Once-daily ciclesonide in children: efficacy and safety in asthma. Assessment of the Long-term Safety of Inhaled Ciclesonide on Growth in Children With Asthma Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma Onset of effect of budesonide and formoterol administered via one pressurized metered-dose inhaler in patients with asthma previously treated with inhaled corticosteroids. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group. Biologic mechanisms of environmental tobacco smoke in children with poorly controlled asthma: results from a multicenter clinical trial. Effect of inhaled glucocorticoids in childhood on adult height. [Systemic side effects of long-term treatment with low dose inhaled corticosteroids in children with asthma]. Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma. Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Beclomethasone aerosol in childhood asthma Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. Safety of hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol. Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology. Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma. Side-effects of fluticasone in asthmatic children: no effects after dose reduction Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study) Beclomethasone dipropionate aerosol in childhood asthma Randomized comparison of ciclesonide 160 and 640 microg/day in severe asthma. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Growth, systemic safety, and efficacy during 1 year of asthma treatment with different beclomethasone dipropionate formulations: an open-label, randomized comparison of extrafine and conventional aerosols in children. Systemic effect comparisons of six inhaled corticosteroid preparations. Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. Steroid Aerosols in Asthma: An Assessment of Betamethasone Valerate and a 12-month Study of Patients on Maintenance Treatment Long-term inhaled corticosteroids in preschool children at high risk for asthma. Montelukast versus formoterol as second-line therapy in asthmatic children exposed to relevant allergens. One-year treatment with different dosing schedules of fluticasone propionate in childhood asthma. Effects on hyperresponsiveness, lung function, and height. Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Low‐dose inhaled budesonide once or twice daily for 27 months in children with mild asthma Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial Long-term effects of budesonide or nedocromil in children with asthma. Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study. Long-term results with beclomethasone dipropionate aerosol in children with bronchial asthma: why does it sometimes fail? Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma. High-dose inhaled budesonide in treatment of severe steroid-dependent asthma. The insulin–like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. Treatment of childhood asthma for 13 months and longer with beclomethasone dipropionate aerosol A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma. Inhaled corticosteroids in children with persistent asthma: effects on growth. Influence of particle size on lung deposition and pharmacokinetics of beclomethasone dipropionate in children. A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma. Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropionate. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Potential effects of fluticasone propionate on bone mineral density in patients with asthma: a 2-year randomized, double-blind, placebo-controlled trial. Salmeterol/Fluticasone Propionate via Diskus™ Once Daily versus Fluticasone Propionate Twice Daily in Patients with Mild Asthma not Previously Receiving Maintenance Corticosteroids Efficacy and safety of inhaled fluticasone propionate chlorofluorocarbon in 2- to 4-year-old patients with asthma: results of a double-blind, placebo-controlled study. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. Beclomethasone Dipropionate Steroid Aerosol in Treatment of Perennial Allergic Asthma in Children Effects of inhaled fluticasone propionate in children less than 2 years old with recurrent wheezing. Efficacy and safety of three ciclesonide doses vs placebo in children with asthma: the RAINBOW study. Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy. A cluster-randomized trial to provide clinicians inhaled corticosteroid adherence information for their patients with asthma. Knemometry, Urine Cortisol Excretion, and Measures of the Insulin-Like Growth Factor Axis and Collagen Turnover in Children Treated with Inhaled Glucocorticosteroids
