Percent Decrease In FEV1 Research Articles

Calcium channel blockers for lung function improvement in asthma: A systematic review and meta-analysis

BackgroundFor decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated. ObjectiveTo assess the effect of CCBs vs placebo on lung function test results in adults with asthma. MethodsVarious databases were systematically searched to identify all randomized clinical trials with adults with asthma. We aimed to assess the influence of CCBs on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and provocative concentration of bronchoconstrictive agents causing a 20% decrease in FEV1 (PC20) compared with a placebo. All effect estimates were pooled by the generic inverse variance method with random-effects meta-analysis. Subgroup analysis, sensitivity analysis, and heterogeneity investigation were performed. ResultsThirty eligible articles with 301 patients were included in this meta-analysis. Our results revealed that in a standard exercise test CCBs could produce a mean maximal percentage decrease in FEV1 of 11.56% (95% confidence interval, 8.97%–14.16%; P < .001) and an increase in postdose FEV1 by 80 mL (95% confidence interval, 0.02–0.15 mL; P = .01). However, there was no statistical significance for CCBs in postdose FVC, PEFR, or PC20 of histamine and methacholine. ConclusionCCBs may be beneficial for lung function improvement in asthma, especially in exercise-induced asthma. However, there is a lack of evidence for CCBs protecting asthma patients from chemical irritation.

PHYSIOLOGIC AIRWAY RESPONSES TO INHALED HISTAMINE AND ACETYLCHOLINE IN PATIENTS WITH MILD ASTHMA AS ANALYZED BY FORCED OSCILLATION.

Asthma is a chronic disease characterized by airway inflammation; it is sometimes difficult to diagnose. For clinical diagnosis, forced oscillation technique (FOT) measures airway reactance and resistance. By FOT, we investigated respiratory resistance and ventilation perfusion ratio inequality in adults with mild asthma. We examined 58 adult patients with mild asthma having no inhaled corticosteroid treatment, and 10 adult patients with post-infectious prolonged cough. Using a MostGraph-01 FOT instrument, we evaluated these patients before and after bronchial hyperresponsiveness to acetylcholine (ACh) or histamine (Hist). We measured the following conditions: change of resistance at 5Hz (R5) and 20Hz (R20), R5-R20, reactance at 5Hz, frequency of resonance (Fres), low-frequency reactance area (ALX), and forced expiratory volume in 1 second (FEV1). There were significant changes of R5, R20, R5-R20, X5, Fres, ALX after provocations for ACh or Hist in all patients with asthma, but not in patients with post-infectious prolonged cough. We calculated the percent decrease in FEV1 after provocation with ACh or Hist. For Ach, this decrease in FEV1 correlated with changes in R20 and Fres for all patients. For Hist, the percent decrease in FEV1 correlated with changes in R5, R20, Fres, and ALX for all patients. Furthermore, we investigated these correlations in patients with normalized bronchial hyperresponsiveness to ACh or Hist. For Ach, the percent decrease in FEV1 correlated with changes in Fres or R5-R20. For Hist, this decrease in FEV1 correlated with changes in R5, R20, and Fres. ROC analysis was used to evaluate the diagnostic value of the ratio of change of Fres in BHR to Hist. The area under the curve was 0.7808 (95% CI=0.657-0.904). A reasonably high specificity (100.0%) and a high sensitivity (53.8%) with a cut-off point of 1.5 in the ratio before and after of Fres were obtained. The changes in FOT parameters (before and after bronchial airway responses) may detect airway resistance and ventilation perfusion ratio inequality even in adult patients with asthma having normalized bronchial hyperresponsiveness to ACh or Hist. That results may be useful for an early diagnosis of asthma.

Comparison of the effectiveness and safety of formoterol versus salmeterol in the treatment of patients with asthma: A systematic review and meta-analysis.

