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Background: The pharmacological stress agents adenosine and dipyridamole are contraindicated in asthma patients because of the risk of adenosine receptor-mediated bronchospasm. Binodenoson, a selective adenosine A(2A) receptor agonist, produces maximal coronary hyperemia during pharmacological stress testing yet has a low affinity for the adenosine A(1), A(2B), and A(3) receptors that are probably responsible for bronchospasm. This study was conducted to assess the safety of binodenoson in 87 healthy young adult volunteers with documented mild, intermittent asthma., Methods and Results: This study consisted of a dose-escalating, single-blinded phase and a placebo-controlled, double-blinded phase conducted in healthy, young adults with documented mild, intermittent, asthma. In the single-blinded phase, 3 sequential cohorts of 8 subjects received intravenous binodenoson (0.5, 1.0, and 1.5 microg/kg). In the double-blinded phase, commenced after medical review of results from the single-blinded phase, subjects were randomly assigned 2:1 to either binodenoson 1.5 microg/kg (n=41) or placebo (n=22). The primary end point was clinically significant bronchoconstriction, defined as a decrease in forced expiratory volume in 1 second of >/=20% from the preinjection measure. Secondary safety end points were changes from preinjection measure in forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow during the middle 50% of the forced vital capacity; vital signs; pulse oximetry; and adverse events. Binodenoson caused no clinically significant bronchoconstriction or alterations in pulmonary function parameters and transiently increased heart rate and systolic blood pressure. The most common treatment-emergent adverse events were tachycardia, dizziness, and flushing., Conclusions: Binodenoson was safe, well tolerated, and caused no clinically significant bronchoconstriction or pulmonary responses in a small population of healthy subjects with mild, intermittent asthma.

Rationale: Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR., Methods: After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR., Results: The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037)., Conclusion: This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

Background: The development of the Asthma Control Test (ACT), a short, simple, patient-based tool for identifying patients with poorly controlled asthma, was recently described in patients under the routine care of an asthma specialist., Objectives: We sought to evaluate the reliability and validity of the ACT in a longitudinal study of asthmatic patients new to the care of an asthma specialist., Methods: Patients (n=313) completed the ACT and the Asthma Control Questionnaire (ACQ) at 2 physician visits (4-12 weeks apart). Pulmonary function was measured, and asthma specialists rated asthma control., Results: Internal consistency reliability of the ACT was 0.85 (baseline) and 0.79 (follow-up). Test-retest reliability was 0.77. Criterion validity was demonstrated by significant correlations between baseline ACT scores and baseline specialists' ratings of asthma control (r=0.52, P<.001) and ACQ scores (r=-0.89, P<.001). Discriminant validity was demonstrated, with significant (P<.001) differences in mean ACT scores across patients differing in asthma control, pulmonary function, and treatment recommendation. Responsiveness of the ACT to changes in asthma control and lung function was demonstrated with significant correlations between changes in ACT scores and changes in specialists' ratings (r=0.44, P<.001), ACQ scores (r=-0.69, P<.001), and percent predicted FEV1 values (r=0.29, P<.001). An ACT score of 19 or less provided optimum balance of sensitivity (71%) and specificity (71%) for detecting uncontrolled asthma., Conclusions: The ACT is reliable, valid, and responsive to changes in asthma control over time in patients new to the care of asthma specialists. A cutoff score of 19 or less identifies patients with poorly controlled asthma., Clinical Implications: In a clinical setting the ACT should be a useful tool to help physicians identify patients with uncontrolled asthma and facilitate their ability to follow patients' progress with treatment.

Two postulated intrinsic anti-inflammatory mechanisms in asthma include the low affinity IgE receptor, or CD23, and interleukin 1 receptor antagonist (IL-1ra). We investigated the role these mediators play in the asthmatic response by measuring local levels in human asthmatics before and after segmental allergen challenge and examined the effect of inhaled corticosteroids on soluble CD23 and IL-1ra levels. Ten subjects underwent bronchoscopy at baseline and 24 hours after antigen challenge. Prior to challenge and every 12 hours afterward subjects received beclomethasone 252 microg or placebo. Fluid was analyzed for sCD23 and IL-1ra using ELISA immunoassays. Eosinophil percentages significantly increased at 24 hours following antigen challenge. sCD23 levels were generally undetectable at baseline and increased significantly following antigen challenge. IL-1ra levels increased 28-fold in the late-phase response. Beclomethasone significantly reduced the late-phase eosinophil percentage at 24 hours compared with placebo but did not attenuate late-phase sCD23 or IL-1ra levels. Our data showed a significant rise in the levels of two mediators thought to play an important role in the attenuation of the asthmatic response. The finding that steroid treatment did not enhance these levels suggests that this may be an independent approach to asthma therapy that should be investigated.