OBJECTIVE To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug ( CIC40 ) , 80 mug ( CIC80 ) , and 160 mug ( CIC160 ) with placebo in children with persistent asthma of all severities . STUDY DESIGN Overall , 1031 children age 4 to 11 years were r and omized into 2 identical double-blinded , placebo-controlled , parallel group studies consisting of a run-in phase followed by 12 weeks of treatment . Both studies were design ed to allow for a prespecified integrated analysis . The primary outcome variable was change in forced expiratory volume in 1 second ( FEV(1 ) ) percent predicted between baseline and study end ; treatment comparisons were assessed using analysis of covariance . Additional endpoints included asthma symptom scores , daily albuterol use , and safety , including hypothalamic-pituitary-adrenal ( HPA ) axis function . RESULTS Baseline characteristics were comparable ; 59.4 % of patients had moderate asthma , and 24.1 % had severe asthma . All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1 ) percent predicted versus placebo ( CIC40 , 11.97 ; CIC80 , 13.58 , P < .05 ; CIC160 , 14.17 , P < .01 ) . Significant improvements in asthma symptoms ( P < .01 ) and reductions in albuterol use were reported . Ciclesonide was well tolerated with no effect on HPA axis function . CONCLUSIONS In this integrated analysis , ciclesonide was effective and well tolerated in children with persistent asthma OBJECTIVE . To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma . METHODS . We performed a multicenter , r and omized , double-blind , placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild , persistent asthma . After a 6-month run-in period , 661 prepubertal children who were aged 5.0 to 8.5 years were r and omly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 μg ( ex-actuator ) or placebo , followed by a 2-month follow-up period . The primary end point was the linear growth velocity ( linear regression estimate ) over the double-blind treatment period . Growth was recorded as the median of 4 stadiometer measurements . Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed . RESULTS . Mean linear growth velocity during run-in was comparable between groups : 160 μg , 6.20 cm/year ; 40 μg , 6.59 cm/year ; placebo , 6.49 cm/year . Mean differences from placebo ( 5.75 cm/year ) in growth velocity over the double-blind treatment period were −0.02 cm/year for ciclesonide 40 μg and −0.15 cm/year for ciclesonide 160 μg . Both ciclesonide treatments were noninferior to placebo with respect to growth velocity . The overall incidence of adverse events was comparable between groups , and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period . CONCLUSIONS . Ciclesonide demonstrated no detectable effect on childhood growth velocity , even at the highest dosage , which may ease concerns about systemic adverse events BACKGROUND Airway hyperresponsiveness , induced sputum eosinophils , and exhaled nitric oxide ( NO ) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma . The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study . METHODS In a r and omised , double blind , placebo controlled , parallel study 25 patients with mild asthma ( 19–34 years , forced expiratory volume in one second ( FEV1 ) > 75 % predicted , concentration of histamine provoking a fall in FEV1 of 20 % or more ( PC20 ) < 4 mg/ml ) inhaled fluticasone propionate ( 500 μg twice daily ) for four weeks  . PC20 to histamine , sputum eosinophil numbers , and exhaled NO levels were determined at weeks 0 , 2 , and 4 , and two weeks after completing treatment . Sputum was induced by inhalation of hypertonic ( 4.5 % ) saline and eosinophil counts were expressed as percentage non-squamous cells . Exhaled NO levels ( ppb ) were measured by chemiluminescence . RESULTS In the steroid treated group there was a significant increase in PC20 , decrease in sputum eosinophils , and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment . Subsequently , each of these variables showed significant worsening during the two week washout period compared with week 4 . These changes were significantly different from those in the placebo group , except for the changes in sputum eosinophils and exhaled NO levels during the washout period . There were no significant correlations between the changes in the three markers in either group at any time . CONCLUSIONS Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine , eosinophil counts in induced sputum , and exhaled nitric oxide levels . The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma BACKGROUND Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler ( pMDI ) has not been evaluated in asthma . OBJECTIVE To evaluate time to onset of clinical ly significant bronchodilation ( > or = 15 % improvement in forced