Evening Peak Flow Research Articles

The temporal distribution of ridership in metro stations from land-use perspective.

A reasonable land use development around subway stations can balance the utilization rates of the subway system during peak and off-peak hours, thereby enhancing its service levels and operational efficiency. Analyzing the temporal distribution patterns of passenger flow and their influencing factors is crucial for determining the optimum ratio of each land use type surrounding metro stations. Thus, this paper employs principal component analysis (PCA) at first to investigate the temporal distribution of metro ridership, and identify their main patterns and factor loadings. Then, using geographically weighted regression, the study examines the spatial dependencies between the main component proportions and influencing factors, focusing on Xi'an subway stations. The results indicate that the temporal distribution of passenger flow can be decomposed into three principal components: the first representing commuting characteristics, and the second and third representing regulating functions. The overall distribution is a composite of these components in varying proportions. Residential and educational land uses primarily drive morning and evening peak flows, with residential land use in the city center and peripheral areas having a more pronounced effect compared to transitional areas. Conversely, commercial & office, healthcare, and recreational & park land mitigate peak flows and increase off-peak flows. External hub enhances passenger flow throughout the day, while industrial land use has negligible impact.

Remote monitoring of the course of bronchial asthma in children

Aim: to evaluate the eff ectiveness and satisfaction of patients with bronchial asthma (BA) using the remote monitoring software product “ASTMATEST”. Materials and methods. A specialized website “ASTMATEST” — ww.asthmatest.ru was developed for conducting remote and timely telemonitoring of the health status of patients with verifi ed BA. An open prospective comparative study was conducted at the pediatric department of the City Children’s Clinical Hospital in Ufa from November 2022 till April 2023. The study included 2 groups of patients, similar in age and demographic indicators: the main group consisted of 38 (57.8 %) children whose parents agreed to use the information system of the website “ASTMATEST” in combination with its traditional methods, the control group included 34 (43.2 %) children whose parents refused to use the software product due to various reasons. The effectiveness of remote monitoring was analyzed by comparing the morning and evening peak flow meter readings, symptom control report data. Satisfaction with the work and use of the remote monitoring technology of the website “ASTMATEST” by patients with BA and their parents was assessed through a sociological survey using questionnaires. Results. In the main study group, the proportion of patients with severe BA decreased to 18.42 % due to an increase in the proportion of patients with mild (up to 34.21 %) and moderate (47.37 %) severity of BA. In the control group, the proportion of patients with mild BA decreased to 40.74 %, due to an increase in the proportion of patients with moderate (up to 44.44 %) and severe (14.82 %) severity. Conclusion. During the survey of patients in the main group using a specially designed questionnaire, it was found that the majority of patients and their parents/legal representatives are willing to continue using the developed software product to assess the level of disease control and adherence to doctor’s recommendations and prescriptions.

Analysis of Flow Characteristics and Step Size of Escalators at Metro Stations

This paper discusses the analysis of flow characteristics on escalators and examines the adequacy of step size. The study was carried out on nine escalators at three metro stations in New Delhi, the capital city of India. Data were collected during morning and evening peak flow periods. Peak flows on the escalators being studied are observed to be higher during evening period as compared to the morning period. Flow values are quite high when compared with flow values at metro stations in China or England or on similar facilities at railway stations. Maximum density was found higher as compared to that reported in China and England and comparable to that at railway stations in India. Space per person was found comparable to the reported values. Relationships between flow characteristics were also developed. Step dimension adequacy was checked and suggested to be modified in the light of person body dimension reported in different guidelines. The outcome will assist the planners to take considered decisions related to escalators.

A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow Limitation.

In Japan, most asthma deaths occur among the elderly. We should improve the control of asthma in elderly patients to reduce the number of deaths due to asthma. This retrospective study aimed to evaluate the efficacy of tiotropium RespimatⓇ (Tio-Res) in symptomatic, never-smoking, elderly asthmatics with irreversible airflow limitation despite the use of high-dose inhaled corticosteroids (ICS) plus long-acting β2-adrenoceptor agonists (LABA). The Asthma Control Test™ (ACT), pulmonary function tests, morning and evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS® peak flow meter), and respiratory impedance (assessed with MostGraph®) were measured before and after a minimum of one year of Tio-Res 5 µg/day administration. Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA, were analyzed. All patients were female (mean age, 81.6 years). Tio-Res led to statistically significant improvements in the total ACT score (19.9 to 23.6), FVC and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also resulted in statistically significant improvements in respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area (ALX). Our retrospective study suggests that Tio-Res improves symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics aged 75 or over with irreversible airflow limitation despite the use of high-dose ICS plus LABA.

