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Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease.
Han, MK, Barreto, TA, Martinez, FJ, Comstock, AT, Sajjan, US
BMJ open respiratory research. 2020;(1)
Abstract
INTRODUCTION Quercetin is a plant flavonoid and has potent antioxidant and anti-inflammatory properties. In a preclinical model of chronic obstructive pulmonary disease (COPD), quercetin reduced markers of both oxidative stress and lung inflammation and also reduced rhinovirus-induced progression of lung disease. Although quercetin appears to be an attractive natural alternative to manage COPD, the safety of quercetin supplementation in this population is unknown. METHODS We recruited COPD patients with mild-to-severe lung disease with FVE1 ranging between >35% and <80% and supplemented with either placebo or quercetin at 500, 1000 or 2000 mg/day in a dose-escalation manner. The duration of quercetin supplementation was 1 week. RESULTS Patients had no study drug-related severe adverse events based on blood tests, which included both complete blood counts and evaluation of comprehensive metabolic panel. One of the patients reported mild adverse events included gastro-oesophageal reflux disease, which was observed in both placebo and quercetin groups. CONCLUSIONS Quercetin was safely tolerated up to 2000 mg/day as assessed by lung function, blood profile and COPD assessment test questionnaire. TRIAL REGISTRATION NUMBER NCT01708278.
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Physiological and perceptual responses to exercise according to locus of symptom limitation in COPD.
Tracey, L, Lewthwaite, H, Abdallah, SJ, Murray, S, Wilkinson-Maitland, CA, Donovan, A, Maltais, F, O'Donnell, DE, Bourbeau, J, Smith, BM, et al
Respiratory physiology & neurobiology. 2020;:103322
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with pulmonary and extra-pulmonary factors contributing to exercise intolerance. The primary self-reported exercise-limiting symptom may reflect the primary pathophysiological factor contributing to exercise intolerance. We compared physiological and perceptual responses at the symptom-limited peak of incremental cardiopulmonary cycle exercise testing between people with COPD reporting breathlessness (B, n = 34), leg discomfort (LD, n = 16), or a combination of B and LD (BOTH, n = 42) as their main exercise-limiting symptom(s). Despite similarly impaired health status, symptomology and peak exercise capacity, the B group had greater restrictive constraints on tidal volume expansion at end-exercise and was more likely to report unpleasant qualities of exertional breathlessness than LD and BOTH groups. In conclusion, reporting breathlessness as the primary exercise-limiting symptom indicated the presence of distinct lung pathophysiology and symptom perception during exercise in people with COPD.
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A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease.
Miki, K, Kitada, S, Miki, M, Hui, SP, Shrestha, R, Yoshimura, K, Tsujino, K, Kagawa, H, Oshitani, Y, Kida, H, et al
The journal of physiological sciences : JPS. 2019;(6):969-979
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The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O2 pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O2 delivery through improvements in primary cardiocirculatory and muscular crosstalk.
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Efficacy and safety of four doses of glycopyrrolate/formoterol fumarate delivered via a metered dose inhaler compared with the monocomponents in patients with moderate-to-severe COPD.
Reisner, C, Pearle, J, Kerwin, EM, Rose, ES, Darken, P
International journal of chronic obstructive pulmonary disease. 2018;:1965-1977
Abstract
PURPOSE To determine the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 36/9.6, 36/7.2, 18/9.6, 9/9.6 µg) using innovative co-suspension delivery technology, compared with glycopyrrolate (GP) MDI 36 µg and formoterol fumarate (FF) MDI 9.6 µg, in patients with moderate-to-severe COPD. METHODS In this Phase IIb, randomized, double-blind, balanced incomplete-block, two-period, cross-over study (NCT01349816), patients received treatment twice-daily for 7 days. The primary efficacy endpoint was forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12) on Day 7. Secondary efficacy endpoints were peak change from baseline in FEV1 through 2 hours; time to onset of action (≥10% improvement in mean FEV1); proportion of patients achieving ≥12% improvement in FEV1 on Day 1; peak change from baseline in inspiratory capacity (IC) on Days 1 and 7; change from baseline in morning pre-dose FEV1; peak change from baseline in FEV1 through 6 hours; and change from baseline in mean evening 12-hour post-dose trough FEV1 on Day 7. Safety was assessed. RESULTS All 185 randomized patients received treatment. All doses of GFF MDI significantly improved the primary endpoint compared with GP MDI 36 µg (all P≤0.0137). For peak change in FEV1 and IC and time to onset of action secondary endpoints, ≥2 doses of GFF MDI demonstrated superiority to GP MDI 36 µg. No significant differences were observed between GFF MDI and FF MDI 9.6 µg for primary and secondary endpoints. The incidence of adverse events was similar between treatments. CONCLUSION While all doses of GFF MDI were superior to GP MDI 36 µg for the primary end-point, in this study neither superiority of GFF MDI to FF MDI 9.6 µg nor a clear dose-response was observed. All treatments were well tolerated with no unexpected safety findings.
