Metabolomics of Lead Exposure and Its Role in Respiratory Disease
Abstract
Background: Military Service personnel and Veterans suffer disproportionately from poor lung health. Evidence suggests that their respiratory system may be permanently damaged by exposure to heavy metals such as lead (Pb) during active service. However, the exact ways in which this damage occurs is poorly understood. One powerful approach to explore the effect of Pb exposure on the respiratory system is by using metabolomic profiling. This method identifies and measures all the small molecules in a biological system, which provides information on the biological status of that system in terms of health, disease, and external influences. Metabolomic profiles (i) provide a deeper biological understanding of the effect of Pb exposure on the respiratory system and (ii) identify molecules or groups of molecules that can act as markers to determine when an individual is exposed to a level of Pb that is likely to cause harm to their respiratory health. Research Strategy: This proposal addresses two areas of encouragement: Metals Toxicology and Respiratory Health, and crucially explores the link between them utilizing a novel “omics” approach. Metabolomics profiling will be conducted on blood samples from 374 Veterans enrolled in the Normative Aging Study (NAS) over 40 years ago and followed up periodically since then who have measures of Pb exposure from bone, toenail, blood, and urine representing past, cumulative, and recent exposures and validated measures of lung function. These profiles, detailing which molecules are present and in what quantities, will be used to determine how molecules in the human body change with Pb exposure (Aim 1); how molecules differ in those with good lung function compared to those with poor lung function (Aim 2); and to identify the link between the molecular changes associated with exposure and the molecular changes associated with lung function, to understand, biologically, how Pb causes poor respiratory health (Aim 3). These molecular changes will be identified using a variety of different statistical approaches. Other factors that may be influencing respiratory health will also be incorporated into these analyses. Innovation: This represents the first study to utilize metabolomics profiling to explore the biology underlying Pb exposure and its effect on respiratory health. Metabolomics is currently underutilized in the study of lung function; however, it represents an ideal approach due to the complex nature of lung function and the fact that it is heavily influenced by environmental factors. This study uses an innovative design, incorporating exposure and disease simultaneously, in addition to novel statistical approaches that have never previously been applied to this question. It is based within a unique population of Veterans, in whom previous studies have revealed innovative and impactful, military-relevant results. The innovative aspects of this study can also be applied to explore other environmental exposure/chronic disease relationships in a variety of contexts. Applicabilty and Impact: This proposal is particularly important and timely as there is now a growing population of aging Veterans who were exposed to Pb during active service in the Gulf, Iraq and Afghanistan, and who represent a significant public health burden for the USA. An improved understanding of the biology underlying the relationship between Pb exposure and respiratory health will benefit both current and future Veterans as well as current and future Service personnel in a three-fold fashion: (i) prevention: by confirming that Pb exposure causes reduced lung function, thereby supporting improved regulations and safeguards pertaining to exposure in the military; (ii) early intervention through the development of markers in the blood that can be used to identify the when Pb exposure is at the critical level that will damage respiratory health; and (iii) treatment of Pb-induced pulmonary dysfunctio
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710533
Entities
People
- Jessica Lasky-Su
Organizations
- United States Army