Effectiveness of air purifier on health outcomes and indoor particles in homes of children with allergic diseases in Fresno, California: A pilot study

ABSTRACTObjective: Epidemiologic studies indicate that indoor air pollution is correlated with morbidity caused by allergic diseases. We evaluated the effectiveness of reducing the levels of indoor fine particulate matter <2.5 micrometer diameter (PM2.5) in Fresno, California using air purifiers on health outcomes in children with asthma and/or allergic rhinitis. Methods: The active group (with air purifiers) and the control group consisted of eight houses each. Air purifiers were installed in the living rooms and bedrooms of the subjects in the active group during the entire 12-week study duration. Childhood asthma control test, peak flow rate monitoring, and nasal symptom scores were evaluated at weeks 0, 6, and 12. Results: At 12 weeks, the active group showed a trend toward an improvement of childhood asthma control test scores and mean evening peak flow rates, whereas the control group showed deterioration in the same measures. Total and daytime nasal symptoms scores significantly reduced in the active group (p = 0.001 and p = 0.011, respectively). The average indoor PM2.5 concentrations reduced by 43% (7.42 to 4.28 μg/m3) in the active group (p = 0.001). Conclusions: Intervention with air purifiers reduces indoor PM2.5 levels with significant improvements in nasal symptoms in children with allergic rhinitis in Fresno.

Dehumidifiers for chronic asthma.

Humidity control measures in the home environment of patients with asthma have been recommended, since a warm humid environment favours the growth of house dust mites. However, there is no consensus about the usefulness of these measures. To study the effect of dehumidification of the home environment on asthma control. The clinical trials registers of the Cochrane Collaboration and Cochrane Airways Group were searched. Searches were current as of March 2013. Randomised controlled trials on the use of humidity control measures in the home environment of patients with asthma were evaluated for inclusion. Data were extracted independently using a pre-designed data extraction form by two review authors. A second trial has been added for the 2013 update of this review. The original open-label trial compared an intervention consisting of mechanical ventilation heat recovery system with or without high efficiency vacuum cleaner fitted in 40 homes of patients with asthma who had positive tests for sensitivity to house dust mite. The new double-blind trial also compared a mechanical ventilation heat recovery system with a placebo machine in the homes of 120 adults with allergy to house dust mite. The new trial, which was at low risk of bias, showed no significant difference in morning peak flow (mean difference (MD) 13.59; 95% confidence interval (CI) -2.66 to 29.84), which was the primary outcome of the trial. However, there was a statistically significant improvement in evening peak flow only (MD 24.56; 95% CI 8.97 to 40.15). There was no significant difference in quality of life, rescue medication, requirement for oral corticosteroids, visits to the GP, emergency department (ED) or hospitalisations for asthma. There was no significant difference in the house dust mite count and the antigen levels in the new trial, in contrast to the previous trial. Evidence on clinical benefits of dehumidification using mechanical ventilation with dehumidifiers remains scanty, and the addition of a new double blind trial to this review does not indicate significant benefit in most measure of control of asthma from such environmental interventions.

Unflued gas heaters and respiratory symptoms in older people with asthma

BackgroundUnflued gas heaters (UFGHs) and cookers are a major contributor to air pollution in homes. Gas appliances have been associated with adverse respiratory outcomes in children and, less consistently, adults....

