Cromolyn sodium, five to six years later. Effects of budesonide inhalation suspension compared with cromolyn sodium nebulizer solution on health status and caregiver quality of life in childhood asthma. The protective effect of inhaled terbutaline, sodium cromoglycate and budesonide on exercise-induced asthma in children. Parents' adherence with nebulizer treatment of their children when using an adaptive aerosol delivery (AAD) system. Cromolyn treatment of asthma. Trials in corticosteroid-dependent asthmatics. Sodium cromoglycate as a replacement for inhaled corticosteroids in mild‐to‐moderate childhood asthma Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1–4-year-old children with moderate asthma Effects of long-term treatment with inhaled cromoglycate and budesonide on bronchial hyperresponsiveness in patients with allergic asthma. Betamethasone valerate compared with sodium cromoglycate in asthmatic children. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. The combined use of betamethasone valerate and sodium cromoglycate in the treatment of asthma Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice. Comparison between sodium cromoglycate (MDI: metered‐dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma A double‐blind, double‐dummy randomized, parallel‐group study Cromolyn therapy for severe asthma in children. Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. Cromolyn versus triamcinolone acetonide for youngsters with moderate asthma. A clinical trial of combined cromolyn/beclomethasone treatment for chronic asthma. Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma. Salmeterol resolves airway obstruction but does not possess anti-eosinophil efficacy in newly diagnosed asthma: a randomized, double-blind, parallel group biopsy study comparing the effects of salmeterol, fluticasone propionate, and disodium cromoglycate. Clinical Equivalence Trial on Budesonide Delivered either by the Novolizer® Multidose Dry Powder Inhaler or the Turbuhaler® in Asthmatic Patients Protective effect of antiasthma drugs on late asthmatic reactions and increased airway responsiveness induced by toluene diisocyanate in sensitized subjects. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial Effect of High Starting Dose of Budesonide Inhalation Suspension on Serum Cortisol Concentration in Young Children with Recurrent Wheezing Episodes A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma. Inhaled steroids compared with disodium cromoglycate in preschool children with episodic viral wheeze. Stepwise selection in small data sets: a simulation study of bias in logistic regression analysis. Anti-inflammatory therapy reduces wheezing after bronchiolitis. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Disodium cromoglycate in the treatment of bronchial asthma. Influence of treatment with beclomethasone, cromoglycate and theophylline on perception of bronchoconstriction in patients with bronchial asthma. Evaluation of FCB, BDP, and DSCG in allergen inhalation challenge test. The efficacy of nedocromil sodium (Tilade) in asthma. Disodium cromoglycate compared with beclomethasone dipropionate in juvenile asthma Response to montelukast among subgroups of children aged 2 to 14 years with asthma. Comparison of nedocromil sodium and sodium cromoglycate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children. Betamethasone 17 valerate aerosol and disodium chromoglycate in severe childhood asthma. Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study). Fluticasone for the treatment of symptomatic bronchial asthma in children treated with sodium cromogylate--a prospective, randomised trial. A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma. Treatment of childhood asthma with sodium cromoglycate and beclomethasone dipropionate aerosol singly and in combination. STEROID SPARING EFFECT OF DISODIUM CROMOGLYCATE IN CHRONIC BRONCHIAL ASTHMA Facilitated referral to asthma specialist reduces relapses in asthma emergency room visits. One-year follow-up of young children hospitalized for wheezing: the influence of early anti-inflammatory therapy and risk factors for subsequent wheezing and asthma. Beclomethasone Dipropionate Steroid Aerosol in Treatment of Perennial Allergic Asthma in Children Effects of Regular Inhalation of Beclomethasone Dipropionate and Sodium Cromoglycate on Bronchial Hyperreactivity in Asthmatic Children Efficacy and tolerability of nedocromil sodium versus placebo in chronic reversible obstructive airways disease. Long-term treatment with sodium cromoglycate, nedocromil sodium and beclomethasone dipropionate reduces bronchial hyperresponsiveness in asthmatic subjects.
Ninety-five children with difficult to treat asthma were given cromolyn in double-blind , crossover studies . Of these , 70 were studied for the next five to six years by open trial cromolyn prophylaxis to determine decreasing dependency on bronchodilators or corticosteroids . Evaluated at two-month intervals , 28 children required prednisone and bronchodilators , 37 required round-the-clock bronchodilators only and five required neither .  Peak expiratory flow rates were below 80 % of predicted normal in eight patients , the remaining 62 showed reversibility of airways obstruction . Exercise-induced asthma was reported by 44 during the first two years but persistent improvement in exercise tolerance occurred in 24 patients . IgE specific RAST indicated a continuing extrinsic element in the etiology of 38 of 45 patients tested . Cromolyn was an effective prophylaxis for children with chronic asthma ; however , it was difficult to evaluate in 17 steroid-dependent subjects . Attempts to reduce the need for and especially to discontinue steroids were not as successful as other reports indicate OBJECTIVE To compare the effects of 2 nebulizable controller asthma medications on caregiver and pediatric quality of life .  METHODS In this 52-week , r and omized trial , children aged 2 to 6 years with mild to moderate persistent asthma received budesonide inhalation suspension 0.5 mg ( total daily dose ) once or twice daily ( n = 168 ) or cromolyn sodium nebulizer solution 20 mg 4 times daily ( n = 167 ) for 8 weeks , with dosage adjustment thereafter at the investigators ' discretion . The Pediatric Asthma Caregiver 's Quality of Life Question naire ( PACQLQ ) , Compliance/Caregiver Satisfaction Question naire ( CCSQ ) , Modified Child Health Question naire-Parent Form 50 ( CHQ-PF50 ) , and Functional Status-II(R ) ( FS-II[R ] ) Question naire were administered at baseline and weeks 8 , 28 , and 52 . Global assessment s of ease of asthma management and child health status were obtained from caregivers and physicians at the end of the study . RESULTS Improvements from baseline in domain-specific ( activities and emotional function ) and total PACQLQ scores were greater at each time point ( weeks 8 , 28 , and 52 ) for caregivers of patients treated with budesonide compared with caregivers of patients receiving cromolyn sodium . Only the budesonide group met the criterion for a clinical ly important improvement ( > or=0.5 unit change ) in all PACQLQ domains by week 8 , which was maintained at weeks 28 and 52 . Moreover , improvements surpassed the criterion for moderate clinical importance ( 1.0 unit change ) in all PACQLQ domains for the budesonide group , but this level of improvement was only achieved in the activities domain ( at week 28 ) for the cromolyn sodium group . Based on the CCSQ , budesonide result ed in greater caregiver satisfaction , treatment convenience , ease of use , and compliance compared with cromolyn sodium . Thus , 90.7 % of caregivers in the budesonide group were " completely or very satisfied " compared with 53.4 % in the cromolyn sodium group . Over half ( 54.6 % ) of caregivers in the budesonide group rated  budesonide " highly or very convenient " compared with 23 % for cromolyn sodium ; 77 % rated budesonide  " extremely or very easy " to use compared with 47 % for cromolyn .  Adherence with daily medication regimens was reported for 76 % of children in the budesonide group compared with 57 % in the cromolyn sodium group . Child health status , as indicated by mean FS-II(R ) scores , showed improvements from baseline in both groups at weeks 8 , 28 , and 52 . There was a trend for these improvements to be superior in the budesonide group . Additionally , budesonide was superior to cromolyn sodium in caregiver and physician global assessment s. At the end of the study , 76 % of caregivers of children receiving budesonide  reported asthma management to be " a great deal easier " compared with the start of the study , and 74 % rated the overall health status of their child as " much better now than 1 year ago . " In contrast , only 29 % and 37 % of caregivers whose children received cromolyn sodium provided these respective ratings . CONCLUSIONS Budesonide inhalation suspension improved the quality of life for caregivers of children with asthma . Caregivers of children treated with budesonide  had significantly fewer limitations in daily activities and emotional functioning compared with caregivers of children treated with cromolyn sodium nebulizer solution . The improvements in caregiver quality of life occurred earlier with budesonide compared with cromolyn sodium . Only caregivers in the budesonide group had a clinical ly important mean change from baseline in all PACQLQ domains by week 8 . These benefits were maintained at week 52 . Children treated with budesonide inhalation suspension and cromolyn sodium experienced improvements in health status , assessed using the FS-II(R ) . The greatest differences between treatments were seen in the disease-specific portion of the FS-II(R ) , which relates impairments in functional status to the child 's illness . Caregiver and physician global assessment indicated significantly better overall child health after 1 year of treatment with budesonide , supporting an improvement in health status . Clinical trials in children 4 to 16 years of age with asthma have demonstrated greater effectiveness of inhaled corticosteroids versus cromolyn sodium on several clinical measures of efficacy . Measures of asthma control in this study , reported in detail elsewhere [ Leflein et al. Pediatrics 2002;109:866 - 872 ] , also have shown greater improvements with budesonide therapy . Treatment with budesonide inhalation suspension result ed in a significantly lower mean rate of asthma exacerbations , significantly longer times to first asthma exacerbation , significantly longer times to first additional use of chronic asthma therapy , and significant improvements in asthma symptom scores and breakthrough medication use compared with cromolyn sodium therapy . Additionally , children receiving budesonide inhalation suspension experienced more symptom-free days and episode-free days compared with children receiving cromolyn sodium .  