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.

Development and validation of a cough and sputum assessment questionnaire.

Although cough and sputum production may impact patients' well being and functioning in COPD and chronic bronchitis, there is no validated instrument for cough and sputum symptoms and their impact on patients' daily activities. To fill that gap, we developed and validated a specific, multilingual Cough and Sputum Assessment Questionnaire (CASA-Q) that evaluates clinical symptoms and their impact on patients with COPD or chronic bronchitis. In a three-country validation study (n=671), there was adequate internal consistency (Cronbach's alphas, 0.80-0.91) and test-retest reliability (correlation coefficients>0.70) for the CASA-Q. The cough impact and sputum impact domains correlated with the SGRQ impact domain and SGRQ total score, as did the cough impact domain with the SF-36 social functioning domain. The cough symptom and sputum symptom domains correlated with sputum wet weight (p<0.05; r=-0.56), but not with cough recordings. The mean CASA-Q cough symptom and sputum symptom domain scores indicated responsiveness towards both worse and improved symptoms, whereas the impact domains scored already in the upper third of the scale range, indicating the need for further improvement of its properties. Differences in the CASA-Q domain scores by smoking status (current vs. former smokers) were highest for cough symptoms and lowest for sputum impact. These data indicate that the CASA-Q may be a useful measure of cough and sputum production, and their impact in patients with COPD and/or chronic bronchitis. Further validation will need to assess the responsiveness of the CASA-Q to changes in symptoms.