Comparative Study of Budesonide Inhalation Suspension and Montelukast in Young Children With Mild Persistent Asthma

Szefler SJ, Baker JW, Uryniak T, Goldman M, Silkoff PE. J Allergy Clin Immunol. 2007;120(5):1043–1050 PURPOSE OF THE STUDY. To evaluate the efficacy of budesonide inhalation suspension (Pulmicort respules) compared with montelukast (Singulair) for controlling asthma symptoms in young children with mild persistent asthma. STUDY POPULATION. This was a prospective study of 395 children, aged 2 to 8 years, diagnosed with mild persistent asthma recruited from 55 US centers. Approximately 12% of the subjects had previous histories of inhaled corticosteroid (ICS) use. METHODS. Subjects were randomly assigned to receive either budesonide 0.5 mg or montelukast 4 to 5 mg daily and were followed for 52 weeks. Compliance was assessed by daily electronic diary review. For mild asthma exacerbations, step-up therapy consisted of the addition of a morning dose of budesonide 0.5 mg in both arms. For severe asthma exacerbations, subjects received a 3- to 10-day standardized course of oral steroids. The primary end point was evaluated by using the intention-to-treat population and was defined as time to first additional medication for asthma worsening at 52 weeks. Secondary end points included the time to additional asthma medication and rates of occurrence of mild and severe asthma exacerbations. Changes in symptom scores, peak flows, rescue-medication use, and pulmonary-function test results were also evaluated. RESULTS. Kaplan-Meier probability curves showed that the primary outcome measurement, time to the first additional asthma medication, was not significantly different between the 2 groups at 52 weeks (P = .3). There was a significant increase in the time to first additional asthma medication in the budesonide group compared with the montelukast group at 12 weeks (P = .05). The percentage of subjects requiring step-up therapy in the budesonide group versus the montelukast group at 12 weeks was 29.1% versus 38.6% (not significant [NS]), at 26 weeks was 41.3% versus 48.2% (NS), and at 52 weeks was 52% versus 56.9% (NS), respectively. The budesonide group achieved significantly improved morning and evening peak flow values compared with the montelukast group at 12 weeks (P = .005–.007). The rate of mild and severe asthma exacerbations per subject per year in the budesonide and montelukast groups was 1.23 and 1.63, respectively (P = .034). There was no significant difference in the number of severe asthma exacerbations between the 2 groups. Both treatment groups showed nonsignificant improvements in changes from baseline asthma scores, 24-hour rescue-medication use, and medication- and asthma-free days. CONCLUSIONS. Both budesonide and montelukast are effective and well-tolerated as controller medications in children aged 2 to 8 years with mild persistent asthma. Results favored budesonide for several secondary outcome measures. REVIEWER COMMENTS. Previous studies have shown that ICSs are more effective asthma-controller medications compared with montelukast in children older than 6 years. Although this study failed to show statistical significance in the primary outcome, it provides data supporting certain treatment benefits of ICSs in children younger than 6 years (257 of 395 children were &amp;lt;5 years old). Compared with previous studies, these children had milder asthma, with only 12% having taken ICSs before enrollment.

Bronchial Thermoplasty for Asthma

Bronchial thermoplasty (BT) reduces the potential for smooth muscle-mediated bronchoconstriction by reducing the mass of smooth muscle in the walls of conducting airways. This study was conducted to examine the safety and impact on lung function and airway responsiveness of BT over 2 yr. The safety of BT was studied in 16 subjects with mild to moderate asthma. Baseline and 12-wk post-treatment measurements included spirometry, methacholine challenge, daily diary recordings of peak flow, symptoms, and medication usage. Subjects completed follow-up evaluations at 12 wk, 1 yr, and 2 yr. The procedure was well tolerated; side effects were transient and typical of what is commonly observed after bronchoscopy. All subjects demonstrated improvement in airway responsiveness. The mean PC(20) increased by 2.37 +/- 1.72 (p < 0.001), 2.77 +/- 1.53 (p = 0.007), and 2.64 +/- 1.52 doublings (p < 0.001), at 12 wk, 1 yr, and 2 yr post-procedure, respectively. Data from daily diaries collected for 12 wk indicated significant improvements over baseline in symptom-free days (p = 0.015), morning peak flow (p = 0.01), and evening peak flow (p < or = 0.007). Spirometry measurements remained stable throughout the study period. BT is well tolerated in patients with asthma and results in decreased airway hyperresponsiveness that persists for at least 2 yr.

