Morning-to-evening variation in exercise-induced bronchospasm

BACKGROUND: Exercise is one of the most common triggers of asthmatic symptoms. Many factors, including hyperventilation, determine the prevalence and severity of exercise-induced bronchospasm (EIB). However, the influence of time of day has not been adequately described. OBJECTIVE: We sought to compare morning and evening EIB and minute ventilation during exercise (VE). METHODS: Twenty-two patients with stable asthma and 12 control subjects underwent exercise challenge at 7 am and 6 pm. The time of the first challenge was randomly assigned; the second challenge was performed within 1 week of the first. The primary outcomes were EIB intensity (maximum fall in FEV(1)) and VE. RESULTS: The asthma group exhibited lower EIB values in the morning: 14.8% +/- 3.7% at 7 am vs 21.4% +/- 4.2% at 6 pm (P =.004)-ie, 0.37 +/- 0.09 L vs 0.53 +/- 0.10 L, respectively (P =.002). VE was higher at 7 am (55.4 +/- 4.7 L/min) than at 6 pm (52.4 +/- 4.3 L/min; P =.03). Baseline FEV(1) increased from 2.33 +/- 0.13 L (morning) to 2.49 +/- 0.15 L (evening; P =.04), and a significant correlation between baseline FEV(1) and EIB was found in the evening (r = +0.5; P =.049) but not in the morning. Post-exercise FEV(1) was similar at 7 am (1.96 +/- 0.13 L) and 6 pm (1.97 +/- 0.14 L). For the control group, no changes were detected in FEV(1) fall or VE. CONCLUSION: Baseline airway caliber contributes to the mechanisms of the morning-to-evening EIB enhancement.     

Terfenadine blockade of exercise-induced bronchospasm

Terfenadine, in doses of 60, 120, and 180 mg, provided significant bronchodilation for up to four hours after administration. In addition, when the same doses were given four hours prior to exercise, the drug demonstrated significant blockade of exercise-induced bronchospasm at two and five minutes postexercise. These effects on exercise-induced bronchospasm followed a dose-response curve; 180 mg had the most significant effect. All dosing levels, however, produced both bronchodilation and a significant degree of blockade of exercise-induced bronchospasm. No patients were bothered by adverse effects during this single-dose study. Eight of the 11 subjects who completed the study also noted some improvement in their nasal congestion during the testing period when they were on the active drug.     

Effect of body mass on exercise-induced bronchospasm and atopy in African children

BACKGROUND: Sensitization to allergen is common in rural populations in less affluent countries, but atopic disease is less frequent than in richer countries. Variables explaining this dichotomy may provide insight into underlying mechanisms of atopic diseases like asthma. OBJECTIVE: To test whether risk of exercise-induced bronchospasm (EIB) in urbanized African populations is increased in association with greater skin sensitivity or increased body mass. METHODS: A total of 3322 children were enrolled in a prevalence survey of EIB in urban and rural South Africa. Children responding positively to an exercise challenge and a random sample of children responding negatively were recruited into a case-control study (393 controls, 380 cases). Subjects were investigated by using allergen skin prick testing, anthropometry, and assay of IgE. Stools were analyzed for parasite infestation. RESULTS: The prevalence of EIB was higher in urban (14.9%) than rural (8.9%) areas (P < .0001). The difference in risk of EIB between urban and rural subjects was associated with atopy (odds ratio [OR] for upper tertile of skin wheal diameter, 2.65; 95% CI, 1.43-4.89; P < .0001), increasing weight (OR for upper tertile of body mass index [BMI], 2.17; 95% CI, 1.45-3.26; P = .001), and affluence. Increasing BMI was also associated with a greater strength of association between specific IgE and the corresponding skin test (Dermatophagoides pteronyssinus, OR for a positive skin test result in presence of specific IgE: heavier subjects, OR, 34.6; 95% CI, 0.9-109.3; P < .0001; lighter subjects, OR, 8.05; 95% CI, 2.74-23.6; P < .001). CONCLUSION: Increases in BMI of rural children in subsistence economies may lead to an increased prevalence of atopic disease. This observation merits further investigation in prospective studies.     

