Pierre Thoré1,2,3, Xavier Jaïs1,4,5, Laurent Savale1,4,5, Peter Dorfmuller6, Athénaïs Boucly1,4,5, Matthieu Devilder4,7, Olivier Meyrignac4,7, Jérémie Pichon1,4,5, Julie Mankikian8, Marianne Riou9, Emmanuel Boiffard10, Clément Boissin11, Pascal De Groote12,13, Céline Chabanne14, Frédéric Gagnadoux15,16, Anne Bergeron17,18, Nicolas Noel4,19,20, Olivier Sitbon1,4,5, Marc Humbert1,4,5, David Montani21,22,23. 1. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 2. Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Department of Pneumology, Hôpital Brabois, Vandoeuvre-lès-Nancy, France. 3. INSERM UMR_S 1116 "Défaillance Cardiovasculaire Aigüe Et Chronique", School of Medicine of Nancy, University of Lorraine, Nancy, France. 4. School of Medicine, University Paris-Saclay, Le Kremlin-Bicêtre, France. 5. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France. 6. Department of Pathology, University Hospital of Giessen and Marburg (UKGM), Giessen, Germany. 7. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Radiology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 8. Centre Hospitalier Régional Universitaire (CHRU) de Tours, Department of Pneumology, Hôpital Bretonneau, Tours, France. 9. Department of Pneumology, Centre Hospitalier Universitaire (CHU) de Strasbourg, Nouvel Hôpital Civil (NHC) de Strasbourg, Strasbourg, France. 10. Centre Hospitalier Départemental (CHD) de Vendée, Department of Cardiology, Hôpital de La Roche sur Yon, La Roche sur Yon, France. 11. Centre Hospitalier Universitaire (CHU) de Montpellier, Department of Pneumology, Hôpital Arnaud de Villeneuve, Montpellier, France. 12. Centre Hospitalier Universitaire (CHU) de Lille, Department of Cardiology, Hôpital Albert Calmette, Lille, France. 13. Inserm U1167, Institut Pasteur de Lille, Lille, France. 14. Department of Cardiology and Vascular Diseases, Cardio-pneumologic Center, Centre Hospitalier Universitaire (CHU) de Rennes, Rennes, France. 15. Department of Pneumology, Centre Hospitalier Universitaire (CHU) D'Angers, Angers, France. 16. INSERM U1063, School of Medicine, Angers, France. 17. Université de Paris, Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Pneumology, Hôpital Saint-Louis, Paris, France. 18. INSERM UMR_S 1153 "Centre de Recherche Épidémiologie Et Statistique Sorbonne Paris Cité (CRESS)", Hôpital Saint-Louis, Paris, France. 19. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Internal Medicine and Immunology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 20. UMR INSERM/CEA 1184, Le Kremlin-Bicêtre, France. 21. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. david.montani@aphp.fr. 22. School of Medicine, University Paris-Saclay, Le Kremlin-Bicêtre, France. david.montani@aphp.fr. 23. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France. david.montani@aphp.fr.
Abstract
PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.
PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.