Formoterol and salmeterol are two long-acting β2-agonists given by inhalation, with bronchodilating effects lasting for at least 12 h after a single administration. Formoterol has a faster onset of action compared with salmeterol. The aim of this study was to perform a systematic review and meta-analysis on the data published from previous review in order to calculate pooled estimates of effectiveness and safety assessment of formoterol and salmeterol in treatment of patients with asthma. In this study, we conducted an electronic search for medical citation databases including Cochrane, PubMed, Scopus, PsycInfo, and IranMedex. Besides manual search of the databases that record randomized clinical trials, conference proceedings, and journals related to asthma were included. Studies were evaluated by two independent people based on inclusion and exclusion criteria, and the common outcomes of studies were entered into the RevMan 5.0.1 software, after evaluation of studies and extraction of data from them; and in cases where there were homogeneous studies, meta-analysis was performed, and for heterogeneous studies, the results were reported qualitatively. Of the 1539 studies initially found, 13 were included in the study. According to the meta-analysis conducted, no significant difference was found between the inhalation of formoterol 12 μg and salmeterol 50 μg in the two outcomes of mean forced expiratory volume 1 s (FEV1), 12 h after inhalation of medication and Borg score (A frequently used scale for quantifying breathlessness) after inhalation of medication. In addition, salmeterol was more effective than formoterol in the two outcomes of percent decrease in FEV1 after inhalation of methacholine and the number of days without an attack. Since the two outcomes of FEV1 30-60 min after inhalation of medication and morning peak expiratory flow after inhalation of medication were heterogeneous, they had no meta-analysis capabilities, and its results were reported qualitatively. The data from included studies shows that, more efficacy has been achieved with Salmeterol, especially in some outcomes such as the percent decrease in FEV1 after inhalation of Methacholine, and the number of days without an attack; and therefore, the administration of Salmeterol seems to be beneficial for patients, compared with Formoterol.

Refractoriness to inhaled mannitol 3 hours after allergen challenge

BackgroundA positive response to indirect airway challenges (eg, mannitol) that cause release of mast cell mediators causes refractoriness to a repeat exposure to the same or different indirect stimulus that lasts for at least several hours. Allergen challenge causes increased response to methacholine measured at 3 hours. ObjectiveTo compare allergen-induced changes in airway response to methacholine and mannitol 3 hours after completion of an allergen challenge. MethodsTen atopic patients with asthma completed a randomized clinical trial. The provocation concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV1) was measured 24 hours before and 3 hours after a standard allergen challenge. The provocation dose of mannitol causing a 15% decrease in FEV1 was also measured 24 hours before and 3 hours after allergen challenge. The allergen challenges were separated by 7 to 14 days. ResultsThe allergen-induced early responses, expressed as the maximum (SD) percent decrease in FEV1, were 29.7% (11.1%) and 27.8% (7.6%) on the methacholine and mannitol days, respectively. Airway response to methacholine increased significantly after allergen challenge (P = .02). By contrast, the airway response to mannitol was reduced by almost a doubling dose (P = .02) after allergen. ConclusionThree hours after allergen challenge at a time when the airways are more responsive to methacholine, there is a significant refractoriness to the indirect stimulus mannitol. Trial Registrationclinicaltrials.gov Identifier: NCT01699594

Exercise-Induced Bronchoconstriction in Children with Asthma: Is There an Association with Urinary Leukotriene E4 or Exhaled Nitric Oxide

Cysteinyl leukotrienes (LT) and airway inflammation are thought to affect exercise-induced bronchoconstriction (EIB). The aim of this study was to investigate the relations between EIB and urinary leukotriene E4 (LTE4) levels and other noninvasive measures of airways inflammation markers in a sample of children with asthma. Pre-exercise urinary LTE4, fractional concentration of exhaled nitric oxide (FeNO) and blood eosinophil count and pulmonary function were measured in 32 children with asthma (mean age±SD, 11.2±2.9 years). Change in forced expiratory volume in one second (FEV1) was determined at 5, 10, and 15 min following 6 min of exercise on a cycle ergometer. Fifteen of the 32 subjects experienced EIB (≥10% decrease in FEV1). The urinary LTE4, FeNO, and blood eosinophil count were significantly related to the maximal percentage decrease in FEV1 after exercise (r=0.44, P<0.05; r=0.36, P<0.05, and r=0.40, P<0.05, respectively). By multiple linear regression, after adjusting for age, gender, and treatment with inhaled corticosteroids, only the pre-exercise urinary LTE4 level was correlated with the maximal percentage decrease in FEV1 after exercise (β=32, P<0.05). Bronchoconstriction after exercise is related to the pre-exercise urinary LTE4 in children with asthma.

