Efficacy Response of Inhaled HFA-Albuterol Delivered via the Breath-Actuated Autohaler™ Inhalation Device Is Comparable to Dose in Patients with Asthma

Handling difficulties, such as poor coordination of actuation and inhalation, are common in patients using press and breathe (P&Bs) metered-dose inhalers to administer asthma medication. Although spacers can help overcome some difficulties, the cumbersome nature of these devices often detracts from their use for the administration of rescue medications, where portability is important. This randomized, placebo-controlled, multicenter, crossover study investigated the efficacy, dose-response and safety of HFA-albuterol delivered via a breath-actuated Autohaler inhalation device in comparison with the same medication delivered using a conventional P&B device. In total, 39 patients received six study treatments in a random sequence at clinic visits separated by 2-7 days: 2 puffs from a HFA-placebo Autohaler; 1, 2, or 4 puffs from a HFA-albuterol Autohaler; 1 or 2 puffs from a HFA-albuterol P&B. Both active inhalers delivered 90 µg albuterol base equivalent/actuation from the actuator. The change from baseline in forced expiratory volume in 1 s (FEV₁) and the area under the FEV₁ curve (FEV₁ AUC) were significantly greater than placebo for all active treatment groups (p ≤ 0.01) and were suggestive of a dose response for each inhaler. Examination of the pooled slope of the dose responses for the Autohaler and P&B using Finney's Parallel Line Bioassay Methodology found a highly statistically significant relationship indicating the equivalence of the two inhalers on both parameters (p ≤ 0.002). The relative potency of the two inhalers was 0.8 (95% CI: 0.47, 1.46) for the mean change from baseline in FEV₁ and 0.9 (95% CI, 0.56, 1.48) for the change from baseline in FEV₁ AUC. There was also a trend toward an increase in the mean percentage change from baseline in FEV₁ as the number of puffs increased for both inhalers. Furthermore, there were no significant differences between the treatment groups with regard to time to onset of bronchodilator effect and the duration of effect was significantly greater than placebo (p ≤ 0.01) in each of the active groups. Adverse events were generally mild to moderate in nature and were of similar incidence (≤18% of patients) in each group. This study demonstrates a dose-response for HFA-albuterol on bronchodilation using both the Autohaler and P&B devices and illustrates that, in patients with good coordination of inhalation with actuation, the efficacy and safety of the two inhalers is similar at equivalent doses.     

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.     

An Evaluation of Standardizing Target Ventilation for Eucapnic Voluntary Hyperventilation Using FEV1

Athletes are required to provide objective documentation of exercise-induced bronchoconstriction (EIB) to use β₂-agonists during Olympic competition. A positive response to bronchial provocation by eucapnic voluntary hyperventilation (EVH) is considered acceptable confirmation of EIB. Thirty times forced expiratory volume in the first second (FEV₁) is recommended as EVH target ventilation (TV), an intensity intended to estimate 85% of maximal voluntary ventilation (MVV). There is a paucity of data examining the accuracy of predicting MVV from FEV₁ in elite athletes. The purpose of this study was to evaluate the efficacy of 30 × FEV₁ as standardized EVH TV. Maximal minute ventilation during exercise (VEmax) and pulmonary function of 78 elite winter athletes (25 males, 53 females; 25 EIB positive, 53 normal) were analyzed retrospectively. Adequacy and variability of the equation was ascertained by examining the ratio of EVH TV (30 × FEV₁) to VEmax. VEmax was 99 ± 11% of predicted MVV (35 × FEV₁) and was positively related (r = 0.85, p ≤ 0.05). TV was 88 ± 9% of VEmax (range: 64-109). For elite athletes, the high variability in 30 × FEV₁ to standardize TV for EVH may result in under-diagnosis for low-end outliers. Since VEmax of elite endurance athletes is typically known (via maximal aerobic testing) we recommend 85% VEmax as a more accurate and reliable method to establish EVH TV for this group; if VEmax is not available, then 85% of measured MVV may be used.     