Safety profiles were similar between the 2 treatment groups . Budesonide inhalation suspension was associated with significantly greater caregiver satisfaction , convenience , ease of use , and compliance compared with cromolyn sodium nebulizer solution . This greater caregiver satisfaction and quality of life may be related to the greater asthma control achieved in children treated with budesonide therapy compared with cromolyn sodium . In addition , the convenience of once- or twice-daily dosing with budesonide inhalation suspension , compared with 3- or 4-times-daily dosing of cromolyn sodium , may decrease caregiver burden and enhance the willingness of caregivers to adhere to treatment regimens prescribed for their young children with asthma . This effect on caregiver adherence could further improve treatment effectiveness . This is the first clinical trial comparing the effects of a nebulized corticosteroid with that of an alternative nebulized therapy on quality of life in young children with asthma and their families . Compared with nebulized cromolyn sodium , budesonide inhalation suspension not only provides better overall child health status and asthma management , but greater caregiver quality of life and greater caregiver satisfaction , convenience , ease of use , and compliance The effect of single-dose inhaled terbutaline , sodium cromo-glycate and budesonide were compared with control in 11 exercise-induced asthma ( EIA ) patients , aged 9 - 14 years . Patients exercise for 6 minutes , 15 minutes after inhaling drugs . The FVC , FEV1 , PEFR and MMEF were recorded before exercise and after exercise at 5 minutes interval up to 25 minutes . After exercise , the mean ( SEM ) maximal percentage fall in FEV1 after placebo , 200 micrograms of terbutaline , 10 mg of sodium cromoglycate , and 100 micrograms of budesonide were 22.81 ( 3.45 ) , 4.05 ( 2.11 ) , 11.29 ( 1.18 ) , and 20.36 ( 2.33 ) respectively . It was concluded that single-dose inhaled terbutaline and sodium cromoglycate result ed in a significant protective effect on exerxide-induced asthma whereas budesonide did not The objective of this study was to analyze data on parents ' adherence to their child 's prescribed nebulizer treatment regimen and compliance with the dem and s of the nebulizer and the face mask . Data on adherence and compliance were recorded in a 24-week double-blind , r and omized , parallel-group study with budesonide inhalation suspension in 125 young children with mild to moderate asthma .  Budesonide was administered with an Adaptive Aerosol Delivery ( AAD ) system , which recorded adherence to treatment and compliance with the AAD system . A total of 35,481 treatments were recorded and analyzed . A study question naire regarding the parents ' and children 's acceptance of the AAD system has also been analyzed . The adherence to the treatment regimen was 91.3 % , and the compliance with the AAD system was 90.4 % . True adherence , the product of adherence and compliance , was 82.5 % . Approximately 90 % of the parents found the face mask easy to seal and the AAD equipment easy to use , and over 90 % of the children accepted it within 1 week . In conclusion , the results indicate that the AAD system could be of real clinical advantage for treatment of asthma in young children Cromolyn sodium , a specific inhibitor of mediator release induced by antigen-antibody interaction , was studied for corticosteroid sparing effect and clinical usefulness in a double-blind double-crossover , and in a subsequent open trial in 30 corticosteroid-dependent adults with severe perennial asthma . Of 29 patients completing the trials , 19 had corticosteroid dose reduction while receiving cromolyn in the double-blind trial , and 22 had corticosteroid dose reduction in the open trial . Cromolyn was judged to be clinical ly useful for corticosteroid sparing effect or symptomatic improvement , however , in only ten patients . Corticosteroid sparing effect and clinical usefulness were noted in all types of asthmatics studied . One patient noted increased asthma following inhalation of either cromolyn or placebo and did not complete the trial ; no adverse effects of cromolyn per se were noted We investigated whether sodium cromoglycate 10 mg three times daily , delivered as an aerosol via Nebuhaler ( in addition to terbutaline 0.5 mg three times daily ) , could replace inhaled steroid in children with mild‐to‐moderate asthma . Children ( mean age 10.3 years ) were r and omly allocated to 12‐week treatment with sodium cromoglycate 10 mg plus terbutaline 0.5 mg ( group A ; n= 30 ) or placebo plus terbutaline 0.5 mg ( group B ; n= 32 ) , both taken three times a day . The daily steroid dose was reduced by 50 μg/week for 4 weeks from a starting dose of 200 μg . Fewer patients withdrew owing to worsening asthma from group A ( n= 1 ) than group B ( n = 11 ) . Symptom scores , morning and evening peak flows , and additional β2‐agonist usage , recorded on diary cards , were better in group A than group B. Lung function measured at clinic visits was unchanged in either group . Overall opinions of efficacy favoured Group A. Adverse events were similar in the groups  . Sodium cromoglycate plus terbutaline substituted effectively for inhaled steroid therapy In a controlled prospect i ve study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide  and compared these findings with those obtained from children not treated with corticosteroids . Two hundred and sixteen children were followed at 6 monthly intervals for 1 - 2 years without inhaled budesonide and then for 3 - 6 years on inhaled budesonide .  Sixty-two children treated with theophylline , beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3 - 7 years ( controls ) . During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms ( P < 0.01 ) and no signs of tachyphylaxis to the treatment were seen . Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma ( from 0.03 to 0.004 per child , P < 0.001 ) . In patients not treated with budesonide an annual decrease in % predicted FEV1 of 1 - 3 % was seen . In contrast FEV1 improved significantly with time during budesonide treatment , both compared with the run-in period and with the control group ( P < 0.01 ) . Furthermore , there was a significant ( P = 0.01 ) relationship between the duration of asthma at the start of budesonide and the annual increase in FEV1 during budesonide therapy . After 3 years of treatment with budesonide , children who started this therapy later than 5 years after the onset of asthma had significantly lower FEV1 ( 96 % ) than the children who received budesonide within the first 2 years after the onset of asthma ( 101 % ) ( P < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children . The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children . We studied the feasibility and effects of this therapy compared with placebo in children aged 1 - 4 years . METHODS 218 children aged 1 - 4 years with moderate asthma were recruited through 151 general practitioners between March , 1995 , and March , 1996 . They were r and omly assigned sodium cromoglycate ( 10 mg three times daily ) or placebo , given by inhaler with spacer device and face-mask for 5 months . Rescue medication ( ipratropium plus fenoterol aerosol ) was available during the baseline period of 1 month and the intervention period . Parents completed a daily symptom-score list . The primary outcome measure was the proportion of symptom-free days in months 2 to 5 . Analysis was by both intention to treat and on treatment . FINDINGS 167 ( 77 % ) children completed the trial . 