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

Effect of Different Antiasthmatic Treatments on Exercise-Induced Bronchoconstriction in Children With Asthma

Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P. J Allergy Clin Immunol. 2008;121(2):383–389 PURPOSE OF THE STUDY. To compare the effectiveness of different patterns of antiasthmatic treatments to protect children from exercise-induced bronchospasm (EIB). STUDY POPULATION. This was a randomized, double-blind, placebo-controlled study of 100 children aged 6 to 18 years with atopic asthma sensitive only to house dust mites and EIB. Subjects must have had a resting forced expiratory volume in 1 second (FEV1) of ≥70% predicted and at least a 20% drop in FEV1 after exercise to qualify for the study. METHODS. Participants were randomly assigned to a 4-week double-blind, placebo-controlled trial to receive 1 of the following treatments: (1) budesonide 100 μg + formoterol 4.5 μg twice daily; (2) budesonide 100 μg twice daily + montelukast 5 or 10 mg at bedtime; (3) montelukast 5 or 10 mg at bedtime; (4) budesonide 100 μg twice daily; or (5) placebo alone. All study arms had matching placebo medications from which active drugs were omitted (eg, group 1 had placebo tablets in place of montelukast, etc). At randomization and after 4 weeks on the study medication(s), a treadmill exercise test was performed to evaluate the effectiveness of treatment. RESULTS. Ninety-one subjects with a median age of 11.3 to 12.2 among the groups completed the study. Preexercise FEV1 and EIB, as represented by the area under the curve of time-response curve and by maximum percentage decrease in FEV1 after exercise, did not differ at baseline between the groups. EIB was diminished with all treatments when compared with placebo. The effect of treatment with budesonide plus montelukast and with montelukast alone were greater than budesonide alone or budesonide plus formoterol (P &amp;lt; .001). The budesonide-plus-formoterol group was also better than budesonide alone, but these results did not reach significance (P = .59). CONCLUSIONS. Budesonide plus montelukast or montelukast alone were the most effective treatments for EIB in children. REVIEWER COMMENTS. This was the first study in asthmatic children that evaluated both monotherapy and combination therapy for the reduction of EIB. This study highlights the importance of controller therapy in childhood asthma and the effects on EIB between therapeutic options recommended for childhood asthma. In particular, consideration for the use of montelukast as monotherapy or in combination therapy with inhaled corticosteroids is indicated for EIB in children with similar asthmatic phenotypes.

Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies

Increases in T helper (Th) 2 cytokine concentrations have been seen in atopic asthma, with interleukin 4 and interleukin 13 thought to have a role in the physiological response to allergen challenge. Our aim was to assess the therapeutic effect of pitrakinra, an interleukin-4 variant that targets allergic Th2 inflammation by potently inhibiting the binding of interleukin 4 and interleukin 13 to interleukin-4Ralpha receptor complexes. In two independent randomised, double-blind, placebo-controlled, parallel group phase 2a clinical trials, patients with atopic asthma were treated with pitrakinra or placebo via two routes. In study 1, patients were randomly assigned to receive either 25 mg pitrakinra (n=12) or placebo (n=12) by subcutaneous injection once daily. In study 2, patients were randomly assigned to receive either 60 mg pitrakinra (n=16) or placebo (n=16) by nebulisation twice daily. Inhaled allergen challenge was done before and after 4 weeks of treatment. The primary endpoint for study 1 was maximum percentage decrease in forced expiratory volume in 1 s (FEV1) over 4-10 h after allergen challenge, whereas that in study 2 was average percentage decrease in FEV(1) over 4-10 h after allergen challenge. All patients except those with baseline data only were included in our analyses. These trials are registered with ClinicalTrials.gov, numbers NCT00535028 and NCT00535031. No patients dropped out or were lost to follow-up in study 1; in study 2, two patients in the placebo group and one in the pitrakinra group dropped out or were lost to follow-up. These individuals had baseline data only, and were excluded from the analyses. In study 1, there was a 17.1% maximum percentage decrease in FEV1 in the pitrakinra group; by contrast, the maximum decrease was 23.1% in the placebo group (difference 6%, 95% CI -4.37 to 16.32; p=0.243). In study 2, there was a 4.4% average percentage decrease in FEV1 in the pitrakinra group; by contrast, the average percentage decrease was 15.9% in the placebo group (3.7 [95% CI 2.08-6.25] times lower in the pitrakinra group; p=0.0001). There were fewer asthma-related adverse events (p=0.069) and fewer adverse events requiring beta-agonist rescue (p=0.031) after subcutaneous administration of pitrakinra than with placebo. There were too few asthma-related adverse events in study 2 to assess the effect of inhalation of pitrakinra on adverse events. Local treatment, targeted at inhibition of interleukins 4 and 13 in the lung, could substantially diminish the symptoms of asthma.