Formoterol Delivered via the Dry Powder Aerolizer® Inhaler Versus Albuterol MDI and Placebo in Mild-to-Moderate Asthma: A Randomized,Double-Blind,Double-Dummy Trial

The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 µg and 24 µg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 µg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12–75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 µg, formoterol 24 µg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV₁), both formoterol 12 µg and 24 µg were statistically superior to placebo at all time points on all test days (p ≤ 0.017) and to albuterol at most time points on all test days (p ≤ 0.001). The onset of improvement in FEV₁ was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 µg, formoterol 24 µg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV₁ area under the curve, percentage of predicted FEV₁, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.     

Mouthpiece Versus Facemask for Delivery of Nebulized Salbutamol in Exacerbated Childhood Asthma

We compared the bronchodilator response to salbutamol (albuterol) delivered by a compressed air nebulizer through a mouthpiece and via a facemask in 18 asthmatic children, to determine the most appropriate delivery method. Patients using a mouthpiece had significantly better mean percent increases in forced expiratory volume in 1 sec (FEV₁) and in forced vital capacity (FVC) than those using a facemask 30 min after inhalation (FEV₁: 56.4 ± 32.6 % vs. 28.9 ± 19.1%, FVC: 34.4 ± 26.4% vs. 7.5 ± 14.9%, respectively). Nebulized therapy plays an important role in the management of bronchial asthma in children and should be delivered by a mouthpiece whenever possible in cases of exacerbated asthma.     

A One-Week Dose-Ranging Study of Inhaled Salmeterol in Children with Asthma

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 μg and 42 μg administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral β-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vita signs, electrocardiogram (ECC), and 24-hr ECG (Holter) monitoring. Both the 21 -μg and 42-μg doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV₁) (p ≤ 0.02) and PEFR (p ≤ 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-μg dosage producing consistently higher serial FEV₁and PEFR than did the 21 -μg dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p ≤ 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECCs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 μg or 42 μg twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 μg twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 μg.     

Fenoterol Delivery by Respimat® Soft Mist Inhaler Versus CFC Metered Dose Inhaler: Cumulative Dose-Response Study in Asthma Patients

Objectives. Respimat® (RMT) soft mist inhaler (SMI) is a novel, propellant-free alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of this study was to evaluate the safety and establish the equipotent dose of fenoterol delivered by RMT SMI vs. a conventional MDI. Design. Double-blind, randomized, crossover, comparative study between fenoterol inhaled via RMT (either 50 µg/actuation, RMT50; or 100 µg/actuation, RMT100) and MDI (100 µg/actuation; MDI100). Patients and interventions. A total of 41 asthma patients received cumulative doses of fenoterol 600 µg (RMT50) or 1200 µg (RMT100 and MDI100) on 3 test days. Measurements and results. The bronchodilator response (forced expiratory volume in 1 second [FEV₁]) was considered therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals for the difference in their mean changes from baseline were within limits of ± 0.15 L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse events (AEs) were recorded. RMT50 and RMT100 produced noninferior bronchodilatation to MDI100 from 30 minutes after the first dose. RMT50 showed equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher incidence of AEs, a significantly greater plasma potassium reduction and a significant increase in pulse rate. Fenoterol plasma levels were twice as high with RMT100 as with RMT50 or MDI100. Conclusions. The nominal dose of fenoterol administered via RMT SMI can be at least halved to achieve equivalent efficacy, safety, and tolerability to a MDI.     

