Clayton L Cruthirds1, Nicolaas E P Deutz2, Rajesh Harrykissoon3, Anthony J Zachria4, Mariëlle P K J Engelen5. 1. Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, United States. Electronic address: CL.Cruthirds@ctral.org. 2. Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, United States. Electronic address: nep.deutz@ctral.org. 3. Pulmonary, Critical Care and Sleep Medicine, Scott and White Medical Center, College Station, TX, United States. Electronic address: raj.harrykissoon@gmail.com. 4. Pulmonary, Critical Care and Sleep Medicine, Scott and White Medical Center, College Station, TX, United States. Electronic address: azack11@gmail.com. 5. Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, United States. Electronic address: mpkj.engelen@ctral.org.
Abstract
BACKGROUND & AIMS: Postabsorptive whole body protein kinetics are related to age, gender, body mass index (BMI), and habitual protein intake level. It is unclear how protein synthesis, breakdown, and postabsorptive protein balance rates are affected in Chronic Obstructive Pulmonary Disease (COPD)) and whether these relate to disease severity, lifestyle characteristics and poor daily functioning. METHODS: We studied 91 COPD (GOLD 1-4) and 56 age matched control subjects without COPD or other chronic or acute health disease/condition in the postabsorptive state and measured body composition by Dual-energy X-ray Absorptiometry, and disease severity and comorbidities by medical screening, blood analysis and questionnaires. We assessed whole body production rates of phenylalanine and tyrosine by pulse stable isotope tracer infusion to calculate whole body protein breakdown (PB) and hydroxylation of phenylalanine to tyrosine, representative of postabsorptive protein balance. We measured muscle and cognitive function, and physical performance by isokinetic dynamometry, cognitive assessments, and 6-min walk test. We assessed physical activity level, mood and dietary protein intake by questionnaires. We measured plasma enrichments by LC-MS/MS and statistics by Fisher's exact test or analysis of covariance. Data are mean [95% CI]. RESULTS: The COPD patients had moderate to severe airflow obstruction, multiple comorbidities, and elevated values for plasma high sensitivity c-reactive protein (hs-CRP) and glucose. Although PB (3630 [3361, 3900] vs 3504 [3297, 3711] umol/h, p = 0.1649) was not different, postabsorptive protein balance was lower in COPD patients (274.2 [242.4, 306.1] vs 212.9 [194.7, 231.0] umol/h, p < 0.0001), both compared to control subjects. A lower postabsorptive protein balance was associated with age (p < 0.0001) and higher levels for systolic blood pressure (p = 0.0051) and hs-CRP (p = 0.0046) but not with lung function. Furthermore, a lower postabsorptive protein balance level was associated with a lower intake of total calories and protein (p < 0.0001) and lower muscle strength (p = 0.0248), while only in COPD with a lower physical performance (p = 0.0343). We found no association with cognitive function or mood. For all subjects, a cumulative model that included group, gender, age, BMI, systolic blood pressure, hs-CRP, caloric intake, protein intake, and leg strength was able to explain 55% of the variation in postabsorptive protein balance. CONCLUSION: These data suggest that systemic inflammation, high blood pressure and low protein intake are risk factors of a lower postabsorptive protein balance in COPD patients. A lower postabsorptive protein balance is associated with markers of poor daily physical functioning.
BACKGROUND & AIMS: Postabsorptive whole body protein kinetics are related to age, gender, body mass index (BMI), and habitual protein intake level. It is unclear how protein synthesis, breakdown, and postabsorptive protein balance rates are affected in Chronic Obstructive Pulmonary Disease (COPD)) and whether these relate to disease severity, lifestyle characteristics and poor daily functioning. METHODS: We studied 91 COPD (GOLD 1-4) and 56 age matched control subjects without COPD or other chronic or acute health disease/condition in the postabsorptive state and measured body composition by Dual-energy X-ray Absorptiometry, and disease severity and comorbidities by medical screening, blood analysis and questionnaires. We assessed whole body production rates of phenylalanine and tyrosine by pulse stable isotope tracer infusion to calculate whole body protein breakdown (PB) and hydroxylation of phenylalanine to tyrosine, representative of postabsorptive protein balance. We measured muscle and cognitive function, and physical performance by isokinetic dynamometry, cognitive assessments, and 6-min walk test. We assessed physical activity level, mood and dietary protein intake by questionnaires. We measured plasma enrichments by LC-MS/MS and statistics by Fisher's exact test or analysis of covariance. Data are mean [95% CI]. RESULTS: The COPD patients had moderate to severe airflow obstruction, multiple comorbidities, and elevated values for plasma high sensitivity c-reactive protein (hs-CRP) and glucose. Although PB (3630 [3361, 3900] vs 3504 [3297, 3711] umol/h, p = 0.1649) was not different, postabsorptive protein balance was lower in COPD patients (274.2 [242.4, 306.1] vs 212.9 [194.7, 231.0] umol/h, p < 0.0001), both compared to control subjects. A lower postabsorptive protein balance was associated with age (p < 0.0001) and higher levels for systolic blood pressure (p = 0.0051) and hs-CRP (p = 0.0046) but not with lung function. Furthermore, a lower postabsorptive protein balance level was associated with a lower intake of total calories and protein (p < 0.0001) and lower muscle strength (p = 0.0248), while only in COPD with a lower physical performance (p = 0.0343). We found no association with cognitive function or mood. For all subjects, a cumulative model that included group, gender, age, BMI, systolic blood pressure, hs-CRP, caloric intake, protein intake, and leg strength was able to explain 55% of the variation in postabsorptive protein balance. CONCLUSION: These data suggest that systemic inflammation, high blood pressure and low protein intake are risk factors of a lower postabsorptive protein balance in COPD patients. A lower postabsorptive protein balance is associated with markers of poor daily physical functioning.