fluticasone-propionate--salmeterol-xinafoate-drug-combination and Dyspnea

The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.. Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks.. Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]).. Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Dyspnea; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic

In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.

Topics: Aged; Bronchodilator Agents; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Health Status; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Severity of Illness Index; Sex Factors; Tiotropium Bromide; Vital Capacity

The purpose of this exploratory physiological study was to evaluate the effects of inhaled fluticasone/salmeterol combination (FSC) on sensory and physiological responses to exercise in subjects with mild-to-moderate COPD. In a randomized, double-blind, placebo-controlled, crossover study, subjects underwent 6-week treatments with FSC or placebo (PLA). Detailed pulmonary function and constant-work rate cycle exercise tests were performed following each treatment period. Fifteen subjects completed the study (mean ± SD): age 64 ± 10 years; smoking history 47 ± 29 pack-years; post-bronchodilator forced expiratory volume in 1 s 86 ± 15 %predicted (10 mild and 5 moderate COPD); peak incremental oxygen uptake 71 ± 16 %predicted. Compared with PLA, FSC treatment was associated with improved: FEV1 by 0.23 ± 0.18 L; inspiratory capacity by 0.18 ± 0.23 L; functional residual capacity by -0.28 ± 0.30 L; and specific airways resistance by -4.6 ± 4.5 cmH2O s (all p < 0.01). There were no significant changes in dyspnea intensity throughout exercise and endurance time did not change significantly (1.2 ± 3.0 min, p = 0.149). Following FSC, inspiratory capacity at rest and throughout exercise increased by 0.2-0.3 L with concomitant increases in tidal volume and ventilation (p < 0.05). Compared with PLA, the work of breathing and the ratio of respiratory muscle effort to tidal volume improved with FSC during exercise (p < 0.05). In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise. Despite important mechanical improvements, there were no significant effects on dyspnea intensity and exercise endurance.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Cross-Over Studies; Double-Blind Method; Drug Combinations; Dyspnea; Exercise; Exercise Test; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Oxygen Consumption; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Respiratory Mechanics; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation.. The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control.. COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 μg/day or FP/S 500/100 μg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index.. Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S.. BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Androstadienes; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Dyspnea; Ethanolamines; Exercise Test; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Functional Residual Capacity; Glucocorticoids; Humans; Italy; Lung; Male; Middle Aged; Plethysmography, Whole Body; Pulmonary Disease, Chronic Obstructive; Residual Volume; Time Factors; Total Lung Capacity; Treatment Outcome

To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD.. This was a randomized, double-blind, parallel-group study.. Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal.. Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50.. A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50.. We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Lung Volume Measurements; Male; Middle Aged; Physical Endurance; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Function Tests; Respiratory Mechanics; Salmeterol Xinafoate; Tidal Volume; Time Factors

This is a proof of concept study that aims to establish feasibility and safety of a new strategy that includes an action plan for early treatment of acute exacerbations of COPD (AECOPD) with doubling dose of a combination of a long-acting beta2 agonist and an inhaled corticosteroid, and to explore its potential for avoiding the requirement of prednisone and its safety. Thirty-seven COPD outpatients with previous exacerbations were enrolled and followed-up for 12 months. The written action plan included a standing prescription to be used in the event of an AECOPD: Antibiotic, for 5 days (for purulent exacerbations) and doubling a combination of Salmeterol and Fluticasone Propionate for 10 days. The primary outcome was "treatment success" defined as "no need of prednisone within 30 days of the onset." Twenty-seven patients experienced an AECOPD and doubled their combination dose. Among the 27 patients, there were 21 patients (78%) who did not require prednisone, and none of those had cardiovascular events, pneumonia, ER and hospital admissions. We have assessed that an early treatment of AECOPD with doubling the dose of a combination of Salmeterol and Fluticasone Propionate appears to be safe, well-tolerated and adhered to, and results in no requirement of systemic corticosteroid in a large proportion of patients presenting with mild-to-moderate worsening of dyspnea. This trial has the potential to change the approach of treatment of AECOPD and reduce the use of oral corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Anti-Bacterial Agents; Clinical Protocols; Disease Progression; Dyspnea; Early Medical Intervention; Feasibility Studies; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; Proof of Concept Study; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Topics: Actuarial Analysis; Albuterol; Androstadienes; Body Mass Index; Bronchial Hyperreactivity; Bronchodilator Agents; Cardiovascular Diseases; Drug Combinations; Dyspnea; Exercise; Fluticasone-Salmeterol Drug Combination; Humans; Hypercapnia; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Assessment; Smoking Cessation

To explore asthma symptom perception and the relationship between asthma symptom perception and adherence to asthma treatment.. Adult patients (N=120) of asthma/allergy specialty clinics, taking Advair as a controller medication, were enrolled in this cross-sectional descriptive study.. Ninety-seven participants completed 4 weeks of daily diaries to assess subjective symptom perception and measured peak expiratory flow rates (PEFR), both done twice daily. Individual perceptual accuracy scores (PAS) were determined by correlating the subjective symptom perception scores with the PEFRs. Measures included demographic variables, illness identity (personal control and treatment control, consequences, and timeline-cyclical subscales of the IPQ-R), asthma severity (FEV1 percentage) and a single-item indicator of perceived asthma severity. Adherence was measured by the Medication Adherence Report Scale (MARS) and by an Advair dose count (percentage of doses taken as prescribed).. Independent t tests comparing adherence rates of good versus poor perceivers were not significant, using either the percentage Advair dose count or the MARS. Multiple regression analyses showed that years with asthma, illness identity, and peak flow variability were all significant explanatory variables for perceptual accuracy.. Peak flow variability adds complexity to the relationship between perceptual accuracy and adherence that warrants further investigation.

Topics: Adaptation, Psychological; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Awareness; Cross-Sectional Studies; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Health Knowledge, Attitudes, Practice; Humans; Internal-External Control; Male; Middle Aged; Models, Psychological; Nursing Methodology Research; Patient Compliance; Patient Education as Topic; Peak Expiratory Flow Rate; Regression Analysis; Self Care; Self Concept; Severity of Illness Index; Sick Role; Surveys and Questionnaires