Lung capillary blood volume and membrane diffusion in precapillary pulmonary hypertension

Laurent Godinas; David Amar; David Montani; Edmund M Lau; Xavier Jaïs; Laurent Savale; Mitja Jevnikar; Olivier Sitbon; Gérald Simonneau; Marc Humbert; Pierantonio Laveneziana; Gilles Garcia

doi:10.1016/j.healun.2015.12.022

Lung capillary blood volume and membrane diffusion in precapillary pulmonary hypertension

J Heart Lung Transplant. 2016 May;35(5):647-56. doi: 10.1016/j.healun.2015.12.022. Epub 2016 Jan 6.

Affiliations

¹ Assistance Publique-Hôpitauxde Paris, Centre deRéférencedel' Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, LeKremlin Bicêtre, France; Faculté de Médecine, Univ. Paris-Sud, Le Kremlin Bicêtre; UMR_S 999, Univ. Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Département de pneumologie, Centre Hospitalier Universitaire, Université Catholique de Louvain Mont-Godinne, Yvoir, Belgium.
² Assistance Publique-Hôpitauxde Paris, Centre deRéférencedel' Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, LeKremlin Bicêtre, France; Faculté de Médecine, Univ. Paris-Sud, Le Kremlin Bicêtre; UMR_S 999, Univ. Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
³ Assistance Publique-Hôpitauxde Paris, Centre deRéférencedel' Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, LeKremlin Bicêtre, France; Faculté de Médecine, Univ. Paris-Sud, Le Kremlin Bicêtre; UMR_S 999, Univ. Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia.
⁴ Assistance Publique-Hôpitauxde Paris, Centre deRéférencedel' Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, LeKremlin Bicêtre, France; Faculté de Médecine, Univ. Paris-Sud, Le Kremlin Bicêtre; UMR_S 999, Univ. Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée (Département "R3S"), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Institut National de la Santé et de la Recherche Médicale, L'Unité Médicale de Recherche Scientifique 1158 Neurophysiologie respiratoire expérimentale et clinique, Paris, France.
⁵ Assistance Publique-Hôpitauxde Paris, Centre deRéférencedel' Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie, Hôpital de Bicêtre, LeKremlin Bicêtre, France; Faculté de Médecine, Univ. Paris-Sud, Le Kremlin Bicêtre; UMR_S 999, Univ. Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. Electronic address: gilles.garcia@bct.aphp.fr.

PMID: 26987595
DOI: 10.1016/j.healun.2015.12.022

Abstract

Background: Combined diffusion capacity of the lung for carbon monoxide (DLco) and nitric oxide (DLno) measurements allow for the estimation of pulmonary capillary blood volume (Vc) and alveolar membrane diffusion (Dm). The clinical usefulness of these measurements in pulmonary hypertension (PH) is unclear.

Methods: Combined DLco and DLno were measured in 290 consecutive patients with precapillary PH (pulmonary arterial hypertension (PAH), n = 153; pulmonary veno-occlusive disease (PVOD), n = 33; and chronic thromboembolic pulmonary hypertension (CTEPH), n = 104). Clinical correlates of Vc and Dm were assessed in a sub-group of PAH patients without comorbidities.

Results: PVOD patients compared with PAH and CTEPH patients displayed the lowest values of Vc (29.4 ± 16.8 ml vs 56.3 ± 26.5 ml vs 56.9 ± 26.2 ml, p < 0.01, respectively) and Dm (27.7 ± 11.6 ml/mm Hg/min vs 43.4 ± 14.8 ml/mm Hg/min vs 44.7 ± 17.7 ml/mm Hg/min, p < 0.01, respectively). The DLno/DLco ratio was highest in the PVOD group (5.82 ± 2.04 vs 4.95 ± 1.31 vs 5.16 ± 1.58, p < 0.05). In a sub-set of 69 PAH patients without comorbidities, Vc and Dm correlated significantly with functional capacity (6-minute walking distance, oxygen consumption) and New York Heart Association Functional Classification but not with invasive hemodynamics. Only Dm was significantly associated with survival. On receiver operating characteristic curve analysis, Vc, Dm, and DLno/DLco were not superior to DLco for discriminating PVOD from PAH or CTEPH.

Conclusions: PVOD patients display higher values of the DLno/DLco ratio compared with PAH and CTEPH, suggesting proportionally greater reduction in Vc relative to Dm. However, partitioning of diffusion failed to be more clinically relevant than conventional DLco for detection of PVOD.

Keywords: chronic thromboembolic disease; lung capillary blood volume; membrane diffusion; pulmonary arterial hypertension; pulmonary veno-occlusive disease.

MeSH terms

Blood Volume
Humans
Hypertension, Pulmonary*
Lung
Pulmonary Diffusing Capacity
Respiratory Function Tests