An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm

Background. Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 μg (two actuations of 45 μg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. Methods. This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were ≥18 years, had a ≥6-month history of EIB, ≥ 70% baseline predicted forced expiratory volume in 1 second (FEV1), and a 20% to 50% decrease in FEV1 after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV1 from baseline (postdose/pre-exercise). The percentage of protected (≤ 20% decrease in post-exercise FEV1) patients was also assessed. Results. Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo (LS mean ± SE; −4.8% ± 2.8% versus −22.5% ± 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV1 compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. Conclusion. Levalbuterol HFA MDI (90 μg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. Clinical Implications. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.

Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast

Leukotriene modifiers have been shown to protect against exercise-induced bronchoconstriction (EIB) with repeated, chronic dosing. To study the onset and duration of protection against EIB after a single dose of montelukast, a leukotriene receptor antagonist. In this randomized, crossover, double-blind study, 51 adult asthma patients with EIB (> or = 20% postexercise decrease in forced expiratory volume in 1 second [FEV1]) received a single oral dose of montelukast (10 mg), or placebo followed by exercise challenge 2, 12, and 24 hours after dosing. The primary end point was maximum percentage decrease in FEV1 from preexercise baseline during 60 minutes after the 2-hour challenge. At 2, 12, and 24 hours after dosing, the maximum decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for placebo, respectively (P < or = .001 at each time point). Postexercise recovery was quicker with montelukast than with placebo (P < or = .001); mean (95% confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), -16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes) at the 3 time points, respectively. At all time points, area under the curve for percentage decrease in FEV1 during 60 minutes after exercise was smaller after montelukast (P < or = .001); montelukast protected more patients against EIB (P < or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours after dosing with montelukast (P = .03). Montelukast provided significant protection against EIB as soon as 2 hours after a single oral dose, with persistent benefit up to 24 hours.

Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma

Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects. We sought to evaluate exercise-induced bronchoconstriction (EIB) as a method of determining the dose and time responses of inhaled corticosteroid therapy. In this double-blind, randomized, cross-over study with 2 parallel arms, 4 doses of inhaled ciclesonide (40 microg and 160 microg or 80 microg and 320 microg) were compared over 3 weeks of treatment. Twenty-six asthmatic subjects (age range, 14-27 years) with baseline FEV1 values of greater than 70% of predicted value were enrolled. The primary outcome was the maximum percentage decrease in FEV1 after standardized exercise challenge. After 1 week of therapy, the mean +/- SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-microg/80-microg dose group was 9% +/- 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-microg/320-microg dose group, there was an 8.7% +/- 2.5% (95% CI, 3.7% to 13.7%) reduction in maximum decrease in FEV1 after week 1, which continued in a linear fashion during subsequent weeks of treatment. No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment. The maximum percentage attenuation in EIB achieved was 51.1% +/- 7.9%, which was achieved by using the 320-microg dose after 3 weeks of treatment. A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 microg/320 microg of ciclesonide resulted in a continuing improvement in FEV1 with time, and no plateau was seen in protective effect during 3 weeks of treatment. Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 microg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 microg, even after 3 weeks of therapy.