Short-Term Safety and Tolerability of??Double-Dose Salmeterol/Fluticasone??Propionate in Adult??Asthmatic Patients

The incidence of asthma exacerbations in patients receiving salmeterol/fluticasone propionate (Seretidetrade mark or Advair((R))) is low. However, when asthma control deteriorates, clinicians may instruct patients to double the dose of their inhaled corticosteroid medication for a short period. The purpose of this study was to demonstrate that doubling the dose of Seretidetrade mark for a period of 2 weeks in subjects with persistent asthma is safe and well tolerated. This randomised, double-blind, parallel-group study was conducted in primary-care centres. Adults with a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of >/=70% predicted were stratified to receive a single dose of Seretidetrade mark 50mug/100mug, 50mug/250mug or 50mug/500mug twice daily from a Diskustrade mark inhaler for a 4-week run-in period, dependent on the dose of inhaled corticosteroid on entry. Subjects were then randomised to receive either an extra inhalation of the same dose of Seretidetrade mark received during the run-in (double dose) or an inhalation of matching placebo (single dose) for 14 days in a 2 : 1 ratio. Subjects were asked to record any adverse events, morning and evening heart rate (HR), peak flow and relief medication use in daily record cards. The primary endpoint was tremor as perceived by the subject. Clinic evaluations included HR, 12-lead ECG, and potassium and glucose levels. 110 and 208 subjects received single- and double-dose Seretidetrade mark, respectively. Only one subject experienced tremor. This was classified as mild and occurred in a subject receiving double-dose Seretidetrade mark (50mug/100mug). There was no difference between the treatment groups in the incidence of tremor (difference <1%; 95% CI -6, 8). Other salmeterol-related adverse events (palpitations, muscle cramps and headache) and fluticasone propionate-related events (oral candidiasis and hoarseness) occurred in a similar percentage of subjects in each treatment group. The treatment differences for morning and evening HR measurements showed small differences between the two groups (<2 beats/min). The adjusted mean treatment difference (double dose - single dose) in morning HR was 1.1 beats/min (95% CI 0.2, 2.0) and evening HR was 0.9 beats/min (95% CI 0.1, 1.7). Seven percent of subjects receiving single-dose Seretidetrade mark and 8% receiving double-dose Seretidetrade mark had a QTc change from baseline in the interval 30-59 msec. No increases above 59 msec were seen in either group. There were no clinically significant changes from baseline for potassium levels. Two percent of subjects in the single dose and <1% in the double-dose group had a change from a non-clinically significant baseline blood glucose assessment to a clinically significant abnormality at the end of treatment. In circumstances in which a physician may be considering doubling the dose of Seretidetrade mark for a short period of time in adult asthmatics, this study demonstrates that doubling the dose for a period of 2 weeks is safe and well tolerated.

Inhaled short acting beta2-agonist use in asthma: regular vs as needed treatment.

Inhaled beta2-adrenergic agonists delivered by inhalation are very widely used in asthma. There has been much controversy of the use and possible consequences of the use of these agents for regular, as opposed as-needed use in asthma. This review to assessed the clinical trial evidence to test whether using regular use of short-acting beta2-agonists reduced asthma control and pulmonary function; worsened symptoms, airway reactivity and quality of life; and increased the rate of exacerbations. A search was carried out of the Cochrane Airways Group "Asthma and Wheez* RCT" register using the terms: regular AND [beta agonist OR bronchodilator OR salbutamol OR albuterol Or terbutaline OR isoproterenol OR reproterol OR fenoterol]. Bibliographies of existing trials were searched and primary trial authors and pharmaceutical companies were approached for additional trials. Randomised controlled trials in which the short-acting beta2-agonist was given regularly in the experimental group, together with an inhaled bronchodilator for relief of symptoms ('rescue use'). The control group consisted of matching placebo inhaled regularly, with an inhaled bronchodilator for as-needed 'rescue use'. Data were extracted and quality assessments were made by both reviewers. Parallel group and cross-over trials were analysed separately. Where possible data were pooled using a fixed effects model. Over 800 abstracts were identified, following a review, 60 papers were requested for full assessment by both reviewers. 34 trials from 30 papers met the entry criteria. Data from 31 outcomes were analyzable. There was little difference between the treatments for nearly all outcomes. In cross-over studies, evening peak flow was better with regular treatment, weighted mean difference (WMD) 13.1 l/min (95% confidence interval 24.3, 1.9). In contrast, the FEV1 was better with as-needed treatment (WMD 157 ml (95% CI: 123, 192). Bronchial hyper reactivity was slightly better in the as-needed group, standardised mean difference 0.23, 95% CI: 0.52, 1.12. These results support current guidelines. There is little advantage in using short-acting beta2-agonists regularly, and potentially some small clinical disadvantage.

