Clinical relevance of microvascular endothelial dysfunction in idiopathic pulmonary fibrosis

Jean Pastré; Hélène Salvator; Priscilla Henno; Sven Günther; Alexandre Chabrol; Stanislas Grassin-Delyle; Dominique Israël-Biet; Philippe Devillier

doi:10.1183/23120541.01265-2024

Clinical relevance of microvascular endothelial dysfunction in idiopathic pulmonary fibrosis

ERJ Open Res. 2025 Oct 20;11(5):01265-2024. doi: 10.1183/23120541.01265-2024. eCollection 2025 Sep.

Authors

Jean Pastré¹, Hélène Salvator^{2

3

4}, Priscilla Henno⁵, Sven Günther^{5

6}, Alexandre Chabrol², Stanislas Grassin-Delyle^{3

4}, Dominique Israël-Biet⁷, Philippe Devillier^{3

4}

Affiliations

¹ Service de Pneumologie et Soins Intensifs, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
² Service de Pneumologie, Hôpital Foch, Suresnes, France.
³ Laboratoire VIM-Suresnes, UMR_0892 INRAE, Université Paris Saclay, Suresnes, France.
⁴ Faculté des Sciences de la Vie Simone Veil, UVSQ, Montigny le Bretonneux, France.
⁵ Unité d'Explorations Fonctionnelles Respiratoires et du Sommeil, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
⁶ University Paris Cité, Innovative Therapies in Haemostasis, INSERM UMR_S1140, Paris, France.
⁷ Université Paris Cité INSERM UMR_S1140, Paris, France.

Abstract

Background: Endothelial dysfunction (ED) is involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF). Reactive hyperaemia peripheral arterial tonometry (RH-PAT) is a rapid, reproducible, noninvasive technique for assessing peripheral microvascular endothelial function.

Methods: We conducted a prospective study of endothelial function (reactive hyperaemia index (RHI) as measured by RH-PAT) in patients with IPF, in order to explore the association between ED and respiratory symptoms, lung function and the disease prognosis. Adult patients with IPF underwent a baseline assessment of respiratory symptoms (including dyspnoea on the modified Medical Research Council scale), blood gas levels, pulmonary function tests, a 6-min walk test (6MWT) and endothelial function. The same examinations were performed 12, 24 and 36 months after inclusion.

Results: 42 patients with IPF (men: 76%) were enrolled. The median (IQR) age was 70 (61-75) years. The median (IQR) forced vital capacity and diffusing capacity of the lung for carbon monoxide (D _LCO) were 77% (66-93%) and 43% (33-53%) predicted, respectively. The median (IQR) RHI was 1.86 (1.60-2.48). An ED defined at the RHI reference cut-off of 1.67 was observed in 13 (31%) patients. After 1 year of follow-up, there was a significant decline in endothelial function (median (IQR) difference: 0.65 (0.35-0.85), p=0.009). The RHI was associated with dyspnoea (r= -0.33, p=0.036), D _LCO (r=0.36, p=0.025) and oxygen saturation at the end of 6MWT (r=0.33, p=0.049). The subgroups of patients with and without ED did not differ significantly in terms of mortality or the occurrence of acute exacerbations, although there was a nonsignificant trend to greater functional disease progression in patients with ED.

Conclusion: Finger ED was correlated with respiratory symptoms and functional variables and worsened during the first year of follow-up. Our results suggest that the severity of IPF is associated with ED, although further studies are needed to assess the value of RH-PAT in the management of IPF.