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European Respiratory Society guidelines for the diagnosis and management of pulmonary alveolar proteinosis

  • Cormac McCarthy*
  • , Francesco Bonella
  • , Marissa O'Callaghan
  • , Clairelyne Dupin
  • , Tiago Alfaro
  • , Markus Fally
  • , Raphael Borie
  • , Ilaria Campo
  • , Vincent Cottin
  • , Aurelie Fabre
  • , Matthias Griese
  • , Alice Hadchouel
  • , Stephane Jouneau
  • , Maria Kokosi
  • , Effrosyni Manali
  • , Helmut Prosch
  • , Bruce C. Trapnell
  • , Marcel Veltkamp
  • , Tisha Wang
  • , Ingrid Toews
  • Alexander G. Mathioudakis, Elisabeth Bendstrup
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP. METHODS: A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations. RESULTS: The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy. CONCLUSIONS: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.

Original languageEnglish
Article number2400725
Number of pages22
JournalThe European respiratory journal
Volume64
Issue number5
DOIs
Publication statusPublished - 1 Nov 2024

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