Cormac McCarthy1, Maria Kokosi2, Francesco Bonella3. 1. Department of Respiratory Medicine, Rare Lung Disease Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland. 2. Interstitial Lung Disease Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK. 3. Department of Pneumology, Centre for Interstitial and Rare Lung Disease, Ruhrlandklinik, University Hospital Essen, Essen, Germany.
Abstract
PURPOSE OF REVIEW: Pulmonary alveolar proteinosis (PAP) can be considered the archetype of ultra-rare diseases with a prevalence of under 10 cases per million. We discuss the classification of PAP, the current diagnostic practice and the supplementary role of genetic testing and granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in the diagnosis of congenital and hereditary PAP. We report on novel therapeutic approaches such as GM-CSF substitution, stem cell transplantation, pioglitazone, statins and immunomodulation. RECENT FINDINGS: The discovery of new genetic mutations underlying this syndrome raises the question whether the classification should be radically revised in the future. Serum GM-CSF autoantibody is the best diagnostic marker for autoimmune PAP, the most common form, but does not correlate with disease severity. Several circulating biomarkers have been investigated to assess disease activity and predict outcome. Imaging techniques have also enormously evolved and offer new tools to quantify disease burden and possibly drive therapeutic decisions. Promising clinical trials are ongoing and will generate new treatment strategies besides or in addition to whole lung lavage in the next future. SUMMARY: Despite impressive advances in understanding pathogenesis, PAP remains a rare syndrome with several unanswered questions impacting diagnosis, management and treatment, and, as a result, patients' quality of life.
PURPOSE OF REVIEW: Pulmonary alveolar proteinosis (PAP) can be considered the archetype of ultra-rare diseases with a prevalence of under 10 cases per million. We discuss the classification of PAP, the current diagnostic practice and the supplementary role of genetic testing and granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in the diagnosis of congenital and hereditary PAP. We report on novel therapeutic approaches such as GM-CSF substitution, stem cell transplantation, pioglitazone, statins and immunomodulation. RECENT FINDINGS: The discovery of new genetic mutations underlying this syndrome raises the question whether the classification should be radically revised in the future. Serum GM-CSF autoantibody is the best diagnostic marker for autoimmune PAP, the most common form, but does not correlate with disease severity. Several circulating biomarkers have been investigated to assess disease activity and predict outcome. Imaging techniques have also enormously evolved and offer new tools to quantify disease burden and possibly drive therapeutic decisions. Promising clinical trials are ongoing and will generate new treatment strategies besides or in addition to whole lung lavage in the next future. SUMMARY: Despite impressive advances in understanding pathogenesis, PAP remains a rare syndrome with several unanswered questions impacting diagnosis, management and treatment, and, as a result, patients' quality of life.
Authors: David Lawi; Estelle Dubruc; Michel Gonzalez; John-David Aubert; Paola M Soccal; Jean-Paul Janssens Journal: Respir Med Case Rep Date: 2020-05-30