Maximum Percentage Fall Research Articles

Allergen bronchoprovocation: correlation between FEV1 maximal percent fall and area under the FEV1 curve and impact of allergen on recovery

BackgroundHouse dust mite (HDM) induces greater responses than other allergens during allergen bronchoprovocation (ABP) testing. The two standardized methods for reporting results of ABP tests are the maximal percent fall in forced expiratory volume in one second (FEV1, max; %) and the area under the FEV1 vs time curve (AUC; %FEV1 x min). The relationship between these methods has not been previously investigated.AimsWe aimed to measure the correlation between FEV1, max and AUC during the early asthmatic response (EAR) and the late asthmatic response (LAR), and to determine if the EAR recovery period for HDM would be longer than other allergens (cat, grass, horse, and ragweed).MethodsWe retrospectively calculated the AUC and correlation between FEV1, max and AUC during the EAR(0-2 h) and LAR(3-7 h) for each allergen. We compared EAR(0-3 h) and LAR(3-7 h) FEV1, max, AUC and absolute difference in FEV1, max to the most recovered FEV1 (FEV1, min). We performed pairwise comparisons of correlation and slope values using Fischer’s r to z transformation and t-tests, respectively. AUC and absolute differences in FEV1, max and FEV1, min were compared using a one-way ANOVA test, followed by a post-hoc Scheffe test.ResultsCorrelation between the FEV1, max and AUC during the EAR(0-2 h) (n = 221) was 0.807, and was 0.798 during the LAR(3-7 h) (n = 157 of 221), (difference p = 0.408). The EAR(0-3 h) AUC and FEV1, max did differ between allergens (both p < 0.0001) but the LAR(3-7 h) AUC and FEV1, max did not (p = 0.548 and 0.824, respectively). HDM did not have a larger AUC or FEV1, max, than all other allergens during the EAR(0-3 h) or the LAR(3-7 h). The absolute difference between the FEV1, max and FEV1, min during the EAR(0-3 h) did not differ between allergens (p = 0.180).ConclusionThe FEV1, max and AUC for both the EAR(0-2 h) and LAR(3-7 h) had excellent correlation, with no significant difference. Thus, significant bronchoconstriction will likely result in a longer recovery period. There was no evidence of delayed EAR(0-3 h) recovery following HDM challenges, so HDM did not induce a larger response compared to all the other allergens examined.Registration: Not registered. This is not a clinical trial. (This study is a retrospective analysis of data collected during several registered trials.)

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

Leptin and exercise-induced bronchoconstriction in obese asthmatic children

Exercise-induced bronchoconstriction (EIB) in asthmatic children has been associated with obesity. Leptin, the proinflammatory adipokine, is typically increased in obesity, whereas cysteinyl leukotrienes (cysLTs) are the main inflammatory mediators implicated in the pathogenesis of EIB. The aim of this work was to study the possible impact of obesity on the severity of EIB in asthmatic children and the possible association with the adipokine leptin. The study included eighty pre-pubertal asthmatic children divided according to their body mass index (BMI) and response to exercise into four groups; obese exercise-responders (n=20), normal-weight exercise-responders (n=20), obese exercise non-responders (n=20), and normal-weight exercise non-responders (n=20). A baseline spirometry test and a standardized exercise challenge test (ECT) were performed. The severity of EIB was assessed by the maximum percentage fall in forced expiratory volume in 1 second (MF%FEV1) after exercise. The level of fasting serum leptin and the release of cysLTs during exercise were compared between the 4 groups. The MF%FEV1 during exercise was significantly greater in obese responder compared to normal-weight responder patients (p=0.004) and MF%FEV1 was positively correlated with cysLT release during exercise, BMI z-score, waist circumference and serum leptin. CysLT release during exercise was positively correlated with the level of serum leptin (r =0.514, p=0.001). This study reports that the severity of EIB is significantly greater in obese compared to normal-weight asthmatic children and suggests an association between leptin and airway hyperresponsiveness to exercise in obese asthmatic children through a mechanism related to cysLT release

Time-Effect of Formoterol Added to Inhaled Fluticasone on Exercise- Induced Bronchoconstriction in Asthmatic Adolescents

