Disturbed Intestinal Integrity in Patients With COPD: Effects of Activities of Daily Living

ABSTRACT BACKGROUND: COPD is accepted to be a multicomponent disease with various comorbidities. The contribution of the gastrointestinal tract to the systemic manifestation of COPD has never been investigated. This metabolically active organ may experience recurring local oxygen deficits during daily life, leading to disturbed intestinal integrity in COPD patients. METHOD: 18 patients with moderate COPD (mean FEV1: 55+/-3%predicted) and 14 matched healthy controls were tested on two occasions, a baseline measurement at rest and, at another day, during the performance of activities of daily living (ADLs). To assess enterocyte damage, plasma intestinal fatty acid binding protein (IFABP) levels were determined, whereas urinary excretion of orally ingested sugar probes was measured using liquid chromatography and mass spectrometry to assess gastrointestinal permeability. RESULTS: Plasma IFABP concentrations were not different between COPD patients and healthy controls at rest. In contrast, 0-3h urinary lactulose/rhamnose and sucralose/erythritol ratios and 5-24h urinary sucralose/erythritol ratios were significantly higher in COPD patients compared to controls, indicating increased permeability of the small intestine and colon. Furthermore, the performance of ADLs led to significantly increased plasma IFABP concentrations in COPD patients but not in control subjects. In line, the intestinal permeability difference between COPD patients and controls was intensified. CONCLUSION: Besides an altered intestinal permeability in COPD patients at rest, performing ADLs led to enterocyte damage in addition to intestinal hyperpermeability in COPD patients but not in controls, indicating functional alteration in the gastrointestinal tract. Hence, intestinal compromise should be considered as a new component of the multisystem disorder COPD. CLINICAL TRIAL REGISTRATION: ISRCTN33686980

Age-graded reductions in quadriceps muscle strength and peak aerobic capacity in COPD

BACKGROUND: Reductions in quadriceps strength and peak aerobic capacity (VO2) in patients with chronic obstructive pulmonary disease (COPD) have been studied in relatively small samples over a short period. Moreover, results were not corrected for confounding variables, such as lean muscle mass, gender, and gas transfer capacity of the lungs. OBJECTIVES: To compare quadriceps muscle strength and peak V.O2 in women and men while stratifying for age and gas transfer capacity. We then corrected for lower-limb lean muscle mass to see whether and to what extent the age-graded reduction remained evident. METHODS: Retrospectively, data of 374 women and 593 men with COPD were analyzed: lung function, current drug therapy, quadriceps strength, peak V.O2, lower-limb lean muscle mass, and gas transfer capacity. RESULTS: Quadriceps strength and peak V.O2 were lower in older women and men with a gas transfer capacity of 50% predicted. Yet, counter to our hypothesis, lower-limb lean muscle mass did not show an age-graded reduction and, in turn, could not account for the relationship of age with quadriceps strength and peak V.O2. CONCLUSIONS: It is apparent that there is an age-graded reduction in skeletal muscle function in patients with COPD. Therefore, prevention of an age-graded decline in quadriceps muscle strength and peak V.O2 may need to become an outcome of pulmonary rehabilitation of patients with COPD

Decreased plasma sRAGE levels in COPD: influence of oxygen therapy

Eur J Clin Invest 2012 ABSTRACT: Background Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. N(epsilon) -(carboxymethyl) lysine (CML), an advanced glycation end product (AGE) and the soluble decoy receptor, sRAGE, are exciting new molecules linked to oxidative stress and inflammation. Here the levels of plasma sRAGE and CML were determined and their variation in relation to lung function, external long-term oxygen therapy (LTOT) and plasma levels of inflammatory molecules in COPD evaluated. Methods Plasma sRAGE and CML levels were measured by ELISA in 146 patients with stable COPD and 81 healthy subjects, subgrouped from a larger case-control study and matched for age, gender and pack-years smoked. Results Decreased levels of plasma sRAGE and no significant difference in levels of plasma CML were found in patients with COPD in comparison with controls. In the total group, plasma sRAGE was positively associated with FEV(1) and forced vital capacity and negatively with pack-years smoked. In patients receiving LTOT, levels of plasma sRAGE were lower compared with those without LTOT. Only in controls, a weak correlation was found between plasma sRAGE and CML. sRAGE did not correlate with measured inflammatory markers, whereas CML was negatively correlated with fibrinogen. Conclusion Plasma sRAGE levels are lower in patients with COPD compared with healthy control subjects, and even lower levels in patients receiving LTOT. Because sRAGE correlated with lung function only in the whole group, sRAGE can be considered a marker of COPD, but not of disease severity. A lack of clear association between sRAGE, CML and systemic inflammation is furthermore evident

Enhanced anabolic response to milk protein sip feeding in elderly subjects with COPD is associated with a reduced splanchnic extraction of multiple amino acids

BACKGROUND & AIMS: We previously observed in elderly subjects with Chronic Obstructive Pulmonary Disease (COPD) an enhanced anabolic response to milk protein sip feeding, associated with reduced splanchnic extraction (SPE) of phenylalanine. Milk proteins are known for their high Branched-chain Amino Acids (BCAA) content, but no information is present about splanchnic extraction and metabolism of the individual BCAA in COPD. OBJECTIVE: To investigate whether BCAA metabolism and SPE of the individual BCAA are altered in COPD during milk protein sip feeding. DESIGN: In elderly subjects with COPD and in healthy age-matched elderly SPE, endogenous rate of appearance (Raendo) of the leucine (LEU), isoleucine (ILE) and valine (VAL) were measured before and during sip feeding of a Whey protein meal. To study the effect of aging, the healthy elderly were compared to a group of healthy young subjects. Stable isotopes of l-[(2)H(3)]-LEU, l-[1-(13)C]-ILE and l-[1-(13)C]-VAL were given on two separate test days orally or intravenously. Simultaneously, l-[ring-(2)H(5)]-phenylalanine (PHE) and l-[ring-(2)H(2)]-tyrosine (TYR) were given to determine the whole body protein breakdown (WbPB), synthesis (WbPS) and NetPS. RESULTS: SPE of all BCAA, TYR, and PHE (p < 0.01) were lower in the COPD group, and the increase in netPS during feeding was higher in the COPD group (P < 0.01) due to higher values for PS (P < 0.001). Raendo of all BCAA, PHE and TYR were higher in the COPD than the healthy elderly group (P < 0.05) before and during feeding (P < 0.001). Sip feeding resulted in a reduction of Raendo of PHE, ILE and VAL (P < 0.05). Postabsorptive Raendo was not different for any of the measured amino acids between the healthy elderly and young group, while sip feeding resulted in a reduction of Raendo of PHE. Only SPE of TYR was higher in the elderly (P < 0.05) and the increase in netPS during sip feeding was independent of aging. CONCLUSION: The enhanced anabolic response to milk protein sip feeding in normal-weight COPD patients is associated with a reduced splanchnic extraction of multiple amino acids including all branched-chain amino acids. Registration ClinicalTrials.gov = NCT01418469