Background Increased frequency of exertional dyspnea has been documented in U.S. military personnel after deployment to Southwest Asia and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD).

Methods We recruited five Iraq and Afghanistan Veterans with post-deployment respiratory syndrome (PDRS) and continued exertional dyspnea to undergo a detailed clinical evaluation including symptom questionnaire, pulmonary function testing (PFT), surface echocardiography, and right heart catheterization (RHC) with exercise. We then performed detailed histomorphometry of blood vasculature in 52 Veterans with PDRS, 13 patients with advanced idiopathic pulmonary arterial hypertension (PAH) and 15 non-diseased (ND) control subjects.

Results All five Veterans involved in clinical follow-up study had a continued dyspnea at exertion. On transthoracic echocardiography, we identified borderline or overt RV enlargement in three out of five Veterans. Right ventricle outflow tract (RVOT) acceleration time, a well-established surrogate measure of pulmonary pressure, was mildly reduced in three out of five Veterans. Of the five Veterans with PDRS who underwent RHC at exercise, we found that three had evidence of post-capillary PH at rest and one had PH at exercise. Morphometric evaluation of lung biopsy samples showed mild/moderate increase of fractional thicknesses of intima and media, and significant fibrosis of adventitia in pulmonary arteries in Veterans with PDRS compared to ND controls and PAH patients. Veterans with PDRS did not display plexiform or dilation/angiomatoid lesions, specific for PAH. Pulmonary veins showed similar levels of intima and adventitia fractional thickening in Veterans with PDRS and PAH patients compared to ND controls. In Veterans, IA veins were characterized by marked fibrous intima and adventitia thickening, usually with increased thickening and formation of multiple layers of elastic laminae, but without features of luminal occlusion, muscular hyperplasia or dilation/angiomatoid lesions seen in pulmonary veno-occlusive disease or chronic thromboembolic PH.

Conclusions Our studies suggest that vasculopathy and PVD may explain exertional dyspnea and exercise limitation in some Veterans with PDRS. Evaluation for PVD should be considered in Iraq and Afghanistan Veterans with unexplained dyspnea.

The authors have declared no competing interest.

Funding sources: Department of Defense W81XWH-17-1-0503, generous donation by Ms. Carol Odess.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Histomorphometrical analysis was performed under the following Vanderbilt IRB approvals: 1) for surgical lung biopsy specimens from Veterans, #161046; 2) for patients with PAH who underwent lung transplantation, #060165; 3) lung tissue from deceased organ donors whose lungs were rejected for transplantation were exempt from IRB review. All clinical studies were approved by the Vanderbilt IRB (#200473 and #210973).

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All data produced in the present study are available upon reasonable request to the authors