Antibody-mediated rejection is well established for renal allografts but remains controversial for lung allografts. Cardinal features of antibody-mediated rejection in renal allografts include antibodies to donor human leukocyte antigen (HLA) and evidence for antibody action, such as complement activation demonstrated by C4d deposition. We report a lung allograft recipient with circulating antibodies to donor HLA who failed treatment for acute cellular rejection but responded to therapy for humoral rejection. To address the second criteria for antibody-mediated rejection, we determined whether complement activation could be detected by measuring C4d in bronchoalveolar lavage fluid (BALF) by ELISA. Airway allergen challenge of asthmatics activates the complement pathway; therefore, we used BALF from asthmatics pre- and post-allergen challenge to measure C4d. These controls demonstrated that ELISA could detect increases in C4d after allergen challenge. BALF from the index patient had elevated C4d concomitant with graft dysfunction and anti-donor HLA in the absence of infection. Analysis of BALF from 25 additional lung allograft recipients showed that C4d concentrations >100 ng/mL were correlated with anti-HLA antibodies (p = 0.006), but were also observed with infection and in asyptomatic patients. The findings support the occurrence of anti-HLA-mediated lung allograft rejection and suggest that C4d measurement in BALF may be useful in diagnosis.

Background: Asthma guidelines indicate that the goal of treatment should be optimum asthma control. In a busy clinic practice with limited time and resources, there is need for a simple method for assessing asthma control with or without lung function testing., Objectives: The objective of this article was to describe the development of the Asthma Control Test (ACT), a patient-based tool for identifying patients with poorly controlled asthma., Methods: A 22-item survey was administered to 471 patients with asthma in the offices of asthma specialists. The specialist's rating of asthma control after spirometry was also collected. Stepwise regression methods were used to select a subset of items that showed the greatest discriminant validity in relation to the specialist's rating of asthma control. Internal consistency reliability was computed, and discriminant validity tests were conducted for ACT scale scores. The performance of ACT was investigated by using logistic regression methods and receiver operating characteristic analyses., Results: Five items were selected from regression analyses. The internal consistency reliability of the 5-item ACT scale was 0.84. ACT scale scores discriminated between groups of patients differing in the specialist's rating of asthma control (F = 34.5, P <.00001), the need for change in patient's therapy (F = 40.3, P <.00001), and percent predicted FEV(1) (F = 4.3, P =.0052). As a screening tool, the overall agreement between ACT and the specialist's rating ranged from 71% to 78% depending on the cut points used, and the area under the receiver operating characteristic curve was 0.77., Conclusion: Results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control.

Background: Subjects with aspirin-intolerant asthma (AIA) respond with bronchoconstriction and extrapulmonary adverse reactions to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit the cyclooxygenase (COX) step in the biosynthesis of prostaglandins. Recently, 2 isotypes of COX have been identified, and COX-2-selective NSAIDs have been developed for treatment of inflammatory disorders., Objective: We investigated whether 33 subjects with a typical history of AIA tolerated the new COX-2-selective NSAID celecoxib., Methods: All subjects displayed current aspirin sensitivity in oral or inhalation challenge tests. The subjects first underwent a double-blind, randomized, cross-over, increasing-dose challenge with placebo or celecoxib (10, 30, or 100 mg in suspension) on 2 occasions 7 days apart. Thereafter, all subjects were exposed to 400 mg of celecoxib administered during an open challenge session as two 200-mg doses 2 hours apart. Lung function, clinical symptoms, and urinary excretion of leukotriene E(4) (LTE(4)) were monitored, with the latter being a sensitive biochemical marker of aspirin intolerance., Results: There were no changes in lung function or extrapulmonary symptoms during the double-blind sessions or in urinary excretion of LTE(4). Also, the highest recommended daily dose of celecoxib was well tolerated, with no symptoms, lung function changes, or alterations in urinary LTE(4) levels., Conclusions: A group of subjects with clinically well-documented AIA tolerated acute challenge with the selective COX-2 inhibitor celecoxib. The findings indicate that the intolerance reaction in AIA is due to inhibition of COX-1. Large long-term studies of COX-2 inhibitors in AIA should be undertaken.

Allergic rhinoconjunctivitis and asthma are becoming more common in industrialized societies, particularly in the second and third decades of life, when those affected are at a vital stage of their education and career. It is therefore of paramount importance that the treatment options available be effective, improve quality of life, and above all, they must be without any significant unwanted effects. National and international guidelines for the treatment of both allergic rhinitis and asthma have been released recently that put forward recommendations based on an extensive evidence-based review of the literature for the care of these diseases that would meet these goals of disease management.

The article provides information on the study which assess the safety of the pharmacological stress agent binodenoson in patient with mild, intermittent asthma. A single-blinded phase and a placebo controlled, dose-escalating and double-blind phase were conducted in patients with mild, intermittent asthma. Findings revealed that the drug caused no clinically significant alterations in patient's pulmonary functions. It further concludes that binodenoson was safe and tolerable by patients.

Objective: To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma.Design: Randomized, double-blind, placebo-controlled study.Setting: University hospitals and private allergy and pulmonary practices.Patients: A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids.Intervention: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks.Measurements: Airway function, beta-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4).Results: Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of beta-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups.Conclusions: Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma. [ABSTRACT FROM AUTHOR]

Discusses the participation of asthmatic children in sports and physical education. Characteristics of asthma; Effect of continuous exercise in an asymptomatic individual; Detection of exercise induced asthma.