Gene L. Colice

Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant

BACKGROUNDnThis study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP.nnnMETHODSnIn this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 microg/d, 400 microg/d, or 800 microg/d of HFA-BDP or 100 microg/d, 400 microg/d, or 800 microg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment.nnnRESULTSnThree hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV(1) percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV(1) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1) percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma).nnnCONCLUSIONSnIncreasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP.

Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography.

A double-blind, randomized, parallel-group pilot study compared the relative efficacy of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP [QVAR]; mass median aerodynamic diameter, 0. 8-1.2 m) versus cholorofluorocarbon-11/12 BDP (CFC-BDP [Beclovent]; mass median aerodynamic diameter, 3.5-4.0 m) in 31 steroid naive patients with mild to moderate asthma (PC(20,) 4 mg/mL). Functional high-resolution computed tomography was used to assess the relative efficacy of HFA-BDP and CFC-BDP on regional air trapping, as an indirect measure of small airways function and on regional hyperreactivity. Pretreatment functional computed tomography was performed at residual volume before and after methacholine challenge. After 4 weeks of treatment, functional imaging was repeated before and after the same concentration of methacholine that was administered before the treatment (n = 19 patients). Quantitative assessment of changes in distribution of lung attenuation was performed. After 4 weeks of treatment, the HFA-BDP group showed significantly more improvement in air trapping overall (a shift in the lung attenuation curve at residual volume toward more attenuation) on the posttreatment computed tomography scan (P <.05; Fishers Exact Test). After an equal constrictor stimulus (methacholine concentration), subjects treated with HFA-BDP (n = 10 patients) showed less increase in air trapping overall than subjects treated with CFC-BDP (n = 9 patients) on the posttreatment scans compared with the pretreatment scans (P <.001; Fishers Exact Test). No significant difference was demonstrated between the 2 treatment groups with respect to improvement in symptoms, spirometry, or methacholine responsiveness assessed by FEV(1), except for a greater reduction in breathlessness in the HFA-BDP group (P <.05). We conclude that HFA-BDP may have greater efficacy in the peripheral airways and that this effect is better assessed with functional imaging computed tomography techniques than with conventional physiologic tests.

Adrenal Effects and Pharmacokinetics of CFC-free Beclomethasone Dipropionate: a 14-Day Dose-Response Study

Since equivalent efficacy is achieved with lower doses of the reformulated beclomethasone dipropionate in the chlorofluorocarbon (CFC)‐free propellant HFA‐134a (HFA) than with the original CFC‐beclomethasone dipropionate formulation, it is possible the HFA‐beclomethasone dipropionate may have less safety concerns than the CFC formulation. Despite its chronic use, the steady‐state pharmacokinetics of beclomethasone dipropionate has never been studied before. This double‐blind study examined adrenal effects and pharmacokinetics after 14 days of dosing with HFA‐beclomethasone dipropionate.

Effect of Anti–IL-13 Treatment on Airway Dimensions in Severe Asthma

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New-onset mild asthma III: A sequel to 2 “Oscar winners”

Haahtela et al have performed a remarkable 3-part experiment in patients with new-onset, mild asthma that has now extended over a period of 13 years of follow-up. These investigators originally randomized 103 patients with new-onset, mild asthma to either budesonide or terbutaline treatment for 2 years. Patients treated with the inhaled corticosteroid (ICS) had better symptom, lung function, and bronchial hyperresponsiveness outcomes. They then performed a crossover study in a subset of these patients for a third year. Switching from a high to a lower dose of ICS was generally effective in maintaining stable asthma symptoms, lung function, and bronchial hyperresponsiveness, but patients switched from ICS to placebo did poorly. In patients initially on the short-acting inhaled b2-agonist, beginning an ICS resulted in improved asthma outcomes but possibly not as good an improvement as those begun on ICS initially. The authors suggested that delayed initiation of ICS might lead to an impaired response. Haahtela et al have most recently re-evaluated 90 of the original 103 patients (reported in this issue of the Journal). Treatment during the 13-year interval between the initial study and this re-evaluation was not controlled—that is, this was a real-life follow-up. At this re-evaluation, these patients would generally be classified, according to the Expert Panel Report 3, as well controlled. However, they still had exacerbations requiring hospitalization, and those patients requiring hospitalizations had a greater loss of lung function over time. Finally, there were subtle indications that the patients randomized to early ICS treatment in the initial study had better outcomes than those receiving the short-acting inhaled b2-agonist. The real-life follow-up asthma care that these patients received must be appreciated in the context of how the initial work of Haahtela et al directly affected efforts to improve asthma care across Finland. In 1993, the Finnish Ministry of Social Affairs and Health recognized asthma as an important health issue and initiated a comprehensive program throughout all structures of health care to address this problem. The steps taken in this program began at the national level, including legislation, development of guidelines and education materials, and advocacy by the Finnish Lung Health Association, but quickly spread to the regional level with emphasis on the role of the primary health care