Nancy K. Ostrom

The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children.

OBJECTIVE To determine the effects of zafirlukast on exercise-induced bronchoconstriction in children. STUDY DESIGN Exercise challenges were done 4 hours after single oral doses of zafirlukast or placebo were administered in asthmatic children (6 to 14 years) treated with beta 2-agonists alone. Subjects randomized to treatment had a >/=20% decrease in forced expiratory volume in 1 second (FEV1 ) after a screening challenge. In a randomized, double-blind, 3-way, crossover design, group 1 (n = 20) received placebo and 5 and 20 mg zafirlukast, and group 2 (n = 19) received placebo and 10 and 40 mg zafirlukast. Maximal percentage fall in FEV1, area under the curve, and time to recovery of FEV1 to within 5% of baseline after the challenge were compared with analysis of variance. RESULTS Mean values for maximal fall in FEV1 ranged from -8.7% +/- 1.7% to -11.1% +/- 1.9% after zafirlukast compared with -17.1% +/- 1.8% and -16.3% +/- 1.9% after placebo. Differences from placebo for fall in FEV1 and area under the curve were significant (P </=.05) after 5, 20, and 40 mg zafirlukast and approached significance (P </=.08) after 10 mg zafirlukast. After all zafirlukast doses, recovery times (means of 5 to 7 minutes) decreased significantly (P </=.05) and by approximately half compared with placebo (11 and 14 minutes). Safety assessments did not differ among treatments. CONCLUSION Four hours after dosing, zafirlukast attenuated exercise-induced bronchoconstriction in children.

Deterioration in Asthma Control When Subjects Receiving Fluticasone Propionate/Salmeterol 100/50 mcg Diskus are “Stepped-Down”

In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or “step down” to either fluticasone propionate (FP) 100mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, “stepping down” to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.

Occupational allergy to honeybee-body dust in a honey-processing plant

We studied a honey-plant employee who developed severe asthma coincident with the seasonal honey-packing process. Symptoms correlated with duration of exposure inside the plant during the honey pack and improved in other environments during that season. The patient was asymptomatic inside the plant at other times of the year. Skin tests to seasonal outdoor aeroallergens were negative, as were inhalation challenges with two insecticides used inside the building during the honey pack. Skin test, RAST, and bronchial provocation test with honeybee whole body extract were positive. We used high-volume air samplers to collect ambient airborne particles on filter sheets outside the patients home and inside the honey plant, both during and after the honey pack. Skin tests, RASTs, and bronchial provocation tests with eluates from these filters were positive only to eluate from the filter exposed inside the plant during the honey pack. The patients positive honeybee whole body RAST could be inhibited by preincubation of her serum with this filter eluate but not by preincubation with eluate from a filter exposed outside the patients home. Collectively, these data support an IgE-mediated, seasonal, occupational sensitivity to honeybee-body dust.

Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma

BACKGROUND Breath-actuated inhalers (BAI) eliminate the need for the hand-breath coordination required with standard metered-dose inhalers (MDI). OBJECTIVE To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) administered via BAI. METHODS This 6-week, phase III, double-blind study included patients aged ≥12 years with persistent asthma. During the single-blind run-in, patients discontinued asthma medications and received twice-daily placebo BAI or MDI. At randomization, BAI patients received BDP BAI 320 μg/day, BDP BAI 640 μg/day, or placebo BAI, and MDI patients received BDP MDI 320 μg/day or placebo MDI. Assessments included standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from 0 to 6 weeks (AUEC[0-6 wk]) (obtained by clinic-based spirometry; the primary end point), morning peak expiratory flow (PEF), trough daily morning FEV1 (obtained by handheld spirometry), withdrawals, and tolerability. RESULTS Of 425 patients randomized, most were white (81%) and female (61%). BDP BAI 320 and 640 μg/day significantly improved FEV1 AUEC(0-6 wk) versus placebo (p < 0.001). The BDP BAI treatment groups exhibited significantly improved morning PEF and daily morning FEV1 versus placebo (p < 0.001). Similar treatment effects were demonstrated for BDP MDI (p < 0.001). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 μg/day (n = 1), BDP BAI 640 μg/day (n = 0), and BDP MDI 320 μg/day (n = 1) versus placebo (n = 10). BDP BAI was well tolerated. CONCLUSION BDP BAI demonstrated significant improvements in pulmonary function versus placebo, with results similar to BDP MDI. The safety profile of BDP BAI was comparable to BDP MDI, with no new safety signals.The study was registered on ClinicalTrials.gov (NCT02513160), www.clinicaltrials.gov.

