Evening Peak Expiratory Research Articles

Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100μg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin TM ) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin TM CFC-free) in patients with mild to moderate asthma. All patients ( n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100μg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.

Regular inhaled salbutamol and asthma control: the TRUST randomised trial

Previous work has suggested that the long-term regular use of inhaled beta2-agonist bronchodilators might lead to a deterioration in asthma control. The aim of TRUST (The Regular Use of Salbutamol Trial) was to study the effects of regular use of inhaled salbutamol, the most widely prescribed bronchodilator in the UK, on the control of asthma. A randomised, double-blind, placebo-controlled trial was undertaken in 983 patients with asthma being treated at least twice a week with short-acting beta2-agonist, alone or in combination with inhaled steroids (2 mg or less) daily. Patients were aged 18 years and over and were recruited from 115 general practices in the UK. 90% (881) of the patients used inhaled corticosteroid therapy, and all patients continued to use their usual inhaled beta2-agonist for symptomatic relief. Patients were randomised to receive 400 microg salbutamol or matched placebo via a Diskhaler four times per day for 12 months. The primary outcome measure was rate of exacerbations of asthma, with criteria based on data from diary cards completed daily by each patient, treatment with additional corticosteroids, or both. There were no differences in the annual rate, timing, or duration of exacerbations between the two groups. The mean morning peak expiratory flow was similar for the two groups. The mean evening peak expiratory flow (p<0.001) and the diurnal variation (p<0.001) were greater, and the use of rescue bronchodilator was less (p<0.001), in the group receiving regular salbutamol. There was no evidence that regular use of inhaled salbutamol 400 microg four times daily for a year increased the exacerbation rate of asthma in the population studied.

Acute effects of bushfires on peak expiratory flow rates in children with wheeze: a time series analysis

ObjectivesTo determine the effects of the January 1994 Sydney bushfire on evening peak expiratory flow rates (PEFR) in children with wheeze. MethodsChildren with a history of wheeze were enrolled in the longitudinal study and completed a daily asthma diary. We obtained daily air pollution, meteorological, pollen and alternaria data. We then used generalised estimating equation techniques to determine associations between the bushfire period and particulate matter less than 10 microns (PM10) and PEFR. ResultsThe maximum daily PM10 level peaked at 210 ug/m3, which was nearly seven times the usual PM10 level for the rest of January and February 1994. There was no significant association between mean PM10 and PEFR (beta-coefficient%-0.009, p=0.86). Children without bronchial hyper-reactivity had a significant negative association between PEFR and PM10 (beta-coefficient%-0.1029, p=0.03). The bushfire period was not significant in any of the models. ConclusionsWe did not find an association between the bushfire period or PM10 and evening PEFR, although in a subgroup of children without bronchial hyper-reactivity, a significant negative association was present between PM10 and evening PEFR. ImplicationsWe conclude that the high levels of particulate pollution caused by the Sydney bushfires did not lead to any clinically significant reductions in PEFR in symptomatic children. Our results have implications for community risk communication during future bushfires.

Equivalence of Two Steroid-Containing Inhalers: Easyhaler Multidose Powder Inhaler Compared with Conventional Aerosol with Large-Volume Spacer

Background and Objectives: An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 μg of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. Methods: One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Results: Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. Conclusion: It was concluded that the devices tested were equivalent in terms of efficacy and safety.

A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease

BACKGROUNDA study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).METHODS288 patients...

