A Low Cost Spacer Device Used for Asthma Treatment in a Calcutta Street Clinic to Improve Efficacy of Metered Dose Inhalers Comparison of two chamber devices in patients using a metered-dose inhaler with satisfactory technique. Comparison of Diskus inhaler, a new multidose powder inhaler, with Diskhaler inhaler for the delivery of salmeterol to asthmatic patients. Canadian Study Group. Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers. Patient satisfaction with the Diskhaler and the Diskus inhaler, a new multidose power delivery system for the treatment of asthma. Terbutaline by metered-dose inhaler: conventional inhaler versus tube spacer for children with asthma. Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma. Cost-effectiveness analysis of a dry powder inhaler (Turbuhaler) versus a pressurised metered dose inhaler in patients with asthma. A clinical comparison of beclomethasone dipropionate delivered by pressurised aerosol and as a powder from a rotahaler. Childhood asthma: improved efficacy of pressurized terbutaline aerosol by use of a 750-ml spacer. Compliance with inhaled medications: The relationship between diary and electronic monitor Importance of the inhalation device on the effect of budesonide. A device for overcoming discoordination with metered-dose inhalers. Results of the first U.S. double-blind, placebo-controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist. Measurement of children's asthma medication adherence by self report, mother report, canister weight, and Doser CT. Comparative lung delivery of salbutamol given via Turbuhaler and Diskus dry powder inhaler devices Influence of spacer device on drug delivery to young children with asthma. Comparison of a new multidose powder inhaler (Diskus/Accuhaler) and the Turbuhaler regarding preference and ease of use. Asthma management in indigenous children of a remote community using an indigenous health model. Relative efficacy of three different inhalers containing salbutamol in patients with asthma Treatment adherence among low-income children with asthma. Safety of hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol. Effects of treatment with formoterol on bronchoprotection against methacholine. Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in patients with asthma. Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma. The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction. Effect of multiple actuations, delayed inhalation and antistatic treatment on the lung bioavailability of salbutamol via a spacer device. Reduction of morbidity in asthmatic children given a spacer device. What are minimal important changes for asthma measures in a clinical trial? Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow-rates in asthmatic children. Questionnaire study of effect of sex and age on the prevalence of wheeze and asthma in adolescence Maximum bronchodilator effect of pirbuterol and procaterol administered as sprays with and without an aerochamber. A comparative study of the inhaled dry powders of salbutamol and fenoterol and their delivery systems. Clinical comparability of ventolin formulated with hydrofluoroalkane or conventional chlorofluorocarbon propellants in children with asthma. Importance of training for correct Turbuhaler use in preschool children Patient compliance in a clinical trial with inhaled budesonide in children with mild asthma. Evaluation of a new spacer device for drug inhalation Compliance in clinical trials of two nonbronchodilator, antiasthma medications. A comparison of terbutaline inhaled by Turbuhaler® and by a chlorofluorocarbon (CFC) inhaler in children with exercise‐induced asthma Aerosol treatment of bronchoconstriction in children, with or without a tube spacer. Evaluating the Outcome of Two Teaching Methods of Breath Actuated Inhaler in an Inner City Asthma Clinic Paper spacers coupled to metered dose inhalers in family practice. Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group. Comparable Bronchodilation with Hydrofluoroalkane-134a (HFA) Albuterol and Chlorofluorocarbons-11/12 (CFC) Albuterol in Children with Asthma Patient perception of the diskus inhaler: a comparison with the turbuhaler inhaler. Measuring health-related quality of life in patients with venous leg ulcers Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma. An assessment of a new breath actuated inhaler device in acutely wheezy children. A cost-effectiveness analysis of breath-actuated metered-dose inhalers. Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma. Budesonide treatment of moderate and severe asthma in children: a dose-response study. Variability of aerosol delivery via spacer devices in young asthmatic children in daily life. Comparison of bronchodilating effects of two salbutamol dry powder inhalers in asthmatic patients. Asthma drug adherence in a long term clinical trial Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy. Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. EDICI. Evaluation of the Autohaler actuator: the effect of written patient instructions on correct use. Effect of different inhaled bronchodilators on recovery from methacholine-induced bronchoconstriction in asthmatic children. Therapeutic Equivalence and Acceptability of Two Multidose Powder Inhalers in the Treatment of Asthma Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Prevention of Exercise-induced Bronchospasm in Pediatric Asthma Patients: A Comparison of Two Salmeterol Powder Delivery Devices Correlates of asthma morbidity in primary care. Reducing electrostatic charge on spacer devices and bronchodilator response. Home-made spacers for bronchodilator therapy in children with acute asthma: a randomised trial Lifestyle changes in mild asthma during intermittent symptom-related use of terbutaline inhaled via 'Turbohaler'. Proventil HFA prevents exercise-induced bronchoconstriction in children. Bronchospasmolytic effects of salbutamol as powder inhalation in patients with reversible bronchial obstruction. Clinical equivalence of salmeterol/fluticasone propionate in combination (50/100 microg twice daily) when administered via a chlorofluorocarbon-free metered dose inhaler or dry powder inhaler to patients with mild-to-moderate asthma. Equivalent asthma control after dose reduction with HFA-134a beclomethasone solution aerosol. Comparative Inhaled Steroid Investigation Group (CISIG). A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration. An intervention to improve the inhalatory technique of children and adolescents with asthma. Comparison of Bricanyl Turbuhaler and Ventolin Rotahaler in children with asthma. Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. Survey of unlicensed and off label drug use in paediatric wards in European countries Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group. Clinical comparison of Gentle-Haler Actuator and Aerochamber Spacer for Metered Dose Inhaler (MDI) use by asthmatics. Comparison of the effects on lung function of two methods of bronchodilator administration. Equivalence of asthma control with new CFC-free formulation HFA-134a beclomethasone dipropionate and CFC-beclomethasone dipropionate. Influence of inspiratory flow rate upon the effect of a Turbuhaler. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. Placebo-controlled, comparative study of the efficacy and safety of triamcinolone acetonide inhalation aerosol with the non-CFC propellant HFA-134a in patients with asthma. Azmacort HFA Clinical Study Group. Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine. Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma. Assessment of the ability of young children to use a powder inhaler device (Turbuhaler). Ease of handling and clinical efficacy of fluticasone propionate Accuhaler/Diskus inhaler compared with the Turbohaler inhaler in paediatric patients. UK Study Group. A systemic bioactivity comparison of double-strength and regular-strength beclomethasone dipropionate MDI formulations. How to use a rotahaler. Comparison of a new multidose powder inhaler with a pressurized aerosol in children with asthma. Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma. Treatment of asthma in pre‐school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. A double‐blind comparison between a new multi‐dose powder inhaler (Turbuhaler®) and metered dose inhaler in children with asthma [Maximum inspiratory flows in healthy children and asthmatics 4 to 8 years old. The implications for the inhalation of drugs in powder form]. Inhaled Terbutaline Administered via a Spacer Fully Prevents Exercise-Induced Asthma in Young Asthmatic Subjects: A Double-Blind, Randomized, Placebo-Controlled Study Dose response to inhaled terbutaline powder and peak inspiratory flow through Turbuhaler in children with mild to moderate asthma. Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children. Sodium cromoglycate via inhaler and Autohaler. A comparison of the bronchodilatory effect of 50 and 100 microg salbutamol via Turbuhaler and 100 microg salbutamol via pressurized metered dose inhaler in children with stable asthma. Albuterol treatment for children with asthma: a comparison of inhaled powder and aerosol. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Inhaled beclomethasone (BDP) with non-CFC propellant (HFA 134a) is equivalent to BDP-CFC for the treatment of asthma. Diskus and diskhaler: efficacy and safety of fluticasone propionate via two dry powder inhalers in subjects with mild-to-moderate persistent asthma. Comparison of preference and ease-of-use of breath-actuated inhalation devices in children. Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma. Effectiveness of inhaled bronchodilator delivery systems for elderly patients. Efficacy of salbutamol via Easyhaler unaffected by low inspiratory flow. Comparison of handling and acceptability of two spacer devices in young children with asthma Assessment of a new device (aerochamber) for use with aerosol drugs in asthmatic children.
INTRODUCTION Inhaled asthma therapy is clinical ly preferable , offering low therapeutic dose , rapid action onset and minimal side effects ' . The metered dose inhaler ( MDI ) is the cheapest , most commonly available inhaler device . However , some practitioners are reluctant to prescribe it since usage difficulties can limit benefits 2 . This is a particular problem amongst the young , the elderly , and when large patient numbers , language barriers or cultural obstacles make teaching and assessment of inhaler technique difficult . Spacer devices simplify inhaler technique , improving MDI e f f i ~ a c y ~ . ~ . Unfortunately , spacers may be costly and inaccessible . We describe the use of a soft drinks bottle as an effective , low cost , alternative spacer A r and omized clinical crossover trial was carried out to compare the use in the home , during 1-week periods , of two commercially available chamber devices ( the Aerochamber and the Spacer ) and a st and ard metered-dose inhaler ( MDI ) in 24 patients with reversible bronchospasm and satisfactory inhaler technique . Measurements of peak flow , forced expiratory volume in 1 second ( FEV1 ) , forced vital capacity ( FVC ) , ratio of FEV1 to FVC and forced midexpiratory flow rate were made immediately before and 15 minutes after inhalation of terbutaline sulfate . No difference was noted in results of spirometry , peak flow readings or side effects between the devices . The results of spirometry were better during the trial than immediately before it ( p less than 0.01 ) . The mean score for inhaler technique was significantly lower at follow-up than during the trial ( p less than 0.001 ) . The results suggest that in this population there is no advantage to using either a chamber device rather than an MDI or one chamber device rather than the other Administration of the long-acting beta 2-adrenoceptor agonist salmeterol from a new , easy-to-operate , multidose powder inhaler ( Diskus ) containing 60 sealed doses in a foil strip has been compared with administration from a Diskhaler inhaler in a multicenter , double-blind , double-dummy , parallel-group study . Asthmatic patients taking anti-inflammatory treatment , with baseline FEV1 > or = 60 % and < or = 90 % predicted were treated for 4 weeks with salmeterol 50 micrograms twice daily from either the Diskus or Diskhaler inhaler . The two treatments were equivalent ( 90 % CLs for the difference in mean morning PEFR : -2.2 , 8.7 L/min ) . The Diskus inhaler was rated easier to use and was preferred by more patients than the Diskhaler inhaler ( 73 % vs. 15 % ) AIM The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler ( pMDI ) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers . In addition , we aim ed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination . METHODS Particle size distribution and output from salbutamol pMDIs containing either CFC propellants ( Ventolin ) or HFA propellants ( Airomir ) were measured using a multistage liquid impinger ( MSLI ) and compared to that through both detergent-coated ( non-static ) or untreated ( static ) large volume ( Nebuhaler , Volumatic ) and small volume ( Aerochamber ) plastic spacers .  Flow-volume curves ( FEV1 ) were obtained from twelve asthmatic children with known significant bronchodilator response ( 8 males ) , aged 13 - 17 years , r and omly inhaling salbutamol from a CFC-pMDI through a static spacer  ( Nebuhaler ) and from  an HFA-pMDI through a non-static spacer  ( Nebuhaler ) . RESULTS In vitro output of particles in the respirable range ( < 6.8 microns ) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers . Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17 - 82 % . The mean ( SD ) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1 % ( 6.3 % ) compared to 17.5 % ( 7.9 % ) after inhalation from an HFA-pMDI through a non-static spacer ( p = 0.002 ) . CONCLUSIONS Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI . However , electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers , and can be reduced by soaking the spacer in a household detergent . Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response To evaluate patient satisfaction with two breath-actuated powder inhalers ( Diskhaler and Diskus ) , investigators asked patients to complete question naires as part of a r and omized , double-masked , double-dummy , placebo-controlled study of fluticasone propionate powder ( 500 mg twice daily ) in the treatment of chronic persistent asthma . At baseline , patients rated the importance of various inhaler attributes ( i.e. , ease of use , ease of loading with medication , ease of holding and operating , ease of cleaning , and ease of telling how many doses of medication are left ) . After 2 weeks of placebo and 6 and 12 weeks of active therapy , patients rated the inhalers on these same attributes . They also rated their general satisfaction with the inhalers and how comfortable they were using them . After 12 weeks , patients also rated the durability and convenience of carrying each device and were asked to indicate which they preferred . Data were available from 213 patients . All seven inhaler attributes measured were considered important by the majority of patients ( 71 % to 91 % ) , contributing to the validity of the patient-rated performance assessment s. After 12 weeks of use , 57 % to 88 % of patients expressed a high level of satisfaction with the performance of the Diskhaler on all attributes ; a high level of overall satisfaction ( 72 % ) and comfort ( 79 % ) was reported with this inhaler . Patients rated the performance of the  Diskus inhaler  very favorably , with 76 % to 96 % expressing a high level of satisfaction on all attributes ; a high level of overall satisfaction ( 87 % ) and comfort ( 85 % ) was reported with this inhaler . At end point , 61.4 % preferred the Diskus inhaler , 25.4 % preferred the Diskhaler inhaler , and 13.2 % expressed no preference . These breath-actuated powder inhalers may be acceptable alternatives to traditional metered-dose inhalers for the treatment of patients with asthma We compared terbutaline administered through an 80-mL , 10 X 3.2-cm tube spacer versus a conventional metered-dose inhaler in 34 asthmatic patients , aged 8 to 16 years . In this double-blind , single-dose study , three groups of children ( spacer active , conventional active , and placebo )  were assessed clinical ly and with spirometry before and at one-half hour intervals for two hours after therapy . One investigator taught inhaler use and monitored patients ' errors in technique . Compared with placebo , terbutaline delivered by either the tube spacer or the conventional inhaler significantly improved pulmonary function from one-half to two hours after treatment . Both the spacer and conventional inhaler were equally effective in improving pulmonary function from the baseline state . Only 4/34 ( 11.7 % ) children used both inhalers without any error . Adverse effects were mild , transient , and infrequent and did not differ between the groups . Terbutaline aerosol , whether delivered by the tube spacer or conventional actuator , provides effective bronchodilation for children with asthma , in spite of frequent errors in technique of inhaler use We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler , the Turbuhaler , or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age . The bronchodilator response did not differ between the two inhalational devices . The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used In an open r and omised parallel-group study , 1004 patients with asthma in 7 countries were r and omised to receive asthma treatment via 2 different kinds of inhalers : an aerosol pressurised metered dose inhaler ( pMDI ) and a dry powder inhaler ( Turbuhaler ) . The patients were treated for 52 weeks with inhaled corticosteroids and /or inhaled beta 2-agonists . All patients were considered adequately treated with inhaled corticosteroids and /or inhaled beta 2-agonists via pMDI before inclusion in the study . Healthcare utilisation variables were attached to the case record forms of the patients , thus making an economic analysis possible . Because of the difficulty of comparing costs between countries , each country was analysed separately . Canadian patients constituted the largest sub population ( 445 patients ) and were therefore used in this analysis . From the analysis , we concluded that the effectiveness of treatment ( measured as the number of exacerbations and days with exacerbation ) was significantly better for patients treated via Turbuhaler than via a pMDI ( p = 0.03 ) . Furthermore , the total annual costs of treatment were , on average , $ Can331 less ( p < 0.01 ) for patients using Turbuhaler than for those using a pMDI ( mainly due to lower costs for hospitalisation and medication ) . The cost differences between inhaled corticosteroids and inhaled beta 2-agonists were significantly in favour of treatment via Turbuhaler ( p < 0.01 ) . Thus , the results of this study suggest that treatment via Turbuhaler is a cost-effective strategy in patients with asthma in Canada 14 children with severe asthma were studied for 2 months in a double-blind cross-over trial to compare the efficacy of beclomethasone dipropionate delivered as an aerosol and as a powder from a rotahaler . Inhalation via the aerosol was satisfactory in 13 patients , each of whom used the rotahaler correctly . Younger children preferred to use the rotahaler . Comparison of daily symptoms , twice daily peak expiratory flow rate ( PEFR ) , and use of salbutamol  during the 2 months of the trial showed that control of asthma was equally good , irrespective of the device used to deliver active beclomethasone A bronchodilator aerosol , terbutaline sulphate , was administered to 18 asthmatic children , mean age 8.0 years ( range 4.9 - 13.7 years ) in a cross-over trial using either a common actuator or a 750-ml collapsible spacer . With the spacer , peak expiratory flow rate was significantly higher ( p less than 0.05 ) at 5 , 20 , and 60 min after administration of 0.25 mg terbutaline sulphate . The mean maximum value during this period was 92 % of the predicted normal value with the spacer compared to 86 % with the common actuator . The difference was significant ( p less than 0.01 ) . This study confirms previous findings that a 750-ml spacer is beneficial in bronchodilator aerosol therapy in children with asthma Self-report is a frequently-used