Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate.

OBJECTIVE: Intranasal beclomethasone dipropionate (BDP) has generally been considered to have no systemic activity at recommended doses, but the potential for long-term effects on growth has not previously been evaluated. This study was undertaken to assess the effects of 1 year of treatment with intranasal BDP on growth in children. STUDY DESIGN: In this double-blind, randomized, parallel-group study, 100 prepubertal children 6 to 9 years old with perennial allergic rhinitis were treated with aqueous BDP 168 microg twice daily (n = 51) or placebo (n = 49) for 1 year. Subjects' baseline heights were required to be between the 5th and 95th percentile, and skeletal age as determined by left wrist radiograph was required to be within 2 years of chronological age. Washout periods for medications known to affect growth, including other forms of corticosteroids, were established, and these medications were prohibited during the study. However, short courses of oral prednisolone lasting no more than 7 days, and short courses of dermatologic corticosteroids lasting no more than 10 days, were allowed. Height was measured with a stadiometer after 1, 2, 4, 6, 8, 10, and 12 months of treatment. The hypothalamic-pituitary-adrenocortical axis was assessed by measurements of 8 AM basal cortisol concentrations and response to. 25 mg cosyntropin stimulation. The primary safety parameter was the rate of change in standing height. Statistical analyses were based on all randomized subjects who received at least 1 dose of medication (intent-to-treat principle). The rate of change in standing height was analyzed for all subjects who entered the study and for those completing the full 12 months of treatment (n = 80). The rate of change in standing height over the 1-year study was calculated as the slope of a linear regression line fitted to each subject's height measurements over time. Because there was a statistically significant between-group difference in standing height at baseline, an analysis of covariance was performed for all analyses of standing height data. RESULTS: Of the 100 subjects enrolled, 90 completed the study. The 2 treatment groups were generally comparable at baseline; however, at baseline, mean age and mean height were significantly greater in the BDP treatment group that the in placebo treatment group. In both analyses, overall growth rate was significantly slower in BDP-treated subjects than placebo-treated subjects. The mean change in standing height after 1 year was 5.0 cm in the BDP-treated subjects compared with 5.9 cm in the placebo-treated subjects. The difference in growth rates was evident as early as the 1-month treatment visit, suggesting that the effect on growth occurred initially. The growth-suppressive effect of BDP remained consistent across all age and gender subgroups, and among subjects with and without a previous history of corticosteroid use. Use of additional exogenous corticosteroids during the study was similar in both groups and did not affect the results. Because there was a baseline imbalance in height, a supplemental analysis of the differences in prestudy growth rates was performed. This analysis found no baseline imbalance in prestudy growth rates. To determine whether the difference in growth rates during the study could be attributed to preexisting growth rates, a z score analysis was performed. The heights of both groups were normalized at baseline and at the end of the study using the US National Center for Health Statistics data for mean and standard deviations of height. This analysis confirmed that the difference in growth rates between the 2 groups was primarily attributable to the treatment rather than to any preexisting difference in growth. Additional analyses confirmed that the results were not influenced by outlier values. No significant between-group difference were found in the hypothalamic-pituitary-adrenocortical axis assessments. No unusual adverse events were observed. (ABSTRACT

Administration of budesonide once daily by means of turbuhaler to subjects with stable asthma.

BACKGROUND: Optimal management of chronic, mild-to-moderate asthma with inhaled steroids may include use of the lowest possible doses, as recommended in guidelines, and a reduction in the frequency of daily administration for greater convenience. Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials. OBJECTIVES: The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma. METHODS: Once daily budesonide was assessed in 309 adult subjects, including those who were and were not using an inhaled steroid at baseline. The subjects were stratified by inhaled steroid use and randomly assigned to one of 3 treatments: 200 microgram budesonide, 400 microgram budesonide, or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks. Beyond this point, treatment was continued unchanged for another 12 weeks (maintenance) in those receiving 200 microgram budesonide once daily and placebo. In those who received 400 microgram budesonide once daily, the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks (400/200 microgram group). Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow. RESULTS: Once daily budesonide was well tolerated and resulted in significant improvements in all efficacy endpoints, even though baselines were well stabilized. Baseline lung function was elevated with little room for improvement; however, mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups, respectively, versus a decrease of -0.09 L in the placebo arm (P <.001). Results for peak expiratory flow were similar. Significant improvements in secondary endpoints, including symptoms, beta-agonist use, and quality of life, also developed with budesonide 200 and 400 microgram once daily. CONCLUSION: Inhaled budesonide, in doses as low as 200 microgram, may be an appropriate introductory or maintenance dose in subjects with stable, mild-to-moderate asthma.

