Efficacy and safety of fluticasone/formoterol combination therapy in patients with moderate-to-severe asthma

Background: The inhaled corticosteroid, fluticasone propionate, and the long-acting b2-adrenergic agonist, formoterol fumarate, are both highly effective treatments for bronchial asthma. This study (NCT00393952/EudraCT number: 2006-005989-39) compared the efficacy and safety of fluticasone/formoterol combination therapy (flutiform®; 250/10 mg) administered twice daily (b.i.d.) via a single aerosol inhaler, with the individual components (fluticasone 250 mg b.i.d.; formoterol 10 mg b.i.d.), in adult and adolescent patients with moderate-to-severe asthma. Methods: This was a 12-week, double-blind, randomised, parallel-group, multicentre, placebocontrolled phase 3 study. The co-primary efficacy endpoints were: i) the mean change in the forced expiratory volume in the first second (FEV1) from morning pre-dose at baseline to pre-dose at week 12 (fluticasone/formoterol 250/10 mg vs. formoterol), ii) the mean change in FEV1 from morning pre-dose at baseline to 2 h post-dose at week 12 (fluticasone/formoterol 250/10 mg vs. fluticasone), and iii) the number of patients who discontinued prematurely due to lack of treatment efficacy (fluticasone/formoterol 250/10 mg vs. placebo). The secondary endpoints included measures of lung function, disease control, and asthma symptoms. Safety was assessed based on adverse events, vital signs, and clinical laboratory evaluations. Results: Overall, 395 (70.9%) patients completed the study. Fluticasone/formoterol 250/10 mg b.i.d. was superior to the individual components and placebo for all three co-primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses. Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks. Conclusion: Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma

Chronic cough and sputum production are associated with worse clinical outcomes in stable asthma

SummaryBackgroundChronic cough and sputum production (chronic mucus hypersecretion) is a poorly described clinical feature of asthma. Our objective was to identify clinical, immunological and computed tomography (CT) measures of airway wall dimensions associated with these symptoms in smokers and never smokers with asthma.MethodsCross-sectional data was analysed from 120 smokers and never smokers with asthma. Participants with and without a history of chronic mucus hypersecretion were compared for clinical outcomes, sputum differential cell counts and CT measures of airway dimensions (wall thickness, luminal area and percent wall area).ResultsChronic mucus hypersecretion occurred in a higher proportion of smokers with asthma (56%) than never smokers with asthma (20%), (p < 0.001) and the proportion of patients with these symptoms increased with asthma severity (p = 0.003). Smokers with asthma and chronic mucus hypersecretion had worse current clinical control than smokers without those symptoms [ACQ score 2.3 versus 1.6, p = 0.002]. A greater proportion of never smokers with chronic mucus hypersecretion required short courses of oral corticosteroids in the last year (58% versus 19%, p = 0.011). Sputum neutrophil and eosinophil counts were similar in asthma patients with or without chronic mucus hypersecretion. Of those with severe asthma and chronic mucus hypersecretion, a CT measure of airway lumen area was reduced in smokers compared to never smokers (11.4 mm2 versus 18.4 mm2; p = 0.017).ConclusionsChronic mucus hypersecretion occurs frequently in adults with stable asthma, particularly in smokers with severe disease and is associated with worse current clinical control in smokers and more exacerbations in never smokers