expiratory volume in 1 second ) and patient-perceived onset of effect ( OE ) in patients previously receiving inhaled corticosteroids . METHODS In two 12-week studies , patients 12 years and older with moderate to severe ( study 1 ; n = 596 ) and mild to moderate ( study 2 ; n = 480 ) persistent asthma received budesonide/formoterol pMDI , budesonide pMDI plus formoterol dry powder inhaler ( study 1 only ) , budesonide pMDI , formoterol dry powder inhaler , or placebo . Postdose time to 15 % or greater improvement in forced expiratory volume in 1 second and patient-perceived OE ( assessed in a subset of patients 18 years and older [ study 1 , n=553 ; study 2 , n=405 ] ) were evaluated [ corrected ] RESULTS More budesonide/formoterol-treated patients achieved onset of clinical ly significant bronchodilation within 15 minutes ( median , 13 minutes ) of administration at r and omization vs those taking budesonide or placebo ( P < .001 ) . More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away ( P < or = .004 ; end of week 1 ) . Similar results ( P < .001 ) were observed for patient satisfaction with how quickly they felt their medication begin to work ( except budesonide/formoterol vs budesonide , study 1 [ P = .073 ] ) . Time to onset of clinical ly significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar . CONCLUSION Budesonide/formoterol demonstrated a more rapid onset of clinical ly significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid result ed in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid . The aim of this three group study was to compare the effects of a moderate dose of beclomethasone , the same dose of beclomethasone with salmeterol , and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma . A total of 177 children already treated with inhaled corticosteroids , were r and omized in a double-blind parallel study either to salmeterol 50 microg twice daily ( BDP400+salm ) , beclomethasone 200 microg twice daily ( BDP800 ) , or placebo ( BDP400 ) in addition to beclomethasone 200 microg twice daily . No significant differences between groups were found in FEV1 , PD20 methacholine , symptom scores , and exacerbation rates after 1 yr . Salmeterol result ed in slightly better PEF in the first months of treatment . FEV1 , and PD20 methacholine significantly improved in all groups . After 1 yr mean changes in FEV1 , percent predicted were 4.3 % ( 95 % CI 1.3 ; 7.2 ) , 5.8 % ( 95 % CI 2.9 ; 8.7 ) , and 4.3 % ( 95 % CI 2.1 ; 6.5 ) for BDP400+salm , BDP800 , and BDP400 , respectively . Changes in airway responsiveness were 0.60 ( 95 % CI 0.05 ; 1.14 ) , 1.30 ( 95 % CI 0.73 ; 1 . 87 ) , and 0.80 ( 95 % CI 0.33 ; 1.27 ) doubling doses . Growth was significantly slower in the BDP800 group . We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication BACKGROUND Environmental tobacco smoke ( ETS ) negatively affects children with asthma . The prevalence of ETS exposure among children with poor asthma control may be changing . Importantly , the mechanisms by which ETS worsens asthma control are poorly understood . OBJECTIVE We describe how ETS affects gastroesophageal reflux ( GER ) , respiratory infections , and leukotriene production among children with poor asthma control . METHODS We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial . We evaluated prevalence and determinants of ETS exposure by interview , question naire , and urinary cotinine and the association of ETS exposure on leukotriene production , respiratory infections , GER , lung function , and asthma control . We used multivariable linear , logistic , and Poisson regressions to assess outcomes . RESULTS ETS prevalence estimates ranged from 6 % to 30 % . Children with domestic indoor exposure had worse asthma control ( c-Asthma Control Test , 17.8 vs 21.5 ; P = .04 ) , worse FEV1 % predicted ( 84.1 vs 90.7 ; P = .02 ) , and a trend for increased mean urinary leukotriene E4 . ETS from any setting was associated with increased symptomatic respiratory infections ( adjusted incidence rate ratio : 1.30 ; P = .02 ) . However , children exposed to ETS did not have symptoms or pH probe results , suggestive of heightened GER . CONCLUSIONS Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy . ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections . Further investigation is required to eluci date ETS mechanisms in poor asthma control BACKGROUND The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children . The result ing decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height . METHODS We measured adult height  in 943 of 1041 participants ( 90.6 % ) in the Childhood Asthma Management Program ; adult height was determined at a mean ( ±SD ) age of 24.9±2.7 years . Starting at the age of 5 to 13 years , the participants had been r and omly assigned to receive 400 μg of budesonide , 16 mg of nedocromil , or placebo daily for 4 to 6 years . We calculated differences in adult height for each active treatment group , as compared with placebo , using multiple linear regression with adjustment for demographic characteristics , asthma features , and height at trial entry . RESULTS Mean adult height was 1.2 cm lower ( 95 % confidence interval [ CI ] , -1.9 to -0.5 ) in the budesonide group than in the placebo group ( P=0.001 ) and was 0.2 cm lower ( 95 % CI , -0.9 to 0.5 ) in the nedocromil group than in the placebo group ( P=0.61 ) . A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height ( -0.1 cm for each microgram per kilogram of body weight ) ( P=0.007 ) . The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment ( -1.3 cm ; 95 % CI , -1.7 to -0.9 ) . During the first 2 years , decreased growth velocity in the budesonide group occurred primarily in prepubertal participants . CONCLUSIONS The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height , although the decrease was not progressive or cumulative . ( Funded by the National Heart , Lung , and Blood Institute and the National Center for Research Re sources ; CAMP Clinical Trials.gov number , NCT00000575 . ) OBJECTIVE To observe the systemic side effects of low dose inhaled Beclomethasone dipropionate ( BDP ) in children with mild asthma . METHODS 30 children with mild asthma were r and omly divided into 3 groups to receive treatment with inhaled placebo ( group A ) , BDP 200 micrograms/d ( group B ) and BDP 400 micrograms/d ( group C ) respectively . Bronchial hyperresponsiveness ( BHR ) , height growth , bone mineral density ( BMD ) , calcium and phosphate metabolism and hypothalamic-pituitary-adrenal axis ( HPAA ) function were measured . RESULTS Inhaled BDP of 200 micrograms/d and 400 micrograms/d reduced BHR in mild asthmatic children and there was no significant difference between two groups [log(PD20-FEV1)]:(2.04 + /- 0.47 ) micrograms to ( 2.70 + /- 0.13 ) micrograms in group A and ( 1.94 + /- 0.46 ) micrograms to ( 3.15 + /- 0.18 ) micrograms in group B ( P < 0.01 ) . Serum osteocalcin , calcium , phosphate , alkaline phosphatase , basic cortisol and BMD did n't change significantly after BDP treatment in three groups ( all P > 0.05 ) [ In group A , B and C , concentrations serum osteocalcin were ( 29 + /- 12 ) micrograms/L , ( 22 + /- 6 ) micrograms/L , ( 31 + /- 11 ) micrograms/L , serum calcium : ( 2.49 + /- 0.11 ) mmol/L , ( 2.39 + /- 0.28 ) mmol/L , ( 2.20 + /- 0.35 ) mmol/L , serum phosphate : ( 1.8 + /- 0.6 ) mmol/L , ( 1.7 + /- 0.7 ) mmol/L , ( 1.5 + /- 0.4 ) mmol/L , radius BMD : ( 0.44 + /- 0.02 ) g/cm2 , ( 0.42 + /- 0.05 ) g/cm2 , ( 0.40 + /- 0.10 ) g/cm2 , ulna BMD:(0.35 + /- 0.04 ) g/cm2 , ( 0.36 + /- 0.08 ) g/cm2 , ( 0.32 + /- 0.07 ) g/cm2 , serum alkaline phosphatase : ( 410 + /- 113 ) U/L , ( 337 + /- 99 ) U/L , ( 351 + /- 122 ) U/L , serum basic cortisol : ( 350 + /- 86 ) nmol/L , ( 407 + /- 199 ) nmol/L , ( 365 + /- 71 ) nmol/L , lumbar spine ( L4 - 5 ) BMD : ( 0.64 + /- 0.06 ) g/cm2 , ( 0.59 + /- 0.08 ) g/cm2 , ( 0.62 + /- 0.09 ) g/cm2 respectively ] . Height growth had a trend of reducing after BDP treatment though not reaching statistical difference . Height st and ard deviation score ( SDS ) : 1.1 + /- 0.7 to 1.2 + /- 0.9 in group A , 1.3 + /- 0.7 to 1.3 + /- 0.9 in group B and 1.1 + /- 0.7 to 1.0 + /- 0.7 in group C. Serum cortisol after ACTH stimulation reduced significantly in group C [ ( 621 + /- 199 ) nmol/L to ( 482 + /- 97 ) nmol/L , P < 0.01 ] . CONCLUSION The results of this study suggest that 200 micrograms/d BDP can reduce BHR significantly and has no detected systemic side effects in mild asthmatic children , and 400 micrograms/d BDP can reduce serum cortisol after ACTH stimulation . The long-term dose of BDP should be controlled to be less than 400 micrograms/d in children with mild asthma BACKGROUND Results of recent growth studies suggest that inhaled glucocorticosteroids may affect  growth in children . OBJECTIVE Three 52-week , open-label extension studies ( studies A , B , and C ) were conducted to compare the effects of budesonide inhalation suspension ( BIS ) with conventional asthma therapy ( CAT ) on long-term safety , including intermediate-term growth , in 3 different pediatric asthma population s. METHODS Pediatric asthma patients ( ages 6 months to 8 years ) from 3 multicenter , r and omized , 12-week , double-blind , placebo-controlled studies were eligible to enroll in the 52-week , open-label extension studies . The extension studies were multicenter , r and omized , open-label , active-controlled , parallel-group studies performed at 26 centers in the United States . Subjects in each extension study were r and omized in a 2:1 ratio to receive either BIS or CAT . BIS was initially administered at a dose of 0.5 mg once ( studies A and C ) or twice daily ( study B ) , with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control , as judged by the investigator . CAT consisted of any available therapy for asthma , including inhaled glucocorticosteroids in studies B and C only . Height SD scores , growth velocity , and skeletal age ( only in studies B and C ) were examined . RESULTS In total , 670 subjects were r and omized ; 223 subjects received CAT and 447 received BIS . Mean ages at entry were 63.0 months and 60.9 months in  CAT  and BIS groups , respectively . Median total daily doses of BIS  ranged from 0.5 to 1 . 0 mg and the mean duration of treatment exposure was 304 + /- 119 days and 342 + /- 83 days in CAT and BIS groups , respectively . Changes in height SD scores differed significantly between the BIS and CAT groups in study A ( -0.19 , P = .003 ) , and there was a small , statistically significant decrease in growth velocity ( -0.8 cm/y , P = .002 ) in the BIS-treated group compared with the CAT group . No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B ( + 0.10 and + 0.7 cm/y , respectively ) and C ( + 0.12 and + 0.8 cm/y , respectively ) . No differences in skeletal age were observed between BIS and CAT  groups in studies B and C. CONCLUSION There was a small , statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study ( study A ) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study . In the studies ( B and C ) where inhaled glucocorticosteroids were allowed in the CAT group , no differences were observed in height SD scores or growth velocity . The clinical relevance of these effects , including impact on final adult height , remain to be determined in prospect ively planned studies that assess growth in children The aim of the present study was to examine the efficacy of low-dose inhaled budesonide ( BUD ) administered via Turbuhaler once or twice daily on symptoms , lung function and bronchial hyperreactivity in children with mild asthma . One hundred and sixty-three children ( mean age 9.9 yrs , 56 females/107 males ) with mild asthma ( forced expiratory volume in one second ( FEV1 ) 103 % of predicted , morning peak expiratory flow ( PEF ) 87 % pred , reversibility in FEV1 3 % , fall in FEV1 after exercise 10.4 % from pre-exercise value ) and not previously treated with inhaled steroids , were included in a double-blind , r and omized , parallel-group study . After a two-week run-in period , the children received inhaled BUD 100 microg or 200 microg once daily in the morning , 100 microg twice daily or placebo for 12 weeks . Exercise and methacholine challenges were performed before and at the end of treatment . After 12 weeks of therapy , the fall in FEV1 after an exercise test was significantly less in all three BUD groups ( 43 - 5.1 % ) than in the placebo group ( 8.6 % ) . Bronchial hyperreactivity to methacholine with the provocative dose causing a 20 % fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo ( ratio at the end of treatment 156 % ) . Changes in baseline lung function ( FEV1 and PEF ) were less marked than changes in bronchial responsiveness . In conclusion , low doses of inhaled budesonide , given once or twice daily , provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function Twenty children have been treated with the steroid aerosol beclomethasone , half of them in an open trial and the other half in a controlled cross-over trial . Children were assessed by means of clinical examination , diary records , and twice-daily peak flow rate measurements made at home . After 1 to 2 months all but 1 of the 16 children who were initially taking systemic steroids or corticotrophin  were weaned off these drugs . The cross-over trial showed a significant improvement on the active drug , in terms of diary score , bronchodilator use , steroid dose , and twice-daily peak expiratory flow measurements . Adrenal function was entirely normal after 1 and 3 months on the drug as measured by morning cortisol levels and the response to tetracosactrin . There were no side effects , apart from the reappearance of hay fever or eczema in some children previously on systemic steroids . Follow-up for a mean of 4·5 ± 2·2 ( SD ) months showed the continuing efficacy of beclomethasone , though an increase in dose has been needed in some children . The advantages of aerosol steroid therapy in children are noted BACKGROUND Because of potential toxicities of inhaled corticosteroid ( ICS ) use in pediatric