method of assessing compliance with prescribed medications in patients with chronic illnesses . Most research ers agree , however , that self-report misrepresents patient adherence to regimen prescription . In this r and omized , controlled study evaluating inhaler medication compliance , diary data was compared to electronic monitoring in 55 adults with asthma . Subjects r and omized to the treatment group received a six-week self-management program . An electronic monitor , the MDI Chronolog , was used in this study to assess inhaler use . The MDI Chronolog records the date and time of each inhaled activation . The self-report measure used was a daily asthma diary . Subjects were asked to use their inhaled medications as usual and record the date and time they administered their medication over a one-week period . Moderate correlations ( rs=.55 , Mdnd=95.8 , Mdnc=91.6 ) were found when comparing the number of administrations calculated using the MDI Chronolog to the number of administrations reported in the subject ’s diary . When the dosing interval was examined , however , the correlation was weaker ( rs=.44 , Mdndiary=92.8 , Mdnchronolog=37.5 ) . In each case , self-reported compliance was higher than monitored adherence Two hundred and forty one children with chronic perennial asthma , who had been treated with budesonide via a metered dose inhaler with a spacer device ( Nebuhaler )  , had their normal dose of budesonide reduced by 50 % to determine if they had been overtreated . Within three weeks , asthma control deteriorated in 126 patients to such an extent that budesonide had to be increased to the normal dose . After stabilising their asthma , these children were enrolled in a r and omised , double blind , double dummy , parallel study , performed to compare the effect of budesonide via Nebuhaler with that of half the dose of budesonide via Turbuhaler . The study started with a two week run-in during which patients were treated with their normal dose of budesonide via Nebuhaler . After run-in , 64 children were r and omised to treatment with their normal budesonide treatment and the remaining 62 children to treatment with half their normal dose via Turbuhaler for nine weeks . Throughout the study , patients recorded asthma symptoms , peak flow measurements , and beta 2 agonist use in a diary . Pulmonary function tests , exercise tests , and 24 hour urine sample collection s were performed at hospital visits during run-in and the study period . Apart from beta 2 agonist use , which was significantly lower for patients on Turbuhaler treatment than on Nebuhaler treatment , there were no differences between the groups in any of the parameters studied during run-in or during the study period . Furthermore , there was no trend of deterioration in asthma control when the dose of budesonide was reduced by 50 % when Turbuhaler was the inhalation device . It is concluded that budesonide via Turbuhaler is more effective than via Nebuhaler in the treatment of asthma . Based on this finding , attempts should be made to reduce the dose of budesonide when patients are switched from Nebuhaler to Turbuhaler treatment BACKGROUND Despite widespread acceptance of metered-dose inhalers ( MDIs ) in the treatment of asthma , many patients fail to operate these devices correctly . Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy . METHODS We evaluated Autohaler Inhalation Device ( 3 M Pharmaceuticals , St. Paul , Minn. ) , a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec . We compared bronchodilator effect of pirbuterol acetate ( Maxair ) , inhaled from Autohaler and a st and ard MDI , under conditions that ensured optimal technique in 20 patients with asthma . Spirometric variables ( forced expiratory volume in 1 second [ FEV1 ] , forced expiratory flow between 25 % and 75 % of vital capacity [ FEF25 - 75 ] , forced vital capacity [ FVC ] ) were measured before and at 15 , 30 , 60 , and 90 minutes after two inhalations of full inspiratory reserve volume for each device . RESULTS Both devices produced significant and similar bronchodilation . Mean FEV1 increased 32 % above baseline 60 minutes after use of Autohaler and 31 % after use of a st and ard MDI . Similar changes were noted in FEF25 - 75 and FVC for the two devices . Differences between devices for all spirometric variables were not statistically significant . CONCLUSION Autohaler provides a promising alternative to the st and ard MDI by overcoming breath-h and discoordination Pranlukast ( SB 205312 ; ONO-1078 ) , a potent , orally active selective cysteinyl-leukotriene receptor antagonist ( LTRA ) , was developed in Japan for the treatment of asthma . This article reports results of the initial U.S. clinical evaluation of pranlukast . The primary objective of this multicenter study was to evaluate the safety and tolerability of pranlukast administered at doses of 337.5 mg b.i.d . and 450 mg b.i.d . in 65 patients with mild to moderate asthma .  Pranlukast , a novel LTRA , is safe and well tolerated at doses of 337.5 mg b.i.d . and 450 mg b.i.d . Pranlukast has demonstrated clinical activity in patients with asthma BACKGROUND Accurate assessment of medication adherence has been difficult to achieve but is essential to drug evaluation in clinical trials and improved outcomes in clinical care . OBJECTIVE This study was conducted to compare four adherence assessment methods : child report , mother report , canister weight , and electronic measurements of metered dose inhaler ( MDI ) actuation . METHODS Participants included 27 children with mild-to-moderate asthma who were followed prospect ively for 6 months . All patients used an MDI equipped with an electronic Doser attached to their inhaled steroid . At each 2-month follow-up visit , Doser and canister weight data were recorded , while child and mother were interviewed separately regarding medication use . RESULTS Children and mothers reported , on average , over 80 % adherence with the prescribed inhaled steroid . Canister weight revealed , on average , adherence of 69 % , significantly lower than self-report . When adherence recorded by the electronic Doser was truncated to no more than 100 % of prescribed daily use , average adherence was 50 % . Older children and adolescents , nonwhite children , and those from poorer functioning families were least adherent . CONCLUSIONS Electronic adherence monitoring was significantly more accurate than self-report or canister weight measures . Such accuracy is an essential prerequisite to increasing underst and ing of the treatment , setting , and patient factors that influence adherence , and to the consequent design of effective intervention strategies Abstract Objective : The environmental concerns surrounding the use of chlorofluorocarbons ( CFC ) have led to a resurgence of interest in dry powder inhaler devices . The aim of our study was to compare two commonly used dry powder inhaler devices , namely the Turbuhaler and Diskus . Methods : Eight healthy volunteers with a mean ( SEM ) age of 21 years ( 0.8 ) were studied using a r and omised single-investigator blind crossover design . Single doses of 1.2 mg salbutamol as Turbuhaler ( 12 × 100 μg ) and Diskus ( 6 × 200 μg ) were administered over 6 min . Mouth rinsing was performed after every inhalation . Lung delivery from each device was assessed by measuring the early plasma salbutamol profile at 5 , 10 , 15 and 20 min after inhalation . Results : Significant differences in lung delivery were found between the Diskus and the Turbuhaler for salbutamol Cmax 3.21 vs 4.04 ng · ml−1 , respectively and Cav 2.65 vs 3.73 ng · ml−1 , respectively . This amounted to a 1.28-fold difference ( 95 % CI 1.09 to 1.45 ) between these devices for Cmax and a 1.42-fold difference ( 95 % CI 1.57 to 1.66 ) for Cav . Conclusion : We have demonstrated that , in vivo , the Turbuhaler dry powder inhaler produces significantly greater lung delivery of salbutamol than the Diskus . This illustrates that dry powder inhaler devices may have different in vivo deposition characteristics The budesonide dose delivered to the patient from three different spacer devices ( Nebuhaler = 750 ml , Aerochamber = 140 ml , and Babyspacer = 260 ml ) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient . Twenty children aged 10 - 25 months were given a single dose of 200 micrograms budesonide from each spacer device in a r and omised crossover study . All spacers had a facemask attached and a one way valve system . The children breathed through the inhalation system for 30 seconds . Furthermore , the minute ventilation of the children through a tightly fitting facemask was measured . The filter dose of budesonide  was significantly lower after Aerochamber treatment ( 39.4 micrograms , range 19 - 67 micrograms ) than after Nebuhaler ( 53.5 micrograms , range 34 - 88 micrograms ) and Babyspacer ( 55.5 micrograms , range 39 - 76 micrograms ) treatment . The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min ( mean 5.0 l/min ) . This was sufficient to empty all spacers within the 30 seconds of inhalation . It is concluded that spacer volume does not seem to be so important for children aged 10 - 25 months as long as spacers with a volume lower than 750 ml are used Many patients with asthma or chronic obstructive pulmonary disease ( COPD ) use their inhaler ineffectively . Several studies revealed that inhaler-specific design features contributed significantly to the failure rate , which clearly demonstrates the need for developing more " foolproof " inhalers . This study compared ease of use and patient preference of the Diskus/Accuhaler ( DA ) with the Turbuhaler ( TH ) .  Fifty patients with asthma or COPD aged 15 years and older were included in a r and omized , crossover comparison of DA with TH regarding patient preference and ease of use . All had to be naïve to DA and TH , but currently had to be using inhaled medication with another device . Inhalation technique was assessed using inhaler-specific checklists and patients had to state a preference for DA or TH regarding various aspects , as well as overall preference . With DA 46 patients ( 92 % ) made no errors regarding essential inhalation maneuvers , compared to 37 patients ( 74 % ) using TH ( p = 0.023 ) . This difference is exclusively caused by not loading the TH properly . When patients were asked which inhaler they would prefer , 17 wanted the DA , 25 the TH , and 8 did not state a preference . The difference was not significant . TH was favored over DA regarding factors related to size and the number of available dosages . The counting mechanism of the DA was preferred over the TH . It seems that patients have a clear , although not statistically significant , preference for TH , but with the DA fewer patients make crucial errors OBJECTIVE To describe the management of  asthma in children in a remote indigenous community and the delivery of subspecialist service through the indigenous health-care model . METHODOLOGY Children referred by indigenous health-care workers were evaluated prospect ively by paediatric respiratory physicians , based on a st and ardized protocol , at a primary health care setting at Thursday Isl and , Queensl and . RESULTS Forty of the 54 children referred with a provisional diagnosis of asthma did have asthma , with 30 % having persistent asthma . Only 59 % of parents knew the dose of the medication prescribed and 80 % had minimal knowledge of the medications . In 88 % of children , the management of asthma was improved by introduction of an appropriate spacer device and changing the dose and type of medications . CONCLUSIONS The management of children with asthma in the Torres region can be improved substantially by the use of age appropriate delivery devices and medications , and improving knowledge of asthma . Specialist delivery service to remote indigenous communities can be effectively delivered in partnership with the indigenous health service . The high proportion of persistent asthma in the Torres Straits community in comparison to urbanised Australia raises issues of inequity of appropriate medical service delivery to remote indigenous communities Objective : To investigate the relative efficacy of three inhalers containing salbutamol : Turbuhaler ( TBH ) , Rotahaler ( RH ) and Diskhaler ( DH ) . Methods : A r and omized , open , three-way crossover , cumulative dose response study was performed in 20 patients with asthma with mean forced expiratory volume in 1s ( FEV1 ) values of 60 % of predicted ( range 41–90 % ) and a 27 % reversibility in FEV1 ( range 15–61 % ) . Four doses of salbutamol were inhaled at 30-min intervals : 50 μg , 50 μg , 100 μg and 200 μg by TBH and 200 μg , 200 μg , 400 μg and 800 μg by both RH and DH  . FEV1 was measured at baseline and 25 min after each dose . Results : The increases in FEV1 after the first doses ( 50 μg by TBH , 200 μg by RH and by DH ) were not statistically significantly different ( 23.6 % , 25.1 % and 28 % , respectively ) . Based on the parallel shift in the dose response curves , salbutamol TBH was calculated to be 2.4 times as potent as salbutamol RH ( 95 % confidence interval 1.4–3.3 ) and 2.2 times as potent as salbutamol DH ( 90 % CI 1.3–3.3 ) . Additionally , during dosing with TBH , fewer patients experienced adverse events than during dosing with RH or DH . Conclusion : Turbuhaler is a twofold more efficient inhaler for salbutamol than Rotahaler or Diskhaler as measured by its bronchodilating effect OBJECTIVE To investigate the adherence behaviors ( MDI use , MDI/spacer technique , appointment attendance , smoking in the home ) of low-income , urban , primarily African American children with asthma . METHOD Participants were 55 children ages 6 to 17 with moderate to severe asthma . Adherence to MDI anti-inflammatory agents was estimated primarily from canister weight at the follow-up appointment . RESULTS The mean use of MDI medication was 44 % of prescribed use , with 27 % of subjects demonstrating MDI/spacer technique likely to prevent drug delivery . Almost half reported that household members smoked cigarettes , and 21 % missed scheduled follow-up appointments . CONCLUSIONS These findings have implication s for how clinicians should assess and improve adherence Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate ( BDP ) which uses the propellant hydrofluoroalkane-134a ( HFA ) for the treatment of asthma .  Acute local tolerability ( as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation ) was similar for both BDP and placebo formulated in either chlorofluorocarbon ( CFC ) or HFA propellants . A total of 43 patients were treated with  HFA-BDP  ( 0 , 200 , 400 or 800 micrograms day-1 ) or CFC-BDP ( 800 micrograms day-1 ) for 14 days and their 24 h urinary free cortisol ( UFC ) excretion and response to cosyntropin stimulation were measured . There was no difference in UFC between any of the doses of HFA-BDP and CFC-BDP . Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient . Two large 12 week phase III trials compared HFA-placebo , HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 ( n = 347 ) , and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 ( n = 233 ) . For HFA-BDP at either dose , CFC-BDP 800 micrograms day-1 and HFA-placebo , the number of patients with morning plasma cortisol concentrations below normal was less than 4.4 % but was 14.6 % for CFC-BDP 1500 micrograms day-1 . The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups ( P = 0.012 ) . The data indicate that , at doses of up to 800 micrograms day-1 , HFA-BDP is at least as well tolerated as CFC-BDP . Other studies have found that equivalent efficacy is reached at lower doses of HFA-BDP than CFC-BDP . Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk : benefit ratio than CFC-BDP when used at the recommended lower doses PURPOSE In addition to their bronchodilatory effects , beta(2)-agonists protect against bronchoconstriction , such as that caused by methacholine challenge . However , tachyphylaxis to this beneficial effect develops after chronic use of beta(2)-agonists . We studied whether the frequency or dose of treatment with a long-acting beta(2)-agonist ( formoterol ) affects the degree of bronchoprotection afforded against methacholine challenge and to compare this with the effects of a short-acting beta(2)-agonist ( terbutaline ) . PATIENTS AND METHODS In a r and omized , parallel group , double-blind study at two centers , patients with stable asthma of mild to moderate severity who were treated with inhaled corticosteroids were treated with formoterol 6 micrograms twice daily , 24 micrograms twice daily , 12 micrograms once daily ; terbutaline 500 micrograms four times daily ; or placebo . Treatments were given by dry powder inhaler for a period of 2 weeks . Of the 72 patients who were enrolled , 67 completed the study . Methacholine challenge was performed to calculate the provocative dose that caused a 20 % fall in forced expiratory volume in 1 second at baseline ( unprotected ) after an initial 1-week run-in without beta(2)-agonists , 1 hour after the first dose of study treatment , and again 1 hour after 7 and 14 days of study treatment . RESULTS Each of the four active treatments exhibited significant tachyphylaxis ( P < 0.05 ) to protection against methacholine challenge when comparing first/last dose ( as geometric mean protection ratio versus baseline ) : formoterol 24 micrograms twice daily ( 9.6-fold/1.6-fold ) , 12 micrograms once daily ( 7.1-fold/2.2-fold ) , 6 micrograms twice daily ( 6.2-fold/2.3-fold ) , and terbutaline 500 micrograms four times daily ( 2.9-fold/2.0-fold ) . There were no significant differences among treatments after 2 weeks in bronchoprotection against methacholine challenge . For all formoterol regimens , the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period . Diurnal control of morning and evening peak flow was significantly better with formoterol 24 micrograms twice daily than with terbutaline . CONCLUSIONS Tachyphylaxis to bronchoprotection against methacholine challenge develops after 2 weeks of therapy with formoterol , a long-acting beta(2)-agonist , at all three dosage regimens that were tested . In contrast , the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment BACKGROUND Environmental imperatives to eliminate the use of chlorofluorocarbon ( CFC ) propellants in metered-dose inhalers have led to the development of metered-dose inhalers with the hydrofluoroalkane ( HFA-134a ) propellants . OBJECTIVES To evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and to compare the efficacy and safety of Ventolin CFC , Ventolin HFA , and placebo in patients with asthma . METHODS Multicenter , double-blind , r and omized safety and efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus placebo for 12 weeks in 313 patients with asthma aged 12 years and older who received Ventolin CFC during a 3-week run-in period . RESULTS Patients who were switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and other measures of asthma control at levels comparable with run-in baseline . Serial pulmonary function testing demonstrated that both Ventolin treatments had significantly greater mean improvement in FEV1 over baseline than the placebo group at treatment day 1 and weeks 6 and 12 ( P < .001 ) . Both Ventolin groups had comparable pulmonary function at every visit . Predose FEV1 values were maintained or improved over time with all treatments . Treatments were well-tolerated . The adverse event profile for both Ventolin treatments was comparable with placebo . No clinical ly relevant effects on ECG , vital signs , or clinical laboratory tests were noted . Asthma exacerbation rates were 4 % to 5 % in the Ventolin groups and slightly higher ( 8 % ) in the placebo group . CONCLUSIONS Patients who were switched from Ventolin CFC to Ventolin HFA  maintained comparable asthma control with a similar safety profile BACKGROUND Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children . However , data regarding therapy with this class of compounds , especially in children under age 6 years , is limited . Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index . Few large prospect i ve clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children . OBJECTIVE We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma . METHODS Fluticasone propionate powder ( 50 microg or 100 microg twice daily ) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children ( 4 to 11 years old ) with persistent asthma for 12 weeks in a r and omized , double-blind , parallel-group , multi-center trial . Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone . RESULTS Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 ( mean increase from baseline of 0.22 to 0.24 L ; p < or = 0.023 ) , clinic morning peak expiratory flow ( mean increase from baseline of 48 to 55 L/min ; p < or = 0.006 ) , patient-measured morning ( p < or = 0.001 ) and evening ( p < or = 0.003 ) peak expiratory flow , and asthma symptom scores ( in all but the 50 microg Diskus group ; p < or = 0.036 ) , as well as reduced albuterol use ( p < or = 0.002 ) and nighttime awakenings ( p < or = 0.019 ) at endpoint . Efficacy parameters were not significantly different between the two doses with either device . More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group ( p < 0.001 ) . Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion . Adverse events were primarily pharmacologic effects of inhaled corticosteroids , and those related to the study drug occurred with low frequency . Patient satisfaction with both the Diskus and Diskhaler devices was high , with a majority of patients ( > 80 % ) rating them favorably . CONCLUSION This study demonstrated that fluticasone propionate powder , at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler , was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone STUDY OBJECTIVE To determine the protective effect of salbutamol , 100 microg , inhaled by different devices ( pressurized metered-dose inhaler [ pMDI ; Ventolin ; GlaxoWellcome ; Greenford , UK ] , pMDI + spacer [ Volumatic ; GlaxoWellcome ] , or breath-activated pMDI [ Autohaler ; 3 M Pharmaceuticals ; St. Paul , MN ] ) on bronchoconstriction induced by methacholine . DESIGN R and omized , double-blind , cross-over , placebo-controlled study . PATIENTS Eighteen subjects with stable , moderate asthma , asymptomatic , receiving regular treatment with salmeterol , 50 microg bid , and inhaled beclomethasone dipropionate , 250 microg bid , in the last 6 months , with high hyperreactivity to methacholine ( baseline provocative dose of methacholine causing a 20 % fall in FEV(1 ) [ PD(20 ) ] geometric mean [ GM ] , 0.071 mg ) . Subjects were classified into two groups : subjects with incorrect ( n = 5 ) pMDI inhalation technique , and subjects with correct ( n = 13 ) inhalation technique . METHODS AND MEASUREMENTS After cessation of therapy for 3 days , all subjects underwent four methacholine challenge tests , each test 1 week apart , each time 15 min after inhalation of salbutamol , 100 microg ( via pMDI , pMDI + spacer , or Autohaler ) , or placebo . The protective effect on methacholine challenge test was evaluated as the change in the PD(20 ) , and expressed in terms of doubling doses of methacholine in comparison with placebo treatment . RESULTS The PD(20 ) was significantly higher after salbutamol inhalation than after placebo inhalation , but no significant difference was observed among the three different inhalation techniques . Only when salbutamol was inhaled via pMDI + spacer , PD(20 ) was slightly but not significantly higher ( pMDI GM , 0.454 mg ; pMDI + spacer GM , 0.559 mg ; and Autohaler GM , 0.372 mg ; not significant [ NS ] ) than other inhalation techniques . Similar results ( mean + /-SEM ) were obtained with doubling doses of methacholine ( pMDI , 2 + /- 0.47 ; pMDI + spacer , 3 + /- 0.35 ; and Autohaler , 2.4 + /- 0.40 ; NS ) . No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered . CONCLUSIONS Our data show that the protective effect of salbutamol , 100 microg , on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques , although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol . These data confirm the clinical efficacy of salbutamol , whatever the device , and the patient 's inhalation technique BACKGROUND : The aim of this study was to extend previous in vitro observations regarding the effects of multiple actuations of aerosols into spacer devices , delayed inhalation , and antistatic treatment of spacer devices on the amount of drug delivered for inhalation . An in vivo study of lung bioavailability of salbutamol from a large volume ( Volumatic ) spacer was conducted . METHODS : Ten healthy volunteers of mean age 20.5 years with a mean forced expiratory volume in one second of 112.1 % predicted were studied in a r and omised single blind ( investigator blind ) crossover study . 1200 micrograms of salbutamol was given with mouth rinsing ( 100 micrograms/puff ) on four study days : single puffs via spacer , multiple puffs via spacer ( 3 x 4 puffs ) , single puffs with 20 second delay before inhalation via spacer , and single puffs via an antistatic treated spacer . All spacers , including those treated with antistatic , were prewashed prior to each study day . Measurements of lung bioavailability were made at five , 10 , and 20 minutes after inhalation to determine peak ( Cmax ) and average ( Cav ) plasma salbutamol levels . Systemic beta 2 responses including finger tremor , heart rate , and plasma potassium levels were also evaluated . RESULTS : Single puffs from the spacer produced higher plasma salbutamol levels and greater systemic beta 2 responses than either multiple puffs or single puffs with delayed inhalation for a 1200 micrograms dose . For Cmax this amounted to a 1.93-fold ( 95 % CI 1.68 to 2.19 ) greater lung bioavailability for single puffs than for multiple puffs and a 1.80-fold ( 95 % CI 1.59 to 2.00 ) greater lung bioavailability for single puffs than for single puffs with a 20 second delay . Comparison of the normal and antistatic treated spacers ( both prewashed ) revealed differences for Cmax with levels 1.23-fold ( 95 % CI 1.04 to 1.41 ) greater for the normal spacer . CONCLUSIONS : Delayed inhalation from a Volumatic spacer and the use of multiple puffs results in a considerable decrease in the delivery of salbutamol to the lungs with an approximate twofold reduction in lung bioavailability . Washing a Volumatic spacer is as effective as an antistatic lining in reducing the effects of static charge on salbutamol delivery in vivo STUDY OBJECTIVE To evaluate whether providing a spacer device and a single , brief demonstration regarding its proper use would result in earlier resolution of asthma symptoms , improved school attendance , and decreased frequency of unscheduled medical visits for asthma among children receiving noncontinuous care in an urban emergency department ( ED ) . DESIGN R and omized controlled trial . SETTING Urban hospital pediatric ED . PARTICIPANTS Eighty-four children with the chief complaint of asthma . INTERVENTION Children were enrolled in the ED at the time of an asthma attack and r and omly assigned to one of two treatment groups . The spacer group received an inhaled beta-agonist at discharge from the ED with a spacer device . The control group received inhaled or oral beta-agonists without a spacer device . Both groups received other medications at the discretion of the evaluating physician who was not the interviewer in any case . A baseline question naire was completed and follow-up by telephone was done at 1 week , and 2 , 4 , and 6 months after enrollment . MEASUREMENTS AND RESULTS The spacer group reported significantly earlier resolution of wheezing ( 0 days vs 2 days , p < 0.01 ) at the 2- and 4-month follow-up assessment s. They reported significantly fewer days of cough after an asthma attack at 2 months ( 1 day vs 3 days , p < 0.01 ) and 4 months ( 0 days vs 3 days , p < 0.01 ) . The spacer group missed significantly fewer days of school following an asthma attack at 2 and 4 months ( 0 days vs 2 days , p = 0.05 ) . There was no difference between the two groups on any outcome measures at the 1-week and 6-month follow-up assessment s. CONCLUSIONS Introducing a spacer device to patients in a busy , inner-city pediatric ED is an effective and efficient intervention that improves the functioning of asthmatic children in terms of resolution of cough and wheeze and school absenteeism In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist .  Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change In vitro studies with the Diskus inhaler at low and high flow rates show consistent doses of drug as fine particles < 4.7 microm . The present study was design ed to ascertain whether this in vitro flow independency translates into flow-independent clinical effect when the device is used by patients at low ( 30 L x min[-1 ] ) and high ( 90 L x min[-1 ] ) flow rates . A pilot study in 129 children aged 3 - 10 yrs demonstrated that 99 % of children of 3 yrs and above can generate a flow > or = 30 L x min(-1 ) through the device , while 26 % performed > or = 90 L x min(-1 ) . Eighteen children aged 8 - 15 yrs with exercise induced asthma inhaled placebo or salmeterol 50 microg at either 30 L x min(-1 ) or 90 L x min(-1 ) . Exercise challenges were carried out 1 h and 12 h after dosing . The maximum percentage fall in forced expiratory volume in one second ( FEVI ) after exercise 12 h after treatment was significantly less after salmeterol at either flow rates as compared to placebo . There was no significant difference in the protection from salmeterol on the day of low-flow inhalation versus the day of high-flow inhalation . Consistent in vitro fine particle dosing from the Diskus inhaler translates into a consistent clinical effect at low and high flow rates in children In early childhood  wheezing and asthma are more common in boys than girls.1 This difference has either disappeared or reversed by early adulthood,2 although the age at which the change occurs is unclear . We therefore measured the age and sex specific prevalence of self reported wheeze and diagnosed asthma in 11 - 16 year old children attending secondary schools in the Nottingham area . In 1996 we completed a  prevalence survey of all pupils attending 44 secondary schools in a defined postcode area in and around Nottingham .  Question naires about lifetime and current wheeze and asthma diagnosed  by a doctor ( Appendix ) were distributed to pupils for self completion during school time . Data were collected on 27 826 pupils ( over 80 % of registered pupils ) aged 11 - 16 years , 51 % of whom were boys . Parental responses to the same questions were obtained for a 1 in 4 r and om sub sample of 3894 pupils ( 59 % response ) . The self reported lifetime prevalence of wheeze was 30.1 % ( 8317/27 632 ) , with 19.0 % OBJECTIVE OF THE STUDY To determine the maximal bronchodilator dose of procaterol and pirbuterol administered by inhalation with an without an aerochamber ( Aerocâmera ) to children with acute bronchial asthma attacks . TYPE OF STUDY Prospect i ve . 18 children ( 6 - 15 years of age ) with acute bronchial asthma attacks ( FEV1 < 80 % of the predicted value ) received pirbuterol ( N = 10 ) or procaterol ( N = 8) by metered-dose inhaler , one puff every 5 minutes , for a total of five doses . During another acute attack , the same patient received the same medication with the aid of a spacer ( Aerocâmera ) . Clinical evaluation and pulmonary function tests were performed 5 minutes after each inhaled dose . RESULTS For both drugs , maximal bronchodilation was obtained after the second dose . No significant side effects were observed even after procaterol doses of 50 micrograms or pirbuterol doses of 1000 micrograms . The results were unaffected by the use of the spacer . CONCLUSIONS The doses that induced maximal bronchodilation were 400 micrograms pirbuterol and 20 micrograms procaterol . Although the spacer did not change the results , it is a valuable aid for patients who have difficulty in using the metered-dose inhaler ( M.D.I. ) A study was design ed to establish whether there was a difference in response to inhaled salbutamol powder ( 400 micrograms ) and fenoterol powder ( 200 micrograms ) and whether the specific inhaler devices were a contributing factor . In the study of 40 children no significant difference could be attributed to the devices , but the salbutamol treated group had a marginally better response in two parameters of lung function BACKGROUND Aerosolized asthma medications with chlorofluorocarbon ( CFC ) propellants are being phased out because of environmental concerns about the ozone layer . Medications are being reformulated with non-ozone-depleting propellants . OBJECTIVE To evaluate the clinical comparability of albuterol sulfate formulated in a new hydrofluoroalkane-134a ( HFA ) propellant ( Ventolin HFA Inhalation Aerosol ) , and conventional CFC-containing albuterol ( Ventolin Inhalation Aerosol ) in children with asthma . DESIGN R and omized , double-blind , placebo-controlled 2-week clinical trial with a 1- to 2-week run-in period . During the run-in , patients took Ventolin CFC as needed . Patients ( n = 135 ) aged 4 to 11 years with asthma then were assigned r and omly to treatment with Ventolin HFA , Ventolin CFC , or placebo administered 4 times daily via metered-dose inhaler for 2 weeks . All patients were allowed rescue albuterol use in matching propellant as needed for relief of breakthrough symptoms . The main outcome measure was the mean percentage of predicted peak expiratory flow ( PEF ) after the morning dose of study drug on day 1 and after 2 weeks as assessed by results of 6-hour serial tests . RESULTS At day 1 , the mean ( + /- SE ) percentage of predicted PEF increased postdose by 14 % ( + /- 1 % ) in the Ventolin HFA group and 13 % ( + /- 1 % ) in the Ventolin CFC group compared with 6 % ( + /- 2 % ) in the placebo group ( P</=.006 ) . At week 2 , mean postdose increases were 11 % ( + /- 1 % ) in the Ventolin HFA and CFC groups compared with 5 % ( + /- 1 % ) in the placebo group ( P<.001 ) . There were no significant differences between the Ventolin HFA and CFC groups in postdose increases in pulmonary function , time to onset of response , duration of response , or peak effects . Safety profiles were similar among the 3 groups . CONCLUSION Ventolin HFA is clinical ly comparable to Ventolin formulated with the conventional CFC-containing propellant when administered to children with asthma . Arch Pediatr Adolesc Med . 2000;154:1219 - 1225 Aim : To study the impact of both audiovisual information and nurse‐training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler . Design : A single‐blind , r and omized , parallel‐group trial studied 72 children aged 3–5 y. All children and their parents were shown an instructional video and given written instruction . After this , peak inspiratory flow ( PIF1 ) through Turbuhaler was measured . Children in group A ( n= 36 ) then received individual training by a nurse while those in Group B ( n= 36 ) did not and PIF2 was measured . Afterwards , Group B received similar individual training while Group A received no additional training , and PIF3 was measured . Group A was given a placebo Turbuhaler and encouraged to practice at home . Two weeks later , both groups returned to the clinic where PIF4 was measured . Results : The number of children who were able to correctly perform PIF1 , PIF2 and PIF4 in Group A was 27 , 34 and 36 , respectively . The corresponding numbers for Group B were 30,29 , and 29 . No effect of training was seen in 3‐y‐old children .  Individual training by a nurse was associated with a statistically significant increase inPIF2 ( 10l/min;p= 0:014 ) . Moreover , 2 weeks of home training was associated with an additional increase in PIF of 8l/min compared with Group B ( p < 0:015 ) . After individual instruction and home  training , mean PIF in children aged 4 and 5 was 56 ( 42‐72 ) and 55 ( 41‐66 ) l/min , respectively . Conclusion : After individual instruction and training at home , the vast majority of children aged 4 and 5 y can use Turbuhaler correctly .  Audiovisual information and individual instruction is not sufficient in the majority of these children . Few 3‐y‐old children can learn the correct use of Turbuhaler Children 's use of inhalation devices can give valuable information about their adherence to asthma therapy . The aim of this study was to examine treatment adherence of low dose inhaled budesonide or placebo administered via Turbuhaler twice daily in children with mild asthma participating in an asthma trial , by comparing diary registration with the number of doses remaining in the inhaler . A total of 163 children ( age 7 - 16 yrs , 56 females , 107 males ) with mild asthma ( mean baseline forced expiratory volume in one second ( FEV1 ) was 103 % of predicted ) , were included into a double blind , r and omized study . After a two-week run-in period , the children received inhaled budesonide , either 100 microg or 200 microg daily , and /or placebo for 12 weeks . All patients used daily diary cards throughout the study . Results from 161 patients were analysed . Mean compliance according to the diary was 93 % , whereas estimated mean compliance when counting remaining doses in the Turbuhaler was 77 % . Overuse of medication was found in 7 % of the children . There was no significant difference in compliance between sex in the study group , whereas children aged < or = 9 yrs had significantly better drug adherence than older children . No significant relationship was found between symptom score and compliance . In conclusion , even with optimal patient follow-up in a clinical trial , adherence to prophylactic asthma treatment is considerably lower than the patients own reports from the use of daily diary cards Summary We have studied the efficacy and acceptability of a new inhalation spacer device . The functional principle of the device , differing from that of conventional spacers , is based on evaporation of the propellant during circular movement of the aerosol in a small spherical chamber . We assessed the bronchodilating effect of salbutamol ( SalbuventR ) inhaled with the new spacer ( RondoR ) compared with salbutamol ( VentolineR ) inhaled with the spacer VolumaticR and with salbutamol ( SalbuventR ) inhaled with a conventional metered dose actuator using a double-blind cross-over arrangement . Fifteen asthmatic patients were treated over a period of 4 weeks . They used each of the three different devices for 2–3 days every week . Peak expiratory flow rates were recorded every morning after one and after two puffs of the study drugs . The bronchodilator responses to the three treatments were similar within narrow ranges of estimate . By visual analogue scale assessment the new spacer was significantly easier to h and le ( P<0.05 ) and more convenient to carry around ( P<0.01 ) than An electronic monitoring device was used to assess patient compliance during clinical trials of two new aerosolized nonbronchodilator , antiasthma drugs .  