The Efficacy and Safety of Beclomethasone Dipropionate Delivered via a Breath-Actuated Inhaler in Adult and Adolescent Patients With Persistent Asthma

Background: To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) delivered via a breath-actuated inhaler (BAI) versus placebo in asthmatic patients. Methods: This phase 3, 6-week, double-blind study (NCT02513160) included patients with persistent asthma (aged ≥12 years). During a 14-to 30-day single-blind run-in, patients discontinued asthma medications and received albuterol metered-dose inhaler (MDI) for rescue and twicedaily placebo BAI or MDI for training. At randomization, BAI patients received BDP BAI 320 mcg/day, BDP BAI 640 mcg/day, or placebo BAI. MDI patients were randomized to receive BDP MDI 320 mcg/day or placebo MDI. Standardized baseline-adjusted trough morning forced expiratory volume in 1 second area under the effect curve from 0 to 6 weeks (FEV1AUEC0–6wk; primary), morning peak expiratory flow (PEF), rescue medication use, asthma symptoms, withdrawals, and tolerability were assessed. Results: The modified intent-to-treat and safety populations each included 425 patients. BDP BAI 320 and 640 mcg/day significantly improved FEV1AUEC0–6wk versus placebo (P<0.0001). Active BAI treatment groups exhibited significantly improved morning PEF, rescue medication use, and asthma symptoms versus placebo (P≤0.0003). Similar treatment effects were demonstrated for BDP MDI (P≤0.0006). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 mcg/day (n=1), BDP BAI 640 mcg/day (n=0), and BDP MDI 320 mcg/day (n=1) versus placebo (n=10). BDP BAI was safe and well tolerated. Conclusions: BDP BAI demonstrated significant improvements in lung function and symptom control versus placebo with similar results for BDP MDI. BDP BAI’s safety profile was comparable to BDP MDI, with no new safety signals.

Novel albuterol multidose dry powder inhaler in patients with exercise-induced bronchoconstriction: A single-dose, double-blind, randomized, 2-way crossover study.

BACKGROUND A novel, inhalation-driven, multidose dry powder inhaler (MDPI) was developed that eliminates the need to coordinate device actuation with inhalation as is required with conventional metered-dose inhalers. OBJECTIVE To evaluate albuterol MDPI efficacy and safety in patients with exercise-induced bronchoconstriction (EIB). METHODS This single-dose, double-blind, 2-way crossover study randomized adolescents and adults with EIB (≥20% fall from pre-exercise challenge FEV(1)) to treatment sequences of albuterol MDPI (180 μg [2 inhalations of 90 μg each])/placebo MDPI (n = 19) or the reverse sequence (n = 19). FEV(1) was measured 30 and 5 min predose, 30 min postdose (ie, 5 min before treadmill exercise challenge; baseline) and 5, 10, 15, 30, and 60 min after exercise challenge. The primary efficacy endpoint was maximum percentage fall from baseline in FEV(1) up to 60 min post-exercise challenge. RESULTS Mean maximum percentage fall in FEV(1) within 60 min post-exercise challenge was 6.2 ± 1.4% for albuterol MDPI versus 22.4 ± 1.4% for placebo MDPI (between-treatment difference: -16.2%; 95% CI: -20.2% to -12.1%; P < 0.0001). A significantly higher percentage of albuterol MDPI-treated patients were protected against EIB (<10% maximum FEV(1) fall post-exercise challenge) versus placebo MDPI (84.2% vs 15.8%; P < 0.0001). Protection with albuterol MDPI was evident within 5 min and maintained through 30 min; recovery was complete for both groups at 60 min. Treatment with a single dose of albuterol MDPI was generally well tolerated. CONCLUSIONS Albuterol MDPI provides clinically significant protection from EIB in adolescents and adults with EIB; no new safety issues were observed with short-term albuterol MDPI use. ClinicalTrials.gov identifier NCT01791972.