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Pulmonary Hypertension in Patients with Common Variable Immunodeficiency

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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.

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Data Availability

The data that support the findings of this study are available from the corresponding author, (DM), upon reasonable request.

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Acknowledgements

We thank all the physicians from the French Pulmonary Hypertension Network.

We especially extend our thanks to doctor Philippe Brenot (Centre chirurgical Marie Lannelongue, Department of Radiology, Le Plessis Robinson, France) for his clinical experience and his expertise in pulmonary angioplasty.

Author information

Authors and Affiliations

  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

    Pierre Thoré, Xavier Jaïs, Laurent Savale, Athénaïs Boucly, Jérémie Pichon, Olivier Sitbon, Marc Humbert & David Montani

  2. Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Department of Pneumology, Hôpital Brabois, Vandoeuvre-lès-Nancy, France

    Pierre Thoré

  3. INSERM UMR_S 1116 “Défaillance Cardiovasculaire Aigüe Et Chronique”, School of Medicine of Nancy, University of Lorraine, Nancy, France

    Pierre Thoré

  4. School of Medicine, University Paris-Saclay, Le Kremlin-Bicêtre, France

    Xavier Jaïs, Laurent Savale, Athénaïs Boucly, Matthieu Devilder, Olivier Meyrignac, Jérémie Pichon, Nicolas Noel, Olivier Sitbon, Marc Humbert & David Montani

  5. INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hôpital Marie Lannelongue, Le Plessis-Robinson, France

    Xavier Jaïs, Laurent Savale, Athénaïs Boucly, Jérémie Pichon, Olivier Sitbon, Marc Humbert & David Montani

  6. Department of Pathology, University Hospital of Giessen and Marburg (UKGM), Giessen, Germany

    Peter Dorfmuller

  7. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Radiology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Matthieu Devilder & Olivier Meyrignac

  8. Centre Hospitalier Régional Universitaire (CHRU) de Tours, Department of Pneumology, Hôpital Bretonneau, Tours, France

    Julie Mankikian

  9. Department of Pneumology, Centre Hospitalier Universitaire (CHU) de Strasbourg, Nouvel Hôpital Civil (NHC) de Strasbourg, Strasbourg, France

    Marianne Riou

  10. Centre Hospitalier Départemental (CHD) de Vendée, Department of Cardiology, Hôpital de La Roche sur Yon, La Roche sur Yon, France

    Emmanuel Boiffard

  11. Centre Hospitalier Universitaire (CHU) de Montpellier, Department of Pneumology, Hôpital Arnaud de Villeneuve, Montpellier, France

    Clément Boissin

  12. Centre Hospitalier Universitaire (CHU) de Lille, Department of Cardiology, Hôpital Albert Calmette, Lille, France

    Pascal De Groote

  13. Department of Cardiology and Vascular Diseases, Cardio-pneumologic Center, Centre Hospitalier Universitaire (CHU) de Rennes, Rennes, France

    Céline Chabanne

  14. Department of Pneumology, Centre Hospitalier Universitaire (CHU) D’Angers, Angers, France

    Frédéric Gagnadoux

  15. INSERM U1063, School of Medicine, Angers, France

    Frédéric Gagnadoux

  16. Université de Paris, Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Pneumology, Hôpital Saint-Louis, Paris, France

    Anne Bergeron

  17. INSERM UMR_S 1153 “Centre de Recherche Épidémiologie Et Statistique Sorbonne Paris Cité (CRESS)”, Hôpital Saint-Louis, Paris, France

    Anne Bergeron

  18. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Internal Medicine and Immunology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Nicolas Noel

  19. UMR INSERM/CEA 1184, Le Kremlin-Bicêtre, France

    Nicolas Noel

  20. Inserm U1167, Institut Pasteur de Lille, Lille, France

    Pascal De Groote

Authors
  1. Pierre Thoré
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  2. Xavier Jaïs
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  3. Laurent Savale
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  14. Céline Chabanne
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  15. Frédéric Gagnadoux
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  16. Anne Bergeron
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  17. Nicolas Noel
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  18. Olivier Sitbon
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  19. Marc Humbert
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  20. David Montani
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Contributions

DM is the guarantor of the content of the article, including the data and analysis. PT and DM contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript. PD reviewed histologic specimens. OM and MD independently analyzed HRCT data. All authors revised the work critically for important intellectual content and gave final approval of the manuscript before submission.

Corresponding author

Correspondence to David Montani.

Ethics declarations

Ethics Approval and Consent to Participate

Commission Nationale de l’Informatique et des Libertés no 842063. All patients gave their consent to be included in the registry of the French PH Network in agreement with French bioethics laws.

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Not applicable.

Conflict of Interest

The authors declared that there is no conflict of interest regarding the publication of this original article.

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Thoré, P., Jaïs, X., Savale, L. et al. Pulmonary Hypertension in Patients with Common Variable Immunodeficiency. J Clin Immunol 41, 1549–1562 (2021). https://doi.org/10.1007/s10875-021-01064-w

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  • DOI: https://doi.org/10.1007/s10875-021-01064-w

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