Etienne-Marie Jutant1,2, Xavier Jaïs3, Barbara Girerd4, Laurent Savale5, Maria-Rosa Ghigna6,7, Frédéric Perros8, Xavier Mignard9,10,11, Mitja Jevnikar3, Delphine Bourlier12, Grégoire Prevot13, Cécile Tromeur14, Fabrice Bauer15, Emmanuel Bergot16, Claire Dauphin17, Nicolas Favrolt18, Julie Traclet19, Thibaud Soumagne20, Pascal De Groote21, Céline Chabanne22, Pascal Magro23, Laurent Bertoletti24,25, Jean-Pierre Gueffet26, Ari Chaouat27, François Goupil28, Pamela Moceri29, Raphael Borie30, Elie Fadel31, Pierre Wolkenstein32, Pierre-Yves Brillet33, Gérald Simonneau34, Olivier Sitbon35, Marc Humbert36, David Montani5,37. 1. INSERM UMR_S 999, Cardiovascular Research Department , Le Plessis-Robinson, France. 2. University of Paris Sud, School of Medicine, Le Kremlin-Bicêtre, France. 3. GHU Paris-Sud - Hôpital de Bicêtre, Service de pneumologie, Le Kremlin-Bicêtre, France. 4. Hopital Antoine Béclère, Pneumolgie, Clamart, France. 5. CHU de Bicetre, Service de Pneumologie, Le Kremlin Bicetre, France. 6. INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. 7. School of Medicine, Université Paris-Sud / Université Paris Saclay, Le Kremlin-Bicêtre, France. 8. Centre Chirurgical Marie Lannelongue, INSERM U999, Le Plessis Robinson, France. 9. Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France, Le Kremlin-Bicêtre, France. 10. INSERM UMR_S 999 «Pulmonary Hypertension: Pathophysiology and Novel Therapies», Hôpital Marie Lannelongue, Le Plessis-Robinson, France, Le Plessis-Robinson, France. 11. 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. , Le Kremlin-Bicêtre, France. 12. Service des maladies respiratoires, Hôpital Haut-Lévêque CHU Bordeaux Pessac, France, Bordeaux, France. 13. CHU Toulouse, Respiratory Medicine, Toulouse, France. 14. CHRU de Brest, 26990, Internal Medicine and Chest Disease, Brest, France. 15. INSERM U1096, Heart Failure Clinic and Pulmonary Hypertension Center, Service de chirurgie cardiaque, Hôpital Charles Nicole, 76031 Rouen CEDEX, FR, Rouen, France. 16. Centre Hospitalier Universitaire de Caen, 26962, Department of Pulmonology, Caen, France. 17. Service de Cardiologie et Maladies Vasculaires, Hôpital Gabriel Montpied, Clermont-Ferrand, France. 18. Service de Pneumologie et Soins Intensifs Respiratoires. CHU François Mitterrand, Dijon, France. 19. Service de Pneumologie, Hôpital Louis Pradel, Lyon, France, Lyon, France. 20. Service de Pneumologie, Hôpital Minjoz, Besançon, France. 21. CHR Lille - Hôpital cardiologique, Clinique de cardiologie, Lille, France. 22. Service de Cardiologie, CHU Lille, Inserm U1167, Institut Pasteur de Lille, F-59000 Lille, France, Rennes, France. 23. Service de Pneumologie, CHU de Tours, Tours, France. 24. Université de Saint-Etienne, Jean Monnet; INSERM, Thrombosis Research Group, EA3065; CIC-CIE3, Saint-Etienne, France. 25. Centre Hospitalier Universitaire, Service de Médecine Interne et Thérapeutique, Saint-Etienne, France. 26. Unité de Soins et de Cardiologie Interventionnelle, Hôpital Privé du Confluent, Nantes, France. 27. Centre Hospitalier Régional Universitaire de Nancy, Département de Pneumologie, Hôpital de Brabois, Vandoeuvre-lès-Nancy, France. Inserm UMR_S 1116, Défaillance Cardiovasculaire Aigüe et Chronique, Faculté de Médecine de Nancy, Université de Lorraine,, Nancy, France. 28. CH, Service de Pneumologie, Le Mans, France. 29. Service de Cardiologie, CHU de Nice, Nice, France. 30. Hopital Bichat, Paris, France. 31. INSERM U999, Recherche medical, Le Plessis Robinson, France. 32. Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Dermatologie, CHU Mondor, Créteil. Université Paris-Est, Creteil, France. 33. AP-HP, Hôpital Avicenne, Radiologie, Bobigny, France. 34. Hopital Bicetre, 41664, Pulmonology, Le Kremlin-Bicetre, France. 35. National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France, Paris, France. 36. Univ Paris Sud, Le Kremlin-Bicêtre, France. 37. INSERM UMRS 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; davidmontani@gmail.com.
Abstract
RATIONALE: Pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1) is a rare and largely unknown complication of NF1. OBJECTIVES: To describe characteristics and outcomes of PH-NF1. METHODS: We reported the clinical, functional, radiologic, histologic and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs and transplant-free survival of patients with PH-NF1 from the French PH registry. RESULTS: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median age at diagnosis of 62 [18-82] years. At diagnosis, 92% were in New York Heart Association (NYHA) functional class III or IV. The 6-minute walk distance was 211 [0-460] m. Pulmonary function tests showed low diffusing capacity of the lung for carbon monoxide (DLCO) (30 [12-79] %) and severe hypoxemia (PaO2 56 [38-99] mmHg). Right heart catheterization showed severe precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure of 45 (10) mmHg and a pulmonary vascular resistance of 10.7 (4.2) WU. High-resolution computed tomography revealed cysts (76%), ground glass opacities (73%), emphysema (49%) and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3 and 5 years was 87%, 54% and 42%, respectively, and 4 patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling. CONCLUSIONS: PH-NF1 is characterized by a female predominance, a low DLCO and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.
RATIONALE: Pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1) is a rare and largely unknown complication of NF1. OBJECTIVES: To describe characteristics and outcomes of PH-NF1. METHODS: We reported the clinical, functional, radiologic, histologic and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs and transplant-free survival of patients with PH-NF1 from the French PH registry. RESULTS: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median age at diagnosis of 62 [18-82] years. At diagnosis, 92% were in New York Heart Association (NYHA) functional class III or IV. The 6-minute walk distance was 211 [0-460] m. Pulmonary function tests showed low diffusing capacity of the lung for carbon monoxide (DLCO) (30 [12-79] %) and severe hypoxemia (PaO2 56 [38-99] mmHg). Right heart catheterization showed severe precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure of 45 (10) mmHg and a pulmonary vascular resistance of 10.7 (4.2) WU. High-resolution computed tomography revealed cysts (76%), ground glass opacities (73%), emphysema (49%) and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3 and 5 years was 87%, 54% and 42%, respectively, and 4 patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling. CONCLUSIONS: PH-NF1 is characterized by a female predominance, a low DLCO and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.
Entities:
Keywords:
Interstitial lung disease; Neurofibromatosis type 1; Outcomes; Pulmonary hypertension
Authors: Reinhard E Friedrich; Jozef Zustin; Andreas M Luebke; Thorsten Rosenbaum; Martin Gosau; Christian Hagel; Felix K Kohlrusch; Ilse Wieland; Martin Zenker Journal: In Vivo Date: 2021 May-Jun Impact factor: 2.155