Maximum Percentage Fall In FEV1 Research Articles

Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study

BackgroundPT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered-dose inhaler. ObjectiveTo evaluate the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB). MethodsIn this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge forced expiratory volume in 1 second [FEV1]) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n = 29) or the reverse sequence (n = 31). Subjects were stratified by background therapy (as-needed short-acting β2-agonist alone or low-to-medium dose inhaled corticosteroid plus as-needed short-acting β2-agonist). FEV1 was measured 5 minutes pre-dose, 30 minutes postdose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30, and 60 minutes postexercise. The primary end point was maximum percentage fall from baseline in FEV1 up to 60 minutes postexercise challenge. ResultsLeast squares mean maximum percentage fall in FEV1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide vs 18.97% with placebo (difference, −13.51% [95% confidence interval, −16.94% to −10.09%]; P < .001). More subjects were fully protected (maximum percentage fall in FEV1 post-exercise challenge < 10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; P < .001). The treatment effect was consistent irrespective of background inhaled corticosteroid therapy, and albuterol/budesonide was well tolerated. ConclusionIn adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes before exercise was significantly more effective than placebo in preventing EIB. Trial RegistrationClinicalTrials.gov Identifier: NCT04234464

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

BackgroundA 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. ObjectiveTo evaluate albuterol MDPI efficacy and safety in patients with exercise-induced bronchoconstriction (EIB). MethodsThis single-dose, double-blind, 2-way crossover study randomized adolescents and adults with EIB (≥20% fall from pre-exercise challenge FEV1) to treatment sequences of albuterol MDPI (180 μg [2 inhalations of 90 μg each])/placebo MDPI (n = 19) or the reverse sequence (n = 19). FEV1 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 FEV1 up to 60 min post-exercise challenge. ResultsMean maximum percentage fall in FEV1 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 FEV1 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. ConclusionsAlbuterol 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.

Onset and duration of attenuation of exercise-induced bronchoconstriction in children by single-dose of montelukast

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed. Patients (n = 66) aged 4-14 years, with preexercise forced expiratory volume in 1 second of (FEV(1)) ≥70% predicted and maximum percentage fall in FEV(1) of ≥20% at two screening exercise challenges were eligible. Patients were to receive single-dose montelukast (4 or 5 mg) or placebo before performing standardized exercise challenges at 2 and 24 hours postdose. A 3- to-7-day washout separated the two crossover periods. The primary end point was maximum percentage fall in FEV(1) after exercise challenge 2 hours postdose. Secondary end points included maximum percentage fall in FEV(1) after the 24-hour postdose challenge; each of the following at 2 and 24 hours postdose-maximum percentage fall in FEV(1) categorized as <10%, 10-20%, or >20%; area under the curve (AUC) during 60 minutes postchallenge; time to recovery of FEV(1) to within 5% of preexercise baseline; and need for rescue medication. The mean maximum percentage fall in FEV(1) after the 2-hour postdose exercise challenge was significantly attenuated after single-dose montelukast compared with placebo (15.35% versus 20.00%; p = 0.020). Montelukast was also significantly more effective than placebo for maximum percentage fall after the 24-hour challenge (12.92% versus 17.25%; p = 0.005), the categorized maximum percent fall in FEV(1) at 2 hours (p = 0.034), and AUC at 2 hours (p = 0.022) and 24 hours (p = 0.013). Single-dose montelukast provided rapid and sustained EIB attenuation in children. Clinicaltrials.gov identifier: NCT00534976.

Effects of Interleukin-13 Blockade on Allergen-induced Airway Responses in Mild Atopic Asthma

Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity. We hypothesized that anti-IL-13 treatment would inhibit allergen-induced late-phase asthmatic responses, airway hyperresponsiveness, and inflammation in subjects with asthma. Fifty-six subjects with mild, atopic asthma were recruited for two double-blind, randomized, placebo-controlled, parallel group trials to compare IMA-638 and IMA-026 IL-13 antibody treatments with placebo treatment. Drug was administered on Days 1 and 8, and allergen challenges were performed on Days 14 and 35. The primary outcome variable was the late-phase area under the curve (AUC), and secondary outcome variables were the early- and late-phase maximum percent fall in FEV(1), early AUC, allergen-induced shift in airway hyperresponsiveness, and sputum eosinophils. The treatment difference with IMA-638 on Day 14 was -19.1 FEV(1) × hour (95% confidence interval: -36.2, -1.9) for the allergen-induced early AUC and -23.8 FEV(1) × hour (95% confidence interval: -46.4, -1.2) for the late AUC (both P < 0.05), but this effect was lost by Day 35. Treatment with IMA-026 did not attenuate the asthmatic responses on Day 14 or Day 35. There was no effect of either antibody on allergen-induced airway hyperresponsiveness or sputum eosinophils. The frequency of adverse events after administration of the IL-13 antibodies was similar to placebo. IL-13 has a role in allergen-induced airway responses in humans. Further study is required to determine whether anti-IL-13 monoclonal antibodies will be beneficial clinically.

O efeito da obesidade sobre parâmetros espirométricos em adolescentes submetidos à broncoprovocação por exercício

The effect of obesity on spirometric parameters in adolescents subjected to exercise bronchoprovocation. The objective of this study was to evaluate the effect of obesity on spirometric parameters in adolescents subjected to a physical exercise bronchoprovocation test. It was a cross-sectional, descriptive and correlational study composed of 15 adolescents of both genders. The diagnosis of asthma was made by clinical history and ISAAC questionnaire, and obesity by BMI above the 95 th percentile. The bronchoprovocation test with physical exercise was used for assessment of exercise induced asthma (EIA), considering positive a decrease in forced expiratory volume in one second (FEV1) > 10% of pre-exercise, and the intensity was calculated by the EIA maximum percentage fall in FEV1 (% Fallmax FEV1). We used the independent t test or Mann-Whitney U test and the Spearman rho correlation (p < 0.05). Significant differences were found between asthmatics and non-asthmatics to % Fallmax FEV1 (p = 0.034). There was a negative moderate relationship to Fallmax FEV1 with leukocytes, and % Fallmax FEV1 with leukocytes. It can be concluded that the spirometric variables presented moderated correlation with the systemic inflammation of obesity.

Exercise-induced bronchospasm in obese adolescents

Background Assess the frequency and severity of exercise-induced bronchospasm (EIB) in obese adolescents. Methods A cross-sectional descriptive study involving 80 adolescents of both genders, aged 10–16 years-old, divided into four groups according to clinical history of asthma and/or allergic rhinitis and body mass index as follows: asthmatic obese (n=18); asthmatic non-obese (n=21); obese non-asthmatic (n=26); and healthy individuals (n=15). An exercise bronchoprovocation test was used for EIB diagnosis, considered positive when the forced expiratory volume in one second (FEV 1) decreased ≥15% in relation to pre-exercise FEV 1. Maximum percent fall in FEV 1 (MF%FEV 1) and area above the curve (AAC 0−30) were calculated to evaluate EIB severity and recovery. Results No significant difference was found in EIB frequency between asthmatic obese (50.0%) and asthmatic non-obese (38.0%) individuals or between obese non-asthmatics (11.5%) and healthy individuals (6.7%). However, the MF%FEV 1 and AAC 0−30 were significantly greater in the asthmatic obese group compared to the asthmatic non-obese (37.7% and 455 vs 24.5% and 214, p<0.03). Conclusions Obesity did not contribute to increased EIB frequency in asthmatics and non-asthmatics. However, obesity did contribute to increased EIB severity and recovery among asthmatics.

TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma

Thromboxane A2 receptor (TBXA2R) gene polymorphism has been associated with atopy and asthma, but few studies have reported the effect of this gene polymorphism on asthma-related phenotype or responsiveness to leukotriene receptor antagonist (LTRA) in asthmatic children. This study investigated associations between asthma-related phenotypes and TBXA2R polymorphism, and also analysed whether the TBXA2R polymorphism has an effect on the efficacy of the LTRA, montelukast, in asthmatic children with exercise-induced bronchoconstriction (EIB). Asthmatic children (n=695) and control children (n=159) were evaluated for asthma-related phenotypes including total IgE, pulmonary function test, and bronchial hyperresponsiveness to methacholine or exercise. Genotypes were detected by PCR-RFLP. In the montelukast study, exercise challenge was performed before and after an 8-week montelukast treatment. The TBXA2R polymorphism was not associated with asthma susceptibility and the clinical parameters of asthma. However, asthmatic children with combinations of the TBXA2R+795T>C and +924T>C risk alleles had significantly higher total IgE levels (P=0.01), total eosinophil counts (P<0.01) and lower forced expiratory volume in 1 s (FEV(1)) (P=0.02) and forced expiratory rates at 25-75% of vital capacity (P=0.02) than those carrying the common alleles. When compared with individuals with the common alleles, patients with the TBXA2R+924T>C TT homozygote and TBXA2R+795T>C hetero- or homozygote (CT or CC) had a 3.67-fold poor response to 8-week montelukast treatment with respect to maximum percent fall in FEV(1) after exercise (odds ratio, 3.67; 95% confidence interval, 1.15-11.15). A combined effect of TBXA2R+795T>C and +924T>C risk alleles may be linked to IgE production, eosinophilic inflammation, and severity of asthma. In addition, the TBXA2R+795T>C genotype may be a predictive marker of a clinical response to the LTRA in Korean asthmatic children with EIB.

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.

Metalloproteinase-9 in Induced Sputum Correlates with the Severity of the Late Allergen-Induced Asthmatic Response

Background: Asthma is characterized by airway inflammation and remodeling in which matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play an important role. Allergen exposure activates the inflammatory/repair process in sensitized subjects. Induced-sputum analysis is a non-invasive method that allows the assessment of changes in inflammatory and remodeling mediators implicated in asthma. Objectives: To evaluate the changes in MMP-9 and its principal inhibitor (TIMP-1) in sputum and plasma of mild allergic asthmatic subjects after whole-lung allergen challenge. Methods: Induced sputum and blood samples were obtained at baseline, and 6 and 24 h after challenge. MMP-9 and TIMP-1 levels in sputum and plasma were measured by ELISA. Results: Allergen challenge increased the percentage of sputum eosinophils and MMP-9 levels 6 and 24 h after the challenge compared to baseline levels, but TIMP-1 levels did not vary significantly. A significant correlation was observed between MMP-9 levels at 6 h and the maximum percent fall in FEV₁ during the late response. Throughout the study, MMP-9 levels correlated significantly with the number of neutrophils in sputum. Conclusions: This study shows that analysis of induced sputum is a useful tool to study the variations in MMP-9 and TIMP-1 levels following allergen challenge, therefore allowing to evaluate their role in allergen-induced airway damage and repair.

Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction

Secondary to the phase-out of chlorofluorocarbons (CFCs), the albuterol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom) pressurized metered-dose inhaler (MDI) has been formulated in a non-ozone-depleting propellant, hydrofluoroalkane (HFA) 134a. To compare the efficacy of albuterol HFA to albuterol CFC and placebo HFA in protecting patients from exercise-induced bronchospasm (EIB). Randomized, double-blind, placebo-controlled, three-way crossover study in patients with documented EIB. Patients (n = 24) aged 18 to 45 years old received albuterol HFA or albuterol CFC, (total dose of 180 microg ex-actuator), or placebo HFA via an MDI, 30 minutes before a standardized exercise challenge. Serial forced expiratory volume in 1 second (FEV1) measurements were made 5 minutes before exercise and 5, 10, 15, 20, 25, 30, and 60 minutes postexercise. The primary outcome measure was the maximum percentage fall in FEV1 over the 60 minutes after exercise. The adjusted mean maximum percentage falls in FEV1 postexercise for albuterol HFA and CFC groups were 15.4% and 14.9%, respectively. The two formulations were comparable with a treatment difference of -0.5% (P = 0.848; 95% confidence interval, -5.3 to 4.4%). When compared with the fall in FEV1 for placebo (33.7%), both active treatments demonstrated a significantly smaller fall in FEV1 postexercise (P < 0.001). Safety profiles were similar among the three treatment groups. The results provide assurance to prescribers that the formulation of albuterol in the non-ozone-depleting propellant HFA 134a has not affected its efficacy in the treatment of EIB in asthmatic patients. Single doses of albuterol HFA and CFC from an MDI are comparable in terms of efficacy and safety on a microgram per microgram basis.

