Consistent improvement in health-related quality of life with tiotropium in patients with chronic obstructive pulmonary disease: Novel and conventional responder analyses.

INTRODUCTION: Improving health-related quality of life (HRQoL) in COPD patients is an important pharmacotherapeutic objective. This study investigated the extent, consistency, and durability of tiotropium maintenance therapy impact on HRQoL in moderate-to-very severe COPD. METHODS: Patients received once-daily tiotropium 18 µg (n = 5244) or placebo (n = 4799) via HandiHaler® (10 trials), or once-daily tiotropium 5 µg (n = 2622) or placebo (n = 2618) via Respimat® inhaler (3 trials). St George's Respiratory Questionnaire (SGRQ) total scores were measured at baseline, and 6 months (13 trials) and 1 year (9 trials) from treatment start. Adjusted mean differences between treatments for change from baseline in total scores were calculated at each time-point for each trial. Responder and deteriorator rates (decrease or increase in score ≥4 units from baseline, respectively), net benefit (responder rate increase plus deteriorator rate decrease), and cumulative improvement and deterioration were determined. RESULTS: Adjusted mean total score differences between treatments for change from baseline were significant (p < 0.05) in favor of tiotropium in 10/13 trials at 6 months and in 8/9 trials at 1 year. In all trials, estimated differences in responder rates between treatments favored tiotropium (significant [p < 0.05]: 5/13 trials at 6 months; 8/9 trials at 1 year). Net benefit favored tiotropium and cumulative improvement rates were consistently greater and deterioration rates consistently lower for tiotropium versus placebo. CONCLUSIONS: Tiotropium maintenance therapy significantly and consistently improved HRQoL in moderate-to-very severe COPD patients in a durable manner. These results may provide a benchmark for assessing benefits on HRQoL of other COPD treatments.

Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial.

BACKGROUND: Many patients with asthma require frequent rescue medication for acute symptoms despite appropriate controller therapies. Thus, determining the most effective relief regimen is important in the management of more severe asthma. This study's objective was to evaluate whether ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI) provides more effective acute relief of bronchospasm in moderate-to-severe asthma than albuterol hydrofluoroalkaline (ALB-HFA) alone after 4 weeks. METHODS: In this double-blind, crossover study, patients who had been diagnosed with asthma for ≥1 year were randomized to two sequences of study medication "as needed" for symptom relief (1-7 day washout before second 4-week treatment period): CVT-MDI/ALB-HFA or ALB-HFA/CVT-MDI. On days 1 and 29 of each sequence, 6-hour serial spirometry was performed after administration of the study drug. Co-primary endpoints were FEV1 area under the curve (AUC0-6) and peak (post-dose) forced expiratory volume in 1 s (FEV1) response (change from test day baseline) after 4 weeks. The effects of "as needed" treatment with ALB-HFA/CVT-MDI were analyzed using mixed effect model repeated measures (MMRM). RESULTS: A total of 226 patients, ≥18 years old, with inadequately controlled, moderate-to-severe asthma were randomized. The study met both co-primary endpoints demonstrating a statistically significant treatment benefit of CVT-MDI versus ALB-HFA. FEV1 AUC0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI (p <0.0001); peak FEV1 response was 357 ml for ALB-HFA, 434 ml for CVT-MDI (p <0.0001). Adverse events were comparable across groups. CONCLUSIONS: CVT-MDI significantly improved acute bronchodilation over ALB-HFA alone after 4 weeks of "as-needed" use for symptom relief, with a similar safety profile. This suggests additive bronchodilator effects of ß2-agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma. TRIAL REGISTRATION: ClinicalTrials.gov No.: NCT00818454 ; Registered November 16, 2009.

The impact of screening tools on diagnosis of chronic obstructive pulmonary disease in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently misdiagnosed or undiagnosed, which can delay disease management interventions. PURPOSE: The Screening, Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 (SEARCH1) study assessed whether screening using the COPD Population Screener (COPD-PS) questionnaire to detect COPD risk factors and symptoms, with or without a handheld spirometer (copd-6) to detect airflow limitation, can increase yields of COPD diagnosis and respiratory-related clinician actions in primary care. DESIGN: A prospective, multi-center, pragmatic, comparative-effectiveness, cluster-randomized study conducted from September 2010 to October 2011 (data analyzed from December 2011 to January 2013). PARTICIPANTS: Men and women aged ≥40 years visiting their participating primary care practice for any reason. INTERVENTION: Practices were randomized to three study arms: COPD-PS + copd-6, COPD-PS alone, and usual care (no interventions). No practices received any specific education about COPD or its diagnosis. MAIN OUTCOME MEASURES: The primary endpoint was yield of new clinical COPD diagnosis; the secondary endpoint was yield of respiratory-related clinician actions. RESULTS: Of 9,704 patients enrolled, 8,770 had no prior COPD diagnosis and were included in endpoint analyses. Both interventions significantly increased COPD diagnostic yield over 8 weeks. Compared with a mean yield of 0.49% (0.13%) (controls), yields were 1.07% (0.20%) (OR=2.20, 95% CI=1.26, 3.84, p=0.006) and 1.16% (0.22%) (OR=2.38, 95% CI=1.38, 4.13, p=0.002) for COPD-PS and COPD-PS+copd-6 study arms, respectively. Respiratory-related clinician actions were not significantly different across study arms. CONCLUSIONS: Office-based assessment can significantly increase COPD diagnosis by primary care physicians. Future trials must evaluate whether screening can improve outcomes for patients with COPD.