Intestinal function is impaired in patients with Chronic Obstructive Pulmonary Disease

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.

Keywords: Comorbidity; Gut dysfunction; Oral sugar tests; Protein digestion and absorption; Short-chain fatty acids; Stable tracer kinetics.

Figure 1:

Consolidated Standards of Reporting Trials flow diagram. COPD: Chronic Obstructive Pulmonary Disease. FEV₁: forced expiratory volume in 1 second.

Figure 2:

Overview of study design. 3-OMG: 3-O-methyl-glucose. PHE: phenylalanine.

Figure 3:

Urinary lactulose/rhamnose ratio, a measure of small intestinal permeability, (A; n_Healthy=16; n_COPD=18) was higher in Chronic Obstructive Pulmonary Disease (COPD) patients than in healthy controls. Among COPD patients, intestinal permeability was higher in active smokers than in participants who never smoked (B; n_{never smoked}=4; n_{former smoker}=8; n_{active smoker}=6). Urinary 3-O-methyl-glucose (3-OMG) recovery rate, a marker for active carrier-mediated glucose transport, was lower in COPD patients (C: n_Healthy=16; n_COPD=17), and decreased to a greater extent in patients who were hospitalized due to an exacerbation in the previous year (D; n_no=12; n_yes=5). Data are presented as means (SEM).

Figure 4:

¹⁵N-spirulina degradation ratio, an indicator of protein digestion and absorption, was lower in Chronic Obstructive Pulmonary Disease (COPD) patients compared to healthy controls (A; n_Healthy=16; n_COPD=21). Protein digestion and absorption was reduced to a greater extent in patients with higher dyspnea grades (B; n_1–2=11; n_3–4=10) and presence of exacerbation(s) in the past year (C; n_no=8; n_yes=13). Data are presented as means (SEM). mMRC: modified British Medical Research Council Questionnaire.

Figure 5:

Correlations between ¹⁵N-spirulina degradation ratio, a marker of protein digestion and absorption, and different clinical parameters related to Chronic Obstructive Pulmonary Disease (COPD). Patients with a higher ¹⁵N-spirulina degradation ratio reported a higher physical activity level (A; n=21), a higher quality of life (B; n=17), and tended to have a higher transcutaneous oxygen saturation (C; n=20).

Figure 6:

Comparison of plasma short-chain fatty acid concentrations, a measure of fiber fermentation by intestinal microbiota. Acetate was lower in Chronic Obstructive Pulmonary Disease (COPD) patients (A), while propionate (B) and butyrate (C) concentrations were similar between groups (All: n_Healthy=16; n_COPD=21). Data are presented as means (SEM).