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Original research
Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort
  1. Axelle Mabo1,
  2. Raphael Borie2,
  3. Lidwine Wemeau-Stervinou3,
  4. Yurdagül Uzunhan4,
  5. Emmanuel Gomez5,
  6. Gregoire Prevot6,
  7. Martine Reynaud-Gaubert7,
  8. Julie Traclet8,
  9. Emmanuel Bergot9,
  10. Jacques Cadranel10,
  11. Sylvain Marchand-Adam11,
  12. Anne Bergeron12,
  13. Elodie Blanchard13,
  14. Benjamin Bondue14,
  15. Philippe Bonniaud15,
  16. Arnaud Bourdin16,
  17. Pierre Regis Burgel17,
  18. Sandrine Hirschi18,
  19. Charles Hugo Marquette19,
  20. Sébastien Quétant20,
  21. Hilario Nunes4,
  22. Cécile Chenivesse3,
  23. Bruno Crestani2,
  24. Yoann Guirriec1,
  25. Delphine Monnier21,
  26. Cédric Ménard21,
  27. Pierre Tattevin22,
  28. Vincent Cottin8,
  29. David Luque Paz1,22,
  30. Stéphane Jouneau1,23
  31. OrphaLung Network
  1. 1Service de Pneumologie, Centre de Compétence pour les Maladies Pulmonaires Rares, Hôpital Pontchaillou, CHU Rennes, Rennes, France
  2. 2Centre de Référence Constitutif des Maladies Pulmonaires Rares, Service de Pneumologie A, Hopital Bichat, APHP, Paris, France
  3. 3Centre de Référence Constitutif des Maladies Pulmonaires Rares, Institut Cœur-Poumon, Service de Pneumologie et Immuno-Allergologie, CHRU Lille, Lille, France
  4. 4Centre de Référence Constitutif des Maladies Pulmonaires Rares, Service de Pneumologie, Hôpital Avicenne, APHP, Bobigny, France
  5. 5Centre de Compétence pour les Maladies Pulmonaires Rares, Département de Pneumologie, Hôpitaux de Brabois, CHRU de Nancy, Vandoeuvre-les Nancy, France
  6. 6Service de Pneumologie, Centre de Compétence pour les Maladies Pulmonaires Rares, Hôpital Larry, CHU Toulouse, Toulouse, France
  7. 7Service de Pneumologie et Transplantation Pulmonaire, Centre de Compétences des Maladies Rares Pulmonaires et de l'Hypertension Pulmonaire, CHU Nord de Marseille, AP-HM, Aix Marseille Université, Marseille, France
  8. 8Service de Pneumologie, Centre National Coordonnateur de Référence des Maladies Pulmonaires Rares, Hôpital Louis-Pradel, Hospices Civils de Lyon (HCL), UMR754, INRAE, Université Lyon 1, ERN-LUNG, Lyon, France
  9. 9Centre de Compétence pour les Maladies Pulmonaires Rares de l'Adulte, Service de Pneumologie et Oncologie Thoracique, Hôpital Côte de Nacre, CHU de Caen, Caen, France
  10. 10Service de Pneumologie et Oncologie Thoracique, Centre Constitutif Maladies Pulmonaires Rares, Hôpital Tenon, APHP, Sorbonne Université, Paris, France
  11. 11Service de Pneumologie, CHRU de Tours, Université François Rabelais de Tours, INSERM U1100, Tours, France
  12. 12Service de Pneumologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
  13. 13Service de Pneumologie, centre de compétence pour les maladies pulmonaires rares, CHU de Bordeaux, Pessac, France
  14. 14Service de Pneumologie, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
  15. 15Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adulte, CHU Dijon-Bourgogne, Inserm U123, Université de Bourgogne, Dijon, France
  16. 16Service de Pneumologie, CHU Montpellier, Université de Montpellier, Inserm U1046, Montpellier, France
  17. 17Service de Pneumologie, Hopital Cochin Pneumologie, AP-HP, Université Paris Cité Paris, Paris, France
  18. 18Service de Pneumologie et Transplantation Pulmonaire, Hopitaux universitaires de Strasbourg, Strasbourg, France
  19. 19Service de Pneumologie, CHU Nice, Fédération Hospitalo-Universitaire OncoAge, Nice, France
  20. 20Service Hospitalo-Universitaire de Pneumologie et Physiologie, Pôle Thorax et Vaisseaux, CHU de Grenoble-Alpes, La Tronche, Grenoble, France
  21. 21Service d’Immunologie, Laboratoire de Biologie Médicale de Référence Lipoprotéinose Alvéolaire, Hôpital Pontchaillou, CHU Rennes, Rennes, France
  22. 22Service de Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Inserm U1230, Université de Rennes, Rennes, France
  23. 23Inserm UMR1085 IRSET, Université de Rennes, EHESP, Rennes, France
  1. Correspondence to Dr David Luque Paz, Pneumologie, Hôpital Pontchaillou, Rennes, France; david.luque.paz{at}


Background Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.

Research question Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections.

Methods We conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data.

Results We included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7–6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardia spp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316–1591) vs 580 (200–1190), p=0.01). Nine patients had died (9%), but only one death was related to infection.

Interpretation Patients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

  • pulmonary alveolar proteinosis
  • GM-CSF autoantibody
  • opportunist lung infections
  • bacterial Infection

Data availability statement

Data can be made available upon reasonable request.

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Data availability statement

Data can be made available upon reasonable request.

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  • DLP and SJ are joint senior authors.

  • DLP and SJ contributed equally.

  • Correction notice This article has been corrected since it was published Online First. Figure 1 has been corrected.

  • Contributors AM fulfilled the role of guarantor. DLP did the analysis. AM, DLP, PT and SJ cowrote the original draft. AM, RB, LW-S, YU, EG, GP, MR-G, JT, EBergot, JC, SM-A, ABergeron, EBlanchard, BB, PB, ABourdin, PRB, SH, CHM, SQ, HN, CC, BC, YG, DM, CM, PT, VC, DLP and SJ contributed substantially to the investigation and data collection, as well to reviewing and editing the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests The authors reported no conflict of interest related to this work. SMA reports having received consultancy for board membership, consultancy or speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis and Roche, GSK, BMS, Chiesi and Pfizer; and travel support from Boehringer Ingelheim. Other authors have nothing to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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