Compliance was poor , but similar , in both trials . Patients took the study drug as instructed on a mean of 37.3 % days ( range 10 % to 77 % ) in one trial and 37.4 % days ( range 0 % to 63 % ) in the other . Both underuse and overuse were observed . Underuse was seen on a mean of 38.9 % days ( range 9 % to 81 % ) and 46.0 % ( range 15 % to 80 % ) respectively ; overuse on a mean of 23.5 % days ( range 6 % to 54 % ) and 16.6 % days ( range 0 % to 41 % ) . In some patients ten or more activations of the device were recorded at the same time . In six patients such multiple simultaneous activations were recorded on two or more separate days . These patients were among the most noncompliant in the study . Multiple simultaneous activations frequently followed underuse days or preceded followup visits , suggesting the possibility of duplicity . Overall compliance was such that valid conclusions about efficacy of the drugs could only have been drawn in six of 34 patients Svenonius E , Arborelius M , Wiberg R , Ståhl E , Svensson M. A comparison of  terbutaline inhaled by Turbuhaler ® and by a chlorofluorocarbon ( CFC ) inhaler in children with exercise‐induced asthma To assess whether an extension tube between the aerosol source and the patient improves drug-inhalation therapy in children with acute bronchoconstriction , we treated 20 children under double-blind conditions with placebo or terbutaline delivered by a conventional aerosol or an aerosol with a tube spacer . Both terbutaline treatments result ed in a significant increase in forced expiratory volume in one second , as compared with placebo ( P less than 0.001 ) , but treatment with the tube-spacer aerosol produced significantly more improvement than did treatment with the conventional aerosol ( P less than 0.01 ) . The number of errors in inhalation technique was reduced when the spacer aerosol was used , and this reduction may account for the greater improvement in the children treated with the spacer Objectives : Our objective was to compare two different teaching methods used to educate patients in the use of a breath actuated inhaler ( BAI ) and to assess the impact of its continued use on their metered-dose inhaler ( MDI ) technique . Design : Prospect i ve , r and omized , controlled trial . Setting : Adult Pulmonary/Asthma clinic of Cook County Hospital , Chicago , IL . Patients : Diagnosed , stable asthmatics . Intervention : The patients were r and omized into two groups . The experimental group received verbal instructions and demonstration on breath actuated inhaler technique while the control group received written instructions only on BAI use . The metered dose inhaler technique of both groups of patients was also evaluated . Measures : A checklist evaluating the key aspects of proper BAI and MDI inhalation techniques was used to assess the use of both types of inhalers at entry into the study and upon postintervention follow-up at 8 to 20 weeks . Results : At baseline , 97 % of patients in the experimental group and 83 % of patients in the control group were initially able to demonstrate BAI inhalation technique correctly . Upon follow-up , 82 % of the control group and 68 % of the experimental group were able to use the BAI correctly , which was a statistically significant deterioration in the experimental group . In both of these groups , there was a statistically significant improvement in MDI technique . Conclusions : Written instructions alone may be an adequate teaching tool for proper inhalation technique of BAI . Continued BAI use appears not to impact adversely on proper MDI technique OBJECTIVES 1 . To assess the clinical efficacy of drug delivery using paper spacer devices coupled to metered dose inhalers ( MDI ) . 2 . To compare the effectiveness of paper spacers with the st and ard volumatic spacer . DESIGN R and omised double-blind placebo controlled clinical trial . SETTING Asthma clinic of a family practice at Kalutara . PATIENTS 134 patients over 12 years of age , who attended the clinic with an acute episode of wheezing . METHOD All patients over 12 years of age with an acute episode of wheezing who could speak a sentence of over 5 words were r and omly allocated into 4 groups and administered salbutamol inhalations through a MDI coupled to a spacer . The first group used a 6-inch paper spacer , second group an 8-inch paper spacer , the third group a 10-inch paper spacer and the fourth group used a st and ard 750 ml volumatic spacer . MEASUREMENTS In each subject , the peak expiratory flow rate ( PFR ) was recorded at the start , after placebo inhalation and after salbutamol inhalation . An increase of PFR of over 20 % from the basal value was assessed as a good response . RESULTS The number of patients who showed a good response after salbutamol inhalations in all four groups were very significant compared with the responses after placebo inhalations ( p < 0.001 ) . No significant differences were found in the effectiveness of salbutamol among the four other groups ( p > 0.1 ) . CONCLUSIONS 1 . All devices show equal efficacy . Metered dose inhalers and all 3 paper devices are as effective as the st and ard volumatic spacer . 2 . The cost of a paper spacer device is negligible compared to that of the volumatic spacer . 3 . The use of paper spacers in Sri Lankan family practice s makes inhaled MDI therapy much cheaper without decreasing the effectiveness of drug delivery This r and omized , double-blind , parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon ( CFC ) pressurized metered dose inhaler ( pMDI ; Ventolin ) or from a non-CFC hydrofluoroalkane ( HFA ) 134a pMDI ( Ventolin CFC-free ) in patients with mild to moderate asthma . All patients ( n = 423 ) continued with their  st and ard 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 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation This was an open-label , parallel group , r and omized , age-stratified , multicenter study design ed to compare the safety and efficacy of regular use of albuterol formulated in hydrofluoroalkane-134a ( HFA albuterol ) and albuterol formulated in chlorofluorocarbons-11/12 ( CFC albuterol ) in children with asthma . Children age 4 - 11 years using a short-acting inhaled beta2-agonist for 6 months to manage stable asthma , and with a pre study forced expiratory volume in 1 sec ( FEV1 ) of > 50 % predicted after withholding short-acting inhaled beta2-agonists for at least 6 hr , an increase in FEV1 ≥ 12 % within 30 min after two puffs of CFC albuterol , and the capability to comply with medication withholding requirements were eligible for study entry . After screening evaluation , patients entered a minimum 7-day run-in period . On study day 1 spirometry and a baseline 12-lead electrocardiogram ( ECC ) were performed , pulse and blood pressure were measured , and patients self administered two puffs of their r and omized study drug , either HFA albuterol or CFC albuterol . Serial spirometry was performed over 6 hr after study drug dosing . Pulse and blood pressure were measured just prior to each spirometry and a 12-lead ECG was performed at 60 min postdose . Patients took two puffs of their study drug four times a day for 4 weeks . At study week 4 , study day 1 procedures were repeated . Patients maintained a daily diary of morning ( a.m. ) and evening ( p.m. ) peak expiratory flow ( PEF ) , daytime asthma symptom scores , nighttime asthma sleep disturbance scores , and study drug use . Demographics and baseline characteristics of the 63 patients r and omized to HFA albuterol ( 33 ) and CFC albuterol ( 30 ) were similar . No significant differences were found between the HFA albuterol and CFC albuterol treatment groups for any of the primary or secondary FEV , efficacy variables either at study day 1 or study week 4 . No significant differences were noted between treatment groups for a.m. and p.m. PEF , individual asthma symptom scores , nighttime asthma sleep disturbance scores , and rescue study drug use over the 4-week study . No significant differences were found between the two treatment groups for change from predose in heart rate , systolic and diastolic blood pressure , and 12-lead ECG intervals at either study day 1 or study week 4 . Adverse event reporting was similar for the two treatment groups . In this study , with regular use of HFA albuterol in children with asthma , there was a similar safety profile and comparable bronchodilator efficacy as with CFC albuterol Asthmatic patients who were regular and experienced users of the metered-dose inhaler ( MDI ) but with no history of powder inhaler use were interviewed by question naire . Most ( 71 % ) of the 159 adults recruited had suffered from asthma for more than five years ; 89 % had used an MDI for more than one year . In all , 153 ( 97 % ) found their current MDI easy or very easy to h and le . Effectiveness in delivering the drug and ease of operation were the two features of the device they were most satisfied with . The two features ' of an ideal inhaler ' rated most highly were the presence of a dose counter and ease of use during an attack ( 58 % and 72 % of respondents , respectively ) . Other important features included hygiene , sensation that a dose had been taken , and small size . When attitudes towards the Diskus inhaler and the Turbuhaler inhaler were compared , 108 ( 68 % ) would have been quite or very happy to have a Diskus inhaler prescribed for them , and 79 ( 50 % ) a Turbuhaler inhaler . The Diskus inhaler scored significantly better than the Turbuhaler inhaler for knowing how many doses were left , the presence of an attached cover , attractiveness ( p < 0.001 ) , hygiene , shape , weight ( p = 0.001 ) , and perceived ease of use ( p = 0.002 ) . The Turbuhaler inhaler scored significantly better in terms of size ( p < 0.001 ) . Overall , the Diskus inhaler was preferred by 104 of 159 patients ( p < 0.001 ) , with perceived ease of use , the dose counter , and shape cited as the main reasons for preference Introduction : The effect on quality of life by healing leg ulcers is not known and no vali date d disease-specific tool is available for measuring health-related quality of life ( HRQoL ) for people with venous leg ulcers . The objective of this paper was to compare four generic instruments [ MOS 36-Item Short-Form Health Survey ( SF-36 ) ; EuroQol ( EQ ) ; McGill Short Form Pain Question naire ( SF-MPQ ) and the  Frenchay Activities Index ( FAI ) ] used for measuring HRQoL in people with venous leg ulcers , and to offer guidance on the most appropriate tool for research ers . Methods : Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a r and omised controlled trial of the cost-effectiveness of community leg ulcer clinics . Subjects completed question naires containing the four instruments on three occasions ( initial assessment , 3 and 12 months ) . The discriminative and evaluative properties of the four instruments were compared . Results : All four instruments were acceptable to patients , taking a mean of 19.3 ( SD 6.3 ) min to complete . At initial assessment , the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration . The FAI was good at discriminating between the different patient groups ( at initial assessment ) in relation to age , mobility and ulcer size . At the three-month follow-up , the SF-MPQ was more responsive than the other measures and detected changes in HRQoL , whereas the EQ and SF-36 did not . At 12 months , the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage . Conclusion : In the absence of a vali date d condition-specific tool for measuring changes in general health status for patients with venous leg ulcers , we make the following recommendations . For evaluating the outcome of interventions with a short-term follow-up ( three months ) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36 , with or without the SF-MPQ OBJECTIVE The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate ( HFA-BDP ) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate ( CFC-BDP ) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control . The present study was undertaken to test this hypothesis . DESIGN A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy ( inhaled beta-agonist and CFC-BDP [ < or = 400 microg/d ] ) . A short course of oral prednisone , 30 mg/d for 7 to 12 days , was followed to establish the patients were steroid responsive and to provide an " in- study " baseline of " optimal " asthma control . PATIENTS A total of 347 patients were then r and omized to HFA-BDP 400 microg/d , CFC-BDP 800 microg/d , or HFA-placebo for 12 weeks . RESULTS Morning peak expiratory flow ( AM PEF ) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment . All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo . The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported . CONCLUSIONS These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied , but at half the total daily dose A r and omised double blind , two period cross over study was design ed to compare the ability of 51 hospitalised asthmatics with acute exacerbations to use each of two inhalers . The inhalers compared were a new breath actuated metered dose inhaler , the Autohaler inhalation device , and a dry powder device , the Rotahaler . Pre assessment data included the measurement of peak inspiratory flow rate ( PIFR ) , peak expiratory flow rate ( PEFR ) , pulse rate , and oxygen saturation . Therapeutic response to each inhaler was compared by measurement of PEFR , oxygen saturation , and pulse rate . PIFR was sufficient in all children to fire the Autohaler , including the youngest . No significant difference was found between the two inhalers as assessed by PEFR . However the Autohaler inhalation device could be actuated 99/100 times successfully compared with 74 for the Rotahaler . There was a consistent , but clinical ly insignificant , increase in pulse rate after use of the Rotahaler compared with the Autohaler . All 11 patients under 6 years of age failed to empty the Rotahaler but five of these patients received a significant benefit from using the Autohaler compared with after the Rotahaler . A significant drop in oxygen saturation was observed 15 minutes after use of either inhaler . This may at times reach levels of clinical importance Managed care plans evaluate therapeutic alternatives to identify the most cost-effective medications for asthma . Three hundred one patients with asthma were r and omized to receive the beta-agonist pirbuterol from either a manually operated metered dose inhaler ( MDI ) or a breath-actuated inhaler ( BAI ) .  Cost effectiveness was evaluated by the cost of the beta-agonist medication used and patient-reported outcomes . No significant differences between the two groups appeared in baseline or follow-up outcomes , which were assessed by self-reported health status and spirometry . However , patients receiving pirbuterol from BAIs used 23 % less than those patients who received the drug from MDIs BACKGROUND The efficacy and safety of the aerosol metered-dose inhaler ( MDI ) formulation of salmeterol for asthma symptoms have been established . Recently , salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler ( Diskus ) . OBJECTIVE A multicenter , r and omized , double-blind , double-dummy , parallel-group , placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus , salmeterol aerosol 42 microg twice daily via MDI , and placebo . METHODS Patients were r and omized to one of the three treatment groups for 12 weeks . Efficacy was assessed by serial measurements of forced expiratory volume in one second ( FEV1 ) over 12 hours , daily peak expiratory flow ( PEF ) , self-rated asthma symptom scores , nighttime awakenings , and supplemental albuterol use . Safety of each treatment was evaluated by monitoring vital signs , electrocardiograms , Holter monitoring , and occurrence of adverse events . RESULTS As compared with placebo , both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use . There were no significant differences in the efficacy of the two salmeterol formulations . The magnitude of improvement in pulmonary function was undiminished over the 12-week study . Both formulations of salmeterol were well tolerated , with safety profiles not significantly different from placebo . CONCLUSION Results of this study indicate that salmeterol , administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI , produces clinical ly significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma OBJECTIVE The purpose of the study was to evaluate the dose-response relationships of the inhaled corticosteroid budesonide in a double blind crossover study in 19 children with moderate and severe asthma . METHODS A 2-week placebo treatment period ( run-in ) was followed by three 4-week treatment periods during which 100 , 200 , and 400 micrograms of budesonide were given per day in r and omized order . Urinary cortisol excretion , lung functions , and protection against exercise-induced asthma were assessed at the end of run-in and each treatment period . Furthermore , morning and evening peak expiratory flow rates , day and night symptoms , and use of rescue beta 2-agonists were recorded throughout the study . RESULTS One hundred micrograms of budesonide per day markedly improved symptoms , morning and evening peak expiratory flow rates , and use of rescue beta 2-agonists ( p < 0.01 ) . No further improvement was seen in these parameters with increasing doses of budesonide . In contrast , a significant dose-response effect was found on lung functions measured at the hospital and fall in lung functions after exercise ( p < 0.001 ) ; 200 micrograms was significantly better than 100 micrograms , and 400 micrograms was significantly better than 200 micrograms . About 53 % of the maximum effect against exercise-induced asthma was achieved by the lowest budesonide dose ( p < 0.001 ) , and about 83 % by the highest dose . No significant differences were seen in urinary cortisol excretion between run-in and the various budesonide doses . CONCLUSIONS Low doses of budesonide , which are not associated with any systemic side effects , have a marked antiasthma effect in children . Protection against exercise-induced asthma requires higher doses than achievement of symptom control Pressurized metered dose inhalers ( pMDI ) are widely used together with spacers for the treatment of asthma in children . However , the variability of daily medication dose for pMDI/spacer combinations is not known . Electrostatic charge is a potential source of dose variability . Metal spacers have no static charge . This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers . This was a r and omized , crossover study in children with stable asthma aged 1 - 4 ( group I , n=17 ) and 5 - 8 ( group II , n=16 ) yrs . In both groups the amount of drug delivered to the mouth by a metal spacer ( Nebuchamber ) and one of two plastic ( polycarbonate ) spacers , i.e. Babyhaler in group I and Volumatic in group II was measured . The metal and plastic spacers were tested at home in a r and omized order for 7 days each , using budesonide ( 200 microg b.i.d . ) . Aerosol was collected on a filter positioned between spacer and facemask or mouth . Budesonide on the filter was assessed by high performance liquid chromatography . The mean filter dose for each child ( mean+/-SD ) during the 7 days was expressed as a percentage of the nominal dose . Within-subject variability was expressed as coefficient of variation ( CV ) . Mean filter dose in group I was 41.7+/-10.1 % for Nebuchamber and 26.0+/-4.0 % for Babyhaler ( p<0.001 ) . Mean filter dose in group II was 50.2+/-9.2 % for Nebuchamber and 19.4+/-7.2 % for Volumatic ( p<0.001 ) . Mean CV in group I was 34 % for Nebuchamber and 37 % for Babyhaler ( p=0.44 ) . Mean CV in group II was 23 % for Nebuchamber and 34 % for Volumatic ( p=0.003 ) . There was substantial within-subject dose variability in aerosol delivery in children using a  pMDI/spacer at home . This variability was lower for the metal than for the plastic spacer in children 5 - 8 yrs of age . The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age In an open , r and omized crossover study two different types of dry powder inhalers ( DPIs ) were compared . Twenty-five adult asthmatic patients inhaled a single dose of 200 micrograms of salbutamol ( CAS 18559 - 94 - 9 ) on two separate days . Salbutamol was administered either from a novel multidose DPI ( Easyhaler , test DPI ) or from another type of DPI ( reference DPI ) . On both study days lung function , blood pressure and heart rate were measured during a 4-h follow-up period . Both powder inhalers caused a clear increase in lung function parameters . The mean ( SD ) maximum forced expiratory volume in 1 s ( FEV1 ) after the test DPI was 3.25 ( 1.30 ) 1 and after the reference DPI 3.28 ( 1.29 ) 1 . The mean relative change from the baseline in FEV1 was similar after administration of both preparations . The mean area under the curve ( AUC0 - 4h ) of the absolute FEV1 values was 729 ( 316 ) and 731 ( 309 ) 1 x min after test and reference DPIs , respectively . The salbutamol doses had no clinical ly significant effects on blood pressure or heart rate and were equally well tolerated . Furthermore , 41 % of patients preferred the test DPI and 19 % the reference DPI , while 40 % felt there was no difference between the devices . In conclusion , the results of this study show that the test DPI , a novel multidose powder inhaler , is an effective , safe and convenient alternative when an inhaled bronchodilator treatment is considered for an obstructive patient AIM To measure drug adherence in children with mild asthma receiving long term prophylactic treatment . METHODS Double blind r and omised placebo controlled trial . Patients received inhaled budesonide 100 μg or 200 μg daily , or placebo for 27 months . All participants were asked to inhale medication or placebo from two different Turbuhalers ( morning and evening ) during the study . A total of 122 children ( 80 boys , 42 girls ) aged 7–16 years with mild asthma ( mean FEV1 103.7 % of predicted ) were included in the trial . Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals . RESULTS A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months , reaching mean values of 40.6 % and 46.9 % for inhaled morning and evening medication respectively . Drug adherence declined more rapidly in the placebo group ( compared to active treatment ) ; this difference became significant after two years of treatment . Children aged 9 years or less had better drug adherence during the entire study period , but the difference was only significant for the first three months of the study . Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months . CONCLUSION Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial . This emphasises the importance of monitoring compliance in clinical trials An open , multi-centre , general practice study was carried out in 1661 asthmatic patients to assess the efficacy , in terms of symptom relief and changes in lifestyle , of budesonide and to record objective lung function changes and any adverse events . After a 1-week run-in period on any pre-trial anti-asthma medication , patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks . Peak expiratory flow rate ( PEFR ) was measured by the doctor on entry , after the run-in , and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance , bronchodilator usage and the severity of cough , wheeze and sleep disturbance , and weekly to record 5 lifestyle assessment s , e.g. physical activity . Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 + /- 3 l/min at the end of the run-in to 368 + /- 3 l/min at the end of the trial ; 77 % of patients had an improved PEFR . Bronchodilator use decreased significantly from 4.2 + /- 0.1 times/day during the run-in period to 3.0 + /- 0.1 times/day at the end of the study ; 65 % of patients used less bronchodilator . Significant improvements were recorded in all the symptoms and lifestyle indices monitored ; 76 % of patients improved in at least 5 of the 11 assessment s. Treatment-emergent adverse events occurred in 103 ( 6 % ) of patients : none was classified as serious or unexpected . No sub-group of patients was identified in which the results were at variance from the full sample . It is concluded that budesonide improves patients ' lifestyle and ability to carry out normal activities , as well as improving PEFR and reducing bronchodilator use , in mild to moderately severe asthmatics treated in general practice Inefficient inhaler technique is a common problem result ing in poor drug delivery , decreased disease control and increased inhaler use . The aim of this study was to assess patients ' use of different inhaler devices and to ascertain whether patient preference is indicative of ease of use and whether current inhaler use has any influence on either technique or preference . We also wished to define the most appropriate method of selecting an inhaler for a patient , taking into account observed technique and device cost . One hundred patients received instruction , in r and omized order , in the use of seven different inhaler devices . After instruction they were grade d ( using predetermined criteria ) in their inhaler technique . After assessment patients were asked which three inhalers they most preferred and which , if any , they currently used . Technique was best using the breath-actuated inhalers ; the Easi-Breathe and Autohaler , with 91 % seen to have good technique . The pressurized metered dose inhaler ( pMDI ) fared poorly , in last position with only 79 % of patients showing good technique , despite being the most commonly prescribed . The Easi-Breathe was by far the most popular device with the patients . The Autohaler came in second position closely followed by the Clickhaler and Accuhaler . The majority of patients ( 55 % ) currently used the pMDI but the pMDI did not score highly for preference or achieve better grade s than the other devices . Only 79 % of patients tested could use the pMDI effectively even after expert instruction yet it continues to be commonly prescribed . This has important repercussions for drug delivery and hence disease control . Prescribing a patient 's preferred device increases cost but can improve efficiency and therefore be cost effective in the long term . Using an inexpensive device ( pMDI ) when technique is good and the patient 's preferred inhaler device when not is one way to optimize delivery and may even reduce cost The Autohaler actuator is a breath-actuated device design ed by 3 M Pharmaceuticals . The objective of this study was to measure and improve the effectiveness of the device 's package insert instructions ( PII ) . Using only the PII for guidance , 5 of 20 ( 25 % ) subjects failed to trigger the device . The PII were revised based on the subject 's performance and suggestions . Using the revised PII , only 1 of 20 ( 5 % ) different subjects failed to trigger the device . These results indicate that relatively minor modifications to instructions can result in significant improvements in patient use . Eighty-five percent of the participants thought the device was easier to use than a metered-dose inhaler Two hundred fourteen children with mild to moderate asthma were studied to determine bronchodilator effects 5 min after administration of five different metered dose inhaler ( MDI ) aerosol formulations available in our country , and results were compared to placebo . Methacholine bronchial challenge was performed by the tidal breathing method , using increasing concentrations until a fall in forced expired volume in 1 s ( FEV(1 ) ) > /=20 % was achieved ( PC20 ) . Immediately after FEV(1 ) had fallen 20 % or more , children were r and omly allocated into 1 of 6 groups to receive : salbutamol 200 microg ( S ) , fenoterol 200 microg ( F ) , salbutamol 200 microg + beclomethasone 100 microg ( S + B ) , fenoterol 200 microg + ipratropium bromide 80 microg ( F + IB ) , salmeterol 50 microg ( SM ) , and placebo ( P ) . The bronchodilator effect was determined by measuring FEV(1 ) 5 min after inhalation of medications . Nonparametric tests were used for statistical analysis . The six groups were similar in anthropometric and in respiratory characteristics . All five inhaled aerosols containing beta-agonists caused a significant bronchodilator effect as compared to placebo . However , the effect was significantly greater in the groups treated with F or F + IB ( P < 0.05 ) compared to other formulations . We conclude that the five types of aerosols used in this study are able to reverse methacholine-induced bronchoconstriction 5 min after inhalation of a bronchodilator Background : Problems in using conventional inhalation aerosols , in addition to environmental reasons , have driven development of the dry powder inhalers . Objective : To compare therapeutic equivalence and acceptability of two dry powder inhalers , Easyhaler ( EH ) and Diskhaler ( DH ) , in the delivery of beclomethasone dipropionate ( BDP ) in the treatment of asthma . Methods : Adult asthmatics ( n = 185 ) , previously treated with inhaled steroids , were recruited in this open parallel-group study . After a run-in period of 2 weeks during which the patients inhaled 800 μg/day of BDP via DH , the patients were r and omly allocated into three groups : EH 200 group ( 62 patients ) using EH 200 μg/dose inhaler ( 1 inhalation q.i.d . ) , EH 400 group ( 62 patients ) using EH 400 μg/dose inhaler ( 1 inhalation b.i.d . ) , and DH group ( 61 patients ) using DH 200 μg/dose inhaler ( 1 inhalation q.i.d . ) for 12 weeks . The primary outcome variables were PEF and FEV1 . Results : The 95 % CI for treatment difference in morning PEF between the EH 200 and DH groups was –16 to 23 litres/min and between the EH 400 and DH groups –18 to 21 litres/min . There was an increase in the morning PEF of 13 litres/min ( p < 0.05 ) in the EH 200 group , and 9 and 11 litres/min in the DH and EH 400 groups . No differences between the groups were seen in the lung function parameters , in the symptom scores , in the use of rescue medication or in the incidence of adverse events . The treatments had no effects on morning cortisol levels . The patients in the EH groups compared the inhalers by using an 11-item question naire . In 8 questions the majority of the patients rated EH superior to DH . Conclusion : The tested inhalers were therapeutically equal . However , based on the acceptability data , the EH was better accepted by the patients than DH The m and atory requirement to eliminate chlorofluorocarbons ( CFCs ) as propellants in pharmaceutical aerosols has provided the opportunity to enhance significantly the delivery of aerosol drugs to the respiratory tract . This r and omized , parallel-group , double-blind , double-dummy , multicentre study was undertaken to assess whether beclomethasone dipropionate ( BDP ) in hydrofluoroalkane-134a ( HFA ) provided equivalent control of moderately severe asthma to BDP in CFC but at approximately half the total daily dose , as might be expected from the improved lung deposition of the HFA-BDP extrafine aerosol . The novel study design included a 10 - 12 day run-in period to confirm that patients met established criteria of moderately severe asthma and were symptomatic on current therapy ( inhaled beta-agonist plus CFC-BDP 400 - 800 micrograms day-1 ) . This run-in period was followed by a short course of oral steroid therapy ( prednisolone 30 mg day-1 for 7 - 13 days ) to demonstrate steroid responsiveness [ > or = 15 % improvement in morning peak expiratory flow ( PEF ) ] and to provide a within- study baseline of improved asthma control . A total of 233 patients were r and omized to treatment for 12 weeks with HFA-BDP 800 micrograms day-1 ( 116 patients ) or CFC-BDP 1500 micrograms day-1 ( 117 patients ) . The mean change from oral steroid treatment in morning PEF with HFA-BDP was equivalent to that seen with CFC-BDP at all time intervals . Changes in other measures of pulmonary function , asthma symptom scores and beta-agonist use were equivalent in the two treatment groups throughout the 12 week treatment period . The safety profile of HFA-BDP compared favourably with that of CFC-BDP with no unexpected adverse events reported . Fewer patients on HFA-BDP than on CFC-BDP had plasma cortisol levels below the normal reference range after 12 weeks of therapy ( 5.1 % vs. 17.3 % , respectively ) . In conclusion , HFA-BDP extrafine aerosol was found to provide equivalent control of moderately severe asthma to CFC-BDP at approximately half the daily dose with a favourable safety profile , suggesting an improved therapeutic ratio Background . A powder formulation of salmeterol has been shown to prevent exercise-induced bronchospasm ( EIB ) in asthmatic children and adults ; however , the delivery device ( Diskhaler ; Glaxo Wellcome Inc , Research Triangle Park , NC ) must be reloaded after 4 doses . A new multidose powder inhaler ( Diskus ) provides 60 doses of salmeterol in a blister pack presentation with a dose counter . Objective . To evaluate the safety and efficacy of 50-μg salmeterol powder via two different delivery systems ( Diskhaler and Diskus ) in preventing EIB in asthmatic children . Study Design . A r and omized , double-blind , double-dummy , single-dose , placebo-controlled , three-way crossover study was conducted in 24 children 4 to 11 years of age demonstrating EIB and mild to moderate asthma . Serial forced expiratory volume in 1 second ( FEV1 ) was measured before and after treadmill exercise challenges conducted at 1 , 6 , and 12 hours after study drug administration . Adverse events were also assessed . Results . During all exercise challenges , EIB-mediated reductions in FEV1 were minimized or prevented in patients receiving single doses of salmeterol powder compared with placebo . Single doses of salmeterol powder delivered via either system were equally effective in preventing EIB . There were no drug-related adverse events , cardiovascular , or other clinical ly relevant safety concerns . Conclusions . Single doses of salmeterol powder delivered by either delivery system are safe and effective in preventing EIB for ≥12 hours in asthmatic children OBJECTIVES --To explore the morbidity of patients diagnosed as asthmatic in general practice , to examine the determinants of this morbidity , and to derive a simple morbidity screening tool for use in primary care . DESIGN --Patient interviews , lung function measurements , and data extraction from general practice case notes . SUBJECTS--300 asthmatic patients aged 5 to 65 years r and omly selected from the repeat prescribing registers of three general practice s in the Southampton area . MAIN OUTCOME MEASURES --Reported morbidity using a calculated index based on three questions ( Are you in a wheezy or asthmatic condition at least once per week ; Have you had time off work or school in the past year because of your asthma ; Do you suffer from attacks of wheezing during the night ? ) ; mean forced expiratory volume in one second and mean peak expiratory flow ( over a seven day period ) ; diurnal variation in peak flow ; and the relation of the morbidity index to lung function . RESULTS --Mean forced expiratory volume in one second was 67 % predicted ( SD 18.4 ) , mean peak expiratory flow was 80 % predicted ( SD 18.9 ) , and mean diurnal variation was 10 % ( SD 7.7 ) . 76 subjects were classified as having low morbidity , 95 medium , and 125 high . The morbidity index was significantly associated with forced expiratory volume in one second , mean peak expiratory flow rate , and diurnal variation ( p less than 0.05 ) ; it was not significantly associated with inhaler technique or use of prophylaxis . CONCLUSIONS --There was a large burden of persisting morbidity across all ages of patients diagnosed as asthmatic in the three well re source d practice s studied . The use of the morbidity index may help to target the asthmatic patients needing more attention by concentrating on those reporting medium to high morbidity AIMS Plastic spacers are widely used with pressurized metered dose inhalers ( pMDI ) . Reducing electrostatic charge by washing spacers with detergent has been shown to greatly improve in vitro and in vivo drug delivery . We assessed whether this finding is associated with an improved bronchodilator response in adult asthmatics . METHODS Twenty subjects ( age 18 - 65 years ) with a known bronchodilator response inhaled in r and om order salbutamol from a pMDI ( Ventolin ) through an untreated new spacer ( Volumatic ) and through a detergent washed spacer . Patients received the following doses of salbutamol via pMDI at 20 min intervals : 100 microg , 100 microg , 200 microg , 400 microg , 800 microg . Spirometry , heart rate and blood pressure were checked prior to each dose and 20 min after the last dose . RESULTS There were no differences between baseline forced expiratory volume in 1 s ( FEV1 ) using either spacer ( 2.61+/-0.56 and 2.52+/-0.45 l , untreated and treated with detergent , respectively ; mean + /- s.d . ) . The provocation dose required to cause a clinical ly significant improvement of 10 % in FEV1 ( PD10 ) was significantly lower when the detergent treated spacer was used ( 1505 + /-1335 and 430+/-732 microg , untreated and treated , respectively , P<0.002 ) . CONCLUSIONS We have demonstrated an improvement in bronchodilator response , in adult asthmatics , after reducing the electrostatic charge in a spacer device by washing it with ordinary household detergent . This finding stresses the importance of an optimal choice of delivery device for asthma medication BACKGROUND A metered-dose inhaler ( MDI ) with spacer is the best way to deliver bronchodilator therapy for treatment of acute asthma . In developing countries , commercially produced spacers are generally unavailable or too costly . We tested the efficacy of home-made spacers ( 500 mL plastic bottle , polystyrene cup ) compared with a conventional spacer for delivery of a beta2 agonist via MDI for children with acute asthma . METHODS We studied children aged 5 to 13 years with acute asthma , stratified into those with mild airways obstruction ( peak expiratory flow [ PEF ] 60 - 79 % of predicted value ) or moderate to severe airways obstruction ( PEF 20 - 59 % of predicted value ) . A beta2 agonist ( fenoterol hydrobromide ) was given via MDI and one of four r and omly assigned spacers ( conventional spacer , sealed 500 mL plastic bottle , unsealed 500 mL bottle , 200 mL polystyrene cup ) . Clinical score , pulmonary function tests , and oximetry were recorded at baseline and 15 min after treatment . If a second bronchodilator treatment was needed , nebulised fenoterol was given and the assessment repeated 15 min later . Primary outcome measures were changes in clinical score and pulmonary function , and need for and response to nebulisation . FINDINGS 88 children were eligible for study . In 44 children with moderate to severe airways obstruction , a cup gave significantly less bronchodilation ( median increase in : forced expiratory volume in 1 s [ FEV1 ] 0 % ; PEF 12 % ) compared with the conventional spacer ( 37 % ; 59 % ) , sealed bottle ( 33 % ; 36 % ) , or unsealed bottle ( 18 % ; 21 % , p<0.05 for difference between groups ) . Nebulisation was required by ten of 11 who had used a cup , nine of 11 who had used an unsealed bottle , eight of 11 who had used a sealed bottle , and only four of 11 who had used a conventional spacer . After nebulisation , improvement in FEV1 ( 15.5 % ) and PEF ( 26 % ) was more marked in children who had used a cup than in those who had used a conventional spacer ( 5.5 % FEV1 ; 4 % PEF ) , sealed bottle ( 3 % ; 0 % ) , or unsealed bottle ( 7 % ; 9 % ) . For 44 children with mild airways obstruction , response to bronchodilator was similar for all spacers and need for nebulisation was not associated with use of a particular spacer . INTERPRETATION A conventional spacer and sealed 500 mL plastic bottle produced similar bronchodilation , an unsealed bottle gave intermediate improvement in lung function , and a polystyrene cup was least effective as a spacer for children with moderate to severe airways obstruction . Use of bottle spacers should be incorporated into guidelines for asthma management in developing countries Beta 2-agonist therapy effectively relieves asthmatic symptoms , but an improvement in patient lifestyle has not been demonstrated . This open study in which patients acted as their own controls , assessed the efficacy and acceptability of intermittent symptom-related use of terbutaline inhaled via ' Turbohaler ' , and its influence on the lifestyle of 1133 inhaler-naive , mild asthmatics treated in general practice . A 1-week run-in period was followed by 4-weeks ' treatment with inhaled terbutaline ( 500 micrograms as required ) . Peak expiratory flow rate ( PEFR ) and ' Turbohaler ' technique were assessed at clinic visits . Diary cards , completed daily , assessed : the number of terbutaline inhalations , the relief obtained after use , the severity of asthma symptoms ( cough , morning wheeze , nocturnal wheeze and wheeze on activity ) , and lifestyle indices ( sleep disturbance , work/school days lost , limitation of normal activity ) . After terbutaline treatment , PEFR increased by 54 + /- 2 l/min ( p less than 0.001 ) , the severity of asthma symptoms was almost halved ( p less than 0.001 ) , with over two-thirds ( 65 % to 76 % ) of patients reporting improvements in each variable , and the adverse effect of asthma on lifestyle was at least halved ( p less than 0.001 ) . Improvements in lung function , asthma symptoms and lifestyle were comparable for all sub-groups : adults ( greater than 16 years ) , school-age children ( 6 to 16 years ) and preschool children ( less than or equal to 5 years ) . This study not only confirmed the efficacy and acceptability of intermittent symptom-related use of terbutaline inhaled via ' Turbohaler ' , but also demonstrated that its use enhanced patients ' lifestyles Short-acting inhaled beta2-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction ( EIB )  in children . This was a r and omized , single-blind , placebo-controlled , four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoroalkane-134a ( HFA ) to albuterol formulated in chlorofluorocarbons ( CFCs ) and to placebo in protecting asthmatic children age 6 - 11 from EIB . Patients self-administered either HFA albuterol , two different CFC albuterol products , or placebo 30 min prior to exercise challenge .  