Exercise-induced asthma: diagnosis and treatment for the recreational or elite athlete.

Exercise-induced asthma: diagnosis and treatment for the recreational or elite athlete. Med. Sci. Sports Exerc., Vol. 31, No. 1 (Suppl.), pp. S33-S38, 1999. Exercise-induced asthma (EIA) is found in 10-50% of recreational and elite athletes, depending on the population studied. The diagnosis may be made with symptoms (cough, wheeze, chest tightness, etc. with exercise) and with pulmonary function measurements (spirometry or peak flow measurements) before and after exercise. Most patients respond well to pre-exercise treatment with an inhaled quick-acting beta agonist. Some patients require additional therapy such as pre-exercise inhaled cromolyn, daily inhaled steroids, salmeterol, theophylline, leukotriene modifiers, or other agents. An occasional patient presents with the symptoms of EIA but responds poorly to treatment. Further investigation may lead to a totally different diagnosis such as vocal cord dysfunction. For most athletes with EIA, proper diagnosis and treatment will allow them to complete at any level.

Risk-benefit assessment of fluticasone propionate in the treatment of asthma and allergic rhinitis.

BENEFITS: Fluticasone propionate (FP) is a new topical corticosteroid spray for the treatment of allergic rhinitis and asthma. FP has been shown to be effective for the treatment of adult and pediatric asthma, even at rather low doses (25 microg twice daily [b.i.d.]); many studies in asthma have shown clinical efficacy of fluticasone at half the dose of the comparison steroid (such as beclomethasone dipropionate [BDP] or budesonide [BUD]). However, exact dose comparisons cannot be made because dose-ranging comparison studies have not been done. Studies in allergic rhinitis in children and adults have shown good efficacy in FP-treated patients at a dose of 200 microg once daily (o.d.), intranasally. In summary, FP is effective in both asthma and allergic rhinitis. RISKS: FP has minimal systemic activity because the portion of drug that is swallowed is not absorbed from the gut. Thus, the amount available for systemic activity is only that which is absorbed through the nasal mucosa (in the treatment of rhinitis) or through the alveoli of the lungs (in the treatment of asthma). When laboratory assays of adrenal function or bone formation are measured, FP and other inhaled corticosteroids can be shown to cause suppression of these markers, especially at high doses. There have been no consistent reports of clinical adrenal suppression or osteoporosis caused by FP. In summary, the risk-benefit ratio of FP at the usual doses (therapeutic ratio) is very favorable. High doses may show evidence of suppression of the hypothalamic pituitary axis as measured by in vitro tests, but evidence of corresponding clinical adverse effects is lacking.

Clinical adverse effects of inhaled corticosteroids: results of a questionnaire survey of asthma specialists.

BACKGROUND: Inhaled corticosteroids are recognized as the mainstay of prophylactic anti-inflammatory therapy in patients with persistent asthma. In large multiclinic trials, the clinical adverse event profiles have been not significantly different than patients treated with placebo or other medications; however, in small studies evaluating very sensitive in vitro measurements of the hypothalamic pituitary adrenal axis there have been adverse laboratory events noted with moderate and high doses of inhaled steroids. OBJECTIVE: To survey asthma specialists in North America with regard to their personal clinical experience of adverse events with the use of inhaled corticosteroids. METHODS: Two hundred thirteen physicians specializing in the treatment of asthma responded to questionnaires asking their experiences with specific adverse clinical events that have the potential to occur after the use of inhaled corticosteroids (see appendix A for questionnaire). RESULTS: There was a 67% response rate for the questionnaire. Eighty percent of the respondents were allergists/immunologists and 20% were pulmonologists. The average length of time they had been in practice was 16 years. In general, side effects from inhaled steroids were seen very infrequently in the hands of these physicians in spite of the fact that they were primarily secondary or tertiary referral physicians for the treatment of asthma. The local oropharyngeal adverse events were seen 48% of the time on an occasional basis but only 3% of the time on a frequent basis. When spacers were used the oropharyngeal symptoms were reduced significantly. Skin changes such as bruising or thin skin were seen frequently 6% of the time and occasionally 24% of the time only. In general, these skin changes were found in elderly or middle-aged individuals. Weight gain was very unusually seen, as were adverse effects on bone (osteoporosis, fractures, growth problems, etc.). Hypothalamic pituitary axis abnormalities were seen quite infrequently and primarily in patients who had also received oral corticosteroids. CONCLUSIONS: This study shows that inhaled corticosteroids are generally safe in the treatment of asthma and are rarely associated with systemic side effects, as detected in routine clinical practice.