Background: Asthma is characterized by chronic airway inflammation that is controlled by a complex cytokine network. Inhaled corticosteroid and short acting β2-agonists treatment improve asthma control. Objective: The aim of the study is to evaluate if a combination of fluticasone and formoterol is effective to assure a protective effect against EIB 15 min and 4 hours after administration in adolescent with persistent asthma. Method: In this study we selected 20 adolescents age 8 and 19 years affected by mild to moderate persistent asthma and EIB. At screening the following were assessed: eligibility, demography, medical history, medications, spirometry and clinical examination. During the study all the patients continued to regularly take a low dose of inhaled steroids; albuterol as rescue medication has been discontinued 8 hours before the exercise test. Results: Formoterol plus fluticasone offered good protection against EIB in 18 patients (90%), the mean maximum percent fall in FEV1 after formoterol was 7.1 ± 4.9% at 15 min (p<0.001). The combination formoterol plus fluticasone was more effective after 4 hours protecting against bronchoconstriction 19 patients (95%) and the mean maximum percent fall in FEV1 after formoterol plus fluticasone was 4.3 ± 4.2% at 4 h (p < 0.001). Conclusions: This study suggests that fluticasone 100 mcg + formoterol 10mcg by MDI + spacer is effective in protecting asthmatic adolescents 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 administration. Keywords: Children, exercise-induced bronchoconstriction, fluticasone, formoterol, physical activity.

THE PROTECTIVE EFFECTS OF VARIOUS WARM-UP MODALITIES ON EXERCISE-INDUCED BRONCHOSPASM (EIB) IN NON-ASTHMATIC ATHLETES

BackgroundExercise-induced bronchospasm (EIB) that is a transient airway obstruction occurring after strenuous exertion can occur in non-asthmatic athletes as well. However acute effects of different warm-up modalities on EIB in...

Abstract PR050

Background & Objectives: Both the alpha 2 agonist, clonidine1 and dexmedetomidine2 have been shown to blunt stress response due to laryngoscopy and tracheal intubation (LTI). However clonidine is more often used as an antihypertensive where as dexmedetomidine is preferentially used as a sedative analgesics. Therefore, we wanted to compare the effectiveness of intravenous (IV) clonidine versus dexmedetomidine in controlling heart rate(HR) and blood pressure(BP) responses to LTI and to compare their effects on sedation. Materials & Methods: Sixty American Society of Anesthesiologists physical class 1/2 adult inpatients scheduled for general endotracheal anaesthesia were randomised to receive either clonidine (2 mcg/kg) or dexmedetomidine (1mcg /kg) IV over 10 minute before anaesthesia induction. Haemodynamic (BP and HR) were noted before and after administration of study drugs at five time points. Sedation level was assessed at base line and after study drug infusion. The haemodynamic data obtained were analysed statistically with repeated measure ANOVA with base line data as control value. Results: The hemodynamic were comparable between the groups at base line. There was a fall in HR over time in both the groups but it reached statistical significance only in dexmedetomidine group after study drug infusion (p=0.000) and at 1 minute post intubation (p=0.005).A significant fall in blood pressure was recorded in both the group after study drug administration which was counteracted to some extent by sympathetic stimulation at 1 minute post LTI (P>0.05 compare to base line) but again continued to fall till the end of study period (p=0.000). The maximum percentage fall in systolic blood pressure, diastolic blood pressure, and mean blood pressure after intubation were significantly higher in the clonidine group than in dexmedetomidine group (26 % vs. 22%, 29.4% vs. 26%, and 28.7% vs. 24%, respectively).The patients in dexmedetomidine group tend to be more sedated compared to clonidine group (4.6±0.6 vs.3.80 ±1.2; p=0.002) after study drug infusion. Conclusion: Dexmedetomidine and clonidine attenuated the heart rate response but the return to base line value was quicker in dexmedetomidine. Both drugs resulted in a significant fall in blood pressure. Dexmedetomidine appears to be superior to clonidine because it resulted in lesser magnitude of hypotensive episodes.

