Sarah K Kirschner1, Nicolaas E P Deutz1, Renate Jonker1, Steven W M Olde Damink2, Rajesh I Harrykissoon3, Anthony J Zachria3, Srinivasan Dasarathy4, Mariëlle P K J Engelen5. 1. Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University, College Station, TX, USA. 2. Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, Netherlands. 3. Department of Medicine, Division of Pulmonary Critical Care, Baylor Scott & White Medical Center, College Station, TX, USA. 4. Departments of Gastroenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, OH, USA. 5. Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University, College Station, TX, USA. Electronic address: mpkj.engelen@ctral.org.
Abstract
BACKGROUND & AIMS: Gastrointestinal symptoms are prevalent extrapulmonary systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD), but have been rarely studied. We dissected the perturbations in intestinal function in human patients with COPD using comprehensive metabolic and physiological approaches. METHODS: In this observational study, small intestinal membrane integrity and active carrier-mediated glucose transport were quantified by sugar permeability test in 21 clinically stable patients with moderate to severe COPD (mean FEV1, 41.2 (3.2) % of predicted) and 16 healthy control subjects. Protein digestion and absorption was analyzed using stable tracer kinetic methods. Plasma acetate, propionate, and butyrate concentrations were measured as markers of intestinal microbial metabolism. RESULTS: Compared with healthy controls, non carrier-mediated permeability was higher (0.062 (95% CI [0.046, 0.078]) vs. 0.037 (95% CI [0.029, 0.045]), P = 0.009) and active glucose transport lower in COPD (31.4 (95% CI [23.4, 39.4])% vs. 48.0 (95% CI [37.8, 58.3])%, P = 0.010). Protein digestion and absorption was lower in COPD (0.647 (95% CI [0.588, 0.705]) vs. 0.823 (95% CI [0.737, 0.909]), P = 0007), and impairment greater in patients with dyspnea (P = 0.038), exacerbations in preceding year (P = 0.052), and reduced transcutaneous oxygen saturation (P = 0.051), and was associated with reduced physical activity score (P = 0.016) and lower quality of life (P = 0.0007). Plasma acetate concentration was reduced in COPD (41.54 (95% CI [35.17, 47.91]) vs. 80.44 (95% CI [54.59, 106.30]) μmol/L, P = 0.001) suggesting perturbed intestinal microbial metabolism. CONCLUSIONS: We conclude that intestinal dysfunction is present in COPD, worsens with increasing disease severity, and is associated with reduced quality of life.
BACKGROUND & AIMS: Gastrointestinal symptoms are prevalent extrapulmonary systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD), but have been rarely studied. We dissected the perturbations in intestinal function in human patients with COPD using comprehensive metabolic and physiological approaches. METHODS: In this observational study, small intestinal membrane integrity and active carrier-mediated glucose transport were quantified by sugar permeability test in 21 clinically stable patients with moderate to severe COPD (mean FEV1, 41.2 (3.2) % of predicted) and 16 healthy control subjects. Protein digestion and absorption was analyzed using stable tracer kinetic methods. Plasma acetate, propionate, and butyrate concentrations were measured as markers of intestinal microbial metabolism. RESULTS: Compared with healthy controls, non carrier-mediated permeability was higher (0.062 (95% CI [0.046, 0.078]) vs. 0.037 (95% CI [0.029, 0.045]), P = 0.009) and active glucose transport lower in COPD (31.4 (95% CI [23.4, 39.4])% vs. 48.0 (95% CI [37.8, 58.3])%, P = 0.010). Protein digestion and absorption was lower in COPD (0.647 (95% CI [0.588, 0.705]) vs. 0.823 (95% CI [0.737, 0.909]), P = 0007), and impairment greater in patients with dyspnea (P = 0.038), exacerbations in preceding year (P = 0.052), and reduced transcutaneous oxygen saturation (P = 0.051), and was associated with reduced physical activity score (P = 0.016) and lower quality of life (P = 0.0007). Plasma acetate concentration was reduced in COPD (41.54 (95% CI [35.17, 47.91]) vs. 80.44 (95% CI [54.59, 106.30]) μmol/L, P = 0.001) suggesting perturbed intestinal microbial metabolism. CONCLUSIONS: We conclude that intestinal dysfunction is present in COPD, worsens with increasing disease severity, and is associated with reduced quality of life.
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