Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma

AbstractInhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 μg day−1 suspension for nebulization and budesonide (BUD) 750 μg day−1 given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40·4% and 51·7% in the BDP and BUD groups respectively in the ITT population (P=0·28), and the mean number of global exacerbations (major plus minor) decreased respectively by −37.5% in the BDP group and −23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 μg day−1 suspension for nebulization and BUD 750 μg day−1 administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children

Lung Volume Reduction Coil Treatment vs Usual Care in Patients With Severe Emphysema: The REVOLENS Randomized Clinical Trial:

IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS: Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95$47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was$782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.Comment in : *Lung Volume Reduction Coils for Severe Emphysema--Reply. [JAMA. 2016] *Coils implanted into lungs show promise for emphysema. [BMJ. 2016] *Lung Volume Reduction Coils for Severe Emphysema. [JAMA. 2016] *Bronchoscopic Lung Volume Reduction in COPD: Lessons in Implementing Clinically Based Precision Medicine. [JAMA. 2016