Airways Hyperresponsiveness in High School Athletes

Adult athletes have a higher prevalence (11%-50%) of exercise-induced bronchoconstriction (EIB) and airways hyperresponsiveness (AHR) than the population at large (7%-11%): reports describing EIB/AHR in adolescent athletes are scant. Hypotheses: 1) a minimum AHR prevalence of 20% would be revealed in a group of high school athletes; 2) demographic data would predict AHR; 3) AHR-positive athletes would preferentially choose low ventilation sports. Eucapnic voluntary hyperpnea (EVH) was used to test for AHR in 23% of all athletes (79 of 343) of a midwestern high school. The AHR was defined by at least a 10%, 20%, or 25% decline in FEV₁, FEF_25-75, or PEFR at 1, 5, 10, or 15-min post-EVH, respectively. Results: 30 of 79 (38%) tested positive for AHR; demographic data tended to predict AHR, as correlations between the total number of years exercised with the greatest decline in FEV₁ and the total number of days exercised with the greatest decline in FEV₁ following the EVH challenge tended to be significant (r = 0.354; p = 0.055 and r = 0.314; p = 0.091, respectively); and 69% of AHR-positive students played only low ventilation sports. Conclusion: AHR prevalence was 38% in athletes of a midwestern high school; demographic data tended to predict AHR; those with AHR preferentially play low ventilation sports.     

Dietary Intake of Soy Genistein is Associated with Lung Function in Patients with Asthma

To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12-75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline [forced expiratory volume in 1 second (FEV₁), peak expiratory flow rate (PEF), asthma symptoms] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV₁ in genistein consumers of at least 250 µg/1000 Kcal/day was 82.1% predicted, 79.9% predicted for those who consumed between 1 and 249 µg/1000 kcal, and 76.2% predicted in genistein nonconsumers (p = 0.006); the PEF was 82.7% predicted, 80.8% predicted, and 78.3% predicted, respectively (p = 0.009). There were no differences in the Asthma Symptom Utility Index (ASUI). We could not account for these results based on differences in demographics, body mass index, or consumption of other nutrients. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.     

Effect of Mouthpiece Washing on Aerosol Performance of CFC-Free Ventolin™

The prescribing information for chlorofluorocarbon (CFC)-free salbutamol metered-dose inhalers carries a strongly-worded instruction to wash the mouthpiece weekly, but patients rarely carry this out. This study investigated the effect of washing/not washing the mouthpiece on CFC-free Ventolin™ aerosol performance. Twelve CFC-free Ventolin™ inhalers were actuated two puffs four times/day, and assessed by unit dose sampler and cascade impactor on Days 1, 7, 8, 14, 15, 21, and 22 (“through-life,” i.e., over the entire content of the inhaler). The mouthpieces of six inhalers were washed after the last actuation on Days 7, 14, and 21. A single priming maneuver, as recommended by the manufacturer, was sufficient for fine particle mass. There were no significant through-life differences in delivered dose between washed and unwashed inhalers. Without washing, fine particle mass fell from 47 µg to 33 µg (Friedman p = 0.002). Fine particle mass increased significantly after washing (median change + 11.2 µg, p = 0.019 cf. unwashed). Large particle mass showed no significant through-life trend for washed or unwashed inhalers, but was significantly reduced after washing (p = 0.04 cf. unwashed). This study shows a progressive through-life reduction in fine particle mass from CFC-free Ventolin™ inhalers, which is prevented by weekly mouthpiece washing. However, in view of the steep bronchodilator dose-response curve for salbutamol, further studies are needed to determine whether such device care is clinically necessary.     

Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma.

Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.     

Peripheral Inflammation in Patients with Asthmatic Symptoms but Normal Lung Function

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function (“asthmatic symptoms group”), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 ± 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 ± 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 ± 0.1 nL/s and 1.0 ± 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 ± 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 ± 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF_50% and FEF_75%). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.     

High-Dose Inhaled Budesonide May Substitute for Oral Therapy After an Acute Asthma Attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler®) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV₁) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 μg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV₁ was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutalineTurbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV, from baseline to day 7 was 1 7.3% in the budesonide Turbuhaler group and 1 7.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.     

Salmeterol Added to Inhaled Corticosteroid Therapy Is Superior to Doubling the Dose of Inhaled Corticosteroids: A Randomized Clinical Trial

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclo-methasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p ≤ 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV₁), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 μg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.     

