Appropriate isolation methods are essential for unravelling the relative contribution of extracellular vesicles (EVs) and the EV-free secretome to homeostasis and disease. We hypothesized that ...ultrafiltration followed by size exclusion chromatography (UF-SEC) provides well-matched concentrates of EVs and free secreted molecules for proteomic and functional studies. Conditioned media of BEAS-2B bronchial epithelial cells were concentrated on 10 kDa centrifuge filters, followed by separation of EVs and free protein using sepharose CL-4B SEC. Alternatively, EVs were isolated by ultracentrifugation. EV recovery was estimated by bead-coupled flow cytometry and tuneable resistive pulse sensing. The proteomic composition of EV isolates and SEC protein fractions was characterized by nano LC-MS/MS. UF-SEC EVs tended to have a higher yield and EV-to-protein rate of purity than ultracentrifugation EVs. UF-SEC EVs and ultracentrifugation EVs showed similar fold-enrichments for biological pathways that were distinct from those of UF-SEC protein. Treatment of BEAS-2B cells with UF-SEC protein, but not with either type of EV isolate increased the IL-8 concentration in the media whereas EVs, but not protein induced monocyte adhesion to endothelial cells. Thus, UF-SEC is a useful alternative for ultracentrifugation and allows comparing the proteomic composition and functional effects of EVs and free secreted molecules.
Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a ...longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density.
We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552.
Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline -1·13 g/L SE 0·06 per year). The annual decline in lung density was more rapid in women (additional -0·41 SE 0·14 g/L per year, p=0·003) than men and in current smokers (additional -0·29 SE 0·14 g/L per year, p=0·047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time.
This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema.
GlaxoSmithKline.
To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, ...it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects.
79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%).
COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract In addition to the six-min walk distance (6 MWD), other six-min walk test (6 MWT) derived variables, such as mean walk-speed (6MWSpeed), 6-min walk-work (6 MWW), distance-saturation product ...(DSP), exercise-induced oxygen desaturation (EID), and unintended stops may be useful for the prediction of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). We studied the association between 6 MWT-derived variables and mortality as well as hospitalization in COPD patients and compared it with the BODE index. A three-year prospective study (ECLIPSE) to evaluate the prognostic value of 6 MWT-derived variables in 2010 COPD patients. Cox's proportional-hazard regressions were performed to estimate 3-year mortality and hospitalization. During the follow-up, 193 subjects died and 622 were hospitalized. An adjusted Cox's regression model of hazard ratio HR for impaired 6 MWT-derived variables was significant referring to: mortality (6 MWD ≤334 m 2.30, 6MWSpeed ≤0.9 m/sec 2.15, 6 MWW ≤20000 m kg 2.17, DSP ≤290 m% 2.70, EID ≤88% 1.75, unintended stops 1.99; and hospitalization (6 MWW ≤27000 m kg 1.23, EID ≤88% 1.25, BODE index ≥3 points 1.40; all p ≤ 0.05). The 6 MWT-derived variables have an additional predictive value of mortality in patients with COPD. The 6 MWW, EID and the BODE index refine the prognosis of hospitalization.
Summary Background According to practice guidelines, educational programmes for patients with COPD should address several educational topics. Which topics are incorporated in the existing programmes ...remains unclear. Objectives To delineate educational topics integrated in current COPD management interventions; and to examine strengths, weaknesses, and methods of delivery of the educational programmes. Data sources A systematic literature search was performed using MEDLINE/PubMed, Cochrane Central Registry of Controlled Clinical Trials, and Web of Science. The authors of included studies were contacted for additional information. Study selection Studies that contained educational programmes incorporated in COPD management interventions were included. Data extraction Data were extracted using a pre-designed data form. The Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM) framework was used for evaluating the strengths and weaknesses of the programmes. Data synthesis In total, 81 articles, describing 67 interventions were included. The majority (53.8%) of the studies incorporated 10 or more educational topics. The following topics were frequently addressed: smoking cessation (80.0%); medication (76.9%); exercise (72.3%); breathing strategies (70.8%); exacerbations (69.2%); and stress management (67.7%). Printed material and/or brochure (90.5%) and demonstrations and practice (73.8%), were the predominant tool and method, respectively. Nurses (75.8%), physicians (37.9%) and physiotherapists (34.8%) were the most involved healthcare professionals. Conclusions Heterogeneity and wide variation in the content and the method of delivery of educational interventions were present. Alignment between educational topics incorporated in the existing programmes and those recommended by the COPD guidelines, involvement of various professionals and combined use of methods should be emphasised.
