Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients.
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BACKGROUND: Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. METHODS: Seventy-eight outpatients with moderate to severe COPD (GOLD II-IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC-MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. <0.05. RESULTS: The COPD depressed (CD, n=27) patients on average had mild depression, were obese (BMI: 31.7 [28.4, 34.9] kg/m2), and were characterized by shorter 6-min walk distance (P=0.055), physical inactivity (P=0.03), and poor quality of life (P=0.01) compared to the non-depressed COPD (CN, n=51) group. Lung function, disease history, body composition, cognitive performance, and daily protein intake were not different between the groups. In the CD group, plasma branched chain amino acid concentration (BCAA) was lower (P=0.02), whereas leucine (P=0.01) and phenylalanine (P=0.003) clearance rates were higher. Reduced values were found for tyrosine plasma concentration (P=0.005) even after adjustment for the large neutral amino acid concentration (=sum BCAA, tyrosine, phenylalanine and tryptophan) as a marker of dopamine synthesis (P=0.048). CONCLUSION: Mild depression in COPD is associated with poor daily performance and quality of life, and a set of metabolic changes in depressed COPD that include perturbation of large neutral amino acids, specifically the BCAAs. Trial registration clinicaltrials.gov: NCT01787682, 11 February 2013-Retrospectively registered; NCT02770092, 12 May 2016-Retrospectively registered; NCT02780219, 23 May 2016-Retrospectively registered; NCT03796455, 8 January 2019-Retrospectively registered.