Early Bronchodilatory Effects of Budesonide/Formoterol pMDI Compared with Fluticasone/Salmeterol DPI and Albuterol pMDI: 2 Randomized Controlled Trials in Adults with Persistent Asthma Previously Treated with Inhaled Corticosteroids

Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged ≥18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 μ g, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 μ g × 2 inhalations (160/9 μ g), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 μ g × 1 inhalation, albuterol pMDI 90 μ g × 2 inhalations (180 μ g), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV₁) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV₁ within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.     

Lung Function and Cytokine Levels in Professional Athletes

Objective. Previous studies have demonstrated that exercise-induced asthma and bronchial hyperresponsiveness commonly occur in athletes. The present study investigates pulmonary function and cytokine levels in professional athletes to explore the impact of various sports on respiratory system function and to evaluate the possible role of systemic anaphylaxis. Methods. Lung function was measured at rest in professional athletes without a history of smoking. Athletes were recruited from 10 different sports including swimming, water ballet, shooting, volleyball, softball, football, kickboxing, fencing, judo, and track and field. Measurements included forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), vital capacity (VC), peak expiratory flow (PEF), maximal mid-expiratory flow curve (MMEF), and forced expiratory flow rate (FEF_{25 - 75}%). In addition, the medical history of all athletes was recorded. Correlations between lung function measurements and the different sports, age, gender, height and weight were analyzed. In some athletes, serum was sampled to detect IL-4 and IL-10 concentrations. In these subjects, the correlation between pulmonary function and cytokine levels was analyzed. Results. A total of 147 professional athletes and 30 healthy volunteers were enrolled in the study. Allergic rhinitis and asthma were detected only in swimmers with an incidence of 56.52% (13/23) and 8.70% (2/23), respectively. Lung function measures were significantly correlated with sport, age, gender, height, and weight. Ventilation functions (including FVC, FEV₁, FEV₁/FVC, and MMV) in male athletes were superior to those in females, and the ventilation functions in swimmers were superior to those in others. However, the small airway functions (MMEF, FEF₅₀, FEF₇₅) in swimmers and in track and field athletes were lower than predicted (swimmers: 72%, 70%, and 78%, respectively; track and field athletes: 79%, 75%, and 99%, respectively). Serum analyses for IL-4 and IL-10 revealed that IL-4 concentrations were higher in swimmers 69.34 ± 22.4 pg/mL relative to non-swimmers (p = 0.000). By contrast IL-10 concentrations were lower in swimmers 34.94 ± 9.71 pg/mL than that in the static group (44.69 ± 16.32 pg/mL; p = 0.027). IL-4 levels were negatively correlated with FEV₁%, FEF₂₅%, FEF₅₀%, and MMEF%. By contrast, IL-10 levels were not correlated with any of these measures. Conclusions. The lung function measurements were correlated with sport, age, gender, height, and weight in the various athletes. The lung capacity of swimmers was greater than that of other athletes. Small airway dysfunction was observed in some swimmers and endurance athletes. We observed an association between systemic anaphylaxis and small airway dysfunction after prolonged regular training, particularly following swimming and endurance training.     

Does Specific Immunotherapy Injection Cause an Increase in Bronchial Reactivity?

Background. Several well-controlled studies have proven the clinical benefit of specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However, whether subcutaneous SIT injection could cause a transient increase in bronchial reactivity (BR) remains unknown. Objective. To investigate whether subcutaneous SIT injection, either during or outside the pollen season, could cause an increase in BR in children with pollen allergy. Methods. Twenty-two children (mean age 13.6 ± 0.7 years) with AR who were receiving maintenance SIT for 15 months were included in the study. Pre-injection BR of the patients was evaluated with methacholine provocation test immediately before maintenance dose of SIT during the peak pollen season and outside the season. The post-injection test was administered 24 hours after SIT injection. Results. There was no difference in FEV₁ measures recorded during [98(93-109)%] and outside [102(96-111)%] the pollen season. There was no significant difference between pre- [64(7-64)mg/mL] and post-allergen injection [32(7.5-64) mg/mL] BR outside the pollen season (p = 0.9). A trend towards improvement following allergen injection [64(5.4-64)] as compared to pre-allergen injection [14.6(3.5-64)] was shown during the pollen season (p = 0.053). Although PC20 measures in the pollen season were lower than outside the season, the difference was not significant. The percentage of the patients with bronchial hyperreactivity was 62% during and 43% outside the season. Conclusion. SIT injections both during and outside the pollen season cause no increase in BR in children with AR. This calls into question the necessity of empirical dose reduction during the pollen season.     

