Cachexia, featuring rapid loss of weight and muscle, is common to many complex diseases such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and cancer. Regardless of the primary disease diagnosis, the presence of cachexia is associated with poor prognosis. Equally important is the observation that not every patient diagnosed with a complex disease such as COPD and CHF becomes cachectic. This information motivated me to hypothesize that there are common genes and pathways influencing cachexia in these different complex, chronic traits. COPD is the third leading cause of death in the United States and it has been estimated that as high as 20% of COPD cases develop cachexia, however this number may be overestimated due to limitations associated with defining cachexia. The development of cachexia is a strong predictor of mortality. This study has three specific aims: 1) Identify genetic and genomic variants associated with cachexia and related traits in COPD; 2) Test for significant relationships between pectoralis muscle area (PMA), fat-free mass (FFM) and gene expression data in COPD cases; 3) Identify gene expression signatures associated with cachexia and PMA in COPD cases. As part of my K99 analyses, I took advantage of the availability of several well-characterized COPD populations in order to investigate markers of muscle wasting and cachexia such as low PMA and change in BMI. However, the field is in need of investigations focused on cohorts of COPD cases phenotyped for muscle wasting and cachexia. The development of such a cohort is a key focus of the R00 phase of her application (Aim 2) and will lead to pilot data for her first R01 applications.

Public Health Relevance

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Cachexia, characterized by rapid loss of muscle and weight, is a strong predictor of mortality and is estimated to occur in as high as 20% of COPD cases. Despite, the public health relevance of cachexia in COPD there have been few studies collecting the necessary information to study cachexia in COPD cases. A better understanding of the etiology of COPD cachexia will improve strategies for patient diagnosis and may lead to the development of targeted therapies to reduce mortality associated with cachexia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Transition Award (R00)
Project #
5R00HL121087-04
Application #
9418079
Study Section
Special Emphasis Panel (NSS)
Program Officer
Tigno, Xenia
Project Start
2017-02-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Martinez, Carlos H; Diaz, Alejandro A; Meldrum, Catherine A et al. (2017) Handgrip Strength in Chronic Obstructive Pulmonary Disease. Associations with Acute Exacerbations and Body Composition. Ann Am Thorac Soc 14:1638-1645
McDonald, Merry-Lynn (2017) Multiomics Approach to Asthma: Navigating the Network. Am J Respir Cell Mol Biol 57:381-382
Hardin, Megan; Cho, Michael H; Sharma, Sunita et al. (2017) Sex-Based Genetic Association Study Identifies CELSR1 as a Possible Chronic Obstructive Pulmonary Disease Risk Locus among Women. Am J Respir Cell Mol Biol 56:332-341
McDonald, Merry-Lynn Noelle; Won, Sungho; Mattheisen, Manuel et al. (2017) Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1. J Cachexia Sarcopenia Muscle 8:428-436