131 ( 78 % ) of these children used at least 80 % of the recommended dose . Of the 51 children who stopped prematurely , 23 had difficulties with inhaled treatment . The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period ( 95 % CI for mean difference 5.1 to 17.5 cromoglycate , 11.9 to 23.3 placebo ) . However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days ( mean 65.7 [ SD 25.3 ] vs 64.3 [24.5]% ; 95 % CI for difference -8.46 to 5.70 ) or in any other outcome measure . INTERPRETATION Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years . However , long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group Twenty two allergic patients with bronchial asthma completed this study . Effects of long-term treatment with inhaled cromoglycate 4 x 2 mg.day-1 were compared to the effects of inhaled budesonide 4 x 0.1 mg.day-1 on symptoms , additional beta 2-agonist  use , lung function and bronchial hyperresponsiveness measured by the provocation concentration of histamine producing a 20 % fall in forced expiratory volume in one second ( FEV1 ) ( PC20 histamine ) and exercise-induced fall in FEV1 . The study was carried out in a double-blind way with a r and omized crossover design using a double-dummy technique . After a single-blind placebo period , the two active treatment periods of 6 weeks were separated by a single-blind placebo period . Symptom score and beta 2-agonist use decreased during both active treatment periods , which showed no mutual differences . Morning and evening peak expiratory flow rates were significantly higher during treatment with budesonide versus placebo ( p less than 0.01 and p less than 0.001 ) , and also versus cromoglycate ( p less than 0.02 and p less than 0.05 ) . FEV1 showed improvement after a 6 week treatment with budesonide versus placebo ( p less than 0.05 ) , although there was no significant difference between the two active treatments . PC20 histamine did not change during treatment with cromoglycate . Budesonide showed a significant increase in PC20 histamine versus placebo ( p less than 0.05 ) and was marginally significantly better than cromoglycate ( p = 0.05 ) . Exercise-induced fall in FEV1 was not changed by cromoglycate , but improved significantly during budesonide in comparison with placebo ( p less than 0.01 ) and also with cromoglycate ( p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS A double-blind , cross-over study was undertaken to compare inhalation of betamethasone valerate ( BV , 800 microgram daily ) with sodium cromoglycate ( SCG , 80 mg daily ) in twenty children requiring bronchodilators for perennial asthma . Each treatment period lasted 4 weeks but statistical comparisons were made only in respect of the last 14 days of each therapy . When the children were using BV they required not only less of the bronchodilator drugs but had fewer symptoms and higher daily peak expiratory flow rates when taking SCG . Statistically , all these differences were highly significant . For 2 weeks before the main trial each child was given a placebo aerosol ( single-blind ) to assess severity of asthma . In comparison with this period , SCG was associated with a significantly increased peak expiratory flow rate a lower symptom score by day but not by night , but their usage of bronchodilators followed a similar pattern . When the BV period was compared with the placebo period , patients had an even more significant rise in peak expiratory flow rate , less day and night symptoms , and took hardly any bronchodilators . The response to the two drugs did seem to depend upon which was given first . No monilial infections were found , nor any measurable defect in adrenal response from either treatment . Betamethasone valerate is considered to be superior to sodium cromoglycate as a treatment for childhood asthma insufficiently controlled on bronchodilators OBJECTIVE Our aim was to compare the 12-month safety and efficacy of fluticasone propionate ( FP ) and sodium cromoglycate ( SCG ) in children aged 1 to 3 years with mild to moderate recurrent wheeze . METHODS The study was a r and omized , parallel-group , open-label multicenter study of 625 children , aged 1 to 3 years , with recurrent wheeze r and omized in a 3:1 ratio to treatment for 52 weeks with FP ( 100 microg twice daily ) via metered-dose inhaler and Babyhaler spacer device or SCG ( 5 mg 4 times daily ) via metered-dose inhaler and Nebuhaler spacer device , respectively . RESULTS There was no significant difference in mean adjusted growth rates between the 2 groups : 84.0 mm/year in the FP group versus 86.4 mm/year in the SCG group ( difference FP-SCG : -2.4 mm/year ; 95 % confidence interval : -6.6 to 1.8 ) . Growth comparisons were independent of age , gender , previous use of steroid , or whether measured as length and /or height . Serum and urinary cortisol concentrations showed a statistically significant suppression of 10 % and 14 % , respectively , but the number of patients with serum cortisol levels below the lower normal limit was reduced during the trial . Both treatments were well tolerated . The most common drug-related adverse events were cough ( 2 % FP vs 1 % SCG ) and hoarseness ( 1 % FP vs 0 % SCG ) . One incident of cataract was observed at baseline and 1 after FP treatment ; the latter had resolved after 12 months . The efficacy of FP was superior to SCG with fewer cases of symptom worsening , exacerbations , and requirements for oral steroid treatment and more symptom-free days and days without use of rescue treatment . CONCLUSIONS Twelve months of treatment with inhaled FP ( 100 microg twice daily ) in preschool children aged 1 to 3 years with recurrent wheeze has no effect on growth and no other clinical ly important side effects but is more efficacious than SCG A double‐blind comparison of betamethasone valerate , sodium cromoglycate and the combination of these two treatments was carried out in twenty‐two adult patients with asthma . Regular fortnightly assessment s were made in the clinic throughout the study and adrenal function was monitored and found to be normal . All patients measured their peak expiratory flow rates in the morning and evening and monitored their symptoms daily on a record card as well as recording bronchodilator usage . Assessment using these parameters indicated that treatment with betamethasone valerate compared with sodium cromoglycate result ed in an improvement in the patients ’ asthma which was statistically significant ( P<0.001 ) . Overall the combined treatment produced a better response than sodium cromoglycate  ( P<0.02 ) but a poorer response compared with the steroid aerosol given alone ( P>0.05 ) . In only two patients was the response to the combined therapy significantly greater than to either drug given alone BACKGROUND Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma . OBJECTIVE To compare the cost-effectiveness of these two treatment strategies in clinical practice , in an open-label , pharmacoeconomic clinical trial . METHODS Health economics were evaluated in 138 children , ages 5 to 11 years , with unstable asthma not previously treated with corticosteroids or cromones . The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily . The children were then r and omly allocated to one of the two treatment strategies aim ing at maintaining asthma control for 12 months ; budesonide 400 microg/day ( N = 69 ) or sodium cromoglycate 60 mg/day ( N = 69 ) . If asthma control was judged unsatisfactory , the doses were increased or the children were switched to the alternate treatment . RESULTS In children continuing on the same treatment , the degree of asthma control was similar in the two groups at study end . To maintain asthma control , 42 % of cromoglycate children switched to budesonide , and then experienced a 14 % increase in symptom-free days . No budesonide patient had to switch therapy because of lack of asthma control . Although not statistically significant , total annual cost per patient was 24 % ( Swedish kronor 4195 ; US $ 487 ; Euro 485 ) lower in the budesonide than the cromoglycate group , mainly due to a lower cost for asthma medication . CONCLUSIONS A budesonide strategy for continued maintenance treatment , after an initial period of stabilizing treatment with budesonide , result ed in lower costs and less drug switches than did a strategy with sodium cromoglycate This study compared the efficacy and tolerability of sodium cromoglycate ( SC ) and beclomethasone dipropionate ( BDP ) in adult patients with bronchial asthma inadequately treated with bronchodilators alone . The study was a double‐blind , r and omized , double‐dummy , parallel‐group study . Patients with mild to moderate symptomatic asthma , inadequately treated with bronchodilators only , were , after a 2–week run‐in ( base‐line ) period , r and omized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 μg four times daily . Salbutamol metered‐dose inhaler was given as relief medication . A total of 37 patients were r and omized for treatment , 19 patients in the SC group and 18 patients in the BD group . Efficacy and safety were determined by daily record card data : morning and evening peak‐expiratory‐flow rates ( PEER ) , daytime and nighttime asthma symptom scores , and rescue salbutamol use . At clinic visits , FEV1 and FVC were measured , as were the physician 's and the patient 's assessment of the medication at the end of the study . The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study . A clinical ly and statistically significant improvement of the asthma in FEV1 , symptom scores , rescue medication , and global opinion of efficacy was observed , and both groups provided equivalent efficacy . The morning PEFR as well as the evening PEFR for both groups improved , but was statistically significant only for the BDP group ( M‐PEFR ) . Both drugs were well tolerated with only a few minor adverse events . This trial shows that SC and BDP are equally effective anti‐inflammatory treatments for mild to moderate bronchial asthma in adults Cromolyn sodium is a new antiasthmatic drug which exerts its action by interfering with the release of the mediators of immediate hypersensitivity reactions from the sensitized mast cells lining the bronchial tree . In a double-blind crossover trial , 36 children with chronic intractable asthma , 23 of whom were corticosteroid dependent , inhaled cromolyn