Lack of Benefit of Continuous Positive Airway Pressure on Lung Function in Patients with Overlap Syndrome

Obstructive sleep apnea (OSA) has been shown to be an inflammatory stimulus and may potentially result in a deterioration in the respiratory status of patients with coexistent chronic obstructive pulmonary disease (COPD) (overlap syndrome). We hypothesized that with treatment of OSA, there would be an improvement in coexistent COPD in overlap patients. We also sought to characterize overlap patients by comparing them with patients with either OSA or COPD alone. We performed a retrospective study of patients who attended a university-affiliated Veterans Affairs hospital. Demographic and clinical data were obtained from the medical charts and pharmacy records for the preceding two years and for the two years following the initiation of continuous positive airway pressure (CPAP) therapy. Overlap patients had moderately severe sleep apnea (AHI 28.6 +/- 4.2) and moderately severe COPD (FEV1= 1.94 +/- 0.10 L). The prevalence of overlap syndrome in COPD patients was 11.9%, and 41% in OSA patients. Overlap patients who were compliant with CPAP therapy experienced a greater decrease in FEV1, percent predicted FEV1, percent decrease in FEV1, FVC, percent predicted FVC, and percent decrease in FVC when compared with noncompliant patients. A very strong correlation was found between the average hours of CPAP use per day and the percent decrease in FEV1 (r = 0.69, p = 0.003). There was a similar strong correlation for the decrease in FEV1 and percent predicted FEV1. OSA is common in COPD patients; similarly, COPD is common in OSA patients. Treatment of OSA with CPAP therapy in patients with overlap syndrome may not lead to an improvement in the coexistent COPD.

Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma

To compare airway responsiveness to methacholine, cycle ergometer exercise and free running in children with intermittent asthma. A randomized study was conducted with 30 children of both genders with intermittent asthma. Each child was submitted to challenge testing on three separate days, in random order: a) Methacholine challenge using a dosimeter; b) Exercise challenge testing -- free running along a 50-meter-long corridor; c) Dry-air exercise challenge on a cycle ergometer. Target heart rate during exercise was 80 to 90% of the maximum predicted value. Spirometry was performed 3, 6,10,15,20 and 30 minutes after exercise. Exercise-induced bronchospasm was defined as a decrease in FEV1 of > or = 10% in comparison to pretest values. Mean age was 11+/-3 years. FEV1 and FEV1/FVC ratios were normal and similar before all provocation tests. The maximum heart rate was 178+/-7 bpm during cycling and 181+/-6 bpm during the free running test (p > 0.05). Significant bronchospasm was observed with methacholine in 23 cases, after free running in 19 and after cycling in 14 children (p < 0.05, methacholine vs exercise tests). Taking all FEV1 measurements after exercise into account, the free running test resulted in greater exercise-induced bronchospasm in comparison with exercise made on a cycle ergometer (p = 0.003, chi2 = 8.948). There was a significant, but poor, correlation between the maximum percentage decrease in FEV1 after free running and cycling (r = 0.46, p < 0.01). Methacholine challenge identifies a greater number of asthmatics in comparison to exercise tests. When bronchial provocation test with methacholine is not available, free running should be the test of choice due to its simplicity and greater ability to induce bronchospasm.

Early pulmonary response to allergen is attenuated during acute emotional stress in females with asthma.

Some asthma patients and physicians who treat asthma have reported that stress worsens their disease. It has also recently been shown that chronic stressful life events increase airway inflammation 6-24 h after inhalation of antigen in patients with allergic asthma. However, there is no data regarding the effect of an acute stressor on the airway constriction that occurs within minutes of antigen inhalation (early pulmonary response) in this same population. The aim of this study was to examine this effect in eight females with allergic asthma. Each subject was challenged with increasing concentrations of inhaled allergen on a control visit (no stress) and on a stress visit, when they were asked to verbally recount an emotionally stressful situation between each concentration. Systolic (SP) and diastolic (DP) blood pressure, cardiac frequency (fC) and forced expiratory volume in one second (FEV1) were measured on both visits. SP, DP and fC were statistically increased on the stress visit as compared to control. Per cent decrease in FEV1 at the same last dose of allergen was significantly less on the stress visit (11.2 +/- 7.0%) compared to control (15.0 +/- 8.7%). These findings suggest that the early pulmonary response to inhaled allergen is attenuated while verbally re-experiencing an acute emotional stressor in females with allergic asthma.

