Red Blood Cell Deformability is an Independent Predictor of Exertional Dyspnea in Deployed Veterans

Abstract

PURPOSE: Respiratory symptoms on exertion that are disproportionate to cardiopulmonary function represent a challenging clinical scenario that has been increasing in frequency among Iraq and Afghanistan veterans following their deployment. Among their exposures were burning trash, dust, sand, and air pollution. We hypothesized that impairment in oxygen delivery, due to impaired red blood cell (RBC) deformability, may contribute to reports of dyspnea in this population. METHODS: We recruited 18 symptomatic Iraq and Afghanistan veterans (34.1±7.0 yrs; 2 female) and 13 asymptomatic controls (n = 13; 34.1±8.9 yrs; 3 female) to participate in this study. All participants completed spirometry and maximal cardiopulmonary exercise testing. Blood samples were obtained before and immediately post-exercise for the determination of RBC deformability, calculated as cell deformation at infinite stress (EIMAX), by laser diffraction analysis using an ektacytometer. Dyspnea was assessed at peak exercise via the Borg breathlessness scale. We examined the association between EIMAX (rest and peak exercise) and peak dyspnea, adjusting for age, body mass index, smoking and airway obstruction (FEV1/FVC). RESULTS: Demographics were similar between groups, but spirometry was reduced in veterans (veterans vs. controls; FEV1: 95.2±18.3 vs. 114.3±14.7% predicted; FVC: 101.0±13.6 vs. 116.0±13.3% predicted; p < 0.01, Hedges’ g = 1.11 - 1.17). Peak exercise capacity was similar (VO2/kg: 34.9±8.9 vs. 36.1±10.5 ml·kg·min-1), but veterans endorsed greater dyspnea (5.6±1.8 vs. 3.6±1.0 Borg units; p = 0.001, g = 1.32). EIMAX was similar at rest (0.59±0.04 vs. 0.57±0.02; p = 0.08, g = 0.67), but not at peak exercise (0.59±0.04 vs 0.56±0.03, p = 0.01, g = 0.83). In our adjusted model, larger EIMAX at rest (β = 22.8, 95% CI 4.7, 40.9, p = 0.016) and immediately post-exercise (β = 19.2, 95% CI 3.1, 35.3, p = 0.016) were associated with greater dyspnea at peak exercise. CONCLUSION: In our sample, increased RBC deformability measured at rest and immediately post-exercise was independently associated with exertional dyspnea. Future studies are necessary to confirm these findings and investigate mechanisms of altered RBC rheology in the contexts of dyspnea. Funding: VA RR&D (1I21RX001079; MJF)