Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients

Abstract

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. ɑ < 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.

Lipogenic Lung Fibroblast-derived Extracellular Vesicles Mitigate Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Pathologies through LAT1-mediated Alveolar Type II Cell Restoration

“…Recent studies have indicatedb disruptions in amino acid homeostasis in patients with COPD, showing changes in various amino acid levels in the blood and tissues 44 . Specifically, alterations in amino acid profiles, including decreases in branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine, have been observed 45 . Our examination of the total amino acid content in AT2 cells sourced from both COPD and non-COPD (including non-COPD smokers and never-smokers) lungs revealed a significant reduction, specifically within AT2 cells derived from COPD lungs ( Fig.…”

Branched chain amino acids harbor distinct and often opposing effects on health and disease

“…Prior BCAA observational studies examined associations with cancer 6 , cardiovascular 5 , metabolic 4 , 21 , cognition 22 , and respiratory 23 phenotyps, among others. To enable comparison with this body of literature, we also examined broad phenotypic categories using two data sources: data measured by UK Biobank investigators (investigator-defined phenotypes, n = 249) and phenotypes constructed from inpatient episode records (phecodes, n = 192) (Table 1 ).…”

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17 / Treg balance and gut-lung axis microbiota

“…The results showed that cysteine, glycine and glutamate, the components of glutathione synthesis, increased in the lung of idiopathic pulmonary fibrosis compared with the control group [73]. Amino acids are directly involved in cell metabolism and are also neurotransmitters [74], and the change of amino acid metabolism may be a way to cause depression in COPD patients [75]. Additionally, amino acids are the basic nutrients of infected microorganisms, and the levels of some amino acids (such as tryptophan) will be reduced due to infection and/or inflammation [76].…”