Spirometry was performed predose and 5 , 10 , 15 , 30 , 45 , 60 , 75 , and 90 min after the exercise challenge was completed . The smallest percent change from the predose forced expiratory volume in 1 sec ( FEV1 ) after exercise challenge was similar for the three active treatments , and each of the active treatments was significantly better than placebo . Each active treatment had significantly fewer patients unprotected from EIB ( unprotected defined as having > 20 % fall in FEV1 after exercise challenge ) than placebo . Changes in heart rate , blood pressure and electrocardiogram ( ECG ) intervals were similar for the three active treatments following exercise . HFA albuterol is as effective as albuterol products formulated in CFCs and more effective than placebo in protecting asthmatic children from EIB In a double-blind double-dummy crossover study , the effects of salbutamol dry powder inhaled from Salbutamol cyclocaps Pharbita 0.4 mg with the Pharbita inhaler and from a reference product were compared . On the first trial day , a single dose of one of the two preparations was administered , and 2 days later a single dose of the another preparation was administered , in r and om order . The effects on lung function ( FEV1 ) were monitored from 15 to 360 min after administration . For both products the increase in FEV1 with reference to baseline values was statistically highly significant . There was no significant difference between the products This multi-centre , r and omized , double-blind , double-dummy , parallel-group study was design ed to investigate the hypothesis of equivalent efficacy and comparable safety of two inhaled presentations of salmeterol/fluticasone propionate combination product ( SALM/FP ) 50/100 microg administered twice daily to patients with mild-to-moderate asthma for 12 weeks . The delivery systems were a 25/50 microg strength hydrofluoroalkane ( HFA ) metered-dose inhaler ( MDI ) and a Diskus inhaler ( 50/100 microg strength ) . A third group received FP 100 microg twice daily via a chlorofluorocarbon MDI ( 50 microg strength ) . A total of 497 patients aged 11 - 79 years with reversible airways obstruction who were symptomatic on inhaled corticosteroid ( ICS ) therapy and had room for improvement in lung function were r and omized to treatment in a double-blind , parallel-group design ( SALM/FP MDI : n=165 ; SALM/FP Diskus : n=167 ; FP MDI : n=165 ) for 12 weeks . A total of 383 patients completed the study according to the protocol . According to the primary efficacy variable , increase in mean morning PEF over weeks 1 - 12 , the two inhaled presentations of SALM/FP were clinical ly equivalent ( adjusted mean increases 43 and 46 l min(-1 ) ; treatment difference 3 l min(-1 ) ; 95 % confidence interval : -6 to 11 l min(-1 ) ) . Equivalence was also demonstrated by all secondary efficacy measures . The SALM/FP MDI was significantly superior to the FP MDI for increase in mean morning PEF ( treatment difference 19 l min(-1 ) ; P<0.001 ) and for all secondary measures except FEV1 and symptom-free nights . There was no significant difference between the groups with respect to adverse events and serum cortisol levels . These results demonstrate that the SALM/FP 25/50 microg HFA MDI ( two inhalations twice daily ) is clinical ly equivalent to the SALM/FP 50/100 microg Diskus ( one inhalation twice daily ) . Patients switching to SALM/FP from other MDI-based asthma treatments may now do so without a change of delivery device AIM The replacement of chlorofluorocarbon ( CFC ) by hydrofluoroalkane has the potential to improve airway deposition of BDP . We investigated whether HFA-BDP extra-fine solution aerosol 400 microg day(-1 ) is as effective as CFC-BDP 1000 micro day(-1 ) in patients with stable , moderate asthma , having persistent bronchial hyperresponsiveness . PATIENTS AND METHODS One hundred and fifty patients with moderate asthma from 20 centres , on inhaled steroids for < or = 3 months , entered a 4-week run-in period with 1000 microg day(-1 ) CFC-BDP . Patients were then allocated to a 10-week study phase , receiving CFC-BDP 1000 microg day(-1 ) or HFA-BDP 400 microg day(-1 ) . Symptom score and PEF were measured daily and recorded as biweekly means . Spirometry , PC20FEV1 , blood eosinophils and serum ECP were determined on days 15 , 29 , 43 and 71 , and compared to the last visit of the run-in period . All group members were trained in a quality control centre . RESULTS Treating the population of the HFA-BDP group ( n = 72 ) and the CFC-BDP group ( n = 78 ) did not show significant differences in terms of symptoms , lung function , airway hyperresponsiveness and serum markers of inflammation at the end of the run-in period and the end of the study phase . CONCLUSION Using HFA instead of a CFC metered dose inhaler , containing less than half the daily dose of BDP , allows control of symptoms and lung function parameters , without changes in bronchial hyperresponsiveness The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has result ed in the development of alternative devices to deliver drug to the pulmonary airways . These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers . The purpose of this study was to compare the single- and multiple-dose pharmacokinetics , pharmacodynamics , and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide ( Azmacort HFA 225 mcg Inhalation Aerosol ) to that of the dry-powder formulation of budesonide ( Pulmicort Turbuhaler 200 mcg ) . This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide , 600 mcg dose of budesonide , or placebo twice a day for 5 days . Serial plasma sample s were collected after the first and last dose of test medication for pharmacokinetic analysis . Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol , 24-hour overnight serum cortisol AUC(0 - 24 ) , and 24-hour urinary-free cortisol after the last evening dose of test drug . Tolerability was assessed through physical examinations , vital signs , 12-lead ECG , routine clinical labs , and adverse events recording . Both compounds were systemically absorbed . However , no significant drug accumulation was noted with chronic dosing . Chronic dosing did result in a statistically significant 20 % reduction in basal 24-hour serum cortisol AUC(0 - 24 ) for both compounds . There were no clinical ly significant abnormalities in physical examination , vital signs , 12-lead ECG , or routine clinical labs noted during the study . Overall , the study drugs were well tolerated , with adverse events characterized as mild to moderate in severity BACKGROUND most patients use their inhalers incorrectly and recent asthma management clinical guidelines recommend demonstrating skills and correcting performance at each asthma follow-up visit . However , this statement is poorly evidence -based and few intervention studies have assessed quantitatively the effectiveness of this recommendation . METHODS from a total of 3,076 children and adolescents with asthma attending an outpatient clinic , a r and om , representative sample of 255 was obtained and assessed at baseline with a st and ardised question naire regarding their skills when using one of three inhaler devices : pressurised direct aerosol ( PDA ) , dry powder ( DP ) and aerosol pressurised in exp and ed camera ( APEC ) . Structured sessions of correct use and h and ling of inhalers were offered and a new assessment was undertaken after an average of 10.5 months ( SD 4.5 ) . RESULTS only 142 asthmatics maintained the same inhaler device during the study period . An increase of correct manoeuvres was observed for all three devices , and the relative risk and 95 % confidence interval ( RR and 95 % CI ) of incorrect post-intervention use was 0.23 ( 95 % CI 0.10 - 0.56 ) for PDA , 0.59 ( 95 % CI 0.38 - 0.92 ) for DP , and 0.54 ( 95 % CI 0.32 - 0.90 ) for APEC . A multivariate analysis indicates that this improvement was observed irrespective of gender and age interval , and that it was even better when parents cooperated with medical and nursing staff . CONCLUSIONS a dramatic improvement in correct manoeuvres with any of three inhaler devices after active performance training was observed . This easy , highly effective , low cost ( in terms of time and personnel ) intervention should be routinely implemented in any control visit of asthmatics , leading to a better management of asthma BACKGROUND Pulmonary administration of beta 2-agonists by means of pressurized metered dose inhaler is widely used in the treatment of asthma . Young children have difficulties in using these inhalers unless a spacer device is used . To overcome this problem inspiratory flow driven dry powder inhalers have been developed . OBJECTIVE The aim of this study was to compare the efficacy and safety of the two powder inhalers Bricanyl Turbuhaler ( terbutaline sulphate 0.5 mg t.i.d . ) and Ventolin Rotahaler ( salbutamol 0.4 mg t.i.d . ) in 20 children 2 to 6 years old with mild to moderate asthma . METHODS The study had an open r and omized crossover design with 1 week run-in without treatment and the two treatment periods of 2 weeks each . Efficacy was measured with peak expiratory flow determination , asthma symptom scores , and need for rescue medication . Adverse events were recorded . RESULTS Peak expiratory flow increased significantly ( P < .001 ) after both treatments . There were no statistically significant differences in peak expiratory flow , asthma symptom scores , need for extra inhalations , or adverse events between the devices . Most children ( parents ) preferred the Turbuhaler . CONCLUSION Both Bricanyl Turbuhaler and Ventolin Rotahaler seem to be effective and well tolerated in the treatment of asthma in preschool children . Of special interest is that even the youngest children in the study group were able to use these powder inhalers Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol ( 1 ) . In this multi-centre , r and omized , double-blind study , the therapeutic equivalence of two formulations of beclomethasone dipropionate ( BDP ) containing CFC or non-CFC ( HFA134a ) propellant , both delivered via the Easibreathe ( Norton Healthcare Ltd , London , U.K. ) inhaler , was determined in 229 asthmatic children . Each child received 100 microg doses of BDP ( containing either CFC or HFA propellant ) twice daily for 12 weeks . Both CFC and HFA formulations produced statistically and clinical ly significant improvements in patient 's lung function and symptom scores when administered via the Easibreathe inhaler . The improvements in mean morning peak expiratory flow ( PEF ) were 41 l min(-1 ) and 34 l min(-1 ) for the BDP-HFA and BDP-CFC products respectively ( P<0.001 ) and for mean evening PEF the improvements were 38 l min(-1 ) and 38 l min(-1 ) , respectively ( P<0.001 ) . Similar findings were demonstrated for the other efficacy parameters . The two formulations were statistically equivalent with respect to efficacy . For mean morning PEF the estimated treatment difference ( BDP-CFC/BDP-HFA ratio ) was 102.6 % ( 95 % CI 99.1 , 106.2 ) . Similar equivalence was shown for the other efficacy parameters . Both products were well tolerated , with no difference in the adverse event profiles , effects on 24 h urinary cortisol or C and ida colonisation . This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner . This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out . In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children BACKGROUND The prevalence of allergy to natural rubber latex proteins has increased over recent years among healthcare professionals but also in children undergoing multiple operations . Exposure to the antigen mainly occurs through the respiratory mucosa and the percutaneous route . Clinical manifestations range from urticaria to angioedema , rhinoconjunctivitis , bronchial asthma , or anaphylactic shock . Preventive measures have been proposed to reduce the risk of sensitization by using only powder-free or synthetic gloves and latex-free material in operating units , but this is not always possible . OBJECTIVE The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers . METHODS Seventeen patients with latex skin allergy and rhinitis ( 9 of whom also had asthma ) were included in this r and omized , double-blind , placebo-controlled trial ( 9 in the active group and 8 in the placebo group ) for 1 year . Treatment started with a 2-day course of rush immunotherapy in hospital . Treatment efficacy was assessed after 6 and 12 months by means of symptom and medication scores recorded on diary cards . Conjunctival provocation tests were also performed . RESULTS Patients in the active treatment group had a significantly lower total rhinitis score after 6 ( P < . 04 ) and 12 months ( P < .05 ) , conjunctivitis score after 6 months ( P < . 02 ) , and cutaneous score after 12 months ( P < .03 ) than in the placebo group . Asthma symptoms after 6 or 12 months of treatment were not significantly different between the two groups after adjustment for baseline values . The global medication score was markedly decreased in the latex-treated group . A significant difference in conjunctival reactivity was observed in favor of the active group : the number of patients for whom the threshold dose was increased after 12 months of treatment was significantly greater in the active group than in the placebo group ( P < .02 ) . Most injections were well tolerated , but several adverse effects , including hypotension , urticaria , wheezing , and pharyngeal edema , were observed . CONCLUSION The clinical benefits observed during the present study included a significant improvement of rhinitis , conjunctivitis , and cutaneous symptoms . Immunotherapy also decreased allergen-specific conjunctival reactivity . Latex-specific immunotherapy may allow sensitized personnel to remain at work , but further trials need to be conducted in a larger number of patients Abstract Objective : To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries . Design : Prospect i ve study of drugs administered to children in general paediatric medical wards over four weeks . Setting : Children 's wards in five hospitals ( one each in the United Kingdom , Sweden , Germany , Italy , and the Netherl and s ) . Subjects : Children aged 4 days to 16 years admitted to general paediatric medical wards . Main outcome measure : Proportion of drugs that were used in an unlicensed or off label manner . Results : 2262 drug prescriptions were administered to 624 children in the five hospitals . Almost half of all drug prescriptions ( 1036 ; 46 % ) were either unlicensed or off label . Of these 1036 , 872 were off label and 164 were unlicensed . Over half of the patients ( 421 ; 67 % ) received an unlicensed or off label drug prescription . Conclusions : Use of off label or unlicensed drugs to treat children is widespread . This problem is likely to affect children throughout Europe and requires European action . Key messages Many drugs are not tested in children , which means that they are not specifically licensed for use in children Licensed drugs are often prescribed outside the terms of the product license ( off label ) in relation to age , indication , dose of frequency , route of administration , or formulation Over two thirds ( 67 % ) of 624 children admitted to wards in five European hospitals received drugs prescribed in an unlicensed or off label manner 39 % of the 2262 drug prescriptions given to children were off label The problem of off label and unlicensed drug prescribing in children is a European problem that requires European The phasing out of chlorofluorocarbons ( CFCs ) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers ( pMDIs ) . The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane ( HFA ) 134a in patients with mild to moderate asthma . After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI , 547 patients were r and omized to 12 weeks of treatment with salbutamol  200 microg four times daily administered from either an HFA 134a  pMDI ( Ventolin CFC-free ; 277 patients ) or  CFC  pMDI ( Ventolin , 270 patients ) . At the end of this period , all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI ( run-out period ) . On the basis that high doses of beta2-agonists are known to increase heart rate , change in heart rate was selected as the primary outcome variable . Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups ; the 90 % confidence interval for the treatment differences was within the predefined limits for clinical equivalence ( + /- 10 beats min(-1 ) ) . The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm . Furthermore , daily PEF measurements showed comparability in terms of lung function . Symptom scores and use of additional bronchodilator were also similar in both groups . These results demonstrate that salbutamol ( 800 microg day(-1 ) ) , formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy UNLABELLED Spacing devices such as the Aerochamber have been shown to improve delivery of medication from MDIs in patients who could not use proper technique with an MDI alone , but the  Aerochamber may be inconvenient to carry & use because of its bulkiness . We therefore compared clinical responses of asthmatics using a new , smaller MDI actuator ( Gentle-Haler ) with no spacer to their responses using a st and ard MDI actuator & spacer ( Aerochamber ) . METHODS We treated 30 asthmatic patients in 2 sessions with the beta-agonist albuterol  using the above-mentioned devices . Both devices were utilized in each treatment session , with one delivering albuterol & the other generating a placebo . During the second session on a different day , the albuterol & placebo were reversed with respect to the two devices . On each study day , physiologic measurements of FEV1 , FVC , FEF25 - 75 , blood pressure , & pulse were obtained at pretreatment ( baseline ) & after treatment at 15 & 30 minutes & 1 , 2 , 3 , 4 , 5 & 6 hours . Analysis of variance & Student 's t test were used to compare the ratio of physiologic responses to albuterol delivered with the two devices . RESULTS Both devices were equally effective in eliciting desirable increases in FEV1 , FEF25 - 75 , & FVC . No statistically significant differences ( 5 % significance level ) in effectiveness of the albuterol were associated with the use of either device . A very small ( < 7 % ) but statistically significant reduction in diastolic blood pressure ( 3 of 8 time points ) & systolic pressure ( 1 of 8 time points ) was associated with the use of the Gentle-Haler . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to assess if administration of bronchodilator via a metered dose inhaler ( MDI ) , rather than by a nebulizer , avoided the early paradoxical deterioration in lung function but , result ed in equally effective late bronchodilation .  Fifteen children were studied at a median postnatal age of 9 months ( range 9 - 18 ) , all had been born prematurely at a median gestational age of 27 weeks ( range 23 - 31 ) .  Lung function was measured by plethysmography before and 10 min after normal saline and 5 and 15 min after salbutamol given via an MDI and a nebulizer in r and om order . At 5 min , compared to baseline values , airways resistance ( RAW ) deteriorated by 16 % after nebulized salbutamol but improved by 3 % following salbutamol by the MDI ( P < 0.03 ) . At 15 min RAW improved by 14 % following nebulized salbutamol and 15 % after salbutamol via the MDI , there was no significant difference in the magnitude of bronchodilation between the two methods of administration . Our results therefore suggest , that as the early paradoxical deterioration in lung function is usually avoided by administering salbutamol via an MDI , this should be the preferred method of administration The study was design ed to test for equivalence of asthma control between a new aerosol formulation of beclomethasone dipropionate ( BDP ) incorporating a chlorofluorocarbon-(CFC ) free , hydrofluoroalkane propellant ( HFA-134a ) and the conventional beclomethasone aerosol formulated in CFC propellants .  