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group.

OBJECTIVE: To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma. DESIGN: Double-blind, randomized, and placebo-controlled study, with parallel groups. SETTING: Multicenter study in outpatient setting. PARTICIPANTS: Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg. MEASUREMENTS AND INTERVENTIONS: After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals. RESULTS: Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects. CONCLUSION: Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.

The effects of salmeterol on power output in nonasthmatic athletes.

BACKGROUND: Salmeterol xinafoate is a new aerosol inhalant that is used in the treatment of asthma. It is currently banned by the International Olympic Committee because of the concern that it may lend an unfair competitive advantage to the user. OBJECTIVE: The purpose of this study was to determine whether salmeterol improves short-term anaerobic performance in elite nonasthmatic track cyclists. METHODS: Eleven elite track cyclists volunteered to perform a 30-second all-out cycle ergometer test 3 hours after receiving either 42 micrograms of salmeterol xinafoate or placebo applied in a double-blind crossover procedure. During the ergometer test, peak power output, total work, time to peak power, and percent fatigue (decline in power output) were measured. Pulmonary measurements were also taken before and at various time points after inhalation and the ergometer test. A methacholine challenge was administered to each subject before participation in the study to ensure that none of the subjects had any reactive airway diseases. RESULTS: There were no significant differences (p > 0.05) between the placebo and salmeterol trials for peak power output, total work performed during the 30-second test, percent fatigue, and time to peak power. No differences between trials were observed for the pulmonary function test variables at any of the time points. Blood lactate concentrations before and after administration of drug or placebo were also not significantly different between trials. Additionally, salmeterol did not affect the maximal heart rate achieved during the test as compared with the placebo. CONCLUSIONS: Short-term salmeterol use within the prescribed dosage was not shown to increase short-term power output in nonasthmatic cyclists.

Treatment of allergic rhinitis: effects of allergic rhinitis and antihistamines on performance.

Antihistamines are the most commonly used drugs for allergic rhinitis, and many antihistamines may cause subclinical side effects which are not noticeable by the patient. These include impaired driving performance, impaired work performance, reduced coordination, reduced motor skills, sleepiness and impaired information processing (arithmetic, verbal, and office skills). The newer nonsedating antihistamines should be used for the treatment of allergic rhinitis because they do not produce these effects. Recent studies have shown that children's learning in school may also be negatively affected by traditional antihistamines, and therefore, school children should definitely be given the nonsedating antihistamines. Not only does the treatment cause some impaired performance, but allergic rhinitis itself may result in changes in the patient's mood affect, and other aspects of personality. Physicians who treat allergic rhinitis should be aware of the potential performance effects of medications that they prescribe and the potential effects of the disease itself on the patient's personality.

Update on exercise-induced asthma: a report of the olympic exercise asthma summit conference.

Exercise-induced asthma (EIA) can be easily overlooked and underdiagnosed, especially in school children or recreational athletes. It affects individuals of all levels of activity, from recreational sports to competition. This article summarizes the results of the Olympic Exercise Asthma Summit Conference, organized by the Sports Medicine Division of the US Olympic Committee. Making the correct diagnosis of EIA is very important and usually requires some form of pulmonary function testing. Because effective pharmacologic and nonpharmacologic treatment is available for this condition, patients should be followed until the condition is controlled.

Improving the treatment of nocturnal asthma: use of an office questionnaire to identify nocturnal asthma symptoms.

