Pulmonary Vascular Dysfunction after Deployment-Related Exposures

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Military environmental exposures are pervasive in Iraq and Afghanistan, including particulate air pollution levels that are 10 times higher than urban cities in the United States. Although a causal relationship is unclear, respiratory symptoms are frequently reported both during and following deployment, and deployment to Iraq or Afghanistan is associated with an increased risk of respiratory conditions. Despite the presence of symptoms, the majority of Veterans have normal lung volumes and airflows as detected by spirometry. However, spirometry may be insensitive in this population and does not assess the primary function of the lung which is gas-exchange. Gas-exchange is assessed at rest via the measurement of lung diffusing capacity of carbon monoxide (DLCO), and our preliminary data suggest that DLCO is commonly reduced in Veterans despite normal spirometry. The pattern of normal lung volumes and airflows but low DLCO – i.e., an isolated reduction in DLCO – suggests early pulmonary vascular or parenchymal lung disease. An isolated reduction in DLCO has previously been reported in exposure-related bronchiolar disorders, including a case series of active duty soldiers with dyspnea on exertion. We hypothesize that exposure to particulate air pollution during deployment results in deposition of small particles in the distal airways, resulting in focal pulmonary vascular injury, release of vasoactive mediators and systemic vascular dysfunction which manifests as respiratory symptoms and dyspnea on exertion. Our aims are: Aim 1) To non-invasively assess resting and exercise gas-exchange as well as the pulmonary hemodynamic response to incremental and maximal exercise, and Aim 2) To identify systemic markers of vascular injury, including circulating levels of vasoactive mediators and systemic vascular reactivity. Pulmonologists in the Departments of Veterans Affairs and Defense have recognized the biggest challenge in evaluating post-deployment respiratory symptoms is the individual with normal spirometry; therefore, we will focus on this group of post-9/11 Veterans. Specifically, we will recruit two groups of Veterans with normal lung volumes and airflows, but with (Normal PFT) and without reduced DLCO (Low DLCO). By classifying Veterans into groups based on pulmonary function patterns (Normal PFT vs. Low DLCO), we will be able to discern whether an isolated reduction in DLCO is an unusual variant or a harbinger of deployment- related lung disease. To complement our aims, we will conduct exploratory follow-up evaluations (annually over the duration of the award) on a subset of Veterans to determine how pulmonary vascular function and systemic markers of subclinical pulmonary vascular disease progress over time. Through these studies, we expect to uncover new knowledge about deployment-related respiratory disease as well as the short- and long- term consequences of military environmental exposures, which may facilitate earlier diagnosis and treatment of symptomatic post-9/11 Veterans.