Once-Daily Administration of Budesonide Turbuhaler® was as Effective as Twice-Daily Treatment in Patients with Mild to Moderate Persistent Asthma

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler®, 200 µg once every night (q.n.), 100 µg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler®, 200 µg, q.n. without loss of asthma control.     

Proventil HFA Prevents Exercise-Induced Bronchoconstriction in Children

Short-acting inhaled beta₂-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction (EIB) in children. This was a randomized, single-blind, placebo-controlled, four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoro-alkane-134a (HFA) to albuterol formulated in chlorofluorocarbons (CFCs) and to placebo in protecting asthmatic children age 6-11 from EIB. Patients self-administered either HFA albuterol, two different CFC albuterol products, or placebo 30 min prior to exercise challenge. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 min after the exercise challenge was completed. The smallest percent change from the predose forced expiratory volume in 1 sec (FEV₁) after exercise challenge was similar for the three active treatments, and each of the active treatments was significantly better than placebo. Each active treatment had significantly fewer patients unprotected from EIB (unprotected defined as having ≥20% fall in FEV, after exercise challenge) than placebo. Changes in heart rate, blood pressure and electrocardiogram     

Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration

BACKGROUND: There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists. OBJECTIVES: The purpose of the study was to evaluate whether regular treatment with formoterol affects the bronchodilator response to repeated puffs of albuterol, and also to assess the effects of acute administration of a bolus dose of IV or inhaled corticosteroid. MATERIALS AND METHODS: Twelve patients (mean [SD] age, 43 [15] years; FEV(1), 57 [17] % predicted) with stable, moderate to severe persistent asthma who were all taking inhaled corticosteroids were evaluated in a randomized, placebo-controlled, double-blind, double-dummy, crossover study. Patients received treatments each for 2 weeks followed by a bolus (IV/inhaled) of corticosteroid or placebo: (1) placebo inhaler bid + bolus placebo; (2) formoterol Turbuhaler 24 microg metered dosage bid (delivered dosage 18 microg bid) + placebo; (3) formoterol 24 microg bid + bolus IV hydrocortisone, 200 mg; or (4) formoterol 24 microg bid + bolus inhaled budesonide, 1,600 microg. Bronchodilator response to repeated puffs of albuterol (200 to 1,600 microg) for > 80 min was measured at 2 h after bolus administration of placebo or corticosteroid. The study was powered at the 80% level to detect a 20% difference in area under curve between 20 and 80 min (AUC) for FEV(1) response to albuterol as change from baseline (primary end point). RESULTS: There was significant subsensitivity (p = 0.01) of the mean albuterol FEV(1) response (as AUC, L x s) after formoterol alone (737) as compared to placebo (1,453) along with partial reversal by steroid administration: formoterol + hydrocortisone (1, 050), and formoterol + budesonide (942). There was a similar pattern of subsensitivity (p = 0.03) for the mean albuterol forced expiratory flow between 25% and 75% of vital capacity response (as AUC, L): placebo (2,149), formoterol alone (1,002), formoterol + hydrocortisone (1,402), and formoterol + budesonide (1,271). CONCLUSION: Regular treatment with formoterol produced significant bronchodilator subsensitivity to repeated puffs of albuterol, which was partially reversed by a bolus dose of systemic or inhaled corticosteroid.