Pulmonary function and airway responsiveness in mild to moderate asthmatics given repeated inhaled doses of zanamivir

Zanamivir is a potent and specific inhibitor of influenza A and B virus neuraminidase, that is now approved for the treatment, and is currently under development for the prophylaxis of influenza. To assess the safety of this drug in asthmatics, 13 subjects with mild/moderate asthma [forced expiratory volume in 1 sec (FEV1)≥70% predicted, reversibility of FEV1to salbutamol ≥15%, concentration of methacholine causing a drop of 20% in the FEV1(PC20FEV1)≤8 mg ml−1], were recruited to a double-blind, randomized, placebo controlled, two way cross-over study. Subjects received 10 mg zanamivir as a dry powder (2×5 mg blisters via a Diskhaler®Sovnn Plastics Ltd., Berkshire, U.K.), or a matching placebo, twice daily on day 1 and then four times daily from day 2 to day 14, in two separate periods separated by a washout period of 7 days. PC20FEV1to methacholine was determined pre-study, on day 1 after the evening dose and on day 14 after the last dose of the study drug. FEV1was measured pre-study and at regular intervals on days 1 and 14. Laboratory safety tests were performed on days 1, 7 and 15. Morning and evening peak expiratory flow rate (PEFR) and any adverse events were recorded in a diary card.Eleven subjects completed the study. One was withdrawn due to non-compliance, and one due to an adverse event that occurred during the placebo period. On day 1 the geometric mean PC20for zanamivir was 36% lower than for placebo [ratio to placebo 0·64, (90% CI 0·44, 0·93)] and on day 14 this was 33% lower with zanamivir [ratio to placebo 0·67 (90% CI 0·38, 1·15)]. Both these confidence intervals were within the pre-defined interval of ‘no clinically significant effect’ of 0·25–4 (i.e. a change of two doubling doses of methacholine PC20FEV1which was considered clinically significant). The time weighted mean FEV1was 0·15 l (5·4%) lower for zanamivir on day 1 compared to placebo (90% CI 0·03, 0·28;P=0·050) and 0·01 l higher compared to placebo on day 14 (90%CI −0·12, 0·10;P=0·912). The day 1 changes were not associated with any significant symptoms or requirement for rescue bronchodilator therapy. Furthermore there was no apparent treatment difference over the 14 day dosing period in FEV1data (90% CI: −0·11, 0·05, P=0·57). The mean morning PEFR was 4 l min−1less for zanamivir than for placebo (90% CI: −11, 3) and mean evening PEFR was 9 l min−1less (90% CI: −24, 5). The study treatments were well tolerated by the subjects with no clinically significant adverse events attributable to zanamivir treatment. Zanamivir inhaled as a dry powder does not significantly affect the pulmonary function and airway responsiveness of subjects with mild/moderate asthma and therefore its use in such patients subjects is not precluded.

Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant

Background: This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP. Methods: In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 μg/d, 400 μg/d, or 800 μg/d of HFA-BDP or 100 μg/d, 400 μg/d, or 800 μg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled β-agonist for symptom control on diary cards were assessed over 6 weeks of treatment. Results: Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV 1 percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV 1 percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV 1 percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 μg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma). Conclusions: Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP. (J Allergy Clin Immunol 1999;1215-22.)

Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics

Previous results have demonstrated addition of long-acting β 2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800–1600 μg day −1). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 μg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 μg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV 1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period ( P < 0·01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo ( P = 0·001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed β 2-agoinist therapy between sensitivity and treatment periods compared with placebo ( P < 0·05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.

Efficacy of budesonide inhalation suspension in infants and young children with persistent asthma