Abstracts

Abstracts

Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study

Background: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from...

Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma

Purpose To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting β 2-agonists. Subjects and methods A total of 440 patients (≥12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting β 2-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 μg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV 1], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations. Results Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV 1 (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. –5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001). Conclusion Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids.

Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma

Background: Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma. Objective: We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma. Methods: Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 μg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment. Results: At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV1) in comparison with placebo (P < .05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P < .05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P < .05) morning and evening peak flow, nighttime β2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P < .05) with regard to peak flow. Triamcinolone produced suppression (P < .05) of overnight urinary cortisol/creatinine and serum osteocalcin. Conclusion: Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree. (J Allergy Clin Immunol 2002;109:68-74.)

A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma

PurposeTo compare the short-term efficacy and safety of low-dose fluticasone propionate with that of oral zafirlukast therapy for patients previously treated with beta-2-agonists alone, and to evaluate the potential therapeutic benefit of switching from zafirlukast to a low-dose inhaled corticosteroid. Subjects and methodsThis study consisted of a 4-week randomized, double-blind treatment period followed by a 4-week open-label period. Two hundred ninety-four patients ≥12 years old with asthma previously uncontrolled with beta-2-agonists alone were randomly assigned to treatment with low-dose inhaled fluticasone (88 μg twice daily) or oral zafirlukast (20 mg twice daily). After 4 weeks, all patients discontinued their double-blind therapy and received open-label fluticasone (88 μg twice daily). Outcomes included pulmonary function, asthma symptoms, albuterol use, asthma exacerbations, and adverse events. ResultsDuring the double-blind treatment period, fluticasone patients had significantly greater improvements in morning peak flow (29.3 L/min vs. 18.3 L/min), percentage of symptom-free days (19.8% vs. 11.6%), and daily albuterol use (−1.8 puffs per day vs. −1.1 puffs per day) compared with zafirlukast patients (P ≤0.025, each comparison). During the open-label treatment period, patients switched from zafirlukast to fluticasone experienced additional improvements in morning peak flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV1 (0.11 liter) and daily albuterol use (−0.9 puffs daily) compared with values obtained at the end of the double-blind treatment period (P ≤0.001, each comparison). ConclusionLow-dose fluticasone was more effective than zafirlukast in improving pulmonary function and symptoms in patients with persistent asthma. In addition, switching patients from zafirlukast to fluticasone further improved clinical outcomes.

Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial

Controlled trials suggest that leukotriene receptor antagonists can improve lung function and reduce requirement for oral or inhaled corticosteroids in patients with asthma. We aimed to assess whether montelukast, a leukotriene receptor antagonist, can improve symptoms or lung function in patients with chronic asthma with symptoms already taking corticosteroids. We did a double-blind, placebo-controlled, crossover, randomised add-on study in which 100 patients with asthma and symptoms despite treatment with inhaled corticosteroids and additional therapy were given 10 mg montelukast sodium for 14 days in an outpatient clinic setting. Outcome measures were symptoms and peak flow diaries. 72 patients had diary data for analysis. Compared with placebo, addition of montelukast did not result in any significant change in symptom scores (mean difference between the last 7 days of each treatment period 0.05; 95% CI --0.86 to 1.14), rescue inhaled beta(2) agonist use (mean difference in puffs per day 0.41; -0.29 to 0.57), or twice daily peak expiratory flow (PEF) measurements (mean difference in morning PEF 1.18 L/min; -14.29 to 17.14), and mean difference in evening peak flow (-0.50; -17.42 to 12.86). When treatment response was defined as a 15% or greater increase in mean peak flow readings, there were four responders to montelukast and seven responders to placebo. Based on PEF data from our previous studies of a similar patient group we would have expected to detect changes of more than 5%. Used as additional therapy in a hospital outpatient clinic setting, montelukast did not provide such additional benefit in patients with moderate or severe asthma.

Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

BACKGROUNDTheophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to...

Bronchodilator tolerance and rebound bronchoconstriction during regular inhaled β -agonist treatment

There is uncertainty about the development of airway tolerance to β -agonists and the phenomenon of rebound bronchoconstriction on β -agonist withdrawal. We have recently completed a study of the regular terbutaline and budesonide treatment in asthma. We report our observations on the effect of starting and stopping terbutaline treatment on morning and evening peak flows.The study was a randomized four-way, double-dummy, cross-over comparison of regular inhaled terbutaline (500–1000 μ g four times daily), budesonide, combined treatment and matching placebo. Each treatment was given for 6 weeks following a 4 week single-blind placebo washout. Ipratropium was used for symptom relief. No other asthma medication was permitted during either the treatment or wash-out periods. Evaluable data were obtained from 52 subjects for both placebo and terbutaline treatment. Changes in mean morning and evening peak flows during terbutaline treatment were compared to the baseline peak flows during the last 2 weeks of the preceding washout. The peak flow changes on stopping terbutaline were also analysed.Mean morning peak flow was not significantly different during terbutaline treatment when compared to either baseline or placebo treatment. Evening peak flows were significantly higher during terbutaline treatment [mean increase 23·1l min−1(95%CI=18·8, 27·4)]. Analysis of the peak flow changes on a day-by-day basis revealed an initial increase in morning peak flows for the first 2 days of treatment of 19·2 and 13·4l min−1[increases of 25·0 and 17·3l min−1in comparison with the corresponding values during placebo (P<0·01)] followed by a return to baseline. The increase in evening peak flows was also greater for the first 2 days of treatment than for the remainder of the treatment period (P<0·01). On ceasing terbutaline treatment there was a fall in mean morning peak flow below the baseline on the following morning of 21·6l min−1(P<0·05 compared to placebo).The temporary increase in morning peak flows and greater than expected rise in evening peak flows for the first 2 days of treatment suggest the development of tolerance to the bronchodilator effect of terbutaline. Similarly, the fall in morning peak flows on treatment withdrawal suggests rebound bronchoconstriction. These effects are likely to be mediated by downregulation of the β -receptor during treatment. The clinical significance of these changes is uncertain in view of the stability of overall asthma control during terbutaline treatment, but sudden withdrawal of β -agonist treatment could conceivably lead to a deterioration in asthma control.

Budesonide for chronic asthma in children and adults.

Inhaled budesonide is a widely used inhaled corticosteroid for asthma. The objectives of this review was to compare the efficacy of budesonide with placebo in the treatment of chronic asthma. The Cochrane Airways Group Trial Register and reference lists of articles was searched. We contacted trialists for additional studies and searched abstracts of major respiratory society meetings (1997-1999). Randomised trials in children and adults comparing budesonide to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. 43 studies met the inclusion criteria (2801 subjects). In non-oral steroid treated asthmatics, budesonide led to significant improvements in a number of measures of airway function. These included FEV1, Weighted Mean Difference (WMD) 3.7% predicted (95% CI 0.1, 7.2%); improvement in morning peak flow (PEF) from baseline WMD 29 L/min (95% CI 22, 36 L/min); improvement in evening PEF from baseline WMD 21 L/min (95% CI 13, 29 L/min). Varying methods of reporting symptoms limited the pooling of studies but all high methodological quality studies demonstrated significant improvements compared to placebo. Health status was not reported. Risk of trial withdrawal due to asthma exacerbation was lower with budesonide compared to placebo, relative risk 0.17 (95% CI 0.09, 0.33). Doses of 500-800 mcg/d appeared to have slightly larger effect sizes than lower doses, but no advantage for high doses were apparent. A single high quality RCT reported significant reductions in daily prednisolone requirement and the number of patients able to discontinue prednisolone completely in budesonide treated subjects compared to placebo. No difference in risk of oropharyngeal soreness/hoarseness or oral Candidiasis was apparent for budesonide compared to placebo. Long-term risk of adrenal insufficiency was not reported. This review strongly supports use of budesonide in chronic asthma. Consensus guidelines for chronic asthma suggest titrating inhaled steroid dose to individual requirements. Evidence from this review of trials does not present a case for routine dose titration above 800 mcg/d.