Comparison of Mometasone Furoate Dry Powder Inhaler and Fluticasone Propionate Dry Powder Inhaler in Patients with Moderate to Severe Persistent Asthma Requiring High-Dose Inhaled Corticosteroid Therapy: Findings from a Noninferiority Trial

Background. Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. Methods: The efficacy and safety of mometasone furoate (MF) 400 μg twice daily (BID) and fluticasone propionate (FP) 500 μ g BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). pm PEFR, forced expiratory volume in 1 second (FEV₁), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. Results. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. Conclusion. MF-DPI 400 μ g BID was therapeutically equivalent to FP-DPI 500 μ g BID in patients with moderate-to-severe persistent asthma.     

Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Health Effects of Ultraviolet Irradiation in Asthmatic Children's Homes

Objective. Centrally installed ultraviolet (UV) irradiation units were investigated to determine the potential health benefits in mold-sensitized asthmatic children. Methods. Nineteen mold-sensitized asthmatic children 5 to 17 years of age with home central ventilation systems were enrolled in a 28-week double-blinded placebo controlled cross-over trial. Clinical outcome measurements included morning and evening peak expiratory flow rates (PEFR), PEFR variability, change in forced expiratory volume in 1 second (FEV₁), change in total rhinoconjunctivitis and asthma symptom scores, change in rhinoconjunctivitis and asthma quality-of-life scores, and total (rescue and controller) medication use from baseline and between time periods. Environmental outcomes included changes in temperature, relative humidity, dew point, and indoor airborne mold and bacterial counts from baseline and between time periods. Analysis of variance (ANOVA) and regression analysis and t test were used to evaluate relationships between environmental exposure(s) and clinical outcome measurements during each study period. Results. Twelve male and seven female children, average age 10.6 years, were enrolled. A statistically significant improvement in PEFR variability in subjects receiving CREON2000 units followed by placebo units was observed (p < 0.05) across both treatment periods. Within group analysis during treatment period 1, a statistically significant improvement in reduction of asthma symptom scores, the number of days with asthma symptoms, total asthma medication use, and PEFR variability were observed in subjects receiving CREON2000 units versus placebo units (p < 0.05). No significant differences were observed between the CREON 2000 and placebo units for other clinical or environmental outcome measurements. Conclusions. Central UV irradiation was effective at reducing airway hyperresponsiveness manifested as PEFR variability and some clinical symptoms. A larger cohort controlled longitudinal study to validate the clinical health effects of UV irradiation as a primary indoor environmental intervention for allergic asthma is necessary to confirm this finding.     

The Efficacy and Safety of Mometasone Furoate Delivered via a Dry Powder Inhaler for the Treatment of Asthma

Inhaled corticosteroids are the gold standard of daily therapy for effective control of all stages of persistent asthma. For this review of the new inhaled corticosteroid mometasone furoate, a MEDLINE/PubMed search using the terms “mometasone furoate AND asthma” found 57 articles, 17 of which presented data from efficacy and safety studies reviewed herein. In clinical trials, once-daily evening dosing of mometasone furoate delivered via dry powder inhaler (200 or 400 μ g/day) was effective in patients with mild to moderate asthma previously treated with short-acting β₂-agonists alone and in those previously maintained on inhaled corticosteroid therapy. In patients with severe asthma, mometasone furoate 400 μ g twice daily eliminated or reduced the need for oral prednisone while improving lung function, asthma symptoms, and quality of life. Clinical studies have shown that mometasone furoate is generally well tolerated and has minimal systemic activity at recommended doses. In conclusion, mometasone furoate provides primary care and specialty physicians with a safe, effective, and convenient option to meet the challenges of asthma management.     