Sixty-eight asthmatic patients entered an eight-week , r and omised , double-blind crossover study . All patients , previously stabilised on BDP , were r and omised to receive the same dose of BDP from each of the study treatments . Statistically significant equivalence was demonstrated between HFA-BDP and CFC-BDP for asthma control parameters : FEV1 , morning and evening PEF , sleep disturbance , wheeze and cough , morning breathlessness and bronchodilator use . Such equivalence was also demonstrated for safety parameters . To conclude , it has been demonstrated that HFA-BDP achieves a level of asthma control that is clinical ly and statistically equivalent to CFC-BDP in terms of efficacy and safety , at total daily doses ranging from 200 micrograms to 600 micrograms in asthma patients previously stabilised on inhaled CFC-BDP The effect of a new breath actuated dry powder inhaler , the Turbuhaler , was found to be reduced at inhalations slower than 28 1/minute . This flow rate could be generated by virtually all children aged greater than or equal to 6 years , by 42 of 57 children less than 6 years ( 74 % ) , and by six of 15 preschool children with acute wheeze ( 40 % ) BACKGROUND Salmeterol , a long-acting beta2 -agonist , and zafirlukast , a leukotriene receptor antagonist , are both indicated for the treatment of asthma in adolescent and adult patients . OBJECTIVE We sought to compare the effect of 4 weeks of treatment with inhaled salmeterol xinafoate versus oral zafirlukast in the treatment of persistent asthma . METHODS This was a r and omized , double-blind , double-dummy , parallel-group , multicenter clinical trial . Patients , over 80 % of whom were on a concurrent inhaled corticosteroid regimen , were treated for 4 weeks with either inhaled salmeterol xinafoate 42 microgram twice daily administered by means of a metered-dose inhaler or oral zafirlukast 20 mg twice daily . The primary efficacy measure was morning peak expiratory flow ( PEF ) ; secondary efficacy measures included evening PEF , asthma symptom scores , supplemental albuterol use , nighttime awakenings , sleep symptoms , asthma exacerbations , and FEV1 . RESULTS Both inhaled salmeterol and oral zafirlukast result ed in within-group improvements from baseline in measures of pulmonary function , asthma symptoms , and supplemental albuterol use . Salmeterol treatment result ed in significantly greater improvements from baseline compared with zafirlukast for most efficacy measurements , including morning PEF ( 29.6 vs 13.0 L/min ; P < /= .001 ) , percentage of symptom-free days ( 22.4 % vs 8.8 % ; P < /= .001 ) , and percentage of days and nights with no supplemental albuterol use ( 30.5 % vs 11.3 % ; P < /= .001 ) . There were no differences in safety profiles as assessed by adverse event monitoring . CONCLUSION In patients with persistent asthma , most of whom were concurrently using inhaled corticosteroids , treatment with inhaled salmeterol provided significantly greater improvement than oral zafirlukast in overall asthma control over the 4-week treatment period BACKGROUND Triamcinolone acetonide ( TAA ) inhalation aerosol ( Azmacort Inhalation Aerosol ) , a well-established corticosteroid treatment for bronchial asthma , utilizes the chlorofluorocarbon ( CFC ) propellant P-12 , which will be phased out because of environmental concerns . Two TAA aerosol formulations have been developed using a non-chlorofluorocarbon propellant , HFA-134a ( Azmacort HFA Inhalation Aerosol delivering TAA 75 microg/puff or 225 microg/puff ) . OBJECTIVE This study compared the efficacy and safety of the new 225 microg/puff formulation ( TAA-HFA 225 ) to the marketed TAA inhalation aerosol ( TAA-CFC ) and to placebo in adult patients with moderate-to-severe persistent asthma . METHODS After a 5-day to 21-day baseline period during which all patients received TAA-CFC 150 microg/day , 538 patients were r and omized to one of the following treatment schedules : TAA-HFA 450 , 900 , or 1800 microg/day ; TAA-CFC 450 or 900 microg/day ; or placebo for 12 weeks . RESULTS All active treatment groups showed statistically significant improvement compared with placebo in pulmonary function ( FEV1 , FEF25 - 75 % , morning and evening PEF ) , use of rescue albuterol , and asthma symptom scores . Improvements in all variables occurred within 1 week of treatment . CONCLUSIONS The TAA-HFA 225 exhibited similar safety and efficacy profiles to the two equivalent doses of TAA-CFC studied . Our findings indicate that TAA-HFA is a safe and effective replacement for the currently marketed CFC-containing product . The higher strength 225 microg/puff formulation provides effective control of asthma with fewer inhalations Because chlorofluorocarbons ( CFCs ) contribute to depletion of stratospheric ozone , CFC-containing metered-dose inhalers ( MDIs ) such as Ventolin and Proventil are being phased out of production . In terms of delivery of albuterol to the lungs , we compared an alternative delivery system , the Spiros dry-powder inhaler ( DPI ) , with Ventolin , using a methacholine challenge-based clinical bioassay . Twenty-four adults and adolescents with asthma completed this double-blind , four-period crossover study . Doses evaluated were one and three actuations each of Spiros and Ventolin ( 90- and 270-microgram albuterol base ) . A methacholine challenge ( Cockcroft method ) was initiated 3 h before and 0.25 h after albuterol . Predose PC(20)FEV(1 ) values were not significantly different between study days . Postdose PC(20)FEV(1 ) results met st and ard bioassay study validity criteria : i.e. , a significant dose-response relationship was present ( p = 0.0002 ) ; tests for deviation from parallelism and overlap of dose-response curves were nonsignificant ( p = 0.08 , 0.69 ) . By using Finney 2-by-2 bioassay analysis , we estimate that each Spiros actuation delivers 1.12 times as much albuterol to the airways as one Ventolin actuation ( 90 % confidence interval , 0.68 to 1.94 ) . There were no significant differences in markers of systemic effects ( vital signs , potassium , and blood glucose concentrations ) . We conclude that Spiros and Ventolin inhalers deliver comparable quantities of albuterol to the airways STUDY OBJECTIVE This study compares the efficacy and safety of one and two actuations of albuterol sulfate powder delivered via a breath-actuated , effort-assisted , investigational inhaler ( Spiros , Dura Pharmaceuticals , Inc ) and albuterol delivered via a conventional propellant-driven metered dose inhaler ( Ventolin , Glaxo , Inc ) . DESIGN R and omized , double-blind , placebo-controlled , 5-way crossover study . PARTICIPANTS Sixty patients with mild-to-moderate asthma ( FEV1 59 % predicted ) were enrolled and 44 completed the study . MEASUREMENTS AND RESULTS FEV1 values over 6 hours were analyzed by ANCOVA and the Finney relative potency model . The relative potency of the inhalers ( albuterol MDI : albuterol DPI ) was 1.132 ( 90 % CI , 0.680 to 2.252 ) indicating 1.132 actuations of albuterol MDI provided the same bronchodilation as one actuation of albuterol DPI . ANCOVA analyses further indicated that there were no significant differences between the two delivery systems with respect to FEV1 , FVC , FEF25 - 75 % , or PEF . Both inhalers had similar effects on serum potassium levels , QTc interval , blood pressure , and heart rate . CONCLUSIONS In patients with mild-to-moderate asthma in this study , the albuterol DPI was determined to be therapeutically comparable to albuterol MDI in the delivery of one and two actuations of albuterol The purpose of the study was to determine the age at which young asthmatic children could master the use of a new powder inhaler device ( Turbuhaler ) . We studied 59 children with asthma between the ages of 3 and 6 years who consecutively attended the asthma clinic of the pediatric department .  Efficiency of inhalation and the pharmacological effect of the terbutaline in the inhaler were measured by scores for inhalation technique and clinical response . None of the 3-year-old children used the device efficiently , but 43 % of the 4-year-old , 67 % of the 5-year-old , and 80 % of the 6-year-old children used the inhaler correctly . Although inhaler technique was not perfect in the younger age group , 50 % of the 3-year-old children demonstrated clinical improvement of asthma symptoms after inhalation . In the older age groups , 79 % , 92 % , and 100 % of the 4 , 5 , and 6-year-old children demonstrated clinical improvement of asthma symptoms after inhalation . It is concluded that the new mode of dry powder delivery system ( Bricanyl Turbuhaler ) can be used in young asthmatic children who are 4 years of age and above A total of 323 children aged 4 - 11 years who were receiving , or had symptoms indicating a clinical requirement for , inhaled corticosteroid at a daily dose of 400 micrograms budesonide ( BUD ) or beclomethasone dipropionate ( BDP ) , or 200 micrograms fluticasone propionate ( FP ) , were r and omised into this multicentre , open-label , parallel group study . Patients received either FP 100 micrograms b.d . administered via the Accuhaler/Diskus inhaler ( n = 159 ) or BUD 200 micrograms b.d . administered via a Turbohaler inhaler ( n = 164 ) for four weeks and recorded daily their morning and evening peak expiratory flow ( PEF ) , asthma symptoms and use of relief medication . Device h and ling was assessed by a question naire , with responses recorded on three- or five-point ordinal scales . The primary efficacy parameter was mean percent predicted morning PEF . The device h and ling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use , ease of telling how many doses were left , ease of knowing whether a dose had been inhaled and overall liking of the device . More patients in the Accuhaler/Diskus group ( 85 % ) than in the Turbohaler group ( 58 % ) said they would be happy to receive the same device again , while 8 % and 25 % respectively said they would not be happy to be given it again . In addition , the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group , indicating that FP 200 micrograms daily via Accuhaler/Diskus inhaler is at least as clinical ly effective as BUD 400 micrograms daily via the Turbohaler inhaler BACKGROUND The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use . A more concentrated formulation delivering 84 microg per puff was developed to provide for a more convenient twice-daily dosing regimen . OBJECTIVE This r and omized , single-blinded , positive and placebo-controlled , parallel-group , multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 microg double-strength metered-dose inhaler ( Vanceril 84 microg Double Strength Inhalation Aerosol/Key ) to cause hypothalamic-pituitary-adrenocortical axis suppression . METHODS Beclomethasone dipropionate double-strength 84 microg was compared with beclomethasone dipropionate regular-strength 42 microg , orally administered prednisone , and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma .  Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 microg of beclomethasone dipropionate . Oral prednisone was administered by mouth at 10 mg once a day . The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone ( ACTH ) stimulation test using cosyntropin 250 microg in 500 mL normal saline infused over six hours on the 36th day of treatment . Sixty-four patients completed this study . RESULTS No clinical ly significant post- study findings were observed from physical examination , electrocardiogram , or clinical laboratory evaluation for any treatment group . No serious or unexpected adverse events were reported . On the 36th day of treatment , there was a significant ( P < .01 ) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion . There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group . In addition , comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference . CONCLUSION Beclomethasone dipropionate , administered either via a double-strength ( 84 microg/puff ) or regular-strength ( 42 microg/puff ) inhaler dosed at 840 microg/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma The bronchodilator response after five different modes of salbutamol inhalation by rotahaler was assessed in 15 asthmatic children in a double blind cross over study . Inspiratory flow rates lower than 50 litres/minute were associated with a significant reduction in response compared with flow rates higher than 60 litres/minute , but tilting the head back during inhalation and holding the breath for 10 seconds had no significant effect on bronchodilation . Peak inspiratory flow rates measured in 150 normal children and 13 asthmatic children with acute wheeze showed that many young children and many children with severe bronchoconstriction were unable to generate a sufficiently high inspiratory flow rate to obtain maximum benefit from rotahaler treatment . Children using a rotahaler should be taught to inhale as quickly as possible and not with a quiet deep breath as recommended in the instruction leaflets Thirteen children with asthma were treated with cumulative doses of terbutaline delivered as a pressurized aerosol and from a new multidose powder inhaler ( Turbuhaler ) in a r and omized cross-over dose-response study . The cumulative dose of terbutaline was 2 mg on each study day . All children used a correct aerosol inhalation technique . At no time was there any difference in forced expiratory volume in 1 s ( FEV1 ) , forced midexpiratory flow , forced vital capacity , peak expiratory flow rate , or percent increase in these parameters between the two inhalers . The mean total increases in FEV1 after 2 mg terbutaline were 60 % ( aerosol ) and 62 % ( Turbuhaler ) ; 90 % of these increases were measured after a cumulative dose of 0.5 mg terbutaline . One milligram of terbutaline inhaled from a Nebuhaler at the end of each study day did not result in additional increase of pulmonary functions , indicating that maximal bronchodilation had been achieved with both inhalers . After a cumulative dose of 2 mg terbutaline from the aerosol seven children complained of tremor and one of restlessness . No side effects were reported when the Turbuhaler was used ( P less than 0.02 ) . 1989 ; 7:00 - 00 A total of 198 children aged 3 to 15 years inhaled a single dose of 200 micrograms budesonide from a Nebuhaler pressurized metered dose inhaler ( pMDI ) and a Turbuhaler dry powder inhaler in a r and omized crossover study . The budesonide dose delivered to a patient was assessed by measuring the amount of drug deposited on a filter inserted between the inhaler outlet and the patient 's mouth . The dose of budesonide deposited on the filter and the estimated dose of particles with a mass median aerodynamic diameter ( MMAD ) of 5 microns or less after inhalation from the Turbuhaler were both approximately twice the values inhaled from the pMDI Nebuhaler in children less than 5 years of age ( P < 0.01 ) . The variation in the dose delivered to the patient was similar for the two inhalers in children over 5 years old . In 3- to 4-year-old children , dose delivery to the patient was higher and /or more consistent from the pMDI Nebuhaler than from the Turbuhaler . Filter dose after Turbuhaler treatment varied significantly from peak inspiratory flow rate through the Turbuhaler ( PIFTbh ) ( P < 0.01 ) . The percentage of children producing a PIFTbh greater than 50 L/min decreased with age ( 89 % , 45 % , and 14 % in 5- , 4- , and 3-year-old children , respectively ) . It is concluded that drug delivery to a child with asthma varies with age and inhalation device . Further studies are needed to assess the clinical importance of this finding The aim of this study was to evaluate the efficacy , safety and preference of pre‐school children with regard to two different devices for treatment of bronchial asthma with terbutaline . Turbuhaler , a powder inhaler preloaded with pure terbutaline for inhalation , was compared with a pressurized metered dose inhaler , attached to a Nebuhaler . The study had an open , cross‐over r and omized design . Each treatment period consisted of 2 weeks . Diary cards were filled in every morning and evening by the parents regarding PEF , asthma symptoms , extra inhalations of terbutaline , and side effects .  Twenty‐one children ( mean age 3.9 years ) were included in the study . A highly significant ( P < 0.001 ) increase in peak expiratory flow ( PEF ) was obtained after inhalation with both devices . The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher ( P= 0.046 ) than those with Nebuhaler . Further , the PEF baseline values in the evenings before inhalation were also significantly higher ( P= 0.03 ) with Turbuhaler .  No difference was found in asthma symptoms and extra medication between the two devices . Side effects were mild and few with both devices . The parents found Turbuhaler easier to h and le and 19 of 21 preferred this device for future use OBJECTIVE To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler ( Turbuhaler ) in children with moderate to severe persistent asthma . STUDY DESIGN In our r and omized , double-blind , placebo-controlled , parallel-group , multicenter study , a total of 404 children with asthma , who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy  , were r and omly assigned to receive either 100 , 200 , or 400 micrograms of budesonide or placebo twice daily for 12 weeks . At baseline , mean forced expiratory volume in 1 second ( FEV1 ) was 74.6 % ( range , 30.7 % to 123.3 % ) of the predicted normal value . RESULTS Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function ( morning peak expiratory flow and FEV1 ) , in asthma symptoms , and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo . Improvements were evident within 2 weeks and were maintained throughout the 12 weeks . Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function , and the incidence of reported adverse events was similar in all treatment groups . CONCLUSION Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children ( 6 to 18 years of age ) with moderate to severe persistent asthma Turbuhaler ® is a ready‐loaded multiple dose inhaler which does not require co‐ordination between release of dose and inhalation . 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler ( MDI ) . The trial consisted of two parts . In the first part of the study , which made use of a double‐blind cross‐over design , the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI . In the second part , which was open , all patients were treated with Turbuhaler for 2 weeks . At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference . There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI . A majority of the patients thought Turbuhaler had the best effect and was easy to use Twenty-two asymptomatic asthmatic children and twenty-one healthy controls aged between 4 and 8 years old were studied in order to determine peak inspiratory flow ( PIF ) in baseline conditions through a Turbuhaler powder aerosol device .  