sodium or a placebo four times per day for two 4 week periods . Although clinical improvement with cromolyn therapy was not statistically superior to the placebo , 36 patients noted subjective improvement from the cromolyn sodium and entered a 12 month open-end clinical trial . Twenty-six patients completed this second study ; 19 of them showed clinical improvement . Of the 18 steroid-dependent patients who completed 12 months of cromolyn sodium therapy , 7 discontinued corticosteroids , 10 decreased their dosage , and one patient increased his corticosteroid requirement . Even though cromolyn sodium is not always clinical ly efficacious , it should be considered in the management of intractable asthma in children Regular salbutamol use can exacerbate allergen-induced airway eosinophilia in asthmatics , but its effect on airway eosinophil chemokine responses is unknown . Asthmatic subjects ( n=14 ) were treated for 10 days with placebo or salbutamol in a double-blind , cross-over study , then given same-dose allergen challenges . Their sputa were then analysed 1 and 7 h later for a panel of eosinophil-related cytokines . Eosinophils from five test and three control subjects were tested for expression of CXCL8/interleukin (IL)‐8 , and its receptors and responsiveness to CCL11/eotaxin and CXCL8/IL‐8 . Sputum CXCL8/IL‐8 , but not IL‐5 , CCL5/regulated on activation , T‐cell expressed and secreted , CCL7/monocyte chemotactic protein‐3 , CCL11/eotaxin , granulocyte-macrophage colony-stimulating factor or tumour necrosis factor levels , were increased ( 42 % ) by the salbutamol treatments . The CXCL8/IL‐8 levels correlated with the proportions of sputum eosinophils and these cells , but not other sputum cells , stained strongly for CXCL8/IL‐8 . The circulating eosinophils of the tested subjects ( n=5 ) expressed CXCL8/IL‐8 receptors and secreted high levels of this chemokine . Neutralisation of sputum CXCL8/IL‐8 reduced eosinophil chemotactic responses to these sample s by 19±5 % . These data suggest that regular use of salbutamol can augment airway CXCL8/interleukin‐8 responses to allergen challenge and that this CXCL8/interleukin‐8 could contribute to the airway inflammatory response Single-dose salbutamol ( 200 micrograms ) , beclomethasone dipropionate ( 200 micrograms ) , and sodium cromoglycate ( SCG ) ( 10 mg ) administered by inhalation 10 minutes before allergen challenge were examined with regard to inhibition of allergen-induced early ( EAR ) and late ( LAR ) asthmatic responses and allergen-induced increase in bronchial responsiveness to inhaled histamine . Ten atopic subjects with asthma participated in a blinded , crossover , placebo-controlled trial . The EAR was inhibited by salbutamol and SCG but not by beclomethasone dipropionate or placebo ( p less than 0.01 ) . The LAR ( p less than 0.01 ) and the allergen-induced increased bronchial responsiveness to histamine 7 hours ( p less than 0.01 ) and 30 hours ( p less than 0.05 and p less than 0.01 for various comparisons ) were inhibited by SCG and beclomethasone diproprionate but not by salbutamol or placebo . The allergen-induced LAR and associated increased responsiveness are now believed to be more important clinical ly than the EAR . The clinical relevance of these results is to stress the importance of the prophylactic nonbronchodilator drugs ( SCG and steroids ) and the potential inadequacy of bronchodilators used alone in the treatment of both perennial and seasonal allergic asthma Although both cromolyn ( C ) and inhaled corticosteroids are anti-inflammatory therapies for childhood asthma , there are few controlled comparisons of these medications for asthma therapy in children . None were conducted in the United States , and none specifically study triamcinolone acetonide ( T ) versus C. This 12-week evaluation followed 31 youths , aged 8 to 18 years , with moderate asthma who were assigned to receive C or T according to a prer and omized and blinded code . Patients were instructed to take two inhalations from the study metered-dose inhaler ( active T or placebo ) and to inhale the contents of one study -provided ampule ( C , 20 mg , or placebo ) from a compressor-driven home nebulizer three times per day . Patients also used albuterol , two inhalations from a metered-dose inhaler , three times a day ( before study medication ) and , additionally , if needed . Patients maintained a daily diary , recording extra medication use , adverse experiences , peak flow rates morning and night , and asthma symptom scores . Laboratory assessment of pulmonary function was done at 1 , 4 , 8 , and 12 weeks .  Cosyntropin challenge and methacholine bronchoprovocation challenge  were performed at the beginning and end of the study . C and T provided similar , adequate asthma control . Symptoms of wheezing , cough , and chest tightness decreased , and daily peak expiratory flow rate increased with both regimens compared to during a 2-week baseline when patients received medication only as needed . There was no significant change in methacholine sensitivity and no change in endocrine function , as measured with fasting plasma control before and after administration of cosyntropin . ( ABSTRACT TRUNCATED AT 250 WORDS Some patients with chronic asthma treated with beclomethasone aerosol ( BA )  derive significant symptom benefit , yet have persisting adrenal suppression due in part to their BA therapy . The daily dose of BA required is higher in patients with atopy . We therefore assessed the usefulness of ancillary treatment with cromolyn sodium ( CS ) , a drug known to inhibit atopic asthma , to try to improve the balance of risk vs benefit in such patients . Thirty asthmatics , well controlled on high-dose BA ( mean , 1,040 micrograms + /- 97 SE ) but with morning cortisol levels averaging approximately 10 micrograms/dl , were allocated r and omly to placebo or CS inhalant , used in addition to their regular BA and other asthma medications . After 4 wk , their BA dose was halved . Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows , and by spirograms and morning serum cortisol tests every 4 wk . Mean cortisol levels rose 27 % after BA dose reduction ( p less than 0.05 ) but asthma worsened . Risk-benefit assessment s 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75 % . The distributions of good , fair , and poor risk-benefit responses were the same in both CS and placebo-treated groups ( p = 0.20 ) . In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients , CS might prove useful , but in these adult chronic asthmatics with this particular therapeutic problem , there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate ( FP ) 50 micrograms twice daily ( b.i.d . ) or sodium cromoglycate ( SCG ) 20 mg four times daily ( q.i.d . ) . After a 2-week run-in , asthmatic children aged 4 - 10 years from 15 UK centers were r and omized in a 3:4 ratio to open-label FP ( n = 52 ) or SCG ( n = 70 ) . After 8 weeks , those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn .  St and ing height was measured ( Holtain stadiometry ) at baseline , after 8 weeks and at 6 weeks intervals thereafter for 1 year . Morning peak flows ( PEFam ) were recorded by patients for 2 weeks during baseline , and 1 week before each visit during treatment . Urinary free cortisol ( 24 h ) was measured at baseline , 6 months , and 1 year . After 8 weeks , 22 patients were withdrawn from SCG group ( and were switched to FP ) , and five patients were withdrawn from the FP group due to poor asthma control  . A further 21 and 11 patients were withdrawn from the SCG and FP groups , respectively , during the course of the study . There were no significant differences between patients who received FP and SCG for 1 year ( n = 34 and n = 26 , respectively ) in terms of height velocity adjusted for age and gender ( HV ) , or height velocity st and ard deviation scores adjusted for gender ( HVSDS ) . Mean HV ( mean HVSDS ) were 6.0 cm/yr ( 0.1 ) and 6.5 cm/yr ( 0.5 ) for FP and SCG , respectively . There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months . Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group . We concluded that growth was normal in mildly asthmatic children receiving FP ( 50 micrograms bid ) for 1 year . There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG BACKGROUND Salmeterol ( SLM ) is a long-acting beta(2)-receptor agonist that produces bronchodilatation for 12 hours in asthmatic subjects . The effects of the regular use of long-acting beta(2)-agonists on airway inflammation are largely unknown . OBJECTIVES We examined the effects of 16 weeks of treatment with 50 microg SLM bid , 250 microg fluticasone propionate ( FP ) bid,5 mg disodium cromoglycate ( DSCG ) qid , or placebo on airway inflammation in bronchial mucosa . METHODS Airway inflammation was assessed in bronchial biopsy specimens before and after treatments and bronchial hyperresponsiveness ( BHR ) in 80 patients with newly diagnosed asthma . Inflammatory cells and tenascin in the basement membrane were studied with immunohistochemical methods . Peak expiratory flow rate ( PEF ) , symptoms , and need for rescue medication were recorded . RESULTS SLM , FP , and DSCG  reduced symptoms and need for rescue medication ( P < .04 ) . Both SLM and FP improved PEF and increased PD15FEV(1 ) to histamine by 2.8 and 5.2 doubling dose units , respectively . Both compounds reduced BHR more than placebo ( P < .05 ) . Both SLM and placebo had no effect on any inflammatory cell type . In both FP-treated and DSCG-treated patients , the number of EG2-positive eosinophils in the airway mucosa decreased ( P = .002 and P < .05 , respectively ) . CONCLUSIONS SLM showed no anti-eosinophil properties in this study , but it provided good symptom control . FP provided the best anti-eosinophil properties and symptom relief of the studied compounds Background and Objectives : To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer ® , i.e. a multidose dry powder inhaler , or by the Pulmicort ® Turbuhaler ® in asthmatic patients in terms of efficacy , safety and tolerability during a 12-week treatment . Methods : A total of 315 patients were r and omised in this open , multicentre study . Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity ( ranging from 60 % to a maximum of 90 % predicted FEV1 ) , need for anti-inflammatory therapy , inhalation of β2-sympathomimetics on an as needed to regular basis , reversibility of airway obstruction of > 12 % after inhalation of 2 actuations of 100 µg salbutamol  . Primary variable was FEV1 , secondary were other pulmonary function test variables , PC20FEV1 for histamine challenge , morning and evening PEFR , salbutamol usage , asthma symptoms , reactions after inhalation , st and ard safety variables . Results : The comparison of the FEV1 at study endpoint indicated that the Novolizer ® was at least as efficacious as the Turbuhaler ® ( p < 0.001 ) . All other variables of the pulmonary function tests as well as the asthma symptoms , nocturnal awakenings , PEFR measurements , or salbutamol usage indicated no relevant difference . Only 1 patient ( Turbuhaler ® ) discontinued prematurely due to lack of efficacy . None of the other safety variables ( adverse events , laboratory variables , vital signs , etc . ) indicated any difference between the groups . Conclusions : The budesonide Novolizer ® is therapeutically equivalent to the Pulmicort ® Turbuhaler ® for the long-term treatment of patients with mild to moderate persistent asthma To determine whether 4 drugs used in the treatment of asthma inhibit the late asthmatic reaction and the associated increase in airway responsiveness induced by toluene diisocyanate ( TDI ) , we studied 24 sensitized subjects divided into 4 groups . Beclomethasone aerosol ( 1 mg bid ) , slow-release theophylline ( 6.5 mg/kg bid ) , slow-release verapamil ( 120 mg bid ) , and cromolyn ( 20 mg qid via spinhaler ) , were administered for 7 days , respectively , to 1 of the 4 groups , according to a double-blind , crossover , placebo-controlled study design . When the subjects were treated with placebo , verapamil , or cromolyn , FEV1 markedly decreased and airway responsiveness increased after exposure to TDI . By contrast , beclomethasone prevented the late asthmatic reaction and the associated increase in airway responsiveness to methacholine induced by TDI . Slow-release theophylline partially inhibited both the immediate and the late asthmatic reactions but had no effect on airway hyperresponsiveness to methacholine . These results suggest that only high-dose inhaled steroids can completely block TDI-induced late asthmatic reactions BACKGROUND Although inhaled glucocorticosteroids are recommended for persistent asthma , their long-term effect on recent onset , mild , persistent asthma has yet to be established . METHODS We did a r and omised , double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide  in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids . Patients aged 5 - 66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications . The daily budesonide dose was 400 microg , or 200 microg for children younger than 11 years . The primary outcome was time to first severe asthma-related event , and analysis was by intention to treat . FINDINGS 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation ; hazard ratio 0.56 ( 95 % CI 0.45 - 0.71 , p<0.0001 ) . Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo . Compared with placebo , budesonide increased postbronchodilator forced expiratory volume in 1 s ( FEV1 ) from baseline by 1.48 % ( p<0.0001 ) after 1 year and by 0.88 % ( p=0.0005 ) after 3 years ( expressed as percent of the predicted value ) . The corresponding increase in prebronchodilator FEV1 was 2.24 % after 1 year and 1.71 % after 3 years ( p<0.0001 at both timepoints ) . The effect of treatment on all outcome variables was independent of the baseline lung function ( prebronchodilator or postbronchodilator ) or baseline medication . In children younger than 11 years , 3-year growth was reduced in the budesonide group by 1.34 cm . The reduction was greatest in the first year of treatment ( 0.58 cm ) than years 2 and 3 ( 0.43 cm and 0.33 cm , respectively ) . INTERPRETATION Long-term , once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset Introduction . There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes . We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration . Methods . A r and omized double-blind , placebo-controlled design was used . Twenty-nine children ages 6 months to 3 years were divided into three groups : ( 1 ) high starting dose : 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25 % every second day for 8 days ( n = 11 ) ; ( 2 ) low starting dose : 0.25 mg twice daily for 8 days ( n = 11 ) ; ( 3 ) placebo ( n = 7 ) . The 8 AM ( fasting ) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment . Results . Before treatment and after 8–10 days of treatment , there was no significant difference in mean serum cortisol concentration in the high starting dose , low-dose and placebo groups , either at 8 AM or at 1 hour after ACTH stimulation . Conclusion . The administration of nebulized suspension of budesonide at a high starting dose ( 2 mg/day for 2 days ) followed by a rapid stepwise decrease over 8 days was safe , causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo After a run-in period of 2 weeks , receiving a regimen of inhaled beta 2-agonists and /or theophyllines , 38 atopic patients with asthma with perennial symptoms were r and omly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate ( SCG ) , 2 mg four times daily , and placebo beclomethasone dipropionate ( BDP ) , or BDP , 200 micrograms twice daily , and placebo SCG . After crossover , each group received the opposite treatment for the final 8 weeks . FEV1 , FVC , and provocation concentration of histamine causing a 20 % fall in FEV1 ( PC20 ) were determined monthly and peak expiratory flow ( PEF ) daily throughout the study . A significant increase in FEV1 , FVC , and PEF ( p less than 0.01 ) was observed after BDP treatment was started , and likewise , in the second period , an increase in both FEV1 and PEF ( p less than 0.05 ) was observed . The total effect on logarithm-natural ( Ln ) ( PC20 ) , i.e. , the mean effects of the two periods , was also significant ( p less than 0.01 ) . SCG , however , was most effective when it was used as the first drug , indicated by a significant increase in FVC in the first period ( p less than 0.05 ) . Neither in the first nor in the second period did SCG treatment influence the Ln ( PC20 ) value positively , and the SCG treatment administered in the second period could not maintain the improvement in the pulmonary function ( i.e. , FEV1 , FVC , and PEF ) obtained initially with the BDP treatment . When the effect of BDP on FEV1 , FVC , PEF , and Ln ( PC20 ) was compared to the effect of SCG in the first 8-week treatment period , no significant difference was observed ( p greater than 0.1 ) . ( ABSTRACT TRUNCATED AT 250 WORDS In school children with atopic asthma the beneficial effects of disodium cromoglycate ( DSCG ) and beclomethasone dipropionate ( BDP ) are well-established . In preschool children , wheezing is quite common , and in the majority of cases the symptoms are episodic and reported to be associated with viral infections rather than atopy . We compared the efficacy of regular treatment with DSCG and BDP for prevention of  wheezing in preschool children . We were interested to establish whether regular treatment with inhaled anti-inflammatory drugs could lead to a decrease in bronchial responsiveness . In 15 patients ( median age , 56 months ; range , 43 - 66 months ) bronchial responsiveness was assessed by measuring specific airway resistance ( sRaw ) during a histamine provocation test . The concentration of histamine eliciting a 100 % increase in sRaw ( PC100his ) was determined . In a double-blind crossover study , patients inhaled either DSCG 10 mg three times a day or BDP 100 microg three times a day for 2 months . After a wash-out period , treatment was changed to BDP or DSCG , respectively . Daily peak flow measurements were carried out , and exacerbations were noted . PC100his was measured at the start and end of each treatment period . No significant decrease in bronchial responsiveness was seen ( PC100his DSCG : before 1.3 , after 1.66 mg/ml , Pvalue not significant ; BDP : before 1.1 after 1.22 mg/ml , Pvalue not significant ) . Significantly higher morning peak flows were observed on BDP therapy ( 160 on BDP vs. 150 L/min on DSCG , P < 0.03 ) . BDP treatment result ed in significantly fewer wheezing exacerbations ( 7 vs. 16 , P < 0.005 ) compared with DSCG therapy . We conclude that in preschool children with episodic virally induced wheezing , BDP therapy was superior to DSCG aerosol treatments for the prevention of exacerbations of wheezing , although no significant effect on bronchial responsiveness was noted during either treatment protocol Stepwise selection methods are widely applied to identify covariables for inclusion in regression models . One of the problems of stepwise selection is biased estimation of the regression coefficients . We illustrate this " selection