Evaluation of exercise-induced bronchospasm in the adult asthmatic

It has been shown that most asthmatics respond to exercise with bronchospasm. This study was undertaken to develop a safe and reliable method for quantifying exercise-induced bronchospasm in the asthmatic adult. Five normal adult volunteers and 12 stable asthmatics were exercised to 80% of their predicted maximal heart rate according to a multistage branching treadmill protocol. Their responses in terms of forced expiratory volume in 1 sec (FEV₁) and maximum midexpiratory flow rate (MMEFR) at 5, 15, and 30 min after exercise were assessed, while standing, with a Jones Pulmonar II waterless spirometer. This submaximal stress test was chosen because 80% of predicted maximal heart rate could be obtained by all individuals and allowed the asthmatics to exercise long enough for inducible bronchospasm to occur. Audible wheezing was induced in 100% of the asthmatics and in none of the nonasthmatics. In the normal individuals, FEV₁ and MMEFR increased significantly during the postexercise period. When compared to normal subjects, the 12 asthmatic patients demonstrated a significant reduction in FEV₁ an MMEFR (ΔFEV₁: 5 min, ?300; 15 min, ?304; 30 min, ?208 ml; ?18%, ?17%, and ?15%; ΔMMEFR: 5 min, ?15; 15 min, ?9; 30 min, ?1L/M; ?23%, ?18%, and ?6%) (p < 0.01). The use of a rigidly controlled exercise stress with a cardiovascular endpoint in the measurement of FEV₁ and MMEFR in the postexercise period appears to be a useful tool in assessing the presence and severity of exercise-induced bronchospasm in the adult asthmatic.     

Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children.

The new anticholinergic compound Sch 1000 (ipratropium bromide) has been reported to be an effective bronchodilator without significant atropine-like side effects. We evaluated the effectiveness of different doses of nebulized Sch 1000 (40 microgram and 80 microgram) aerosolized atropine sulfate (1 mg) and placebo in the prevention of exercise-induced bronchospasm (EIB) in 20 children with atopic bronchial asthma. A random, crossover double-blind protocol was used. Standard exercise on a cycloergometer was used to induce EIB. Pulmonary function was determined before and after drug administration and exercise. Following no treatment or placebo, exercise resulted in average reductions of 33% to 43% in plethysmographic specific airway conductance (SGaw), of 20% to 25% in forced expiratory volume in 1 sec (FEV1), and of 25% to 32% in maximal midexpiratory flow rate. Exercise following no treatment or placebo resulted in average increases of 23% to 30% in thoracic gas volume (Vtg). Prior to exercise atropine and either dose of Sch 1000 caused significant increases in SGaw (48% to 59%). After pretreatment with Sch 1000 or atropine, exercise caused SGaw to fall to values that were not significantly different from pretreatment medication values, but were significantly higher than values following exercise without pretreatment or after pretreatment with placebo. No significant differences were noted between the effects of atropine and Sch 1000 on EIB. We conclude that at the doses used atropine and Sch 1000 cause equivalent degrees of bronchodilation but neither drug specifically inhibits EIB.     

Measurement of plasma prostaglandins during exercise-induced bronchospasm

Bronchospasm following exercise is a phenomenon which occurs in most patients with reversible airway disease. The pathophysiologic mechanism leading to this bronchoconstriction with exercise has not yet been defined. Recently, prostaglandins have been implicated in the etiology of asthma. The purpose of this investigation was to determine changes in plasma prostaglandins occurring during exercise-induced asthma. Eight ambulant asthmatics were chosen for baseline pulmonary spirometry and peripheral venous blood prostaglandin E and F levels. The asthmatics were then exercised to 80% of their age-predicted maximal heart rate via a multistage branching treadmill protocol. At 5, 15, and 30 min following exercise, pulmonary spirometry was again performed and peripheral venous blood collected at the indicated times. Clinical bronchospasm as characterised by audible wheezing and >15% decrease in FEV₁ and MMEFR was obtained in all of the asthmatics. Peripheral PGE and PGF_2α determinations following this exercise protocol were not altered significantly: (PGE: 0 mm, 238; 5 min, 185; 15 min, 248; 30 min, 256 pg/ml); (PGF_2α: 0 min, 50; 5 min, 24; 15 min, 25; 30 min, 17 pg/ml) (p > 0.1). In summary, no significant change in peripheral blood prostaglandin E and F_2α levels as determined by radioimmunoassay was noted at the time of exercise-induced bronchospasm.     