Initiation of Maintenance Therapy with Salmeterol/Fluticasone Propionate Combination Therapy in Moderate Asthma: A Comparison with Fluticasone Propionate

The objective of this study was to investigate initial maintenance treatment with salmeterol/fluticasone propionate (Seretide) 50/250 μ g twice daily (SFC) compared with fluticasone propionate (Flixotide) 250 μ g twice daily (FP) (both via Diskus inhaler, GlaxoSmithKline, Greenford, UK) in patients with moderate persistent asthma currently only treated with inhaled short-acting β₂-agonists. A total of 362 adults and adolescents (12 to 80 years of age) were randomized to this 12-week double-blind parallel-group study. The primary endpoint was mean morning peak expiratory flow (PEF). Secondary efficacy endpoints included median percentages of symptom-free and rescue-free days and nights; the percentage of patients who achieved the pre-defined criteria for well-controlled asthma over weeks 5 to 12; and the incidence of asthma exacerbations. Safety was assessed by the incidence of adverse events. Superiority of SFC over FP alone was demonstrated for the primary and each secondary endpoint. The difference in adjusted mean change from baseline in morning PEF between SFC and FP was 21 L/min (95%CI: 11, 31; p < 0.001). Significantly more patients achieved well-controlled asthma during treatment with SFC (46%) compared with FP (32%) (odds ratio 1.84; 95%CI: 1.17, 2.89; p = 0.008). Both treatments were safe and well-tolerated. This study demonstrates that initial maintenance treatment with SFC 50/250 μg twice daily provides superior efficacy to FP 250 μ g twice daily alone in patients with moderate persistent asthma.     

Budesonide/Formoterol Pressurized Metered-Dose Inhaler versus Budesonide: A Randomized Controlled Trial in Black Patients with Asthma

Objective. Concerns exist that responses to long-acting β₂-adrenergic agonists in black patients may differ from the general population. The efficacy and safety of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (BUD DPI) were evaluated in adolescent and adult black asthma patients. Methods. This 12-week, randomized, double-blind, multicenter, phase IV US study was conducted in 311 self-reported black patients aged ≥12 years with moderate to severe persistent asthma, previously receiving medium- to high-dose inhaled corticosteroid. After 2 weeks on BUD 90 μg × 2 inhalations twice daily (bid), symptomatic patients were randomized to BUD/FM 160/4.5 μg × 2 inhalations bid or BUD 180 μg × 2 inhalations bid. Results. Improvement in predose forced expiratory volume in 1 second from baseline to the treatment mean (primary variable) was greater with BUD/FM versus BUD (0.16 vs. 0.07 L; p = .008); this effect was also observed at weeks 2, 6, and end of treatment (p ≤ .032). Greater improvements (p < .001) in peak expiratory flow with BUD/FM versus BUD were seen at first measurement and maintained during 12 weeks (morning: 25.34 vs. 7.53 L/minute, respectively; evening: 21.61 vs. 7.67 L/minute, respectively); greater improvements in daily asthma symptom score and rescue medication use were also observed (p ≤ .039). Both treatments were well tolerated, with similar safety profiles. Conclusions. In this population of black asthma patients, BUD/FM pMDI resulted in greater improvements in pulmonary function and asthma control versus BUD DPI, with similar safety profiles.     

Efficacy and Safety of Indacaterol,a New 24-hour β 2-Agonist,in Patients with Asthma: A Dose-Ranging Study

Background. Indacaterol is a new once-daily inhaled β₂-agonist in clinical development for asthma as a component of a fixed-dose combination with an inhaled corticosteroid. Objectives. To investigate the efficacy and safety of indacaterol in patients with chronic persistent asthma. Methods. A total of 115 patients were randomized in a double-blind, incomplete-block cross-over design to sequences of four 7-day treatment periods (separated by 7-day washouts) with indacaterol 100, 200, 300, 400, or 600 μ g or placebo, once daily, via single-dose dry-powder inhaler. After the fourth washout, patients received 1 day of open-label formoterol 12 μ g twice daily. Forced expiratory volume in 1 second (FEV₁) was measured for 24 hours post-dose on days 1 and 7. Results. For standardized (with respect to time) FEV₁ area under the curve at 22 to 24 hours (AUC_22–24h) on day 1, indacaterol doses ≥200 μ g were superior to placebo (p < 0.05) and similar or greater than formoterol 12 μg twice daily. By day 7, mean differences from placebo in FEV₁ standardized AUC_22–24h were 0.08, 0.16, 0.15, 0.11, and 0.16 L for indacaterol 100, 200, 300, 400, and 600 μg, respectively (all p < 0.05 vs. placebo). Mean FEV₁ for indacaterol doses ≥ 200 μg on day 7 was higher than placebo (p < 0.05) pre-dose and at all post-dose time points. AEs were generally mild in severity; no serious AEs occurred. No clinically meaningful differences were observed between treatments in any safety assessments. Conclusions. Once-daily indacaterol demonstrated sustained 24-hour bronchodilator efficacy, with similar efficacy on days 1 and 7, and was generally well tolerated.     