bias " with logistic regression in the GUSTO-I trial ( 40,830 patients with an acute myocardial infa rct ion ) . R and om sample s were drawn that included 3 , 5 , 10 , 20 , or 40 events per variable ( EPV ) . Backward stepwise selection was applied in models containing 8 or 16 pre-specified predictors of 30-day mortality . We found a considerable overestimation of regression coefficients of selected covariables . The selection bias decreased with increasing EPV . For EPV 3 , 10 , or 40 , the bias exceeded 25 % for 7 , 3 , and 1 in the 8-predictor model respectively , when a conventional selection criterion was used ( alpha = 0.05 ) . For these EPV values , the bias was less than 20 % for all covariables when no selection was applied . We conclude that stepwise selection may result in a substantial bias of estimated regression coefficients OBJECTIVE To evaluate whether early anti-inflammatory therapy with nebulized cromolyn sodium or budesonide reduces wheezing after bronchiolitis . DESIGN AND SETTING A r and omized , controlled study in a university hospital that provides primary hospital care for all pediatric patients in a defined area . PATIENTS One hundred consecutive infants younger than 24 months treated in the hospital for acute bronchiolitis . INTERVENTIONS Thirty-four patients received cromolyn sodium , 20 mg four times a day for 8 weeks and 20 mg three times a day for 8 weeks , and 34 patients received budesonide , 500 micrograms twice a day for 8 weeks and 250 micrograms twice a day for 8 weeks , by a foot pump with a face mask ; 32 patients in the control group received no therapy . MAIN OUTCOME MEASURES Numbers of physician-diagnosed wheezing episodes , hospital admissions for bronchial obstructions , and symptomatic days recorded by the parents . RESULTS Children in the cromolyn sodium ( 19 % ) and budesonide ( 16 % ) groups had significantly fewer physician-diagnosed wheezing episodes than those in the control group ( 47 % ) during the second 8-week period ( P < .05 ) . A significant reduction in hospital admissions for bronchial obstructions was seen in the budesonide group and in the children with atopy in both treatment groups ( P < .05 ) . The children with atopy had significantly more subsequent wheezing episodes and hospital admissions than those without atopy ( P < .05 ) . The numbers of symptomatic days did not differ significantly among the three groups . CONCLUSIONS Early anti-inflammatory therapy with nebulized cromolyn sodium or budesonide reduces the number of wheezing episodes and hospital admissions after bronchiolitis . Children with atopy are at high risk of subsequent wheezing episodes , and they particularly benefit from anti-inflammatory therapy OBJECTIVE The availability of antiinflammatory asthma medications for infants and young children has been limited . The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma . METHODS We conducted a r and omized , parallel-group , 52-week , open-label study in 36 US clinical sites . Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication ; 287 children ( 86 % ) completed the study . Patients received budesonide inhalation suspension , 0.5 mg daily ( n = 168 ) , or cromolyn sodium nebulizer solution , 20 mg 4 times daily ( n = 167 ) , for 8 weeks , followed by dose titration at the investigator 's discretion . The main outcome measure was the rate of asthma exacerbations over 52 weeks . Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy , asthma symptom scores , rescue medication use , and health care re source use . RESULTS The budesonide group had a mean ( median ) asthma exacerbation rate of 1.23 ( 0.99 ) per year compared with 2.41 ( 1.85 ) for the cromolyn group , significantly longer times to first exacerbation and first use of additional long-term asthma medication , greater improvements in asthma symptom scores , reduced use of rescue medication , and fewer urgent care visits . Both treatments were well tolerated . CONCLUSIONS Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma . Both treatments were well tolerated with similar adverse event profiles Abstract A double-blind cross-over trial of disodium cromoglycate was undertaken in 28 patients with asthma . This differed from previous trials in that isoprenaline was not included in the active or in the placebo capsules . 10 of the 28 patients improved clinical ly whilst  on cromoglycate  . F.E.V. 1·0 , dyspnœa on exertion , and disturbance of sleep were all improved by cromoglycate 1 . Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows . This study was design ed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function . 2 . Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone  were studied during four different drug treatments over 3 months . Subjective self- assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow , using a coded electronic peak flow meter . This was recorded not less than three times daily on diary cards . Observations were recorded during the second week of each of four treatments : ( i ) a run-in period using only inhaled salbutamol as required , ( ii ) inhaled beclomethasone , ( iii ) inhaled cromoglycate and ( iv ) oral theophylline at a dose adjusted to achieve blood levels of 10 - 20 mg/l . Inhaled salbutamol was permitted during the other treatments as required . Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment . Dynamic lung volumes were measured in the clinic before the study and after each treatment period . 3 . In the group as a whole , theophylline improved lung function ( mean peak flow and dynamic lung volumes ) without affecting mean visual analogue scores , beclomethasone improved mean visual analogue scores with much less effect on lung function , while cromoglycate had a small though consistent effect on both . 4 . Perception of asthma , measured by the relationship between peak flow rate and visual analogue scores , was unaffected by cromoglycate . On theophylline , perception of asthma was heightened in five subjects despite a definite improvement in their peak flow . On beclomethasone , perception of asthma was reduced in most subjects , often with no discernible improvement in mean peak flow or dynamic spirometry . 5 . Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition . Theophylline may produce a paradoxical increase in awareness of asthma in some individuals . With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow The protective effect of a new inhaled steroid , fluocortin butyl ( FCB ) , was compared to that of disodium cromoglycate ( DSCG ) and beclomethasone dipropionate ( BDP ) in patients with extrinsic asthma by means of the allergen-inhalation challenge test . Three different groups of 12 patients each participated in the study . One group was treated with FCB and BDP , the two others with FCB and DSCG , all in a r and omized crossover study plan . After an initial allergen challenge ( FEV1 fall greater than 15 % ) , the patients were allocated to either treatment for 7 - 10 days . A second challenge test was then carried out , followed by a washout period of 4 days . The treatments were then crossed-over , and a third allergen challenge was carried out at the end of the second treatment period . With BDP 5 of 12 patients were protected ; with FCB , 6 of 12 in two groups and 8 of 12 patients in a third group . With DSCG 3 of 12 patients were protected in the group in which the last medication was given 12 h before challenge , and 8 of 12 patients in the second group in which medication was given 1 - 2 h before challenge . In the same groups on FCB no such time-dependent effect was observed . No statistically significant differences were found between either FCB and BDP , or FCB and DSCG in either group Nedocromil sodium is a new antiasthmatic drug with properties similar to sodium cromoglycate . We examined the efficacy of nedocromil sodium compared to placebo in 71 asthmatic patients in a three-centre double-blind parallel group study over 12 weeks . During the study the patients ' maintenance inhaled corticosteroids were progressively withdrawn . Nedocromil sodium had an advantage over placebo in the number of withdrawals related to uncontrolled asthma , 14 and 24 respectively ( p = 0.03 ) . Changes in symptom scores , peak flow rates and bronchodilator use favoured nedocromil sodium occasionally during the study . The unusual taste of the active drug was reported frequently . Nedocromil sodium is more efficacious than placebo in asthma maintenance , but does not replace inhaled corticosteroids In a double‐blind controlled crossover trial of  inhaled disodium cromoglycate and beclomethasone dipropionate  in juvenile asthma , beclomethasone produced higher therapeutic scores but significantly so in only two indices – wheeze‐free days and morning peak flow rates . Combined treatment offered no advantage over beclomethasone alone . No side‐effects were noted . The findings confirm other studies of cromoglycate and a steroid aerosol ( betamethasone 17‐valerate ) but disagree with the only other comparative trial of cromoglycate and beclomethasone , in which both were found equally effective BACKGROUND Determining who responds to asthma therapies , particularly leukotriene modifiers , continues to be explored . OBJECTIVE We sought to identify patient characteristics predictive of response to montelukast . METHODS We used data from 2 clinical trials in which children with asthma received either montelukast or placebo . Symptoms , beta-agonist use , and unanticipated health re source use caused by asthma were recorded in vali date d daily diaries for children 2 to 5 ( n = 689 ) and 6 to 14 ( n = 336 ) years old . We defined primary end points of days without asthma in 2- to 5-year-old patients ( 24 hours without symptoms , beta-agonist use , or asthma attack ) and change in percent predicted FEV(1 ) in 6- to 14-year-old children . Asthma attack was defined by the use of rescue oral corticosteroids or by an unscheduled visit to a medical provider . Patients were grouped according to baseline characteristics , such as family history of asthma , personal history of allergy , frequency of asthma symptoms , eosinophilia , and concomitant use of inhaled corticosteroids or cromolyn . We examined the stratum-specific effects of montelukast on the percentage of days without asthma , change in percent predicted FEV(1 ) , asthma attack , and a variety of secondary symptom and FEV(1 ) end points . RESULTS We did not identify characteristics that predicted response to montelukast in either preschool or 6- to 14-year-old children . These findings were consistent across all symptom and FEV(1 ) outcomes . There was also no differential response to montelukast in either age group when asthma attack was the outcome . CONCLUSION The patient characteristics studied do not appear to provide an indication of who will benefit most from treatment with montelukast To compare the effectiveness of nedocromil sodium ( NS ) and sodium cromoglycate ( SCG ) administered by metered dose inhaler ( MDI ) in preventing exercise-induced asthma ( EIA ) , 12 asthmatic children with EIA were studied in a r and omized , double-blind , cross-over , placebo-controlled study . NS and SCG were given by MDI alone , and by MDI with a 700 ml spacer device ( Fisonair , Fisons , UK ) , in order to assess the benefit of using such a device . Following a baseline exercise challenge , the protective effect of NS , SCG or placebo was evaluated in each subject . The percentage fall in forced expiratory volume in one second , and percentage protection were measured . NS and SCG provided a significant and comparable protection from EIA , and both were better than placebo . No further improvement was observed after drug administration via the spacer . Both NS and SCG are effective in preventing EIA  in children , when administered at the recommended clinical dose , and the use of a spacer for administering the drug provides no advantage if the technique of inhalation is good Eleven children with severe perennial asthma and a poor clinical response to disodium cromoglycate were studied in a 4-month , double blind trial involving 1 month 's treatment with placebo , disodium cromoglycate , betamethasone 17 valerate , and both drugs combined according to a predetermined r and om design . Each drug apparently reduced symptoms and improved daily peak flow and fortnightly spirometric measurements compared with placebo , but the improvement after betamethasone 17 valerate was greater in part because of the way this group of patients was selected . There did not appear to be any additional benefit when both drugs were used together . Betamethasone 17 valerate was not compared with beclomethasone diproprionate aerosol and there is no reason to believe it may be superior . Corticosteroid aerosols have potential hazards which may prove to equal those of long-term systemic steroids , but they offer the prospect of satisfactory control of symptoms without the risk of growth suppression in children with severe asthma . Disodium cromoglycate remains the drug of choice in severe childhood asthma and the use of corticosteroid aerosols should be confined to those children who fail to respond satisfactorily to disodium cromoglycate The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate . Seventy-five asthmatic children were r and omly divided into three treatment groups : 30 to the fluticasone propionate ( FP ) , 30 to the budesonide ( BUD ) , and 15 to the  cromone ( CROM ) group .  FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter . The respective BUD doses were 800 and 400 microg/day . A low dose ACTH ( 0.5 microg/1.73 m2 ) test was performed before treatment and 2 , 4 , and 6 months later . The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean ( < 330 nmol/L ) . The low dose ACTH test was abnormal after both the high and low steroid doses in 23 % of the children . At the 4 month measurement there were more abnormal tests in the BUD ( n = 9 ) than in the FP ( n = 5 ) group ( P < 0.05 ) . At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group ( P < 0.01 ) , whereas the difference between the FP and CROM groups was not significant . During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD , 0.03 in the children treated with FP , and 0.09 in the children treated with CROM ; the difference between the BUD and FP groups was significant ( P < 0.05 ) . In conclusion , the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids . A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing . As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids , current guidelines continue to recommend sodium cromoglycate ( SCG ) as first line regular medication for children with frequent symptoms . Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children . This study compares SCG with the new inhaled corticosteroid , fluticasone propionate ( FP ) , which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability . This was a r and omized , open , multi-centre , parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks , preceded by a 2-week baseline period . Sixty-two general practice s and two hospital centres enrolled 225 asthmatic children aged 4 - 12 years ( 110 received FP ; 115 received SCG ) . Outcome measures improved in both groups , with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights . No significant difference was observed for FEV1 , or relief medication use .  Two children taking  FP and 10 children taking  SCG  withdrew because of adverse events . This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma .  Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy BACKGROUND Children with persistent mild to moderate bronchial asthma require anti-inflammatory therapy . According to current treatment guidelines both sodium cromoglycate ( SCG ) and inhaled corticosteroids can be used . If children remain symptomatic despite regular SCG therapy , corticosteroids are the next therapeutic option . AIMS To determine whether combined SCG and fluticasone ( inhaled corticosteroid ) therapy is of additional benefit in children who are symptomatic on SCG compared with simply switching to fluticasone . PATIENTS AND METHODS Children with mild or moderate persistent asthma aged 6 to 16 years who had been treated with inhaled SCG for at least 3 months prior to the study received either 2 mg SCG four times daily from a metered dose inhaler plus fluticasone propionate powder 50 microg b.i.d . from the Diskus inhaler ( group FS ) or fluticasone 50 microg b.i.d . only ( group F ) . The r and omised , controlled , parallel-group study had a 2 week run-in phase and an 8 week treatment period . Morning and evening peak expiratory flow rates ( PEFR ) were measured daily by patients and recorded in diaries . Asthma symptoms , use of rescue medication and spirometry were also documented . RESULTS Paediatricians from 21 study centres recruited 124 children with asthma , of whom 104 fulfilled r and omisation criteria and were allocated to study medication . Morning PEFR increased by 47 l/min and by 45 l/min after 8 weeks of treatment in groups F and FS , respectively . The adjusted difference between groups was 0.84 % of predicted ( 95 % CI , -7.3 to 5.6 , p=0.80 ) . Asthma symptoms and lung function also improved with no significant differences between treatment groups ( p>0.24 ) . Frequency and severity of adverse events was similar in both groups . CONCLUSION In children who are symptomatic while taking sodium cromoglycate four times daily , the combination of inhaled fluticasone and SCG is not superior to fluticasone alone . SCG can safely be withdrawn when commencing fluticasone , thus facilitating asthma treatment Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa . We compared the effects of ketotifen , disodium cromoglycate ( DSCG ) , and beclomethasone dipropionate ( BDP ) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma . In this 12-week parallel study , 32 patients were r and omly allocated to either the ketotifen  group ( 2 mg day-1 , n = 13 ) , DSCG group ( 8 mg day-1 , n = 9 ) or BDP ( 400 micrograms day-1 , n = 10 ) . Each subject recorded daily asthma symptoms and peak expiratory flow ( PEF ) . Before and after treatment , pulmonary function and bronchial responsiveness to methacholine were evaluated , and fibreoptic bronchoscopy and biopsy were performed before and after treatment . Biopsy specimens were obtained by bronchoscopy . We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils ( EG2 ) , mast cells ( AA1 ) , and T cells ( CD3 , CD4 , and CD8 ) . Our clinical findings showed significant improvement in symptom score and bronchial responsiveness ( P < 0.01 ) each ) in all groups . Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group ( P < 0.05 , both groups ) . PEF significantly increased in the DSCG group in comparison to the ketotifen ( P < 0.01 ) and BDP ( P < 0.05 ) groups , FEV1 % increased significantly in the DSCG ( P < 0.01 ) and BDP ( P < 0.05 ) groups in comparison to the ketotifen group . Compared with their baseline values , treatment significantly decreased EG2 + activated eosinophils , and CD3 + and CD4 + T cells , in each group ( P < 0.01 ) . Both the DSCG ( P < 0.05 ) and the BDP groups ( P < 0.01 ) exhibited significant decreases in AA1 + mast cell count , but this was not observed in the ketotifen group . Comparing before- and after-treatment values , only the DSCG group exhibited a significant decrease in the number of CD8 + T cells ( P < 0.01 ) . Ketotifen , DSCG , and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients ; and both the DSCG and BDP groups had better clinical responses than the ketotifen group Neonatal pneumothorax : survey and prevention H V PRICE ........................................................ 