Atopy may be related to exercise-induced bronchospasm in asthma

BACKGROUND: Recent studies suggest that atopy may be associated with exercise-induced bronchospasm (EIB) in asthma. However, it is not clear whether atopy is related to EIB, regardless of airway hyper-responsiveness (AHR) to methacholine, because asthmatic subjects often show AHR to exercise and methacholine simultaneously. OBJECTIVE: To investigate whether atopy is related to EIB in asthmatic subjects, independently of AHR to methacholine. METHODS: Fifty-eight male asthmatic subjects were studied. Initial spirometry was performed. Skin prick test was carried out, using 53 common allergens including mites dust antigen. Atopy score was defined as a sum of mean weal diameters to all allergens tested. Methacholine bronchial provocation testing was performed. Twenty-four hours later, free running test was performed. Positive EIB was defined as a 15% reduction or more in FEV1 from baseline after exercise. RESULTS: All subjects had AHR to methacholine. The degree of AHR to methacholine in asthmatics with EIB was similar to that in asthmatics without EIB. However, atopy score and skin reaction to Dermatophagoides pteronyssinus significantly increased in asthmatics with EIB compared with those without EIB (P < 0.05, respectively). Furthermore, the degree of EIB significantly correlated with atopy score in all subjects (r = 0.35, P < 0.01). This relationship was maintained even after the exclusion of EIB-negative asthmatic subjects. CONCLUSION: Atopy defined as skin test reactivity may contribute to the development of EIB in asthma, independently of AHR to methacholine.     

Formoterol provides long-lasting protection against exercise-induced bronchospasm.

BACKGROUND: Patients with exercise-induced bronchospasm (EIB) may benefit from a prophylactic beta2-adrenergic agonist that combines rapid onset with long duration of action. OBJECTIVE: To compare the protective effect against EIB of a single inhaled dose of formoterol powder delivered via the Aerolizer inhaler (Novartis Pharmaceuticals, East Hanover, NJ) with the effect of placebo and albuterol. METHODS: Eighteen patients with EIB were randomized to treatment in a double-blind, placebo-controlled, four-way, crossover study. Seventeen patients completed all four crossover periods. Each patient received in random sequence a single dose of formoterol (12 or 24 microg), albuterol (180 microg), or placebo at intervals of 5 +/- 2 days. Pulmonary function measurements were taken before and after exercise challenge tests (ECTs) at 15 minutes postdosing and at 4, 8, and 12 hours postdosing. RESULTS: Both doses of formoterol produced significantly greater protection against EIB, compared with placebo, at all timepoints (P < or = 0.016). The two doses of formoterol were not significantly different from one another at any time. Protection against EIB with albuterol was clinically significant only for the 15-minute ECT and was statistically superior to placebo for the 15-minute and 4-hour ECTs. Although formoterol and albuterol exhibited a rapid onset of action, formoterol provided longer-lasting protection over the 12-hour observation period. Rescue medication was used substantially less with either dose of formoterol, compared with albuterol or placebo. All treatments were well tolerated. Two-hour postdosing electrocardiograms and vital signs were unremarkable for all study treatments. CONCLUSION: A single dose of formoterol (12 or 24 microg) provides protection against EIB within 15 minutes of dosing and persists for up to 12 hours. Formoterol is safe and well tolerated.     