This paper reviews the results from 3 randomized, double-blind, placebo-controlled, multicenter studies that assessed the efficacy and safety of once- and twice-daily dosing of budesonide inhalation suspension (BIS) in infants and young children with persistent asthma. In children with mild persistent asthma that was previously treated with bronchodilators or noncorticosteroid anti-inflammatory agents (study A), nighttime and daytime asthma symptoms were significantly improved in 0.25-mg once daily, 0.5-mg once daily, and 1.0-mg once daily BIS treatment groups compared with placebo ( P ≤ .05). Rescue medications were used significantly less in all BIS groups (approximately 2 days of every 14 days) compared with placebo ( P < .05). The proportion of patients who discontinued this therapy because of worsening asthma was greater in the placebo group than in the BIS groups, with the difference between placebo (23%) and the 1.0-mg BIS group (13%) being statistically significant ( P = .020). All BIS doses except 0.5 mg once daily showed nonsignificant numeric improvement in morning and evening peak expiratory flow (PEF) compared with placebo. In children with asthma that was previously treated with inhaled corticosteroids (study B), BIS doses of 0.25 mg, 0.5 mg, and 1.0 mg twice daily resulted in significant improvements in nighttime symptoms scores versus placebo ( P ≤ .026). Rescue medications were used significantly less in all BIS groups (approximately 2.5 to 3.5 days of every 14 days) compared with placebo ( P ≤ .032). The proportion of patients receiving placebo who discontinued therapy because of worsening asthma symptoms (36%) was significantly greater compared with the BIS groups (9%; P ≤ .015). Morning PEF levels were significantly greater in each BIS group compared with placebo ( P ≤ .03). For evening PEF levels, all BIS treatment groups showed numeric improvements compared with placebo; the 0.25-mg twice daily budesonide group showed statistically significant improvement ( P < .05). In children with moderate persistent asthma that was previously maintained either on bronchodilators or inhaled corticosteroids (study C), nighttime asthma symptoms significantly improved in the 0.25-mg twice daily, 0.5-mg twice daily, and 1.0-mg once daily BIS groups compared with placebo ( P < .01); there was a numeric improvement for the 0.25-mg once daily treatment group. Rescue medications were used significantly less in all BIS groups (approximately 2 to 3 days of every 14 days) compared with placebo ( P ≤ .014). The proportion of patients who discontinued treatment because of worsening of asthma symptoms was greater in the placebo group than in the BIS groups; the difference between 0.25-mg twice daily group (13%) and the placebo group (26%) was statistically significant ( P = .029). All BIS doses showed numeric improvement in morning PEF levels, and statistically significant improvements were observed in the 0.25-mg twice daily, 0.5-mg twice daily, and 1.0-mg once daily groups compared with placebo ( P < .03). Significant improvements in evening PEF levels were observed for each BIS treatment group ( P ≤ .034), except for the 1.0-mg once daily group. Overall, the 3 studies show that once- and twice-daily dosing of BIS effectively relieves asthma symptoms and improves pulmonary function in infants and young children with mild-to-severe persistent asthma. (J Allergy Clin Immunol 1999;104:S191-9)

Effect of Long-term Salmeterol Therapy Compared With As-Needed Albuterol Use on Airway Hyperresponsiveness

To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge. Randomized, double-blind, placebo-controlled, multicenter study. Thirty-one clinical centers in the United States. Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids. Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available. Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups. Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

Montelukast, A Once-Daily Leukotriene Receptor Antagonist, In theTreatment of Chronic Asthma: A Multicenter, Randomized, Double-BlindTrial

