Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.
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ABSTRACT:
SUBMITTER: Maltais F
PROVIDER: S-EPMC7579818 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.
Maltais F F Naya I P IP Vogelmeier C F CF Boucot I H IH Jones P W PW Bjermer L L Tombs L L Compton C C Lipson D A DA Kerwin E M EM
Respiratory research 20201022 1
<h4>Background</h4>Short-acting β<sub>2</sub>-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.<h4>Methods</h4>The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation ri ...[more]
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Project description:BackgroundSalbutamol bronchodilator response (BDR) test and fractional exhaled nitric oxide (FeNO) have been recommended for the diagnosis of asthma in children, but FeNO levels is affected by many factors. Nonetheless, data of the effect on the FeNO values throughout the bronchodilator test and the differences in FeNO values between BDR positive (BDR+) and negative (BDR-) children with asthma are still limited. We aimed to evaluate the effect of the BDR test on FeNO and the differences in FeNO levels between BDR+ and BDR- children with asthma.MethodsThis was a prospective, observational study performed over a 5-month period (December 2018 to April 2019) and involved 57 children with asthma. The FeNO levels at pre-spirometry, post-spirometry, and post-salbutamol BDR testing were estimated. Finally, the children were divided into two groups i.e., BDR+ and BDR-, and differences in the FeNO levels were compared between the two groups.ResultsThe spirometry results were normal in 2 patients (3.5%). There were 53 (93%) patients with obstructive lung disease, including 40 (70.2%), 11 (19.3%), and 2 (3.5%) patients with mild, moderate, and severe obstruction, respectively. The remaining two patients had mixed lesions (3.5%), none of which were restrictive. The baseline median FeNO levels were significantly higher in the BDR+ group than in the BDR- group [33.00 (23.78, 46.73) vs. 23.00 (9.80, 37.80), (P=0.048)]. Following spirometry, there was a statistically significant decrease in median FeNO levels from baseline to post-spirometry (P=0.002). However, there was no significant difference between the median FeNO levels at baseline and following the BDR test (P=0.976). The impact of spirometry on FeNO was not statistically different in BDR+ versus BDR- children (Z=-0.186, P=0.853); however, the impact of bronchodilators on FeNO exhibited a statistically significant difference between the two groups (Z=3.160, P=0.002).ConclusionsThis study revealed dynamic changes in the FeNO levels during the BDR test. The use of a bronchodilator results in a statistically significant difference in FeNO levels between BDR+ and BDR- children with asthma. Moreover, spirometry leads to a marked decrease in the FeNO levels. Our results will allow clinicians to better interpret FeNO, BDR and pulmonary function outcomes and better develop clinical protocols.
| S-EPMC9636456 | biostudies-literature
Project description:IntroductionSmoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD.MethodsThe 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening.ResultsThe analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV1 at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: - 0.42 [- 0.63, - 0.20]; former: - 0.25 - 0.44, - 0.05]) and salmeterol (current: - 0.28 [- 0.49, - 0.06]; former: - 0.29 [- 0.49, - 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups.ConclusionsIn current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.
| S-EPMC8408076 | biostudies-literature
Project description:The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 μg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 μg) and standard-dose (4 puffs, 400 μg) salbutamol to compare the small airway responses of healthy controls (defined using criteria based on the guidelines developed at the American Thoracic Society) and exclusion subjects (defined as any child that did not meet the inclusion criteria for healthy controls). The oscillometric reactance of small airways is significantly associated with the dose of salbutamol used for BDR testing in exclusion children. We suggest use of the standard-dose of salbutamol for oscillometric BDR testing.
| S-EPMC5543428 | biostudies-other
Project description:Background:Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions. Materials and methods:A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting ?2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). Results:Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD. Conclusion:These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.
| S-EPMC6902852 | biostudies-literature
Project description: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.
| S-EPMC6821007 | biostudies-literature
Project description:Exercise tolerance is an important parameter in patients with COPD and a primary goal of treatment is to reduce dyspnea to facilitate physical activities and improve health-related quality of life. This review examines the link between expiratory flow limitation and dyspnea to explain the rationale for the use of bronchodilators and review the characteristics of different types of exercise tests, with specific focus on which tests are likely to show a response to bronchodilators. An earlier literature search of studies published up to 1999 assessed the effects of bronchodilatort therapy on dypsnea and exercise tolerance among patients with COPD. This current review examines the clinical evidence published since 1999. Thirty-one randomized studies of exercise tolerance associated with short- and long-acting beta(2)-agonists and anticholinergics were identified. Evidence for the efficacy of bronchodilators in enhancing exercise capacity is often contradictory and possibly depends on the exercise test and study methodology. However, further studies should confirm the benefit of long-acting bronchodilators in improving spontaneous everyday physical activities.
| S-EPMC2865026 | biostudies-literature
Project description:Increasing age is associated with poor prognosis in patients with COPD.This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting ?2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ?85 years.In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 ?g or 5/5 ?g, tiotropium 5 ?g or 2.5 ?g (TONADO only), olodaterol 5 ?g (TONADO only), or placebo (OTEMTO only). This analysis used the approved doses of tiotropium + olodaterol 5/5 ?g, tiotropium 5 ?g, and olodaterol 5 ?g. Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0-3) response, and trough FEV1 response.A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ?85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ?85 years, n=13) in TONADO. FEV1 AUC0-3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 ?g at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups. SGRQ scores generally improved with tiotropium + olodaterol 5/5 ?g after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO. In all age groups receiving tiotropium + olodaterol 5/5 ?g compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved.No differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 ?g compared to monotherapies or placebo across all age groups.