Choices of therapy for exercise-induced asthma in children

Cough and wheezing interferes with sport and other forms of physical activity in half of asthmatic children. Airway obstruction can be induced by a standard exercise test in over 70% of children with asthma. A beta-adrenergic agonist or cromone taken by inhalation beforehand will usually inhibit bronchoconstriction provoked by a free running exercise test. The duration of protective effect with salbutamol, terbutaline and cromones is less than 4 h. The long acting beta-adrenergic agonists formoterol and salmeterol give protection against exercise-induced airway obstruction for up to 12 h, which implies that treatment given in the morning will offer protection from the effects of physical activity throughout the day. However, the duration of protective effect after a morning dose declines if these compounds are given regularly. Leukotriene receptor antagonists (LRAs) also provide good protection against exercise-induced asthma. Regular administration of LRAs is not associated with tolerance and loss of protective effect. The oral route makes for unobtrusive administration and this may help adherence to prescribed regimens.     

Exercise-induced laryngochalasia: an imitator of exercise-induced bronchospasm.

BACKGROUND: Patients with exercise-induced laryngochalasia present with dyspnea and stridor during exercise. Symptoms are due to a subtotal occlusion of the larynx resulting from mucosal edema from the aryepiglottic folds being drawn into the endolarynx. METHODS: We report on three patients with exercise-induced bronchospasm, refractory to standard therapy. RESULTS: Spirometry with flow-volume loops revealed truncation of the inspiratory limb. Abnormal movement of the arytenoid region was visualized on laryngoscopy. A diagnosis of exercise-induced laryngochalasia was made. CONCLUSIONS: Evaluation of laryngeal motion in patients with refractory exercise-induced bronchospasm is important. Surgical correction with laser laryngoplasty is effective in carefully selected cases.     

A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm

Inhaled albuterol and cromolyn by spinhaler have both been shown to be effective in the treatment of exercise-induced bronchospasm. Eighty subjects with exercise-induced bronchospasm participated in a randomized parallel group study comparing albuterol (180 microgram) and cromolyn (20 mg) administered 15 minutes prior to a standardized treadmill challenge. The cromolyn group was restudied after 2 and 4 weeks of 4 times/day cromolyn therapy. The albuterol group was also studied at 2 and 4 weeks, but they only used their inhaler as needed between study visits. The mean maximum FEV1 drop post-exercise in the albuterol group improved from 33% (screening visit) to 6% (treatment day 1). The cromolyn group showed significantly less (P less than .01) improvement than the albuterol group (31% drop at the screening visit to 14% drop at treatment day 1). When 2 or 4 weeks of continuous cromolyn therapy was given in addition to a dosage 15 minutes prior to exercise, there was no significant difference compared with acute cromolyn administration alone. In summary, acute administration of albuterol was better prophylaxis for exercise-induced bronchospasm than acute or chronic cromolyn treatment.     

Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of salmeterol powder with albuterol.

BACKGROUND: Exercise-induced bronchospasm (EIB) is a common problem in children with asthma. Pretreatment with the beta2 (beta 2)-adrenoreceptor agonist albuterol is effective for preventing EIB, but is recognized as providing only short-term (2 to 3 hour) protection. OBJECTIVE: To evaluate the 12-hour efficacy and safety of single doses of 25 micrograms and 50 micrograms of salmeterol powder administered via Diskus inhaler versus albuterol aerosol via pressurized metered-dose inhaler and placebo in preventing EIB in asthmatic children. METHODS: A randomized, double-blind, placebo-controlled, double-dummy, single-dose, four-way crossover study was conducted in pediatric patients (4 to 11 years of age) demonstrating EIB and mild-to-moderate asthma. Serial forced expiratory volume in 1 second (FEV1) was measured before and after standard treadmill exercise at hour 1, hour 6, and hour 12 after administration of 25 micrograms or 50 micrograms salmeterol powder, 180 micrograms albuterol aerosol, or placebo. Adverse events were recorded. RESULTS: After completion of the hour 1 exercise challenge, mean minimum % predicted FEV1 was significantly higher following albuterol (91.3%) than for placebo (75.3%) and for both dosages of salmeterol (86.9% and 85.8% for salmeterol 25 micrograms and 50 micrograms, respectively; P < or = .026). After completion of both the hour 6 and hour 12 exercise challenges, the 50-microgram salmeterol treatment produced a significantly higher mean minimum percent of predicted FEV1 (90.6% and 87.3% predicted, respectively) than the mean minimum percent of predicted FEV1 for placebo or albuterol (73.8% to 78.4% of predicted; P < or = .041). At hour 6, the 25-microgram salmeterol treatment was not significantly different from albuterol or placebo. At hour 12, the 25-microgram salmeterol treatment mean minimum percent of predicted was significantly higher than albuterol (87.9% versus 73.8% of predicted; P = .006) and there was also a trend toward significance over placebo (76.9% predicted; P = .056). At all exercise periods, no statistically significant differences in spirometry values were observed between the two salmeterol treatment groups. Safety profiles were similar among treatments, including placebo. No drug-related adverse events or withdrawals due to adverse events occurred. Changes in laboratory values, vital signs, 12-lead ECGs, and physical examinations were unremarkable. CONCLUSIONS: A single 50-microgram dose of salmeterol powder provided effective and safe protection against EIB for at least 12 hours in asthmatic children and provided a significantly more prolonged effect than albuterol aerosol (180 micrograms).     