456 Relationship between mood disturbances and free and total plasma tryptophan in postpartum women GEORGE STEIN , FRANK MILTON , PENNY BEBBINGTON , KEITH WOOD , ALEC COPPEN .............................................. 457 Treatment of childhood asthma with  sodium cromoglycate and beclomethasone dipropionate aerosol singly and in combination I MITCHELL , I C PATERSON , S J CAMERON . , I W B GRANT .................................................. D i s o c l i u i n c r o i i i o o l y c a l c ' ( D S C G ) * is t h e ( h s o t l i u m s a l t 1 , 3 b i s ( 2 c a r h o x y c l i r ( ) n i ( ) n i ; y l ( ) x y ) i l i y d r o x y p i o p a i i e ( I ' l .Ul ) I t h a s b e e n c l e m o n s t i a t e d t h a t t h i s s u b s t a n c e w i l l r e d u c e t h e h i o n c h o c o i i s t n c t o n a l I ' c s p o i i s e a l t c i a e r o s o l a l l c i ' n e i i c h a l l e i i i ^ c i n p a t i e n t s s u l l e i ' i n ^ ' I r n n i b r o n c h i a l a s t h m a { .illotniydii 1 9 6 7 ) . Tn a d o u b l e b l i n d t r i a l i t s \ a l u e in t h e lono t e r m t r e a t m e n t o l a s t h m a M a s i n d i c a t e d { . l l l o i i i i Y / i i i & l l o . v c l l ] ( ) G j ) . T h e r e June now lieen repoi'ted a niimbeiol double bliiitl t r i a l s , and most investigators ha\'e re < j , istered a benelicial e f f e c t iVom DSCCi . Thei-c are , ho\\e\er , mai-ked dil lei'eiices in t h e decree ol improxement ni the groups sUidied , probably beeaLisc there has been contro\'ersy about the assessment ol t h e pat ient response [ ll'oolcork & Read i^fi " ? , Grant et al. 1 9 6 7 , Jloicrl & /Illoiinxdii 1 9 6 7 ) . O S C C i acts by prc-\-enti?iL ; ' the release ol histaniine , SRS-A a n d p e r h a p s o the r biologically ac t i \ e substances a l t e r the c o m b i n a t i o n ol r e a l m s wilh the specilic al lergen m t)'pe I a l l e r c^ i e react ion . Voy this i-cason one could expect a Facilitated asthma-specialist care delivered by allergists was compared to generalist care on the rate of relapse of asthma emergency room ( ER ) visits and hospitalizations and on asthma control in a prospect i ve , controlled study of San Diego Kaiser Health Plan members with asthma . Subjects with asthma between the ages of 6 and 59 years presenting for acute ER care for asthma were systematic ally assigned by alternating , consecutively , the day of their ER visit to receive either ( 1 ) facilitated referral to an asthma specialist within the allergy department and concomitant comprehensive ongoing asthma care ( intervention group , n = 149 ) or ( 2 ) continued outpatient management from generalist physicians ( control group , n = 160 ) . The course of their asthma was evaluated blindly during the subsequent 6 months by review of medical records , initial and follow-up question naires , and spirometry . Compared to the control group , the intervention group noted ( 1 ) a 75 % reduction in the number of , and percent of , subjects with asthma awakenings per night ( p less than or equal to 0.0001 ) , ( 2 ) an almost 50 % reduction in asthma ER relapses ( p = 0.017 ) result ing from a reduction in the frequency of multiple relapse ( p = 0.005 ) , and ( 3 ) a greater use of inhaled corticosteroids ( p less than 0.00001 ) and cromolyn ( p = 0.002 ) . Thus , facilitated referral of subjects with asthma to specialists in asthma therapy after acute ER therapy appears to reduce asthma ER relapses and to improve asthma outcome We investigated the 1-year outcome of children hospitalized for wheezing , paying special attention to the effect of early anti-inflammatory therapy . In addition , we identified risk factors for  recurrent wheezing and asthma . Eighty-eight children under 2 years old treated in the hospital for wheezing were followed for 1 year . Nebulized anti-inflammatory therapy was given for 16 weeks : 31 patients received budesonide , 29 patients cromolyn sodium , and 28 control patients received no therapy . The number of subsequent physician-diagnosed wheezing episodes was recorded . Four months of anti-inflammatory therapy did not significantly decrease the occurrence of asthma 1 year later ; 45 % of patients in the cromolyn group , 42 % in the budesonide group , and 61 % in the control group had asthma , defined as at least two bronchial obstruction episodes during the 1-year period after the original hospitalization for wheezing . An age over 12 months at the time of the initial bronchial obstructing episode [ P=0.009 , risk ratio (RR)=5.4 , 95 % confidence interval (CI)=1.53 - 19.31 ] , failure to identify a viral cause ( P=0.0003 , RR=12.0 , CI=3.16 - 45.40 ) , history of wheezing ( P=0.02 , RR=14.6 , CI=1.59 - 132.10 ) , the presence of atopy ( P=0.01 , RR=5.3 , CI=1.47 - 19.21 ) , a family history of atopy ( P=0.03 , RR=3.6 , CI = 1.15 - 11.12 ) , and serum eosinophil cationic protein ( ECP ) > or = 16 microg/L ( P=0.005 ) were significant risk factors for asthma . We conclude that early anti-inflammatory therapy for 4 months does not significantly decrease the occurrence of asthma during the period of 1 year following hospitalization for the original episode of wheezing . Young children requiring hospital admission for wheezing during a respiratory tract infection are at increased risk of having subsequent asthma if they have wheezed previously , if they have atopy or a family history of atopy , if they have elevated serum ECP , if they are over 12 months of age at the original bronchial obstructive episode , and especially when viral studies are negative Thirty-one chronic perennial asthmatics aged from 2½ to 16 years were treated with beclomethasone dipropionate pressurized aerosols for up to 20 months . Of these , 16 patients dependent on oral corticosteroid or corticotrophin for up to 11 years were successfully transferred to this treatment , with one exception . Steroid withdrawal symptoms were slight . Loss of weight , disappearance of Cushingoid features , and resumption of growth indicated lack of systemic side effects . Fifteen others inadequately controlled on bronchodilators or disodium cromoglycate , were also effectively treated , and no clinical evidence of adrenal suppression was noted ABSTRACT . The efficacy of beclomethasone dipropionate ( BDP ) was compared with sodium cromoglycate ( SCG ) and placebo in a double‐blind parallel group study of 30 asthmatic children over a two‐month period . All the three treatment groups received salbutamol concomitantly . Lung volumes , airway mechanics and the nonspecific bronchial hyperreactivity to carbachol were measured at the beginning and the end of the study . Two patients were excluded because of unequal clinical conditions at the entry and the end of the study and three because of lack of co‐operation . Three patients ( 1 on SCG , 2 on placebo ) dropped out because of worsening clinical symptoms . The improvement in airway mechanics shown by the group treated with BDP ( n=7 ) was significantly greater ( p<0.01 ) than in the group treated with SCG ( n=8 ) . Nonspecific hyperreactivity to carbachol improved significantly in the BDP group ( factor 5.9 ) compared to the SCG group ( factor 1.9 ) . Childhood asthma seems to be better controlled by a combination of BDP and salbutamol , than by SCG and salbutamol In this 8-week , double-blind , comparative trial of nedocromil sodium ( 4 mg q.i.d . ) versus placebo in 42 patients with chronic reversible obstructive airways disease , there was a trend in favor of nedocromil sodium compared to placebo in parameters assessed by patients ( nocturnal symptom scores , evening PEFR values ) and those assessed by clinicians ( asthma severity scores ) compared with baseline values . There was a statistically significant difference ( p < 0.05 ) in favor of nedocromil sodium in the inhaled bronchodilator requirements in the last 2 weeks of treatment . Both patients ' and clinicians ' evaluation of the overall efficacy of treatment was significant in favor of nedocromil sodium ( p < 0.01 and p < 0.05 , respectively ) . The treatments were well tolerated by the majority of patients . From these data , it can be concluded that nedocromil sodium ( 4 mg q.i.d . ) is of value in the preventive treatment of chronic reversible obstructive airways disease 165 patients ( 106 males , 59 females ) entered an open group comparative study of a 12-week test treatment on bronchial hyperresponsiveness ( BHR ) determined by methacholine challenge . Patients were r and omly allocated to receive nedocromil sodium ( 4 mg q.i.d . ) , sodium cromoglycate ( 10 micrograms q.i.d . ) and beclomethasone dipropionate ( 500 micrograms t.i.d . ) . At the end of the study , an 2.25-fold increase of the PD20FEV1 was noted in all the treated patients . No significant difference was noted among the treatments
BACKGROUND Inhaled corticosteroids ( ICS ) and sodium cromoglycate ( SCG ) have become established as effective controller medications for children and adults with asthma , but their relative efficacy is not clear .
OBJECTIVES To compare the relative effectiveness and adverse effects of ICS and SCG among children and adults with chronic asthma .