Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial.

Background: Cough is the most reported symptom in the United States, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway. We sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough. Study design and methods: This was a randomised, placebo-controlled, parallel-design pilot trial of individuals with chronic refractory cough. The effects of 6 weeks of zinc acetate versus placebo on quality of life and symptoms as measured by the Cough Quality-of-Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), cough visual analogue score (C-VAS) and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome. Results: 34 participants, 17 in each group, were enrolled and randomised. Participants were primarily white females with moderate-severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks, while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS and GACC scores, but the treatment effects of zinc acetate versus placebo were small with confidence intervals that did not include the MCIDs. Interpretation: We observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.

Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial.

RATIONALE: Studies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity. OBJECTIVES: To evaluate whether nocturnal CPAP decreased the provocative concentration of methacholine to reduce FEV1 by 20% (PC20). METHODS: One hundred ninety-four individuals with asthma were randomized (1:1:1) to use CPAP with warmed, filtered, humidified air at night at pressures either less than 1 cm H2O (sham) or at 5 cm H2O or 10 cm H2O. The primary outcome was change in PC20 after 12 weeks. MEASUREMENTS AND MAIN RESULTS: Adherence to CPAP was low in all groups. Regardless, all groups had a significant improvement in PC20, with 12 weeks/baseline PC20 ratios of 2.12, 1.73, and 1.78 for the sham, 5 cm H2O, and 10 cm H2O groups, respectively, and no significant differences between the active and sham groups. Changes in FEV1 and exhaled nitric oxide were minimal in all groups. The sham group had larger improvements in most patient-reported outcomes measuring asthma symptoms and quality of life, as well as sinus symptoms, than the 5 cm H2O group. The 10 cm H2O group showed similar but less consistent improvements in scores, which were not different from improvements in the sham group. CONCLUSIONS: Adherence to nocturnal CPAP was low. There was no evidence to support positive pressure as being effective for reducing airway reactivity in people with well-controlled asthma. Regardless, airway reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airway reactivity. Clinical trial registered with www.clinicaltrials.gov (NCT01629823).

Impact of asthma controller medications on clinical, economic, and patient-reported outcomes.

OBJECTIVE: To comprehensively evaluate clinical, economic, and patient-reported outcomes associated with various therapeutic classes of asthma controller medications. PATIENTS AND METHODS: This observational study, which used administrative claims data from US commercial health plans, included patients with asthma aged 18 through 64 years who filled a prescription for at least 1 asthma controller medication from September 1, 2003, through August 31, 2005. Outcome metrics included the use of short-acting beta-agonists (SABAs), the use of oral corticosteroids, inpatient (INP)/emergency department (ED) visits, and asthma-related health care costs. A subset of 5000 patients was randomly selected for a survey using the Mini-Asthma Quality of Life Questionnaire, the Work Productivity and Activity Impairment questionnaire, and the Asthma Therapy Assessment Questionnaire. RESULTS: Of 56,168 eligible patients, 823 returned completed questionnaires. Compared with inhaled corticosteroids (ICSs), leukotriene modifiers (LMs) were associated with lower odds of INP/ED visits (odds ratio [OR], 0.80; P<.001), lower odds of using 6 or more SABA canisters (OR, 0.81; P<.001), and higher annual cost ($193; P<.001). In the subgroup analysis of adherent patients, LMs were associated with higher odds of INP/ED visits (OR, 1.74; P=.04), lower odds of using 6 or more SABA canisters (OR, 0.46; P<.001), and higher annual cost ($235; P<.001). Inhaled corticosteroids and LMs had a comparable impact on all patient-reported outcomes. For combination therapy, ICS plus a long-acting beta-agonist consistently showed at least equivalent or better outcomes in the use of SABAs and oral corticosteroids, the risk of INP/ED visits, cost, asthma control level, quality of life, and impairment in productivity and activity. CONCLUSION: Inhaled corticosteroids were associated with a lower risk of INP/ED visits, and a lower cost if adherence was achieved. When adherence cannot be achieved, LMs may be a reasonable alternative. Combination therapy with ICS plus a long-acting beta-agonist was associated with better or equivalent clinical, economic, and patient-reported outcomes.