Cut offs for fat-free mass index (FFMI) and appendicular skeletal muscle mass index (ASMI) are available for diagnosing low muscle mass in patients with COPD. This study aimed to investigate: (1) the ...frequency of low muscle mass (FFMI and ASMI) applying different cut-offs and (2) the functional translation (clinical impact) of low muscle mass, in patients with COPD stratified into BMI categories.
Patients with COPD were assessed regarding body composition, exercise capacity, quadriceps muscle strength, symptoms of anxiety and depression, dyspnea and quality of life upon referral to pulmonary rehabilitation. The proportion of patients with low muscle mass was compared among BMI categories. Clinical outcomes between patients with normal and low muscle mass within each BMI category were compared.
469 patients with COPD were included for analyses. The frequency of patients classified as low FFMI varied significantly according to the choice of cut-off (32 to 54%; P < 0.05), whereas the frequency of patients with low ASMI was 62%. When applying age-gender-BMI-specific cut-offs, 254 patients (54%) were classified as low FFMI. The choice of the cut-off affected the frequency of patients with low muscle mass in all BMI categories. Overweight and obese patients with low muscle mass were more frequently males and presented worse pulmonary function, exercise capacity and muscle strength compared with overweight and obese patients with normal muscle mass.
Approximately half of the overweight and obese patients with COPD have low muscle mass when applying age-gender-BMI-specific cut-offs. Low muscle mass is associated with worse functional outcomes in overweight and obese COPD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited.
The objective was to study if ...nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.
Methods
Eighty‐one COPD patients with low muscle mass, admitted to out‐patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega‐3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.
Results
The study population (51% males, aged 43–80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (−18%,P = 0.005).
Conclusions
High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.
Summary Background The 6-min walking test (6MWT) is widely used to assess exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Given the prognostic significance of the ...6MWT, it is important to identify why some COPD patients perform poorly in terms of this outcome. We aimed to identify clinical determinants of a poor 6-min walking distance (<350 m) in patients with COPD. Methods 1795 individuals with a diagnosis of COPD underwent spirometry; bio-electrical impedance analysis; low-dose computed tomography scans of the chest; 6MWT; ATS-DLD co-morbidity questionnaire; Center for Epidemiologic Studies of Depression Scale; COPD-specific St Georges Respiratory Questionnaire; modified Medical Research Council (mMRC) dyspnea scale as part of the baseline assessment of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Results Patients with COPD have significant differences in performance in the 6MWT even after stratification for GOLD stages. Moreover, severe airflow limitation by GOLD stage, degree of emphysema by CT, oxygen use during/after the 6MWT, presence of depressive symptoms and moderate to severe symptoms of dyspnea (mMRC grade ≥2) are significant clinical determinants of poor 6MWD performance (<350 m). Conclusions The determinants of poor 6MWD are complex and depend on both physical (both pulmonary and non-pulmonary factors) and psychological factors as evaluated from a large multinational cohort of well-characterised patients with clinically stable moderate to very severe COPD.
Decreased physical performance due to loss of muscle mass (i.e. sarcopenia) is prevalent in ageing and appears more pronounced in chronic disease. A comprehensive profile of the sarcopenic phenotype ...in chronic obstructive pulmonary disease (COPD) is not yet available. The aim of the present study was to characterise prevalence, functional implications and predictive value of sarcopenia with or without abdominal obesity in Dutch COPD patients eligible for pulmonary rehabilitation.505 COPD patients (aged 37-87 years; 57% male) underwent assessment of lung function, body composition and physical functioning, before entering pulmonary rehabilitation. Sarcopenia was assessed by appendicular skeletal muscle index (ASMI) and abdominal obesity by android/gynoid percentage fat mass (A/G%FM) using dual energy X-ray absorptiometry.86.5% of patients were sarcopenic and showed lower physical functioning, while coexistent abdominal obesity (78.0%) resulted in higher physical functioning. Implications on endurance were less pronounced in women. The predictive value for physical functioning was higher for the "three-compartment" model (ASMI, bone mineral content and A/G%FM) than the "two-compartment" model (fat-free mass index and fat mass index) or "one-compartment" model (body mass index).In patients eligible for pulmonary rehabilitation, sarcopenia is highly prevalent in all body mass index categories and associated with impaired strength, and in men also with decreased endurance. Abdominal obesity seems to have protective effects on physical functioning. ASMI is a better predictor for physical functioning than fat-free mass index.
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