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Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial.
Rialp Cervera, G, Raurich Puigdevall, JM, Morán Chorro, I, Martín Delgado, MC, Heras la Calle, G, Mas Serra, A, Vallverdú Perapoch, I
Pulmonary pharmacology & therapeutics. 2017;:30-37
Abstract
BACKGROUND Metabolic alkalosis (MA) inhibits respiratory drive and may delay weaning from mechanical ventilation (MV). MA is common in CO2-retainer patients that need MV. Acetazolamide (ACTZ) decreases serum bicarbonate concentration and stimulates respiratory drive. This study evaluated the effects of ACTZ on the duration of MV in patients with MA and COPD or obesity hypoventilation syndrome (OHS) intubated with acute respiratory failure. METHODS Multicenter, randomized, controlled, double-blind study, with COPD or OHS patients with MV < 72 h and initial bicarbonate >28 mmol/L and pH > 7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH > 7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded. RESULTS 47 patients (36 men) were randomized. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. The mean difference in the duration of MV between placebo and ACTZ group was 1.3 days (95%CI, -2.1-4.8; p = 0.44). Kaplan-Meier curves showed no differences in the duration of MV (Log-Rank p = 0.41). Between-group comparison of estimated marginal means (CI 95%) during MV were, respectively: PaCO2 55 (51-59) vs 48 (47-50) mm Hg, p = 0.002; bicarbonate concentration 34 (32-35) vs 29 (28-30) mmol/L, p < 0.0001; and minute volume 9.7 (8.9-10.4) vs 10.6 (9.2-12.0) L/min, p = 0.26. There were no severe adverse effects with ACTZ administration. CONCLUSIONS Among patients with MA and COPD or OHS, early treatment with ACTZ did not shorten significantly the duration of MV compared with placebo. TRIAL REGISTRY clinical.trials.gov; NCT01499485; URL:.www.clinicaltrials.gov.
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Assessment of energy intake in women with chronic obstructive pulmonary disease: a doubly labeled water method study.
Farooqi, N, Slinde, F, Håglin, L, Sandström, T
The journal of nutrition, health & aging. 2015;(5):518-24
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OBJECTIVES To maintain energy balance, reliable methods for assessing energy intake and expenditure should be used in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to validate the diet history and 7-day food diary methods of assessing energy intake (EI) using total energy expenditure (TEE) with the doubly labeled water (DLW) method (TEEDLW) as the criterion method in outpatient women with COPD. METHODS EI was assessed by diet history (EIDH) and a 7-day food diary (EIFD) in 19 women with COPD, using TEEDLW as the criterion method. The three methods were compared using intra-class correlation coefficients (ICC) and Bland-Altman analyses. The participants were classified according to their reporting status (EI/TEE) as valid-reporters 0.79-1.21, under-reporters < 0.79 or over-reporters > 1.21. RESULTS Diet history underestimated reported EI by 28%, and 7-day food diary underestimated EI by approximately 20% compared with TEEDLW. The ICC analysis showed weak agreement between TEEDLW and EIDH (ICC=-0.01; 95%CI-0.10 to 0.17) and between TEEDLW and EIFD (ICC=0.11; 95%CI -0.16 to 0.44). The Bland-Altman plots revealed a slight systematic bias for both methods. For diet history, six women (32%) were identified as valid-reporters, and for the 7-day food diary, twelve women (63%) were identified as valid-reporters. The accuracy of reported EI was only related to BMI. CONCLUSION The diet history and 7-day food diary methods underestimated energy intake in women with COPD compared with the DLW method. Individuals with higher BMIs are prone to underreporting. Seven-day food diaries should be used with caution in assessing EI in women with COPD.
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Pneumothorax risk factors in smokers with and without chronic obstructive pulmonary disease.
Hobbs, BD, Foreman, MG, Bowler, R, Jacobson, F, Make, BJ, Castaldi, PJ, San José Estépar, R, Silverman, EK, Hersh, CP, ,
Annals of the American Thoracic Society. 2014;(9):1387-94
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RATIONALE The demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined. OBJECTIVES We evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema. METHODS The study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report. MEASUREMENTS AND MAIN RESULTS Pneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33). CONCLUSIONS Among smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
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[Lung functional testing by electroimpedance spirometry: experimental and clinical study].
Mishlanov, VIu, Zuev, AL, Ust'iantseva, TL, Mishlanov, IaV, Savkin, VV
Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova. 2013;(12):1425-34
Abstract
The aim of the study was to investigate 0.9% sodium chloride saline aerosol and airways electrical impedance including experiments with plastic tubes, healthy people and asthmatic patients examination using electrical impedance spirometry. The experimental part of the study consisted of measurements of the 0.9% NaCl aerosol particles size and their flow action on the electrical impedance measure in polyethylene tubes of different diameters. As a result reverse dependence between aerosol particles size, its flow intensity and electrical impedance value were revealed. In the clinical part of the study the mean values of the electrical impedance spirometry were detected in the children groups of different ages, healthy people and bronchial asthma patients. It was found that an active compound of electrical impedance spirometry was correlated with airways diameter and may be used as a criterion of bronchial obstruction syndrome. It was established that small airways disease is the basic mechanism of airways disorders in patients with control bronchial asthma, and small airways as well as large airways both are involved in not controlled bronchial asthma patients.
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Clinical validation of the CHRONIOUS wearable system in patients with chronic disease.
Bellos, C, Papadopoulos, A, Rosso, R, Fotiadis, DI
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference. 2013;:7084-7
Abstract
The CHRONIOUS system defines a powerful and easy to use framework which has been designed to provide services to clinicians and their patients suffering from chronic diseases. The system is composed of a wearable shirt that integrate several body sensors, a portable smart device and a central sub-system that is responsible for the long term storage of the collected patient's data. A multi-parametric expert system is developed for the analysis of the collected data using intelligent algorithms and complex techniques. Apart for the vital signals, dietary habits, drug intake, activity data, environmental and biochemical parameters are recorded. The CHRONIOUS platform is validated through clinical trials in several medical centers and patient's home environments recruiting patients suffering from Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD) diseases. The clinical trials contribute in improving the system's accuracy, while Pulmonologists and Nephrologists experts utilized the CHRONIOUS platform to evaluate its efficiency and performance. The results of the utilization of the system were very encouraging. The CHRONIOUS system has been proven to be a well-validated real-time patient monitoring and supervision platform, providing a useful tool for the clinician and the patient that would contribute to the more effective management of chronic diseases.
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A new class of bronchodilator improves lung function in COPD: a trial with GSK961081.
Wielders, PL, Ludwig-Sengpiel, A, Locantore, N, Baggen, S, Chan, R, Riley, JH
The European respiratory journal. 2013;(4):972-81
Abstract
GSK961081 is a bifunctional molecule demonstrating both muscarinic antagonist and β-agonist activities. This was a 4-week, multicentre, randomised, double-blind, double-dummy, placebo and salmeterol controlled parallel group study. Doses ranging across three twice-daily doses and three once-daily doses were assessed in moderate and severe chronic obstructive pulmonary disease (COPD) patients. Trough forced expiratory volume in 1 s (FEV1) at day 29 was the primary end-point. At days 1 and 28, 12-h FEV1 spirometry was performed in all patients. A subset of patients underwent complete 24-h spirometry at day 28. The study recruited 436 patients. GSK961081 showed statistically and clinically significant differences from placebo in all doses and regimens for trough FEV1 on day 29 (155-277 mL). The optimal total daily dose was 400 μg, either as 400 μg once daily or as 200 μg twice daily, with an improvement in day 29 trough FEV1 of 215 mL and 249 mL, respectively. Other efficacy end-points also showed improvement. No effects were observed on glucose, potassium, heart rate, blood pressure and no dose-response effect was seen on corrected QT elongation. This study showed that GSK961081 is an effective bronchodilator in COPD and appeared to be safe and well tolerated.