Similar efficacy of ciclesonide once daily versus fluticasone propionate twice daily in patients with persistent asthma.

This 12-week, double-blind, parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12-75 years with persistent asthma. Patients were randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro g (n = 259) (all ex-actuator). Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second, asthma symptom scores and rescue medication use (all p < 0.0001). Asthma exacerbation rates were low (each ciclesonide group, n = 2; fluticasone group, n = 1). Adverse event reporting indicated good tolerability. Once daily ciclesonide 80 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.     

Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma

Background and objective:   The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma.
Methods:   Japanese patients (20–75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study.
Results:   Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min ( P  = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab ( P  = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group.
Conclusions:   Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.     

A Randomized,Controlled Trial to Investigate the Effect of Ciclesonide and Beclomethasone Dipropionate on Eye Lens Opacity

Background. Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation. Objective. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma. Methods. Adults (≥ 18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 μ g/day (n = 785) or beclomethasone dipropionate 640 μ g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of ≥ 0.5 for nuclear opalescence, ≥ 0.8 for cortical opacification, or ≥ 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period. Results. Mean changes (± standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 μ g/day: 0.10 ± 0.02, 0.07 ± 0.02 and 0.04 ± 0.01, respectively; beclomethasone dipropionate 640 μ g/day: 0.11 ± 0.02, 0.09 ± 0.02 and 0.03 ± 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 μ g/day was non-inferior to beclomethasone dipropionate 640 μ g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820–1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values. Conclusions. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 μ g/day or beclomethasone dipropionate 640 μ g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.     

Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma.

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.     

Fluticasone Propionate HFA-134a Pressurized Metered-Dose Inhaler in Adolescents and Adults with Moderate to Severe Asthma

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 μg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV₁) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 μg bid; 9.8%, 220 μg bid; 11.2%, 440 μg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.     

Evaluation of Bedoradrine Sulfate (MN-221), a Novel,Highly Selective Beta2-Adrenergic Receptor Agonist for the Treatment of Asthma via Intravenous Infusion

Background. The number of hospitalizations or deaths due to asthma, most of which result from acute exacerbations of asthma, has remained the same for the past 20 years. MN-221 (bedoradrine sulfate) is a novel, highly selective beta₂- (β₂-) adrenergic agonist administered via intravenous (IV) infusion in development for the treatment for acute exacerbation of asthma. Objectives. Trial MN-221-CL-004 assessed the safety profile and preliminary efficacy of MN-221 in escalating doses in patients with stable mild-to-moderate asthma. Study MN-221-CL-005 assessed the safety profile and preliminary efficacy of MN-221 in patients with stable moderate-to-severe asthma when given as a fixed dose over 1- or 2- hr infusion. Methods. Two randomized, placebo-controlled clinical trials (n = 40) were performed to evaluate the pharmacokinetic (PK) and clinical effects of a novel, highly selective β₂-agonist, MN-221, via IV infusion. Safety evaluations included vital signs, adverse events (AEs), clinical laboratory parameters, and electrocardiogram results. Efficacy evaluation included measurement of forced expiratory volume in 1 second (FEV₁) and PK parameters were additionally monitored. The study was reviewed and approved by the Institutional Review Board at each site. Results. Adverse effects were mild or moderate and there were no serious AEs or deaths during the studies. The most frequently reported AEs were tremor, hypokalemia, and headache. There were no consistent dose-dependent effects of MN-221 on any safety parameters, with the exception of heart rate, which was not considered to be clinically significant and did not require any treatment. Moderate hypokalemia occurred once in one subject in the MN-221-CL-004 study and twice in one subject in the MN-221-CL-005 study and were transient and returned to normal range following single oral potassium chloride treatments. PK assessments indicated a linear response in MN-221 plasma concentrations for the doses evaluated. Dose escalation results showed that mean changes in FEV₁ from pre-infusion were significantly greater than placebo and an overall dose response was statistically significant (p < .0001). Post-infusion FEV₁ improvements appeared to plateau at the 30 μg/min dose level despite a higher peak plasma concentration at 60 μg/min. Dose-rate escalation results demonstrated greater mean increases in change in FEV₁ compared to the placebo group with the largest increase associated with the higher MN-221 dose rate and peak plasma concentration. Conclusions. The safety profile of MN-221 and evidence of dose- and plasma-concentration-related bronchodilation supports further clinical development and suggests the potential for clinical benefit without increased clinical risk, particularly for patients where inhaled or nebulized therapy is not adequate or possible. Trial registry name and registration number:Name: MN-221-CL-005Number: NCT00679263     

