Respiratory medicine
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Respiratory medicine · May 2016
Randomized Controlled Trial Multicenter Study Clinical TrialThe bronchodilator effects of extrafine glycopyrronium added to combination treatment with beclometasone dipropionate plus formoterol in COPD: A randomised crossover study (the TRIDENT study).
This multicentre, double-blind, randomised, placebo-controlled, crossover study aimed to determine the dose-response of the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide (GB) when added to beclometasone dipropionate plus formoterol fumarate (BDP/FF) in patients with COPD. Patients received extrafine GB 12.5, 25 or 50 μg twice daily (BID) or placebo for 7 days via pressurised metered dose inhaler (pMDI), and extrafine BDP/FF via pMDI throughout the study. The primary objective was to demonstrate superiority of GB plus BDP/FF versus BDP/FF in terms of FEV1 area under the curve from 0 to 12 h (AUC0-12h) on Day 7. Secondary endpoints included: FEV1 AUC0-12h on Day 1; peak FEV1 and FVC on Days 1 and 7; and trough (12 h post-dose) FEV1, FVC and inspiratory capacity (IC) on Days 1 and 7. Of 178 patients randomised (mean age 62.7 years, post-bronchodilator FEV1 48.9%), 172 (96.6%) completed. Mean FEV1 AUC0-12h on Day 7 was significantly higher (p < 0.001) for all GB doses plus BDP/FF compared to BDP/FF alone, with the difference for the 25 and 50 μg BID doses being clinically relevant (i.e., ≥100 mL). The results for the other spirometry endpoints were consistent with the primary endpoint. Adverse events were reported in 7.4, 5.7 and 8.0% of patients receiving GB 12.5, 25 and 50 μg BID, respectively, versus 11.0% of patients receiving BDP/FF alone. This study confirms the value of adding GB to BDP/FF to improve lung function in COPD patients. The dose of extrafine GB 25 μg BID was associated with the best efficacy/safety profile.
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Respiratory medicine · Feb 2016
Randomized Controlled Trial Multicenter StudyReductions in eosinophil biomarkers by benralizumab in patients with asthma.
Eosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti-interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity. ⋯ In two independent studies, serum IL-5, EDN, and ECP were modulated following benralizumab. Eosinophil depletion after benralizumab also resulted in significant reductions in EDN and ECP concentrations, suggesting that cytotoxic granule proteins were not released after eosinophil reduction.
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Respiratory medicine · Feb 2016
Multicenter StudyDifferences between absolute and predicted values of forced expiratory volumes to classify ventilatory impairment in chronic obstructive pulmonary disease.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity criterion for COPD is used widely in clinical and research settings; however, it requires the use of ethnic- or population-specific reference equations. We propose two alternative severity criteria based on absolute post-bronchodilator FEV1 values (FEV1 and FEV1/height2) that do not depend on reference equations. We compared the accuracy of these classification schemasto those based on % predicted values (GOLD criterion) and Z-scores of post-bronchodilator FEV1 to predict COPD-related functional outcomes or percent emphysema by computerized tomography of the lung. ⋯ Severity criteria based on absolute post-bronchodilator FEV1 or FEV1/height2 yielded similar prediction errors for 6MWD, SGRQ, SF-36 physical health component score, and the MMRC Dyspnea Score when compared to the GOLD criterion (all p > 0.34); and, had similar predictive accuracy when compared with the Z-scores criterion, with the exception for 6MWD where post-bronchodilator FEV1 appeared to perform slightly better than Z-scores (p = 0.01). Subgroup analyses did not identify differences across severity criteria by race, sex, or age between absolute values and the GOLD criterion or one based on Z-scores. Severity criteria for COPD based on absolute values of post-bronchodilator FEV1 performed equally as well as did criteria based on predicted values when benchmarked against COPD-related functional and structural outcomes, are simple to use, and may provide a more accessible and comparable approach to severity classification worldwide, especially in settings where prediction equations are not available.
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Respiratory medicine · Dec 2015
Multicenter StudyAssociation of early suspected acute exacerbations of idiopathic pulmonary fibrosis with subsequent clinical outcomes and healthcare resource utilization.
Idiopathic pulmonary fibrosis (IPF) may be complicated by episodes of acute exacerbation. This study quantified the association between occurrence of suspected acute exacerbations of IPF (AEx-IPF) in the 6 months post-IPF diagnosis with clinical outcomes and IPF-related healthcare resource utilization (HRU). ⋯ Using a large sample of IPF patients from varied practice settings, we found a strong relationship between suspected early AEx-IPF and worse subsequent clinical outcomes and increased IPF-related HRU. This relationship was particularly pronounced for acute resource use.
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Respiratory medicine · Sep 2015
Multicenter StudyPrognostic value of variables derived from the six-minute walk test in patients with COPD: Results from the ECLIPSE study.
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. ⋯ 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.