Resveratrol and metabolic health in COPD:A proof-of-concept randomized controlled trial

Background: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. Methods: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry. Results: Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1 alpha as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95 +/- 1.01 kg vs placebo -0.16 +/- 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol -1.79 +/- 1.67 kg vs 0.37 +/- 0.86 kg, p = 0.026). Conclusion: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

Identifying risk factors for COPD and adult-onset asthma: an umbrella review

BACKGROUND: COPD and adult-onset asthma (AOA) are the most common noncommunicable respiratory diseases. To improve early identification and prevention, an overview of risk factors is needed. We therefore aimed to systematically summarise the nongenetic (exposome) risk factors for AOA and COPD. Additionally, we aimed to compare the risk factors for COPD and AOA. METHODS: In this umbrella review, we searched PubMed for articles from inception until 1 February 2023 and screened the references of relevant articles. We included systematic reviews and meta-analyses of observational epidemiological studies in humans that assessed a minimum of one lifestyle or environmental risk factor for AOA or COPD. RESULTS: In total, 75 reviews were included, of which 45 focused on risk factors for COPD, 28 on AOA and two examined both. For asthma, 43 different risk factors were identified while 45 were identified for COPD. For AOA, smoking, a high body mass index (BMI), wood dust exposure and residential chemical exposures, such as formaldehyde exposure or exposure to volatile organic compounds, were amongst the risk factors found. For COPD, smoking, ambient air pollution including nitrogen dioxide, a low BMI, indoor biomass burning, childhood asthma, occupational dust exposure and diet were amongst the risk factors found. CONCLUSIONS: Many different factors for COPD and asthma have been found, highlighting the differences and similarities. The results of this systematic review can be used to target and identify people at high risk for COPD or AOA

The effect of acute and 7-days dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with chronic obstructive pulmonary disease

Background & aims Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. Methods This double-blind, randomized cross-over placebo controlled trial included 20 mild-to-moderate COPD patients (66.6 ± 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 ± 3 kg/m2) but high prevalence of abdominal obesity (83.3%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (∼8 mmol/day) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated. Results Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure. Conclusion Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients

Fatigue in patients with chronic disease:results from the population-based Lifelines Cohort Study

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5–1.7] with one chronic disease to 5.5 [4.5–6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5–1.6] to 4.9 [3.9–6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach

Nutrition as a modifiable factor in the onset and progression of pulmonary function impairment in COPD:a systematic review

CONTEXT: Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD. OBJECTIVE: The association of dietary intake and nutrient status with COPD risk and onset, as well as pulmonary function decline (change in forced expiratory volume in 1 second, forced vital capacity, or the ratio of the former to the latter) in patients with COPD was investigated in this systematic review. DATA SOURCES: The PubMed database was searched by combining terms of pulmonary function or COPD with diet, nutrient status, or nutritional supplementation. DATA EXTRACTION: Original studies and systematic reviews and meta-analyses were included. Articles obtained were independently screened for relevance on the bases of title and abstract by 2 researchers. Eventually, 89 articles were included in the analysis. RESULTS: The unhealthy Western-style diet is associated with an increased risk of COPD and an accelerated decline of pulmonary function. Intake of fruit, vegetables, dietary fibers, vitamins C and E, polyphenols, and β-carotene were individually associated with lower COPD risk, whereas consumption of processed meat was associated with higher COPD risk. Data on the effect of dietary quality on pulmonary function decline in patients with COPD are limited and inconsistent. Strong evidence for beneficial effects on pulmonary function decline was found only for vitamin D supplementation. CONCLUSION: Considering the increasing burden of COPD, more attention should be given to dietary quality as a modifiable factor in disease development and progression in patients with COPD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021240183

Physical and mental health profile of patients with the early-onset severe COPD phenotype: A cross-sectional analysis

BACKGROUND & AIM: Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD. METHODS: This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1 s (FEV1) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV1%predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups. RESULTS: Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p = 0.029). In line with a large difference in FEV1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p < 0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1 m, p = 0.001, and 25.9%predicted, p < 0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups. CONCLUSION: Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD

The Prevalence of Metabolic Syndrome In Chronic Obstructive Pulmonary Disease: A Systematic Review

Type 2 Diabetes Mellitus (T2DM) and cardiovascular diseases (CVD) are common in patients with chronic obstructive pulmonary disease (COPD). Prevention of these co-morbidities in COPD requires knowledge on their risk factors. Metabolic syndrome (MetS) predisposes to the development of T2DM and CVD but its prevalence in COPD remains unclear. The aim of this review was to assess the prevalence of MetS and its components in COPD patients compared to controls and to investigate the contribution of clinical characteristics to MetS prevalence. We systematically searched PubMed and EMBASE for original studies in COPD that have investigated the prevalence of MetS and its components. In total, 19 studies involving 4208 COPD patients were included. The pooled MetS prevalence was 34%. Compared to controls, the prevalence was higher in COPD (10 studies, 32% and 30%, p = 0.001). The three most prevalent components in both COPD and controls were arterial hypertension (56% and 51%), abdominal obesity (39% and 38%) and hyperglycemia (44% and 47%). Compared to COPD patients without MetS, those with MetS had higher body mass index (BMI) (29.9 and 24.6 kg/m(2), p &lt;0.001), higher forced expiratory volume in 1 second (FEV1) % predicted (54 and 51, p &lt;0.001) and were more frequently female (31% and 25%, p = 0.011). In conclusion, the prevalence of MetS in COPD patients is high and hypertension, abdominal obesity and hyperglycemia are the most prevalent components. Further studies are needed to evaluate the impact of lifestyle factors and medications on MetS in COPD

Physical and mental health profile of patients with the early-onset severe COPD phenotype:A cross-sectional analysis

BACKGROUND & AIM: Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD. METHODS: This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1 s (FEV1) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV1%predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups. RESULTS: Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p = 0.029). In line with a large difference in FEV1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p < 0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1 m, p = 0.001, and 25.9%predicted, p < 0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups. CONCLUSION: Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD