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Autoimmune Pulmonary Alveolar Proteinosis: A Review of Pathogenesis and Emerging Therapies

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Abstract

Purpose of Review

Autoimmune pulmonary alveolar proteinosis is a heterogenous clinical syndrome of disordered surfactant clearance due to a dysfunctional granulocyte–macrophage colony-stimulating factor signaling axis in the setting of polyclonal autoantibody generation. Recent advancements identifying key mechanistic drivers of this disease have been made. This clinical review summarizes current knowledge of autoimmune pulmonary alveolar proteinosis with an emphasis on contemporary findings on pathogenesis and emerging therapies.

Recent Findings

A disturbed granulocyte–macrophage colony-stimulating factor signaling axis leads to downstream dysregulation of cholesterol export within alveolar macrophages. Accumulation of cholesterol impedes surfactant clearance and propagates the syndrome’s disease process.

Summary

Whole lung lavage therapy is an invasive procedure performed under general anesthesia which remains the standard of care for autoimmune pulmonary alveolar proteinosis. Augmentation of the defective signaling axis with recombinant human granulocyte-macrophage colony-stimulating factor is a promising treatment modality.

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Abbreviations

ABCA1:

ATP binding cassette subfamily A member 1

ABCG1:

ATP binding cassette subfamily G member 1

A-aDO2 :

Alveolar-arterial oxygen gradient

DLCO:

Diffusing capacity for carbon monoxide

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

PaO2:

Partial pressure of oxygen in the arterial blood

PAP:

Pulmonary alveolar proteinosis

PPAR-γ:

Peroxisome proliferator-activated receptor gamma

PU.1:

Purine-rich box1

6MWD:

6-Minute walk distance

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Authors and Affiliations

  1. Department of Internal Medicine, University of Florida, Gainesville, FL, US

    Akshay Mathavan & Akash Mathavan

  2. Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 1600 SW Archer Road, M452, P.O. Box 100225, 32610, Gainesville, FL, US

    Swaminathan Perinkulam Sathyanarayanan & Ali Ataya

  3. School of Medicine, University College Dublin, Dublin 4, Belfield, Ireland

    Cormac McCarthy

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Akash Mathavan and Akshay Mathavan performed literature review and drafted the manuscript. Swaminathan Perinkulam Sathyanarayanan and Cormac McCarthy assisted in literature review and drafted portions of the manuscript. Ali Ataya supervised the manuscript, provided subject matter expertise, revised the manuscript, and is responsible for the final content. All authors have agreed on the journal to which the article will be submitted, the final version for publication, and accountability for all aspects of the work.

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Correspondence to Ali Ataya.

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Mathavan, A., Mathavan, A., Sathyanarayanan, S.P. et al. Autoimmune Pulmonary Alveolar Proteinosis: A Review of Pathogenesis and Emerging Therapies. Curr Pulmonol Rep (2024). https://doi.org/10.1007/s13665-024-00356-x

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