Nocturnal asthma is a major problem in many asthma patients and it is important to recognize and treat it. We previously reported the incidence of nocturnal asthma in our practice (1); the current study was done to try to improve upon the incidence of nocturnal asthma in our patients. After our previous survey, which indicated a 67% incidence of nocturnal asthma in our practice, we instituted a previsit questionnaire regarding nocturnal asthma to be filled out by all follow-up asthma patients in our office. After a period of time, we mailed a nocturnal asthma questionnaire to all asthma patients to see if the intervention had improved our incidence of nocturnal asthma. This questionnaire was identical to the one used in our prior study and was mailed to 2019 patients. We had 602 responders, 560 of whom had asthma. A total of 328 of these patients (59%) had nocturnal asthma. This was similar to the results of our previous survey, and our initial conclusion was that the new in-office questionnaire that we instituted had not improved the situation. Then we discovered that the in-office questionnaire had inadvertently been distributed only to the patients of one or our physicians (Dr. A). His patients were then compared with those of the other two doctors (Drs. B and C), and it was found that Dr. A's patients had fewer nocturnal symptoms than did the patients of the other doctors. The percent of asthmatics with nocturnal asthma 4-7 nights per week (more than half the nights in a week) for Dr. A was 16%, for Dr. B 47%, and for Dr. C 39%. The use of a short office questinnaire for asthma patients before they see the doctor for follow-up visits leads to greater recognition and better treatment of nocturnal asthma.

Clinical studies of the efficacy and tolerability of ebastine 10 or 20 mg once daily in the treatment of seasonal allergic rhinitis in the US.

396 adult and adolescent patients with seasonal allergic rhinitis participated in this randomised double-blind parallel-group study in which the efficacy and tolerability of ebastine 10 or 20mg administered once daily in the morning or evening for 3 weeks were compared with those of placebo. Clinical efficacy was assessed by measuring improvement in rhinitis symptoms (nasal discharge, nasal stuffiness, sneezing, itchy nose and itchy/watery eyes) recorded by patients twice daily on diary cards. The improvement in individual and total symptom scores at the end of the 3-week treatment period in patients treated with ebastine 10mg in the morning or ebastine 20mg in the morning or evening was significantly greater than the improvement in placebo recipients. The 20mg dose of ebastine administered in the morning was associated with the greatest improvement in symptom scores. There was no significant effect with the 10mg evening dose compared with placebo. Ebastine was well tolerated by the majority of patients - the incidence of adverse events, including headache, dry mouth, somnolence and asthenia being similar to that reported in placebo recipients. Electrocardiograms showed no evidence of any clinically relevant changes in QTc intervals. In a subsequent nonblinded 4-month study that included 230 patients from the initial study, global evaluations at monthly intervals showed overall symptom improvement in > or = 72% of patients who received ebastine 10mg or 20mg once daily. The drug was well tolerated during prolonged therapy, with adverse events being similar in nature and incidence to those reported in the 3-week double-blind study. In conclusion, ebastine 10mg once daily in the morning is an appropriate starting dose for the treatment of rhinitis, and this can be increased to 20mg as required.

The effects of albuterol on power output in non-asthmatic athletes.

The purpose of this study was to evaluate the effect of the beta 2-agonist albuterol (salbutamol) at twice the normal dosage (360 micrograms) on power output during a 30-second Wingate test and pulmonary function in highly trained cyclists (4 category 1 and 10 category II U.S.C.F. track cyclists). The cyclists did not have a history of exercise induced bronchial spasms, and a 5 step methacholine challenge confirmed all subjects to be non-asthmatic. The project was performed in a random block, double blind design. Twenty minutes before the 30-second Wingate cycle ergometer exercise, albuterol (90 micrograms per dose) or a saline placebo was administered by inhaler in 4 metered doses. Pulmonary function tests were performed at rest, 20 minutes post-inhalation, and 5, 10, 15 minutes post-exercise. After a standard warm-up, a 30-second Wingate anaerobic power test was performed on a cycle ergometer at a resistance of 0.10 kg (kg body mass)-1. Multi-variate ANOVA revealed no significant difference between the albuterol and placebo treatment for the anaerobic power measures: peak power (1,136.7 +/- 40.9 vs 1,124.8 +/- 39.8 W, mean +/- s.e.), total work (27,213.6 +/- 653.1 vs 27,093.3 +/- 677.4j), time to peak power (4.5 +/- 0.2 vs 4.8 +/- 0.5 s), and fatigue index (16.5 +/- 1.8 vs 16.6 +/- 1.8 W.s-1). Peak heart rate (181.6 +/- 3.7 vs 181.4 +/- 3.8 bpm), or blood lactate (14.0 +/- 0.9 vs 13.8 +/- 0.8 mmol.l-1) 3 min after the exercise bout were not significantly different between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)