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Pulmonary Alveolar Proteinosis Syndrome

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Orphan Lung Diseases

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Abstract

Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by the accumulation of pulmonary surfactant resulting in reduced oxygen uptake. It affects men, women, and children without predilection for socioeconomic status, geographic location, or race but occurs more commonly in smokers. Prevalence has been reported at 7–26 per million in the general population. Symptoms include dyspnea, cough, and fatigue. The clinical course includes progressive dyspnea, failure and, in some patients, serious secondary infections, pulmonary fibrosis, hypoxemic respiratory failure, and death. PAP is classified as primary (mediated by disruption of GM-CSF signaling), secondary (mediated by reduced alveolar macrophage functions due to an underlying clinical condition), or congenital (caused by mutations in genes involved in surfactant production). In primary PAP the most common cause is autoimmune PAP, which accounts for over 90% of all PAP syndrome. Pathogenesis is driven by impaired GM-CSF signaling to alveolar macrophages which require GM-CSF stimulation to stimulate surfactant clearance. The diagnosis of autoimmune PAP can be made by testing for an increased level of serum GM-CSF autoantibodies without a requirement for a lung biopsy. Whole-lung lavage is the main current treatment approach designed to remove excess surfactant by physically washing it out of the lungs but a pharmacotherapeutic approaches, inhaled GM-CSF is currently under evaluation.

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Authors and Affiliations

  1. Department of Respiratory Medicine, St. Vincent’s University Hospital, Dublin, Ireland

    Marissa O’Callaghan & Cormac McCarthy

  2. University College Dublin 4, Dublin, Ireland

    Marissa O’Callaghan & Cormac McCarthy

  3. Division of Pulmonary Biology, Translational Pulmonary Science Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Bruce C. Trapnell

  4. Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Bruce C. Trapnell

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  1. Marissa O’Callaghan
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  2. Cormac McCarthy
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  3. Bruce C. Trapnell
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Correspondence to Bruce C. Trapnell .

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Editors and Affiliations

  1. Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases (OrphaLung), Louis Pradel Hospital, University of Lyon, Lyon, France

    Vincent Cottin

  2. Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

    Luca Richeldi

  3. National Jewish Health, Denver, CO, USA

    Kevin Brown

  4. Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Francis X. McCormack

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O’Callaghan, M., McCarthy, C., Trapnell, B.C. (2023). Pulmonary Alveolar Proteinosis Syndrome. In: Cottin, V., Richeldi, L., Brown, K., McCormack, F.X. (eds) Orphan Lung Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-12950-6_22

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