Reiss TF, Chervinsky P, Dockhorn RJ, Shingo S, Seidenberg B, Edwards TBArch Intern Med.158199812131220To determine the clinical effect of oral montelukast sodium, a leukotriene receptor antagonist, in asthmatic patients aged 15 years or more.Fifty clinical centers randomly allocated 681 patients with chronic, stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second (FEV1) 50% to 85% of the predicted value, at least a 15% improvement FEV1(absolute value) after inhaled β-agonist administration, a minimal predefined level of daytime asthma symptoms, and inhaled β-agonist use. Twenty-three percent of the patients used concomitant inhaled corticosteroids.Randomized, multicenter, double-blind, placebo-controlled, parallel-group study. A 2-week, single-blind, placebo run-in period was followed by a 12-week, double-blind treatment period (montelukast sodium, 10 mg, or matching placebo, once daily at bedtime) and a 3-week, double-blind, washout period. FEV1 and daytime asthma symptoms were the primary endpoint measures.Montelukast improved airway obstruction (FEV1, morning and evening peak expiratory flow rate) and patient-reported endpoints (daytime asthma symptoms, “as-needed” β-agonist use, nocturnal awakenings) (P < .001 compared with placebo). Montelukast provided near-maximal effect in these endpoints within the first day of treatment. Tolerance and rebound worsening of asthma did not occur. Montelukast improved outcome endpoints, including asthma exacerbations, asthma control days (P < .001 compared with placebo), and decreased peripheral blood eosinophil counts (P < .001 compared with placebo). The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups.Montelukast, compared with placebo, significantly improved asthma control during a 12-week treatment period. Montelukast was generally well-tolerated, with an adverse event profile comparable with that of placebo.This study appears to be a variation on a theme of previous studies with similar results. Montelukast (Singulair) and zafirlukast (Accolate) seem to be very useful medications for at least mild persistent asthma, particularly in patients who have grown weary of inhaled preparations. Montelukast has advantages over zafirlukast of once daily dosing without regard to food intake, and a pediatric approved chewable preparation. Montelukast has been shown helpful in exercise-induced bronchospasm (Kemp, J Allergy Clin Immunol. 1997;99:S321), aspirin-intolerant asthma (Kuna,Am J Respir Crit Care Med. 1997;155:A975), and in reducing the dose of inhaled corticosteroids (Leff, Am J Respir Crit Care Med. 1997;155:A976). Recent concerns regarding Churg-Strauss vasculitis may dampen some of the enthusiasm.

Relationship between asthma and gastro-oesophageal reflux: significance of endoscopic grade of reflux oesophagitis in adult asthmatics.

The association between asthma and gastro-oesophageal reflux disease (GERD) is well known. The aim of this study was to elucidate the causal relationship between reflux oesophagitis (RE) and asthma. Seventy-two adult asthmatics were examined regarding their GERD symptoms, and each underwent an endoscopic examination. According to the Los Angeles classification, we divided the patients into three groups: group 1 (n= 52), no mucosal break; group 2 (n= 15), RE corresponding to grades A or B; group 3 (n = 5), RE corresponding to grades C or D. The asthmatics in groups 2 and 3 received anti-reflux treatment for their GERD for 8 weeks. Their morning and evening peak expiratory flow rates (PEFR), daily variability of the PEFR and daily use of an inhalation bronchodilator were compared before and after this treatment. The percentage of severe asthma and postprandial exacerbation of asthma in group 3 were significantly higher than those in the other two groups. In contrast, the number of eosinophiles and the serum level of immunoglobulin E in group 3 were significantly lower than those in the other two groups. After the antireflux treatment, significant improvements of both PEFR and daily use of the inhalation bronchodilator were observed only in group 3. The endoscopic severity of RE is associated with the characteristics of adult asthmatics and the treatment of severe RE improved the asthmatics' condition.

Salmeterol vs Theophylline: Sleep and Efficacy Outcomes in Patients With Nocturnal Asthma

To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma.Randomized, double-blind, double-dummy, three-period crossover.Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies.Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study.Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily.Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups.Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.

Fluticasone propionate powder: Oral corticosteroid–sparing effect and improved lung function and quality of life in patients with severe chronic asthma

Background: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. Objective : This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. Methods : Oral prednisone–dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV 1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 μg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. Results : Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 μg fluticasone propionate groups, respectively, versus 9% of the placebo group ( P < .001). FEV 1 , morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance ( P ≤ .009) primarily in the 1000 μg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment ( P ≤ .003). Conclusion : Fluticasone propionate powder (500 or 1000 μg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy. (J Allergy Clin Immunol 1999;103:267-75.)