Drink Temperature Influences Resting Pulmonary Function In Active Individuals

Pulmonary function is thought to be influenced by a variety of dietary factors and more recently the ingestion of fluids. Specifically, recent evidence suggests that the ingestion of a large volume of fluid (~750 mL) decreased resting pulmonary function However, it is unknown whether factors other than volume (i.e. drink temperature) influenced the effect of fluid ingestion on airway function. PURPOSE: Therefore, the purpose of the study was to investigate the effect of both the volume and temperature of fluid ingestion on pulmonary function in recreationally active individuals. METHODS: Eight, healthy, recreationally active individuals completed a randomised, crossover study design consisting of four experimental trials. On separate occasions (separated by ≥2 d) participants visited the laboratory after an overnight fast to complete an experimental trial consisting of the ingestion of: 500 mL cold-temperature [CT] (~2°C) water, 500 mL room-temperature [RT] (~18°C) water, 1000 mL CT (~2°C) water or 1000 ml RT (~18°C) water. Pulmonary function (FEV1, FVC, FEF25-75%) was assessed pre-ingestion and at 1, 5, 10 and 15 min post-ingestion. The maximum percentage fall in forced expiratory volume (FEV1) from the pre-ingestion to the post-ingestion value was calculated to provide an index of airway narrowing. RESULTS: The ingestion of 1000 mL of CT water resulted in a group mean decrease in FEV1 of 7 ± 3% which was significantly reduced compared to 500 mL CT water (2 ± 1%, p=0.005), 500 mL RT water (1 ± 2%, p=0.002) and 1000 mL RT water (3 ± 3%, p=0.002). The maximum reduction in FEV1 following the ingestion of 1000 ml CT was 9 ± 3% and was significantly decreased compared to the 500 mL CT (3 ± 2%, p=0.036) and RT (3 ± 2%, p=0.004) drink. The ingestion of 1000 mL of CT water caused a significant reduction in FVC (7 ± 4%) compared to 500 mL CT water (2 ± 2%, p=0.006), 500 mL RT water (2 ± 2%, p=0.025) and 1000 mL RT water (4 ± 4%, p=0.031). CONCLUSION: The ingestion of a cold, large drink decreased pulmonary function in healthy, active individuals compared to both small volumes of cold and room temperature drinks and a large room temperature drink. These findings suggest an important link between temperature and volume of fluid intake on airway function and should be considered in relation to fluid intake strategies pre-, during, and post-exercise.

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.

A comparison of dexmedetomidine plus ketamine combination with dexmedetomidine alone for awake fiberoptic nasotracheal intubation: A randomized controlled study.

Background and Aims:We designed a study to compare the effectiveness of dexmedetomidine plus ketamine combination with dexmedetomidine alone in search of an ideal sedation regime, which would achieve better intubating conditions, hemodynamic stability, and sedation for awake fiberoptic nasotracheal intubation.Materials and Methods:A total of 60 adult patients of age group 18-60 years with American Society of Anesthesiologists I and II posted for elective surgery under general anesthesia were randomly divided into two groups of 30 each in this prospective randomized controlled double-blinded study. Groups I and II patients received a bolus dose of dexmedetomidine at 1 mcg/kg over 10 min followed by a continuous infusion of dexmedetomidine at 0.5 mcg/kg/h. Upon completion of the dexmedetomidine bolus, Group I patients received 15 mg of ketamine and an infusion of ketamine at 20 mg/h followed by awake fiberoptic nasotracheal intubation, while Group II patients upon completion of dexmedetomidine bolus received plain normal saline instead of ketamine. Hemodynamic variables like heart rate (HR) and mean arterial pressure (MAP), oxygen saturation, electrocardiogram changes, sedation score (modified Observer assessment of alertness/sedation score), intubation score (vocal cord movement and coughing), grimace score, time taken for intubation, amount of lignocaine used were noted during the course of study. Patient satisfaction score and level of recall were assessed during the postoperative visit the next day.Results:Group I patients maintained a stable HR and MAP (<10% fall when compared with the baseline value). Sedation score (3.47 vs. 3.93) and patient satisfaction score were better in Group I patients. There was no significant difference in intubation scores, grimace scores, oxygen saturation and level of recall when compared between the two groups (P > 0.05).Conclusion:The use of dexmedetomidine plus ketamine combination in awake fiberoptic nasotracheal intubation provided better hemodynamic stability and sedation than dexmedetomidine alone.

Peripheral Airway Responsiveness to Sub-maximal Exercise in Asymptomatic Cigarette Smokers.

Cigarette smoking is one of the cardinal causes for the development of bronchial hyperresponsiveness among the smokers. This study was perspectively designed to determine the peripheral bronchial responsiveness to sub-maximal exercise challenge in the asymptomatic smokers. The subjects were between age of 18-25 years without any findings of cardiorespiratory diseases. We performed the 5 min step test exercise at intensity of 80 to 90% of maximum predicted heart rate in 42 young adult male asymptomatic smokers to examine the effect of cigarette smoking on airway responsiveness. Forced expiratory spirogram was recorded before and at 0, 5, 10, 15 min after the completion of exercise. Pre- to post exercise drop in Forced Expiratory Volume in first second ≥ 15% was considered hyperresponsive to the challenge. The analysis of data (mean ± SE) indicated the bronchial hyper-responsiveness in 22 (52%) smokers. The post exercise recovery time pattern showed drop in forced expiratory spirogram from the resting baseline in the responsive smokers and the maximum percentage fall in the parameters or increase in airway resistance which reflect the peripheral airway integrity such as Forced Expiratory Flow 25% (20.30 ± 2.18 Vs 7.88 ± 3.23, p < 0.01), Forced Expiratory Flow 50% (18.46 ± 4.40 Vs 1.93 ± 2.78, p < 0.01), Forced Expiratory Flow 75% (23.94 ± 3.68 Vs 0.80 ± 4.72, p < 0.001) and Forced Expiratory Flow 25-75% (32.50 ± 4.79 Vs 3.64 ± 3.32, p < 0.001) was significantly higher in the responsive than non-responsive subgroup of the smokers. The occurrence of peripheral airway resistance is more in the responsive than nonresponsive subset of smokers to the exercise challenge and hence more prone to develop obstructive airway disease in the long run.