Intravenous NAB 365 (clenbuterol) and terbutaline in exercise-induced bronchospasm (EIB)

In a single-blind, placebo-controlled, cross-over study, the effects of intravenous 20 μg NAB 365 (clenbuterol) and intravenous 250 μg terbutaline were compared in nine asthmatic patients with bronchospasm induced by exercise. The exercise consisted of treadmill running. The two beta-adrenergic bronchodilator drugs effectively prevented post-exercise bronchospasm in eight of the nine patients. The effects were superior to those in the untreated group and in the placebo-treated group. Six of the patients treated with terbutaline complained of adverse reactions (tremor, palpitation, tachycardia). No adverse reactions were observed after clenbuterol.     

Outcome in adulthood of asymptomatic airway hyperresponsiveness to histamine and exercise-induced bronchospasm in childhood.

BACKGROUND: Studies of the clinical outcome in adulthood of asymptomatic airway hyperresponsiveness (AHR) to histamine or exercise-induced bronchospasm (EIB) detected in childhood in general population samples are sparse and have produced conflicting results. OBJECTIVE: To describe the outcome of asymptomatic AHR to histamine and EIB. METHODS: Data from a 12-year follow-up study of a random population sample of individuals aged 7 to 17 years at enrollment were analyzed; only individuals without asthma at enrollment were included in the analysis. AHR to inhaled histamine, EIB, lung function, and sensitization to aeroallergens were measured. RESULTS: Among the 281 nonasthmatic participants studied, 58 (22%) had AHR to histamine, 33 (12%) had EIB, and 82 (29%) had AHR to histamine and/or EIB. At follow-up, 37.9% of individuals with AHR to histamine and 30% of individuals with EIB had developed current asthma, compared with only 5% of individuals in whom these test results were negative. In patients with AHR to histamine, parental asthma (odds ratio [OR], 12.6; 95% confidence interval [CI], 1.5-108.5), furred pets ownership (OR, 6.0; 95% CI, 1.2-19.6), and dermatitis and/or rhinitis in childhood (OR, 2.2; 95% CI, 1.1-5.1) predicted the subsequent development of asthma, whereas no risk factors for the development of asthma could be identified in individuals with EIB CONCLUSION: Asymptomatic AHR to histamine and EIB in childhood predict the subsequent development of asthma in adulthood. A genetic disposition to asthma, furred pets ownership, and concomitant rhinitis or dermatitis increase the risk of asthma development in individuals with AHR to histamine.     

Psychotropic drug therapy in children and adolescents

The author reviews the current indications and dosages of psychotropic medications for children. As part of an overall therapeutic program, various psychotropic drugs may be useful to varying degrees for attention deficit disorder, pervasive developmental disorders and schizophrenic disorders, Tourette's disorder, major depressive disorder, functional enuresis, separation anxiety, and bipolar affective disorder. The limited nature of the literature on drug treatment of some of these disorders is stressed, as is the need to balance benefits against potential side-effects.