PIF was measured r and omly on one of three days using computerized spirometry . In healthy children , baseline PIF ranged from 129 to 244 L/min ; PIF through the Turbuhaler ranged from 72 to 99 l/min . In asthmatics , the ranges were 122 to 236 l/min and 79 to 102 l/min for baseline and Turbuhaler PIF , respectively . PIF was significantly related to age ( p < 0.05 ) . The difference between PIF through the Turbuhaler for asthmatic and healthy children was not significant . PIF of healthy and asthmatic Chilean children between 4 and 8 years of age exceeded the level required to obtain an optimum dose from this type of device . This study suggests that the aerosol powder doses produced by devices such as that used in this study can be used by children from age 4 and older The effects of inhaled terbutaline , a β2-adrenergic agonist , administered via a 750-ml spacer device were studied in young asthmatic subjects with exercise-induced asthma . A double-blind , r and omized , placebo-controlled study of the effects of inhaled 0.5 mg terbutaline and placebo was conducted in 10 asthmatic children ( age range 6–16 years ) with documented exercise-induced asthma . Forced expiratory volume in 1 s ( FEV1 ) was measured at baseline , 15 min after inhaling terbutaline or placebo , and at intervals up to 60 min after exercising . Subjects exercised using a cycle ergometer for 5 min at a submaximal , constant work-load while breathing dry air at room temperature . Terbutaline induced bronchodilation at rest in all subject and fully prevented exercise-induced asthma in nine out of the 10 subjects ; the exercise-induced fall in FEV1 was markedly reduced in the remaining subject . It is concluded that exercise-induced asthma can be inhibited by pretreatment with inhaled terbutaline , administered via a spacer , in a majority of young asthmatics The purpose of this study was to investigate the relative effectiveness of 0.25 mg , 0.5 mg , and 1.0 mg of terbutaline , administered via Turbuhaler , in children with mild to moderate asthma , and to register peak inspiratory flow rates through Turbuhaler ( PIFTBH ) . Thirty-seven children in Portugal ( one center ) and 45 children in Sweden ( one center ) aged 3 - 10 years participated in two separate , double-blind , placebo-controlled , crossover , and r and omized studies of the same design . Because of differences in other therapies for asthma and climate , combination of the two studies into one met analysis did not appear appropriate . The children inhaled 0.25 mg , 0.5 mg , and 1.0 mg terbutaline sulfate and placebo t.i.d . for consecutive 2-week periods without washout periods . Peak expiratory flow rates ( PEF ) were measured at home before and 15 minutes after each inhalation in the morning , afternoon , and evening . PIFTBH was measured twice at each of four clinic visits . At the Portuguese center the increases in mean morning PEF from before to after inhalation were 32 L/min after 0.25 mg , 35 L/min after 0.5 mg , and 40 L/min after 1.0 mg . The corresponding figures in Sweden were 26 L/min , 31 L/min , and 29 L/min after 0.25 mg , 0.5 mg , and 1.0 mg , respectively . For children 3 - 6 years , mean values for PIFTBH were 60 L/min in Portugal ( n = 15 ) , and 58 L/min in Sweden ( n = 23 ) . In the 7 - 10 year group the mean PIFTBH was 72 L/min ( n = 22 ) in Portugal , and 68 L/min ( n = 22 ) in Sweden . We conclude that inhalation of terbutaline sulfate via Turbuhaler at a small dose of 0.25 mg result ed in good bronchodilation and was comparable to inhalations of 0.5 mg and 1.0 mg in children aged 3 - 10 years with mild to moderate asthma . PIFTBH were comparable to values previously recorded in healthy 6-year-old and older children and in adult asthmatic patients Seventeen children with asthma were studied in a double-blind , crossover , placebo-controlled study design ed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma . All drugs were delivered through a metered-dose inhaler ( cromolyn sodium , 10 mg ; nedocromil sodium , 4 mg ; placebo , two puffs ) . Nedocromil sodium and cromolyn sodium provided significant , comparable protection from exercise-induced asthma , and both drugs were better than placebo . We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children One hundred and eighty-one children with asthma were entered into a r and omized , controlled , crossover study comparing sodium cromoglycate via a metered dose inhaler ( MDI ) and a breath-actuated inhaler ( Autohaler ) . There were no significant differences in pulmonary function tests ( FEV1 , FVC , PFER ) , symptom scores and bronchodilator use between the two devices . However both patients ' and clinicians ' opinions of  sodium cromoglycate effectiveness were significantly better ( P < 0.01 ) for the Autohaler . Autohaler was also thought to be easier to use ( P < 0.001 ) and better for co-ordination of actuation with inhalation ( P < 0.001 ) . The Autohaler is as efficacious as the metered dose inhaler used by good co-ordinators . It seems to be the significantly better device with respect to ease of use , actuation and co-ordination which may aid compliance AIM The aim of the study was to compare the efficacy of single doses of salbutamol Turbuhaler ( 50 and 100 microg ) , salbutamol pressurized metered dose inhaler ( pMDI ) ( 100 microg ) and placebo in children with stable chronic reversible airway obstruction .  Primary efficacy variable ( FEV1-av ) was calculated as the area under the curve of forced expiratory volume in one second ( FEV1 ) ( AUC , 0 - 4 h ) and divided by the observed time . DESIGN The study was of a r and omized , single-dose , crossover and double-blind design . Seven centres participated .  FEV1 was measured pre-dose and at 15 min , 0.5 , 1 , 1.5 , 2 , 3 and 4 h post study dose . PATIENTS Forty asthmatic children ( 9 girls ) with a mean age of 9 years ( range : 6 - 12 ) , mean FEV1 of 1.6 l ( range : 0.9 - 2.4 ) and a mean FEV1 in percentage of predicted normal value of 80 % ( range : 61 - 109 ) were r and omized into the study . The mean reversibility 30 min after inhaling 2x100 microg salbutamol from pMDI was 20 % ( range : 9 - 45 ) or 15 % ( range : 8 - 27 ) in percentage of predicted normal value . RESULTS The mean FEV1-av was 1.63 l for placebo , 1.71 l for 50 microg salbutamol Turbuhaler , 1.76 l for 100 microg salbutamol Turbuhaler and 1.76 for 100 microg salbutamol pMDI . Corresponding values for maximum FEV1 were 1.76 , 1 . 85 , 1.87 and 1.87 l , respectively . There were no statistically significant differences between the active treatments in FEV1-av or maximum FEV1 . All active treatments were significantly better than placebo . CONCLUSION No significant differences in bronchodilating effect between 50 , 100 microg salbutamol Turbuhaler and 100 microg salbutamol pMDI in children , aged 6 - 12 years , with stable asthma could be demonstrated . All active treatments were significantly better than placebo A dose-ranging study and a 12-week treatment study were conducted in children with asthma , aged 4 to 12 years , to assess the efficacy and safety of albuterol inhaled as either an aerosol or as dry powder . Both studies were double-blind and placebo-controlled with r and omized assignment to treatment . The dose-ranging study in 30 patients indicated that similar single doses of albuterol aerosol and powder had comparable effects with the intermediate doses ( i.e. , 180 micrograms of aerosol and 200 micrograms of powder ) providing effective bronchodilation with minimal adverse effects . In the subsequent 12-week , parallel-group study , 204 children received  albuterol as either aerosol , 180 micrograms , or powder , 200 micrograms four times a day . Both formulations were equally effective with no untoward cardiovascular effects and only one incident of mild tremor . Among those children who expressed a preference for one of the delivery systems , significantly more children preferred the powder ( 44 % versus 26 % , p less than 0.01 ) . Albuterol taken four times a day as either aerosol or dry powder is both effective and well tolerated in children with asthma The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases . We thus conducted a r and omized , double-blind and double-dummy , four-period crossover study in 13 patients with moderate asthma ( mean age 36 yr ; FEV1 59 % of predicted ) , who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler ( pMDI ) or Turbuhaler ( TBH ) . Pulmonary deposition was 8.1 + /- 2.7 % and 8.3 + /- 2.3 % , respectively , of the nominal dose for pMDI and 19.0 + /- 7.3 % , and 22.0 + /- 8.1 % for TBH . The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI . No significant differences in FEV1 increase were observed between 0.25 mg via TBH , 0.5 mg via pMDI , or 0.5 mg via TBH . Other lung function variables showed similar dose- and device-related changes . We concluded that : ( 1 ) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used ; ( 2 ) TBH delivers about twice the amount of drug to the lungs as the pMDI ; and ( 3 ) the observed difference in deposition is reflected in the bronchodilating effect As part of a development programme for a range of new CFC-free beclomethasone dipropionate ( BDP ) inhalers , two multicentre double-blind studies have been conducted to compare the therapeutic equivalence of a new HFA-134a propellant-formulated BDP metered-dose inhaler ( Norton Healthcare Ltd , London , U.K. ) with a CFC counterpart for the management of adult patients with all grade s of asthma . Doses of 100 micrograms qds for 6 weeks were administered in a low dose study and in a high dose study 500 micrograms qds doses were given for 12 weeks . Efficacy assessment s included lung function ( FEV1 ) in the clinic and asthma symptoms , peak flow rates and bronchodilator use by patients on diary cards . Safety parameters measured included routine haematology and biochemistry ( including serum cortisols ) , clinical adverse events and throat swabs for C and ida spp . Both CFC and HFA-formulations of inhaled BDP produced similar and significant improvements in lung function and asthma symptoms . In the low dose study , baseline to endpoint FEV1 increased from 2.2 + /- 0.51 to 2.5 + /- 0.81 ( P = 0.0001 ) with BDP-CFC and from 2.2 + /- 0.51 to 2.6 + /- 0.81 with BDP-HFA ( P = 0.0001 ) , with no significant difference between treatments . In the high dose study , corresponding increases were 2.1 + /- 0.71 to 2.4 + /- 0.91 ( P = 0.0002 ) for BDP-CFC and 2.1 + /- 0.71 to 2.3 + /- 0.71 ( P = 0.017 ) for BDP-HFA . PEF also improved similarly on both treatments in both studies . Both formulations were well tolerated with no difference in the pattern of adverse events , effect on serum cortisol or C and ida colonization . These studies showed that , in the management of asthma , the new HFA-formulated BDP metered dose inhaler is equivalent to , and directly substitutable for , the older CFC-formulated product at the same dose , making change-over for patients straightforward BACKGROUND Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma . OBJECTIVE This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma . METHODS Fluticasone propionate ( 500 microg twice daily ) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a r and omized , double-blind , double-dummy , parallel-group study for 12 weeks . Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone . Subjects were dropped from the study if they met predefined criteria for lack of efficacy . RESULTS Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone . At endpoint , fluticasone propionate significantly improved forced expiratory volume in 1 second ( P < .001 ) , morning and evening peak expiratory flow ( P < .001 ) , and asthma symptom scores ( P < or = .016 ) , and significantly reduced nighttime awakenings ( P = .016 ; Diskhaler group only ) and rescue albuterol use ( P < .001 ) . Overall , efficacy measurements for the Diskus and Diskhaler were similar . More placebo-treated subjects ( 34 % ) withdrew from the study due to lack of efficacy than subjects in the Diskus ( 5 % ) or Diskhaler ( 5 % ) groups . The incidence and severity of adverse events were similar across groups . Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure . CONCLUSION Fluticasone propionate powder , administered via the Diskus or Diskhaler inhalation devices , was well tolerated and effective in the treatment of mild-to-moderate persistent asthma This study was conducted to evaluate children 's and nurses ' preference among the three breath-actuated devices , Turbuhaler ( Astra ) , Autohaler ( 3 M ) and Accuhaler ( Glaxo-Wellcome ) . This was an open study conducted in the paediatric in-patient department of Kwong Wah Hospital , Hong Kong . Subjects over 6 years of age who had not previously used any inhalation devices were recruited . The three devices were in r and om order . The preferences of subjects and nurses were ranked in a three-point scale . The children had a statistically significant preference for Accuhaler  , while the nurses preferred to teach both Accuhaler and Autohaler but not the Turbuhaler STUDY OBJECTIVE To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System ( Dura Pharmaceuticals ; San Diego , CA ) dry powder inhaler ( DPI ) and albuterol ( Ventolin ; Glaxo Wellcome ; Research Triangle Park , NC ) administration using a metered-dose inhaler ( MDI ) in patients with asthma . MATERIAL S AND METHODS This was a phase III , 12-week , r and omized , double-blind , double-dummy , placebo-controlled , parallel-group , multicenter study of 283 adolescent and adult patients with mild to moderate asthma . The patients were r and omized into one of three treatment groups : the Spiros group , who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base ; the MDI group , who were given 90 microg/actuation of albuterol ; and the placebo group . RESULTS Over the length of the study , the Spiros and MDI groups were comparable in all FEV1 parameters . Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits . With the exception of differences at treatment week 0 for the maximum percent change in the FEV1 , the duration of effect , and the area under the curve at baseline , there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters . Using a repeated- measures analysis , the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4 , 8 , and 12 . The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline ( weeks 4 , 8 , and 12 ) and duration of effect . Adverse events and changes in clinical laboratory values , vital signs , ECG results , and physical examinations were reported with similar incidence in each of the three treatment groups . CONCLUSION Both active treatments were superior to the placebo treatment . The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma A prospect i ve study of inhaler technique using aerosol metered dose inhalers ( MDIs ) , Rotahalers and a breath-activated device ( Aerolin Autohaler ) was undertaken to assess how effectively elderly patients use their inhalers . Fifty-one patients aged 67 - 89 years ( mean 77.4 years ) were enrolled .  Peak flow , FEV1 and FVC were recorded , before and after inhalation of 2.5 mg of salbutamol via a nebulizer , to assess the extent of reversible airways obstruction . Inhaler technique was assessed using a scoring system , based on performance in five aspects of inhaler use . Those with poor technique were r and omly allocated to an alternative inhaler and reassessed . Twenty-nine of 51 patients demonstrated reversibility in their airways disease . Twenty-one of 47 had poor technique using an MDI and were given Rotahaler or Aerolin devices to use . Ten of 11 given Aerolin Autohalers improved but seven of ten using Rotahaler showed no improvement ( p = 0.006 ) . Subsequently , five of these seven were able to improve their technique with the breath-activated autohaler . The breath-activated Aerolin Autohaler is a better delivery system than Rotahalers for inhaled bronchodilators for elderly patients The fine particle dose delivered via dry powder inhalers ( DPIs ) is often affected by the inspiratory flow rate generated during inhalation . This has clinical implication s , since the fine particle dose determines the amount of drug reaching the lungs . With Easyhaler DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30 - 60 l min(-1 ) . The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol ( 100 microg ) delivered via Easyhaler at a target inspiratory flow of 30 l min(-1 ) with the same dose of salbutamol via pressurised metered-dose inhaler ( pMDI ) plus spacer . This was a double-blind , r and omized , cross-over study with double-dummy technique . Twenty-one paediatric and adult asthmatic patients completed the study , which was conducted over 2 study days . The main outcome parameter was forced expiratory volume in 1 sec ( FEV1 ) . The patients were trained to generate a low peak inspiratory flow rate ( PIFR ) of 30 l min(-1 ) , and the actual PIFR through Easyhaler was recorded . The average PIFR through Easyhaler was 28.7 l min(-1 ) . The difference in the maximum value of FEV1 ( FEV1max ) between the treatments after drug inhalation was 0.01 l. The mean of FEV1max was 2.67 l after pMDI plus spacer compared to 2.69 l after Easyhaler . Improvements in FEV1 were clinical ly significant . No significant differences between treatments were found . A reasonably low inspiratory flow rate through Easyhaler produces an equivalent improvement in lung function to a correctly used pMDI plus spacer . Hence , Easyhaler can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate , such as children and the elderly This study compared parents ' preference for two spacer devices , NebuChamber ® and Babyhaler ® for the treatment of young children with asthma . In this open , cross‐over study 141 patients ( aged 5–57 mo ) who used inhaled steroids via a spacer device were r and omized to budesonide via NebuChamber or beclomethasone dipropionate via Babyhaler . Both treatments were given by the parents twice daily for 2 wk . At the final visit parents completed a question naire on preference in general and for a given set of features . Acceptability and h and ling were scored in a diary . Diary scores on acceptability by the child and h and ling of both spacer devices were comparable . In the preference question naire , 68 % of parents preferred NebuChamber [ 95 % confidence interval ( CI ) 60–76 ] and 25 % Babyhaler ( 95 % CI 18–33 ) . The preference was independent of the type of spacer used before the study and was also apparent in the different features : acceptability by child , carrying around , cleaning , close fitting of face mask , assembling and disassembling , damage resistance and size . These differences were statistically significant for all features , except for acceptability by the child We compared the pulmonary response to fenoterol delivered by a conventional MDI with the response after MDI plus the aerochamber ( AC ) . Twelve children with moderate to severe asthma ( mean age 10.8 years ) participated in this double-blind crossover study . On two consecutive days , in r and om order , subjects received one puff of fenoterol hydrobromide ( 200 mcg ) either by MDI or MDI plus AC .  Pulmonary function , cardiovascular response and tremor were assessed over a period of four hours . In a similar fashion , the children received one puff of fenoterol three times a day for six weeks by either method in a r and omized open study . Daily symptoms and peak flows before and after drug were recorded in daily diaries . The patients returned to the pulmonary function laboratory at 6 and 12 weeks for four hour pulmonary function tests . In the short-term study , the magnitude and time course of pulmonary response was similar for both treatment regimens ( p greater than 0.4 ) . No significant effects on blood pressure or pulse or differences in tremor assessment were seen . Similarly , in the long term study the baseline pulmonary function and pulmonary response were markedly consistent between the two treatment regimens ( p greater than 0.05 ) . Peak flows were significantly higher in the evening than in the morning ( p less than 0.001 ) and the magnitude of the response to drug was higher in the morning than the evening ( p less than 0.001 ) . There were no differences between MDI and MDI plus AC in daily symptom scores or use of concomitant medication . We conclude that acute or chronic administration of fenoterol aerosol to asthmatic children by MDI with or without the AC produces similar benefits in pulmonary function , symptomatology and concomitant medication . The AC device would be a useful adjunct for a child who has difficulty in coordinating the metered dose inhaler
Background : This review examines the clinical effectiveness and cost-effectiveness of h and -held inhalers to deliver medication for the routine management of chronic asthma in children aged between 5 and 15 years .
Asthma is a common disease of the airways , with a prevalence of treated asthma in 5–15-year-olds of around 12 % and an actual prevalence in the community as high as 23 % .
Treatment for the condition is predominantly by inhalation of medication .
There are three main types of inhaler device , pressurised metered dose , breath actuated , and dry powder , with the option of the attachment of a spacer to the first two devices under some prescribed circumstances .
Two recent review s have examined the clinical and cost-effectiveness evidence on inhaler devices , but one was for children aged under 5 years and the comparison in the second was made between pressurised metered dose inhalers and other types only .
Objectives : This review examines the clinical effectiveness and cost-effectiveness of manual pressurised metered dose inhalers , breath-actuated metered dose inhalers , and breath-actuated dry powder inhalers , with and without spacers as appropriate , to deliver medication for the routine management of chronic asthma in children aged between 5 and 15 years .
Costs and cost per quality -adjusted life-year : Two approaches have been taken : cost-minimisation and QALY threshold .