Definition of Asthma: A Critical Review: One Brief and One Comprehensive Definition

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (IV) aminophylline 250 mg for 90 min and IV hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting IV aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV₁), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV₁ in the furosemide group by 28.2 ± 5.9% (mean ± SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with IV theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of β₂-agonists.     

Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials

Objective: We aimed to perform a meta-analysis evaluating the efficacy and safety of dupilumab in patients with uncontrolled asthma. Data source: A search of electronic databases was performed using PubMed, Cochrane library and Embase. Study selection: The literature search was conducted independently by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and dupilumab in patients with uncontrolled asthma were included in this analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous data, respectively. Results: A total of four RCTs representing 2,992 patients were included. Pooled analysis showed significant reductions of the annualized rate of severe asthma exacerbation in the dupilumab group compared with placebo (RR 0.44; 95% CI 0.35–0.055; P?<?0.01; I2?=?42%). In addition, the absolute forced expiratory volume at 1?s (FEV1) changes were significantly increased for the dupilumab group (MD 0.14; 95% CI: 0.12–0.17; P?<?0.01; I2?=?0%). Finally, there were no significant differences between both groups in the development of any adverse event, serious adverse events, adverse events leading to death, discontinuation of medication due to adverse event or the occurrence of upper respiratory tract, influenza or bronchitis infections. However, dupilumab was associated with an increased risk of injection site reactions compared with placebo (RR 1.91; 95% CI 1.41, 2.59; P?<?0.01; I2?=?24%). Conclusion: Among patients with uncontrolled asthma, the addition of dupilumab was associated with a reduced risk of severe asthma exacerbations and improvement in FEV1 without an increased risk of adverse events apart from injection site reactions with dupilumab.     

Formoterol used as needed in patients with intermittent or mild persistent asthma

OBJECTIVE: To study the effectiveness and safety of as-needed treatment of formoterol compared with the short-acting alternative terbutaline. METHODS: Two double-blind, 12-month, parallel-group, non-inferiority trials comparing as-needed use of formoterol (Oxis) 4.5 microg and terbutaline (Bricanyl) 0.5 mg via dry-powder inhaler (Turbuhaler), one in 675 patients with intermittent and one in 455 patients with mild persistent asthma, overall 6-87 years of age. Peak expiratory flow (PEF), symptoms, rescue medication use, exacerbations, airway responsiveness (metacholine challenge; subgroup of 127 patients), systemic effects (high single-dose test; subgroup of 87 patients), and safety (adverse events) were assessed. RESULTS: Formoterol 4.5 microg was as effective as terbutaline 0.5 mg with regard to morning PEF (non-inferiority; lower 95% confidence interval limit above -10 L/min). Metacholine sensitivity, exacerbation rates or use of rescue medication did not differ between treatments. Formoterol 54 microg was shown to give less systemic effects than terbutaline 6 mg. Both treatments were safe and well tolerated. CONCLUSIONS: Formoterol 4.5 microg used as needed was at least as effective and safe as terbutaline 0.5 mg used as needed in intermittent and mild persistent asthma, and was associated with less systemic effects when administered as high single doses.     

