Abstract 4373232: Toxicant-Mediated Pulmonary Hypertension in Southwest Asia Veterans

Chronic exertional dyspnea has been documented in US Veterans after deployment to Iraq and Afghanistan with reported environmental inhalation exposures. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD) and pulmonary hypertension (PH). We performed detailed histomorphometry of pulmonary vasculature in 52 Veterans with biopsy-proven post-deployment respiratory syndrome (PDRS). Lung tissue specimens obtained from 15 non-diseased (ND) subjects, 13 end-stage patients with pulmonary arterial hypertension (PAH, Group 1 PH) and 8 patients with pulmonary hypertension due to left heart failure (LHF, Group 2 PH) were used as negative and positive controls, respectively. Then, we recruited nine of these Veterans with continued exertional dyspnea to undergo a follow-up clinical evaluation, including symptom questionnaire, pulmonary function testing, surface echocardiography, and right heart catheterization (RHC). Morphometric evaluation of pulmonary vasculature showed striking pathological changes in all patient groups. In bronchovascular bundle pulmonary arteries (BVB arteries), increased intima and media thicknesses were identified. Observed vascular pathology was not limited to BVBs but also extended to distal compartments, affecting intra-acinar (IA) arteries and veins, which are located within alveolar tissue and not associated with distal bronchioles. We found that the pathological changes in IA arteries in PDRS are less severe than in PAH and similar to LHF. Pathological remodeling of IA veins was characterized by similar fractional thicknesses of intima and adventitia in PDRS and PAH but was much less severe compared to LHF. In comparison to PAH and LHF patients, Veterans with PDRS had more prominent fibrosis (collagen deposition) at all generations of pulmonary vessels analyzed. Of the nine Veterans involved in clinical follow-up study, six had evidence of post-capillary PH on RHC at rest and one had PH at exercise. In contrast to patients with LHF, none of the Veterans who underwent RHC had evidence of systolic or diastolic dysfunction on surface echocardiography. Although further investigations are needed, these findings may suggest that Veterans with undiagnosed exertional dyspnea can develop previously unrecognized toxicant-mediated form of PH, which is post-capillary, may occur in the absence of left heart dysfunction and has unique vascular pathologic features.