Therapeutic Effect of Zafirlukast as Monotherapy in Steroid-Naive Patients With Severe Persistent Asthma

We evaluated the efficacy of the leukotriene receptor antagonist zafirlukast (Accolate), 20 mg twice daily, as monotherapy in patients with severe persistent asthma (defined by an FEV1 < 60% of predicted before treatment and frequent night-time symptoms). Data were analyzed from a subgroup of 261 steroid-naive patients (zafirlukast, n = 149; placebo, n = 112) from four randomized, double-blind, placebo-controlled, 13-week trials with similar experimental designs, entry criteria, and clinical assessments. These patients were mostly men (57%) older than 30 years (56%) with pulmonary obstruction, ie, FEV1/FVC ratio < 0.7 (79%), and reversible airway disease demonstrated by a 15% increase in FEV1 after inhaled bronchodilator use. At end point, patients who received zafirlukast monotherapy had significant (p < 0.05) improvements from baseline, and compared with placebo, in FEV1, morning and evening peak expiratory flow (PEF), daytime asthma symptoms, nighttime awakenings, and beta2-agonist use. A stratified analysis based on the FEV1/FVC ratio showed an interaction between treatment and the amount of airflow obstruction for nighttime awakenings and mornings with asthma. Moreover, 37% of patients in both treatment groups had PEF variability > or = 20% (an indirect measure of airway inflammation). Zafirlukast patients with PEF variability > or = 20% had increases from baseline in the morning and evening PEF of approximately 40 and 11 L/min, respectively. For patients who take zafirlukast and who have a PEF variability of < 20%, the morning and evening PEF increased by 25 and 30 L/min, respectively. Regardless of the degree of PEF variability, zafirlukast significantly (p < 0.05) increased morning and evening PEF compared with placebo. Patients with severe persistent asthma who received zafirlukast as monotherapy had clinically significant improvements across all efficacy measures compared with placebo and significant reductions in PEF variability.

Additive effect of oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly patients with chronic asthma

The efficacy of the addition of inhaled oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly asthmatic patients whose asthma is not well controlled was evaluated. A randomized, open-label cross-over trial comparing 4-week treatment periods with and without regular inhalation of 200 μg of oxitropium bromide four times per day was performed. Twenty-four patients (mean age ± SD: 62 ± 7 years) completed the study. The dose of beclomethasone dipropionate in this patient group was 1300 ± 800 μg/day. Forced expiratory volume in 1 second (FEV1) was significantly improved after treatment with regular inhalation of oxitropium bromide when compared with FEV1 after treatment without oxitropium (1.73 ± 0.60 vs 1.63 ± 0.68). Both morning and evening peak expiratory flow rates were significantly greater during the treatment period with regular inhalation of oxitropium bromide. The score for dyspnea/chest tightness was also significantly improved during the oxitropium bromide period. There was no statistically significant improvement in forced vital capacity, scores for other symptoms or the frequency of rescue inhalation of fenoterol. The results of this study demonstrated that the addition of regular inhalation of oxitropium bromide is beneficial in elderly asthmatics whose asthma is not well controlled, even when treated with high-dose inhaled steroids.

Fluticasone Propionate and Beclomethasone Dipropionate in Asthmatic Patients

Background: Corticosteroid is most potent and effective anti-inflammatory medication currently available and inhaled form has been used in the long-tenn control of asthma. Fluticasone propionate(Flixotide/Flovent: FP) is highly potent and topically active inhaled corticosteroid and has at least twice the potency of beclomethasone dipropionate(BDP) in the control of asthma. The aim of this study was to compare the efficacy of FP and BDP in several aspects. Method: Fifty patients with asthma were treated in a randomized, parallel group study of 4 weeks duration. During 2-week run-in period -agonist was administered. After run-in period, FP was administered via Diskhaler or BDP via reservoir dry-power device. During the run-in and treatment period, morning and evening peak expiratory flow rate(PEFR) were measured daily. Daytime and nighttime asthma symptoms, daytime and night-time rescue bronchodilator use were checked daily. and FVC were measured biweekly in both groups. Results: Three patients treated with FP and seven patient treated with BDP were dropped out. Therefore forty patients completed the study. Morning and evening PEFR was increased and diurnal variation of PEFR decreased significantly in both groups. increased significantly in FP treatment group but not in BDP group. There were also improvements in daytime and night-time asthma symptoms, daytime and night-time rescue bronchodilator use in both groups after treatment There were no significant difference between groups in any of the efficacy parameters. Therapeutic effects were demonstrated earlier in patient treated with FP than BDP. Conclusion: In this study, fluticasone propionate was as effective as beclomethasone dipropionate in the control of asthma. Therapeutic effects were demonstrated earlier in patient treated with FP than BDP without adverse effect.