Pulmonary function response to EDTA, an additive in nebulized bronchodilators

Background: Some nebulized bronchodilator solutions contain additives, such as EDTA, benzalkonium chloride (BAC), or both. Objective: Although BAC-induced bronchoconstriction has been well documented in patients with asthma, there is no information on the effects of EDTA on FEV1 when inhaled in the amounts that would be administered during emergency department treatment of asthma. Methods: Eighteen subjects with stable asthma and airway responsiveness to methacholine were randomly assigned to inhale up to four 600-μg nebulized doses of EDTA, BAC (positive control), and normal saline (placebo) in a double-blind crossover manner on separate days. FEV1 was measured 15 minutes after each dose. Treatments were repeated every 20 minutes until FEV1 decreased by 20% or greater or a maximum of 4 doses were administered. Results: Mean ± SD maximum percent decrease in FEV1 was 1.8% ± 5.8% after EDTA, 16.6% ± 13.9% after BAC, and 3.6% ± 8.2% after placebo (P < .001); there was no significant difference between EDTA and placebo. Conclusion: The amount of EDTA contained in maximum recommended doses of nebulized bronchodilators does not induce bronchospasm. In contrast, BAC induces clinically important bronchospasm, which could decrease the efficacy of a bronchodilator during an emergency. (J Allergy Clin Immunol 2001;107:68-72.)

Clinical outcome after acquisition of Burkholderia cepacia in patients with cystic fibrosis.

Respiratory disease is the major cause of morbidity and mortality in cystic fibrosis (CF). The significance of Burkholderia cepacia (B. cepacia) in the pathogenesis of lung disease in CF is debated, but its exact role remains unclear. To assess the impact of respiratory tract colonisation with B. cepacia in patients with CF by measuring changes in pulmonary function and body mass index (BMI). Three groups of patients were defined based on sputum culture isolates: Group 1 were B. cepacia and Pseudomonas aeruginosa (P. aeruginosa) positive patients; Group 2 were P. aeruginosa positive; and Group 3 were colonised with neither organism. Forced expiratory volume (FEV) and BMI were measured annually from 1987 to 1995 and the year of acquisition of P. aeruginosa or B. cepacia was recorded. The mean annual decrease in FEV1 was significantly different in all three groups: Group 1, -5.4 (5.1)%; Group 2, -3.9 (6.5)%; and Group 3, -1.6 (1.0)%, (p<0.05). The mean percentage decrease in FEV1 of a sub-group of Group 1 patients where the B. cepacia acquisition date was known was 6.1% per year versus 1.55% in Group 2 patients (p<0.05). Acquisition of B. cepacia may be a cause of, rather than a marker for, a decrease in pulmonary function.

Combination Drug Therapy For the Prevention of Exercise-InducedBronchoconstriction in Children

