% of all PAP patients and anti-GM-CSF autoantibodies are 100% sensitive and specific for diagnosis. While there is no FDA-approved therapy, a variety of therapeutic approaches, including several off-label pharmacotherapies are currently used. The aim of this study was to determine the presentation and treatments presently employed in aPAP patients.
Methods: The National PAP Registry includes patients with all types of PAP syndrome. Data from patients with confirmed aPAP who had completed a detailed questionnaire were included to define the clinical features and current treatment patterns.
Results: Among National PAP Registry participants, aPAP was the PAP-causing disease in 88%, and 35 aPAP patients for whom complete data were available were studied further. The mean age of aPAP patients was 44.03+/-1.5 years and 51.4% of patients had a history of smoking. The median time to diagnosis of aPAP from initial symptoms was 1.5yrs (IQR 1.5-2.25yrs, range 0.5-13.5yrs) and presenting symptoms included dyspnea (97%), fatigue (85.7%), persistent cough (68%), sputum production (62.8%) and chest tightness (60%). The median shortness of breath questionnaire scores (SOBQ:range=0-120) was 36.5 (IQR 17-72.5, range 0-95) at registration. Less common symptoms/signs included peripheral cyanosis (20%), hemoptysis (14.3%) and fever (14.3%). In the period just prior to diagnosis of PAP 28.5% of patients had been treated for a presumed pneumonia which failed to improve with antibiotic therapy. Of note, 5.7% of aPAP patients had a history of opportunistic infections of the central nervous system and in 2.8%, this was noted at initial presentation. Whole lung lavage (WLL) had been performed at least once in 77% of patients (n=27/35), the mean time between WLLs was 10.2 months (±5.5 months). There was high variation in treatment frequency (coefficient of variation 54.55%) across patients; 1 WLL (26%), 2-5 WLL (55%) and >5 WLL (18%). Other experimental therapies included GM-CSF therapy (28.5%), rituximab (17.1%), corticosteroids (8.6%) and mycophenolate mofetil (2.8%).
Conclusion: Dyspnea was the most common presenting symptom of PAP and 90% of patients report progression over time. The majority of aPAP patients receiving WLL required this on a recurrent basis, and the frequency was highly variable among individuals. Further studies are needed to better define the safety and efficacy of pharmacotherapies of aPAP.
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