| S-EPMC5098524 | biostudies-literature
Project description:Indacaterol is an inhaled, once-daily long-acting ?(2)-agonist bronchodilator for regular use in patients with chronic obstructive pulmonary disease (COPD). As indacaterol is the first once-daily ?(2)-agonist to be developed, it is relevant to evaluate its bronchodilator efficacy, safety, and tolerability.Data were pooled from three randomized, double-blind, clinical studies in patients with moderate-to-severe COPD treated with indacaterol 150 ?g qd (n = 627) or placebo (n = 1021). Bronchodilator efficacy was assessed as trough (24-hour post-dose) forced expiratory volume in 1 second (FEV(1)) after 12 weeks (primary endpoint in individual studies) and FEV(1) measured serially post-dose. Rescue use of albuterol was monitored.At week 12, indacaterol increased trough FEV(1) by 160 mL compared with placebo (P < 0.001), exceeding the 120 mL level prespecified as clinically important. FEV(1) during the first 12-hour post-dose at week 12 averaged 210 mL higher with indacaterol than with placebo (P < 0.001). Patients receiving indacaterol recorded 53% of days without use of rescue albuterol, compared with 38% of days in the placebo group (P < 0.001). Adverse events (mostly mild or moderate) were reported for 52% and 46% of patients receiving indacaterol and placebo, respectively, and serious adverse events for 4% and 5%. Worsening of COPD was the most frequent adverse event (10% indacaterol; 15% placebo). Indacaterol had little effect on pulse or blood pressure or measures of systemic ?(2)-adrenoceptor activity (blood glucose, serum potassium, and corrected QT interval).Indacaterol was an effective bronchodilator and was well tolerated, with a good safety profile over 12 weeks of treatment. It should prove a useful treatment for patients with moderate-to-severe COPD.
| S-EPMC3186741 | biostudies-literature
Project description:Airflow limitation in COPD patients is not fully reversible. However, there may be large variability in bronchodilator responsiveness (BDR) among COPD patients, and familial aggregation of BDR suggests a genetic component. Therefore, we investigated the association between six candidate genes and BDR in subjects with severe COPD. A total of 389 subjects from the National Emphysema Treatment Trial (NETT) were analyzed. Bronchodilator responsiveness to albuterol was expressed in three ways: absolute change in FEV(1), change in FEV(1) as a percent of baseline FEV(1), and change in FEV(1) as a percent of predicted FEV(1). Genotyping was completed for 122 single nucleotide polymorphisms (SNPs) in six candidate genes (EPHX1, SFTPB, TGFB1, SERPINE2, GSTP1, ADRB2). Associations between BDR phenotypes and SNP genotypes were tested using linear regression, adjusting for age, sex, pack-years of smoking, and height. Genes associated with BDR phenotypes in the NETT subjects were assessed for replication in 127 pedigrees from the Boston Early-Onset COPD (EOCOPD) Study. Three SNPs in EPHX1 (p=0.009-0.04), three SNPs in SERPINE2 (p=0.004-0.05) and two SNPs in ADRB2 (0.04-0.05) were significantly associated with BDR phenotypes in NETT subjects. One SNP in EPHX1 (rs1009668, p=0.04) was significantly replicated in EOCOPD subjects. SNPs in SFTPB, TGFB1, and GSTP1 genes were not associated with BDR. In conclusion, a polymorphism of EPHX1 was associated with bronchodilator responsiveness phenotypes in subjects with severe COPD.
| S-EPMC2745950 | biostudies-literature
Project description:Categorization of patients with COPD as reversible or nonreversible to a bronchodilator may change over time. This post hoc analysis aimed to determine if an individual's reversibility, when treated as a continuous variable, could predict his/her future response to two short-acting bronchodilators: albuterol and ipratropium. The analysis was completed using data from a 4-week, randomized, open-label, two-period crossover study (NCT01691482; GSK study DB2114956). Patients received albuterol (doses: UK =4×100 ?g/puff; US =4×90 ?g/puff) followed 1 hour later by ipratropium (4×20 ?g/puff) or vice versa during treatment Period 1. The order of treatments was reversed during Period 2. Predefined efficacy end points included pre- and post-bronchodilator forced expiratory volume in 1 second. The correlation coefficient between bronchodilator response on Days 1 and 10 was investigated, as well as the correlation between treatment response on Day 1 and the mean treatment response on Days 5-10, for each individual patient. Bronchodilator response to albuterol on Day 1 was strongly correlated with that on Day 10 (r=0.64; n=53). The correlation coefficient of bronchodilator treatment response on Day 1 and Days 5-10 was 0.78 (P<0.001; n=53) and 0.76 (P<0.001; n=54) for albuterol and ipratropium, respectively. A single measurement of the initial bronchodilator response to albuterol or ipratropium was, therefore, highly correlated with the subsequent mean bronchodilator response over 5-10 days, demonstrating its potential usefulness for future treatment decisions.
| S-EPMC5010081 | biostudies-other