scholarly journals Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
F. Maltais ◽  
I. P. Naya ◽  
C. F. Vogelmeier ◽  
I. H. Boucot ◽  
P. W. Jones ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Fractional Polynomial ◽  
Exacerbation Risk ◽  
Symptom Outcome ◽  
Post Hoc

Abstract Background Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. Methods The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. Results At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59–74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. Conclusions In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. Funding GlaxoSmithKline (study number 201749 [NCT03034915]).

scholarly journals Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
François Maltais ◽  
Leif Bjermer ◽  
Edward M. Kerwin ◽  
Paul W. Jones ◽  
Michael L. Watkins ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Inhaled Corticosteroids ◽  
Randomised Trial ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Short Term ◽  
Double Blind ◽  
Once Daily ◽  
Clinically Important Deterioration ◽  
Exacerbation Risk

Abstract Background Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. Methods The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25 μg once-daily, umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Results Change from baseline in trough FEV1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16–25% [p < 0.01]) and salmeterol (by 26–41% [p < 0.001]). Safety profiles were similar between treatments. Conclusions Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.

scholarly journals Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claus F. Vogelmeier ◽  
Paul W. Jones ◽  
Edward M. Kerwin ◽  
Isabelle H. Boucot ◽  
François Maltais ◽  
...  
Keyword(s):  
Lung Function ◽  
Rescue Medication ◽  
Inhaled Corticosteroids ◽  
Full Range ◽  
Medication Use ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Once Daily ◽  
Post Hoc

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids. Methods The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10−30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21–24, and rescue medication use (puffs/day) over Weeks 1–24. Analyses were conducted across the full range of reversibility (−850–896 mL); however, results are presented for the range −100–400 mL because there were few participants with values outside this range. Results The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range. Conclusions FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.

Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity

2009 ◽  
Vol 106 (6) ◽  
pp. 1902-1908 ◽  
Author(s):  
Roberto Rodríguez-Roisin ◽  
Mitra Drakulovic ◽  
Diego A. Rodríguez ◽  
Josep Roca ◽  
Joan Albert Barberà ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Gas Exchange ◽  
Pulmonary Disease ◽  
Forced Expiratory Volume ◽  
Pulmonary Gas Exchange ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Gold Stage ◽  
Stage 1

Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV1) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion (V̇A/Q̇) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaPo2 and V̇A/Q̇ mismatch were clearly abnormal; thereafter, hypoxemia, AaPo2, and V̇A/Q̇ imbalance increased, but the changes from GOLD stages 1–4 were modest. Postbronchodilator FEV1 was related to PaO2 ( r = 0.62) and PaCO2 ( r = −0.59) and to overall V̇A/Q̇ heterogeneity ( r = −0.48) ( P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV1 across the spectrum of severity. V̇A/Q̇ imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of V̇A/Q̇ inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.

scholarly journals Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study

2018 ◽  
Vol 4 (1) ◽  
pp. 00073-2017 ◽  
Author(s):  
John H. Riley ◽  
Chris J. Kalberg ◽  
Alison Donald ◽  
David A. Lipson ◽  
Muhammad Shoaib ◽  
...  
Keyword(s):  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Post Dose ◽  
Double Blind ◽  
Endurance Time ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Randomised Study ◽  
Residual Capacity ◽  
Exercise Endurance

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT).Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed.UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167–246), 3-h post-dose FRC (−346 mL, 95% CI −487 to −204) and CAT score (−1.07 units, 95% CI −2.09 to −0.05) versus placebo at week 12.UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status.

scholarly journals Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Sanjay Sethi ◽  
Brett Haumann ◽  
Srikanth Pendyala ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Outcomes ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Open Label ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Abstract Background Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial. Methods In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium. Results Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. Conclusions Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. Trial registration NCT02518139; Registered 5 August 2015.

scholarly journals Reassessing the Role of Eosinophils as a Biomarker in Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 8 (7) ◽  
pp. 962 ◽  
Author(s):  
Tinè ◽  
Biondini ◽  
Semenzato ◽  
Bazzan ◽  
Cosio ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Real Life ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Exacerbation Risk ◽  
Blood Eosinophils

Blood eosinophils measurement, as proxy for tissue eosinophils, has become an important biomarker for exacerbation risk and response to inhaled corticosteroids (ICS) in Chronic Obstructive Pulmonary Disease (COPD). Its use to determine the pharmacological approach is recommended in the latest COPD guidelines. The potential role of blood eosinophils is mainly based on data derived from post-hoc and retrospective analyses that showed an association between increased blood eosinophils and risk of exacerbations, as well as mitigation of this risk with ICS. Yet other publications, including studies in real life COPD, do not confirm these assumptions. Moreover, anti-eosinophil therapy targeting interleukin (IL)-5 failed to reduce exacerbations in COPD patients with high blood eosinophils, which casts significant doubts on the role of eosinophils in COPD. Furthermore, a reduction of eosinophils might be harmful since COPD patients with relatively high eosinophils have better pulmonary function, better life quality, less infections and longer survival. These effects are probably linked to the role of eosinophils in the immune response against pathogens. In conclusion, in COPD, high blood eosinophils are widely used as a biomarker for exacerbation risk and response to ICS. However, much is yet to be learned about the reasons for the high eosinophil counts, their variations and their controversial effects on the fate of COPD patients.

scholarly journals Roflumilast succeeds where traditional therapy fails: a case report

2015 ◽  
Vol 79 (3-4) ◽  
Author(s):  
Gabriella Guarnieri
Keyword(s):  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
High Dose ◽  
Welding Fumes ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
X Ray ◽  
Clinical Control ◽  
History Of ◽  
Chest X Ray

The case of a 72-year-old man with a long history of chronic obstructive pulmonary disease (COPD, patient D according to Guidelines GOLD 2013) in a subject professionally exposed to welding fumes is presented. Diagnosis was based on symptoms and spirometry and confirmed by chest X-ray examination. Since 1997 the patient has been under different therapies, including high-dose inhaled corticosteroids and bronchodilators, with poor clinical control and frequent exacerbations. Roflumilast 500 μg once daily was started in January 2012 and patient’s respiratory symptoms, number of exacerbations and spirometry values have gradually improved since then. Roflumilast was an effective treatment in this case of difficult to treat severe COPD.

scholarly journals Tiotropium and olodaterol fixed-dose combinationversusmono-components in COPD (GOLD 2–4)

2015 ◽  
Vol 45 (4) ◽  
pp. 969-979 ◽  
Author(s):  
Roland Buhl ◽  
François Maltais ◽  
Roger Abrahams ◽  
Leif Bjermer ◽  
Eric Derom ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Forced Expiratory Volume ◽  
Phase Iii ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Once Daily ◽  
Multicentre Phase ◽  
St George's Respiratory Questionnaire

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-dailyviaRespimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0–3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0–3 and trough FEV1 responseversusthe mono-components in both studies. Statistically significant improvements in SGRQ total scoreversusthe mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components.These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDCversusmono-components over 1 year in patients with moderate to very severe COPD.

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