Benedictus F, Gianluca T, Pazzelli P, Solinas L, Niccoli A, Parente CAnn Allergy Asthma Immunol.801998352356To evaluate the effectiveness of a new precombined aerosol combination of salbutamol and nedocromil in preventing exercise-induced bronchoconstriction compared with salbutamol alone.Twelve subjects (9 boys and 3 girls) 7 to 13 years of age were recruited from the Paediatric Asthma Clinic at Perugia General Hospital. All had asthma as defined by the American Thoracic Society.The study was a double-blind, double dummy, randomized, crossover, placebo-controlled study. Before study entry, a screening exercise test was performed. Those with a drop of 15% or more in forced expiratory volume in 1 second (FEV1) after the screening test entered the blinded part of the study. In random, cross-over, blinded order, each patient was tested on 3 separate days with different treatments given by metered dose inhaler before exercise: salbutamol 200 μg, salbutamol (200 μg)/nedocromil (4 mg), or placebo. Pulmonary function tests and heart rate were measured preexercise and at 1, 5, 10, 15, and 30 minutes postexercise. Complete protection was considered if the percentage drop in FEV1 was <10% while clinical protection was considered if the percentage decrease after receiving the drug was half or less the percentage fall in the screening challenge.No significant difference was noted in the maximum percentage decrease in FEV1 on screening versus placebo days. Both active drugs were significantly more protective than placebo for percentage decrease in FEV1 (salbutamol: P < .001; salbutamol/nedocromil: P < .005), but there was no difference between the two medication formulations. Complete protection was obtained in 12/12 (100%), 10/12 (83%), and 1/12 (8%) of subjects for the salbutamol/nedocromil combination, salbutamol alone, and placebo, respectively. Clinical protection was obtained in 12/12 (100%), 11/12 (92%), and 2/12 (16%) of children by salbutamol/nedocromil, salbutamol alone, and placebo, respectively.P values were <.01 for salbutamol versus placebo and salbutamol/nedocromil versus placebo in both complete and clinical protection. P values were not significant for salbutamol versus salbutamol/nedocromil in both protection parameters.Although inhaled β-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, in a minority of patients a combined treatment with salbutamol and nedocromil may be advantageous. This group may represent a subgroup of subjects who release more, or different, mediators in response to exercise.In theory it seems reasonable that combined medications such as salbutamol/nedocrimil may be of more benefit to selected patients with exercise-induced asthma and may help with compliance by decreasing the number of inhalers. Overall, however, the vast majority of patients appear adequately protected with salbutamol alone.

Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction...

Exercise-induced asthma and cardiovascular fitness in asthmatic children.

The role of physical training in the management of children with exercise-induced asthma is controversial. A study was undertaken to determine whether a relationship could be found between the occurrence of exercise-induced asthma and the degree of cardiovascular fitness in asthmatic children. Twenty eight children aged 6-13 with mild to moderate asthma and dyspnoea during or after physical exercise were tested. All patients had a basal forced expiratory volume in one second (FEV1) of > 80% predicted. Twelve patients were taking corticosteroid maintenance medication by inhalation and 16 were not. Two exercise tests were performed on a treadmill to assess peak oxygen consumption rate (VO2max) and the percentage decrease in FEV1 after exercise. There was no correlation between the VO2max and the percentage decrease in FEV1. Patients not taking steroids showed a greater fall in FEV1 than those receiving corticosteroid medication (mean fall in FEV1 28.7% versus 6.6%). Four of the 12 children treated with steroids and two of the 16 children not taking steroids had a level of cardiovascular fitness lower than the 5th percentile for healthy Dutch children. Normal cardiovascular fitness does not prevent exercise-induced asthma.

Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm.

Physical exercise is a common trigger for bronchial asthma. We evaluated the preventive effect on exercise-induced bronchospasm (EIB) of a single 42 micrograms dose of salmeterol, a uniquely long-acting inhaled bronchodilator, and compared salmeterol with 180 micrograms albuterol in two independent, randomized, double-blind, placebo-controlled studies involving 161 subjects. Three exercise challenges were conducted over 12 h, and bronchoconstriction following the serial challenges was assessed as change in FEV1 compared with predose values. The mean maximal percentage decrease in FEV1 after the three exercise challenges was 5% at 0.5 h, 8% at 5.5 h, and 13% at 11.5 h postdose in the salmeterol group compared with 7, 25, and 27%, respectively, in the albuterol group and 27, 27, and 26%, respectively, in the placebo group (p < 0.001, overall treatment difference). Albuterol provided complete protection against EIB (defined as < 10% decrease in FEV1 compared with predose values) only after the first exercise challenge, but salmeterol continued to provide complete protection in the majority of subjects after each exercise challenge: 80% (44 of 55) at 0.5 h, 70% (37 of 53) at 5.5 h, and 55% (29 of 53) at 11.5 h. Electrocardiographic monitoring revealed no clinically significant changes in any treatment group 15 and 30 min following each exercise challenge. In summary, these data demonstrate that salmeterol is effective against EIB and that a single 42 micrograms dose can prevent EIB for up to 12 h.