A new HFA-134a propellant in the administration of inhaled BDP via the Jet spacer: controlled clinical trial vs the conventional CFC

This study was carried out with the aim of demonstrating the efficacy and tolerability of beclomethasone dipropionate (BDP) aerosol spray 500 microg b.i.d. via a spacer device (Jet, Chiesi Farmaceutici S.p.A.) using a new HFA-134a formulation or chlorofluorocarbon (CFC) propellant. After having completed a 2-week run-in period, 154 adult patients (77 in each group) with mild-to-moderate persistent asthma were randomised into two groups to receive the study treatment for a duration of 12 weeks in a double-blind, multinational, multicentre, parallel-group design. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of day- and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR, FEF25-75%, MEF50 and FEF25) and vital signs were measured at the clinic at study entry, at the start of treatment and every 2 weeks thereafter. Morning serum cortisol (8.00-10.00 a.m.) was measured at the start and at the end of the treatment period. Adverse events were recorded throughout the total study period. Significant improvements over baseline were reported in both groups in terms of lung function, symptoms and use of rescue inhaled salbutamol. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1. No statistically significant differences in the comparisons between groups, except for FEF25 (P=0.044), were observed in any of the other efficacy variables. Adverse events were reported in 31% of patients in the BDP-HFA group and in 32% in the CFC group. Adverse drug reactions were 4 and 2 in the two groups, respectively. No drug-related serious adverse events were reported in either of the groups. No signs of relevant adrenal suppression were observed in both groups: 2 patients in each group had final values below the normal range. In conclusion, the BDP-HFA-134a formulation proved to be equivalent in efficacy and comparable in safety to the standard BDP-CFC product over 12 weeks in adult patients with mild-to-moderate persistent asthma.     

Portable Spirometry During Acute Exacerbations of Asthma in Children

Background. Spirometry is the gold standard for assessment of asthma and is objective and non-invasive. This is a pilot study to evaluate whether portable spirometry can be successfully performed by children in the pediatric emergency department for acute exacerbations of asthma. Methods. We enrolled children more than 6 years of age presenting to an urban pediatric emergency department with a history of asthma during an acute exacerbation. On arrival and after each bronchodilator treatment, vital signs and a clinical score were recorded. Portable spirometry was then performed. Attempts were continued until acceptable and reproducible measurements were obtained or until the patient was unable to perform further attempts. Outcomes included success at spirometry and correlation of spirometry with clinical signs. Results. Thirty-four subjects were enrolled with a median age of 12 years. Ninety-one percent of subjects completed at least one attempt at spirometry. Seventy-three percent of all spirometry attempts were reproducible. Portable spirometry demonstrated increased severity of the exacerbation in comparison to clinical signs and peak expiratory flow. Percent of predicted forced expiratory volume in 1 second, ratio of forced expiratory volume in 1 second to forced vital capacity, and peak expiratory flow are all poorly correlated with degree of wheezing, clinical score, respiratory rate, and oxygen saturation (r < 0.5). Conclusion. Portable spirometry can be successfully performed by children with acute exacerbations of asthma in the emergency department and demonstrated greater degrees of airway obstruction than did clinical signs. Spirometry provides objective, non-invasive measurements of the severity of airway obstruction in the emergency department for children with acute exacerbations of asthma.     

Effect of Omalizumab as Add-On Therapy on Asthma-Related Quality of Life in Severe Allergic Asthma: A Brazilian Study (QUALITX)

Objective. To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. Methods. This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 μg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. Results. In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). Conclusion. Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.     

The C523A β2 Adrenergic Receptor Polymorphism Associates with Markers of Asthma Severity in African Americans

Our goal was to explore associations between β₂ adrenergic receptor polymorphisms and markers of asthma severity in African American and Caucasian patients with asthma. Polymorphisms at loci ?1023, ?654, ?47, 46, 79, 491, and 523 were genotyped and haplotypes were imputed in 143 African Americans and 336 Caucasians. C523A genotype associated with percentage of African Americans (but not of Caucasians) having an asthma exacerbation: AA, AC, and CC genotypes were 17, 29, and 40%, respectively (p = 0.018). Symptom scores, pulmonary function, and rescue inhaler use paralleled exacerbation prevalence. We conclude the 523 A allele modifies asthma severity in African Americans.