Evidence of the Rapid Protective Effect of Formoterol Dry-Powder Inhalation against Exercise-Induced Bronchospasm in Athletes with Asthma

Background: Although formoterol, a new long-acting β₂-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). Aim: The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. Methods: The protective effect of a formoterol (12 µg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. Results: Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV₁ after exercise being 29.3 ± 14.3% and 22.9 ± 13.7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV₁ after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV₁ after formoterol was 5.9±7.2% at 15 min (p < 0.0001), and 5.8 ± 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. Conclusions: This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.

Evaluation of single-dose inhaled corticosteroid activity with an allergen challenge model

Background: Inhaled corticosteroids are the most commonly used antiinflammatory agents for asthma. There is no simple way to compare objectively the relative potency of inhaled corticosteroids. The allergen-induced late asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid. Objective: This study was undertaken to evaluate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids. Methods: We compared doses of 200 and 800 μg of a highly active inhaled corticosteroid (budesonide) with placebo and a marginally active investigational inhaled corticosteroid (D5159). Ten atopic patients with asthma completed a randomized, double-blind, double-dummy, multicenter, four-way, crossover trial. A standardized allergen challenge with the identical dose of allergen was performed 10 minutes after each of four blinded, single-dose treatments: 200 μg of budesonide, 800 μg of budesonide, 8 mg of D5159, and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV 1 between 4 and 7 hours, and the allergen-induced increase in methacholine airway responsiveness at 24 hours was recorded as the Δ log PC 20 from the day before to the day after allergen challenge. Results: There were no significant differences in the early asthmatic responses during the 4 days; the mean maximum percent in FEV 1 fall ranged between 19.5% and 22%. D5159 produced a slight inhibition of the LAR with maximum percent fall in FEV 1 recorded as 28.8% ± 5.0% for D5159 versus 34.1% ± 4.8% for placebo ( p < 0.05). There was a greater reduction recorded after administration of the two doses of budesonide. The mean LAR was 15.1% ± 3.8% for 200 μg of budesonide and 11.2% ± 2.3% for 800 μg of budesonide ( p < 0.01 compared with placebo and D5159). The two doses of budesonide were not statistically different. Airway responsiveness to methacholine increased by 1.07 doubling doses 24 hours after allergen challenge. This increased airway responsiveness was slightly, but not significantly, reduced by the three active treatments (0.6 to 0.91 doubling doses). Conclusion: The allergen-induced LAR model was able to differentiate a single dose of an active inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid from a weak inhaled corticosteroid. The model did not differentiate between 2 fourfold doses of the highly active inhaled corticosteroid (at the doses used in this study), neither for the fall in FEV 1 nor for the increase in airway hyperresponsiveness. (J Allergy Clin Immunol 1997;100:65-70.)

A comparison of the effects of oral cetirizine and inhaled beclomethasone on early and late asthmatic responses to allergen and the associated increase in airways hyperresponsiveness

Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain. We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days. Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.

Protective effect and duration of action of inhaled formoterol and salbutamol on exercise-induced asthma in children

The magnitude and duration of protection against exercise-induced asthma (EIA) afforded by salbutamol and the new, long-acting β 2-agonist, formoterol, were compared in a double-blind, placebo-controlled crossover study. Twelve children with asthma and EIA (>25% fall from baseline at a pretrial exercise test) were studied on 3 different days receiving, in random order, either formoterol, 12 μg, salbutamol, 200 μg, or placebo by inhalation. The effect on EIA was evaluated by standardized treadmill-exercise tests repeated at the following times after medication: 1 2 hour (test 1), 3 hours (test 2), and, if the trial drug still demonstrated an effect, 5 1 2 hours (test 3) and 8 hours (test 4). The mean (SD) maximum percent fall in FEV 1 at the pretrial test was 45% (14%). Placebo treatment had no effect on EIA. The mean (SD) maximum percent fall in FEV 1 was 44% (14%) (test 1) and 39% (13%) (test 2) (not significant). Salbutamol offered good protection against EIA after 1 2 hour (percent fall in FEV 1 18% [18%]; p < 0.02) but was not significantly different from that of placebo after 3 hours, 39% (13%) fall in FEV,. Formoterol blocked EIA in all the children and demonstrated a significant effect in most children for at least 8 hours. The percent fall in FEV, after the various tests were 8% (16%) (test 1), 10% (9%) (test 2), 18% (15%) (test 3), and 18% (7%) (test 4; N = 9) (all tests, p < 0.001). The mean duration of a 50% reduction in EIA was 1 built1 2 hours for salbutamol and 6 1 2 hours for formoterol ( p < 0.001). No side effects were observed. Inhaled formoterol was determined to be more effective and offered four to five times longer protection against EIA than salbutamol.

Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma.

Previous work suggests a role for mast cell derived mediators in exercise induced asthma. The contribution of newly generated contractile prostaglandins to exercise induced asthma was assessed by using a potent and orally active thromboxane (TP1) receptor antagonist, GR32191. The effect of 120 mg GR32191 on exercise induced asthma was observed in 12 asthmatic subjects. For the exercise challenge the subjects performed six minutes of treadmill exercise, breathing dry air at a work load that had previously been shown to induce a fall in FEV1 of 25% or more from the pre-exercise baseline. No effect of GR32191 on pre-exercise baseline airway calibre was evident. There was no significant difference in the mean maximum percentage fall in FEV1 from baseline after exercise between drug and placebo (placebo 30.2%, GR32191 day 31.6%). It is concluded that the thromboxane antagonist GR32191 has no effect on exercise induced asthma. This suggests that prostaglandins, including PGD2, that act via the thromboxane receptor do not have an important role in exercise induced asthma.

Repeated exposure of asthmatic airways to inhaled adenosine 5′-monophosphate attenuates bronchoconstriction provoked by exercise

Inhaled adenosine 5'-monophosphate (AMP) induces bronchoconstriction in subjects with asthma, probably caused by histamine release from airway mast cells, and repeated AMP bronchial challenge leads to attenuation of the bronchoconstrictor response. Since exercise-induced bronchoconstriction may be mediated by hypertonic mast cell degranulation, we postulated that repeated AMP bronchial challenge should reduce the response to subsequent exercise challenge. Eight atopic subjects with asthma took part in an unblinded, randomized trial. On the control study day, a treadmill exercise test previously demonstrated to induce a greater than 20% fall in FEV1 was performed. On the AMP study day, three AMP dose-response bronchial challenges were performed at 1-hour intervals. Each AMP challenge was continued until either a provocative concentration causing a 20% fall in FEV1 had been achieved (PC20) and the PC20 was calculated, or the maximum concentration of AMP (400 mg/ml) had been administered. After recovery of the FEV1 from AMP challenge, a treadmill exercise test identical to the test on the control study day was performed. On the AMP study day, the geometric mean PC20 was 15.3 (7.9 to 29.5) mg/ml for the first test, and 28.2 (10.7 to 77.4) mg/ml for the third test (not significant). On the control study day, the mean maximum percentage fall in FEV1 after exercise was 28.0% +/- 2.7%, whereas on the AMP study day, it was reduced to 13.0% +/- 4.3% (p less than 0.01). A significant correlation was found between the change in responsiveness to AMP induced by repeated challenge and the attenuation of the subsequent exercise response (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for the roles of histamine and prostaglandins as mediators in exercise-induced asthma: the inhibitory effect of terfenadine and flurbiprofen alone and in combination

We investigated the effects of terfenadine, a histamine H1-receptor antagonist, and flurbiprofen, a cyclooxygenase inhibitor, on exercise-induced bronchoconstriction to assess the contribution of the mast cell products histamine and prostaglandins. Eight asthmatics were studied on 4 occasions with treadmill exercise tests. Terfenadine or placebo was administered 3 h prior to exercise, and flurbiprofen or placebo was administered 2 h prior to exercise, in a double-blind randomized trial. Airway calibre was determined by measurement of the forced expiratory volume in one second (FEV1) immediately prior to exercise challenge, and over 30 min post-exercise. Following placebo, the mean maximum percentage fall in FEV1 was 39%. This fell to 25% after terfenadine (p less than 0.05), 27% after flurbiprofen (p less than 0.05), and 30% after the active combination (NS). Analysis of the areas under curves of percentage falls in FEV1 over 30 min showed significant inhibition on all 3 active drug days (p less than 0.05). We conclude that histamine release and prostaglandin generation contribute to exercise-induced bronchoconstriction, although the interaction between these mediators appears complex.