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.

P22 Factors associated with refractoriness to repeat exercise challenge in adults with asthma

IntroductionA proportion of patients with asthma develops a refractory period, during which the bronchoconstrictor response to a second indirect challenge is reduced. A better understanding of factors associated with the...

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.

Pilot study: The effect of reducing treatment on exercise induced bronchoconstriction

SUMMARY RATIONALE: Asthma therapy should be stepped up or stepped down in response to changes in asthma control. However, there is little evidence available on the optimal timing, sequence, and degree of medication reductions. In this study we analyzed clinically stable asthmatic children who underwent a medication reduction from a combination preparation consisting of an inhaled corticosteroid (ICS) and long acting beta2-agonist (LABA) to monotherapy with the same dose of the ICS. We hypothesized that the extent of exercise-induced bronchoconstriction (EIB) would not increase after the cessation of the LABA. Nineteen children, aged 8-16 years, with clinically stable asthma, receiving LABA/ICS combination therapy, were analyzed in this open-label pilot study. Children performed an exercise challenge at baseline and 3 weeks after the medication reduction. Best values of spirometric measurements of the forced expiratory volume in 1 sec (FEV(1)) were used for statistical calculations. Maximum percent fall in FEV(1) was significantly lower after 3 weeks of ICS monotherapy (P = 0.03). Eight of 19 children had a >or=15% fall in FEV(1) after exercise at the initial exercise challenge. In this subgroup, maximum percent fall in FEV(1) after the medication reduction was significantly lower (P < 0.01), and in six children it decreased to <15%, indicating they no longer had EIB. In clinically stable asthmatic children on LABA/ICS combination therapy, the cessation of the LABA can reduce and in most cases abolish EIB.

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.

Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction

IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (-1512A/C, -1112C/T, +2044G/A) through PCR-restriction fragment length polymorphism analysis. Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for +2044G (P=0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%) in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms. The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness.

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.

Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma

Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma, limiting everyday activities important for their physical and social development. The purpose of this randomized, double-blind, placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment, recommended in childhood asthma, to protect patients from exercise-induced bronchoconstriction. Children 6 to 18 years of age with atopic asthma were randomized to a 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive daily 200 microg budesonide (twice daily, 100 microg per dose) + 9 microg formoterol (twice daily, 4.5 microg per dose; n = 20); 200 microg budesonide + 5 or 10 mg montelukast (once daily at bedtime; n = 20); 5 or 10 mg montelukast (n = 20); 200 microg budesonide (n = 20); or placebo (n = 20). A standardized treadmill exercise challenge was performed before and after treatment. Exercise-induced bronchoconstriction, reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise, was significantly diminished after 4 weeks in all active treatment groups, and compared with placebo. Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options. These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma. Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment.

Protection Against Exercise-Induced Bronchoconstriction Two Hours After a Single Oral Dose of Montelukast

The objective of this double-blind cross-over study was to evaluate montelukast for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two patients with EIB (post-exercise decrease in forced expiratory volume in 1 second (FEV1) ≥ 20% at pre-randomization) were randomized to montelukast 10 mg or placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary endpoint was the maximum percent-fall in FEV1 (from pre-exercise FEV1) during 60 minutes after exercise-challenge at 2 hours postdose. This endpoint was improved after montelukast (mean ± SD = 11.7% ± 10.8) versus placebo (17.5% ± 13.8) (p ≤ 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p ≤ 0.001) and a smaller area under the curve for percent-fall in FEV1 during 60 minutes after challenge (p ≤ 0.01) were seen with montelukast at 2 hours. At this timepoint, more patients taking montelukast (45/54) than taking placebo (37/54) were protected against EIB (p = 0.039). We concluded that montelukast provided significant protection against EIB at 2 hours after a single dose.