Daily variations in air pollution and respiratory health in a multicentre study: the PEACE project. Pollution Effects on Asthmatic Children in Europe.

The Pollution Effects on Asthmatic Children in Europe (PEACE) study is a multicentre study of the acute effects of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphur dioxide (SO2) and nitrogen dioxide (NO2) on the respiratory health of children with chronic respiratory symptoms. The study was conducted in the winter of 1993/1994 by 14 research centres in Europe. A total of 2,010 children, divided over 28 panels in urban and suburban locations, was followed for at least 2 months. Exposure to air pollution was monitored on a daily basis. Health status was monitored by daily peak expiratory flow (PEF) measurements and a symptom diary. The association between respiratory health and air pollution levels was calculated with time series analysis. Combined effect estimates of air pollution on PEF or the daily prevalence of respiratory symptoms and bronchodilator use were calculated from the panel-specific effect estimates. Fixed effect models were used and, in cases of heterogeneity, random effect models. No clear associations between PM10, BS, SO2 or NO2 and morning PEF, evening PEF, prevalence of respiratory symptoms or bronchodilator use could be detected. Only previous day PM10 was negatively associated with evening PEF, but only in locations where BS was high compared to PM10 concentrations. There were no consistent differences in effect estimates between subgroups based on urban versus suburban, geographical location or mean levels of PM10, BS, SO2 and NO2. The lack of association could not be attributed to a lack of statistical power, low levels of exposure or incorrect trend specifications. In conclusion, the PEACE project did not show effects of particles with a 50% cut-off aerodynamic diameter of 10 microm, black smoke, sulphur dioxide or nitrogen dioxide on morning or evening peak expiratory flow or the daily prevalence of respiratory symptoms and bronchodilator use.

Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma

There is substantial circumstantial evidence that CD4 lymphocytes have a role in the pathogenesis of chronic asthma. We investigated the efficacy and safety in severe corticosteroid-dependent asthma of a single intravenous infusion of keliximab (IDEC CE9.1), a chimeric monoclonal antibody to CD4. 22 patients were recruited from two asthma clinics. In an ascending-dose design, the first eight patients were assigned 0.5 mg/kg keliximab (six) or placebo (two); the next seven were assigned 1.5 mg/kg (five) or placebo (two); and the last seven were assigned 3.0 mg/kg (five) or placebo (two). Masked data on safety for each dose group were assessed before progression to the next dose. Patients kept a daily symptom diary and measured morning and evening peak expiratory flow (PEF) at home. PEF and forced expiratory volume in 1 s (FEV1) were measured at follow-up clinic visits. Patients given 0.5 mg/kg or 1.5 mg/kg keliximab and placebo recipients did not differ in change from baseline of PEF, FEV1, or symptom score. Those given 3.0 mg/kg keliximab differed significantly from placebo recipients in change in morning PEF (median area under curve [AUC] 445 vs -82.5, p=0.005) and evening PEF (median AUC 548 vs -85, p=0.014). Symptom score showed the same pattern (though differences did not achieve significance), but there was no difference in clinic FEV1. There were no serious adverse effects related to treatment. Two patients had mild exacerbations of eczema and one developed a transient maculopapular rash. All doses of keliximab were associated with a reduction from baseline in CD4 count. Our findings raise the possibility that T-cell-directed treatment may be an alternative approach to the treatment of severe asthma.

Asthma control during long term treatment with regular inhaled salbutamol and salmeterol

BACKGROUNDThe adverse effects of long term treatment of asthma with the short acting β agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to...