asthma , alternative or steroid-sparing therapy is desirable . There are no previous studies evaluating montelukast 's  steroid-sparing effects in children with asthma . OBJECTIVE To evaluate whether ( 1 ) montelukast as add-on therapy improves asthma symptom control and ( 2 ) montelukast provides steroid-sparing effects in children with asthma treated with low to moderate doses of ICS therapy . METHODS In a double-blind , placebo-controlled trial , 36 children ages 6 to 14 years with symptomatic asthma maintained on a stable low to moderate dose of ICSs  were r and omly assigned to receive montelukast or matching placebo for 24 weeks after a run-in period of 2 weeks ( period I ) . During the trial , subjects kept daily asthma diary cards and monthly spirometry was performed . After a 4 week add-on period ( period II ) , the subjects completed a 20-week ( period III ) ICS tapering period based on a predetermined protocol . RESULTS In period II , the difference in the number of rescue-free days was significantly higher in the montelukast group ( P = 0.0001 ) , and the number of rescue-free days per week was also significantly higher in montelukast-treated subjects compared with placebo subjects ( P = 0.002 ) . In period III , the percentage reduction in ICS dose was not significant between montelukast and placebo ( P = 0.10 ) , but the montelukast group experienced an average 17 % decrease in ICS dose and the control group experienced an average 64 % increase in ICS dose . CONCLUSIONS Montelukast treatment significantly increased the number of rescue-free days in symptomatic children with asthma OBJECTIVE Exhaled nitric oxide ( FE(NO ) ) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide , nedocromil , or albuterol  as needed . STUDY DESIGN FE(NO ) , spirometry , total eosinophil count , and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout . RESULTS Budesonide-treated patients had significantly lower median ( 1st , 3rd quartile ) FE(NO ) ( 21.5 [ 13.2 , 84.4 ] vs 62.5 [ 26.2 , 115.0 ] ppb , P < .01 ) and eosinophil cationic protein levels ( 17.4 [ 10.1 , 24.3 ] vs 24.0 [ 15.4 , 33.9 ] mg/dL , P = .05 ) compared with placebo , whereas no differences were noted between nedocromil and placebo groups . After washout , FE(NO ) levels were similar between the three treatments . FE(NO ) levels significantly correlated with degree of bronchial hyperresponsiveness , bronchodilator reversibility , allergen skin prick tests , serum IgE , and total eosinophil count . FE(NO ) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly . CONCLUSIONS Budesonide therapy was more effective than nedocromil in reducing FE(NO ) . Unfortunately , the effects of long-term budesonide were not sustained after its discontinuation . FE(NO ) may be a complementary tool to current practice guidelines in assessing asthma control and medication response 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 BACKGROUND Atopic dermatitis ( AD ) often develops in infancy as the first manifestation of the atopic phenotype . Wheezing is also common in infancy , but it is less clear whether infant wheezing should be considered as an atopic phenotype . If infant wheeze and AD share a common aetiology , this would indicate that infant wheezing is an atopic phenotype . OBJECTIVE To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes , indicating a common etiology . METHODS A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospect ively . Information on wheezing episodes , AD , and prenatal , perinatal , and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation , at 6 and 18 months of age , and by linkage to the Danish Medical Birth Register . Data were analyzed by binary and polytomous logistic regression models . RESULTS The following variables had significantly differential effects on infant wheezing and AD : parental hay fever , parental asthma , parental AD , sex , maternal age , maternal occupation , smoking during pregnancy , season of birth , birth weight , gestational age , head circumference , breast-feeding , number of older siblings , day care attendance , and pets in the home . CONCLUSION The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology . Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease , and infant wheezing should not be used as an indicator of the atopic phenotype 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 To assess long-term effects and side-effects of fluticasone propionate ( FP ) , a 2-yr study was performed , comparing a step-down dose approach ( 1,000 µg·day−1 , with reductions every 2 months to 500 , 200 and 100 µg·day−1 for the remainder of the study ) versus a constant dose ( 200 µg·day−1 ) . In 55 children with chronic persistent asthma , aged 6–10 yrs  , airways hyperresponsiveness ( AHR ) and systemic side-effects ( height , bone parameters and adrenal cortical function ) were assessed at predetermined intervals in a double-blind prospect i ve 2-yr study . AHR improved after 4 months treatment with 1,000 µg·day−1 FP followed by 500 µg·day−1 , without significant differences during long-term treatment between the two approaches . Dose-dependent reduction of growth velocity , adrenal cortical function and biochemical bone turnover was found during therapy with 1,000 and 500 µg·day−1 FP when compared with 200 µg·day−1 . In conclusion , doses of 1,000 and 500 µg·day−1 fluticasone propionate are associated with marked reductions of growth velocity , bone turnover and adrenal cortical function . However , conventional doses ( ≤200 µg·day−1 fluticasone propionate ) appear to be safe in the long-term management of childhood asthma . From a safety point of view , high doses of fluticasone propionate should only be prescribed in exceptions , e.g. in persistent severe asthma Objective : To compare the effect of inhaled budesonide given daily or as-needed on  mild persistent childhood asthma .  Patients , design and interventions : 176 children aged 5–10 years with newly detected asthma were r and omly assigned to three treatment groups : ( 1 ) continuous budesonide ( 400 μg twice daily for 1 month , 200 μg twice daily for months 2–6 , 100 μg twice daily for months 7–18 ) ; ( 2 ) budesonide , identical treatment to group 1 during months 1–6 , then budesonide for exacerbations as needed for months 7–18 ; and ( 3 ) disodium cromoglycate ( DSCG ) 10 mg three times daily for months 1–18 . Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks . Main outcome measures : Lung function , the number of exacerbations and growth . Results : Compared with DSCG the initial regular budesonide treatment result ed in a significantly improved lung function , fewer exacerbations and a small but significant decline in growth velocity . After 18 months , however , the lung function improvements did not differ between the groups . During months 7–18 , patients receiving continuous budesonide treatment had significantly fewer exacerbations ( mean 0.97 ) , compared with 1.69 in group 2 and 1.58 in group 3 . The number of asthma-free days did not differ between regular and intermittent budesonide treatment . Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed . The latter was associated with catch-up growth . Conclusions : Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed . The dose of ICS could be reduced as soon as asthma is controlled . Some children do not seem to need continuous ICS treatment Twenty-five patients with severe childhood asthma were treated with beclomethasone dipropionate . 21 of these children were receiving oral corticosteroid therapy in addition to disodium cromoglycate . Of the total treated , 21 children improved or maintained their asthma status on this treatment over an average period of 4 months , and were able to reduce and stop their regular oral corticosteroid dosage , but 4 children had to revert to their original therapy . No systemic or local toxic effects were experienced by any of the children . Beclomethasone dipropionate appears to be an effective drug in the treatment of severe childhood asthma in those patients who need corticosteroid therapy in addition to disodium cromoglycate OBJECTIVE Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition . In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily ( CIC640 ) versus ciclesonide 160 microg once daily (CIC160)-in  patients with severe persistent asthma . METHODS Patients with bronchial asthma ( 6 months ) were included in this r and omized , double-blind study . After receiving fluticasone propionate 250 microg twice daily during run-in , patients were r and omized to CIC160 ( n=339 ) or CIC640 ( n=341 ) for 12 weeks . Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s ( FEV(1 ) ) . Secondary endpoints included other lung function variables , asthma symptom scores and rescue medication use ( RMU ) . RESULTS Asthma exacerbations occurred in 12.7 % of patients receiving CIC160 and 6.7 % receiving CIC640 . CIC640 was superior for time to first exacerbation ( p=0.0050 , one-sided ) . FEV(1 ) increased significantly with CIC160 and CIC640 ( least squares mean+/-SE of mean : 269+/-31 and 332+/-31 mL , respectively ; p<0.0001 ) , with no significant difference between groups . Change in % predicted FEV(1 ) and morning peak expiratory flow ( PEF ) were significantly higher with CIC640 ( p<0.05 ) . Asthma symptom score sums and RMU decreased in both groups ; CIC640 was statistically superior ( p=0.0108 and 0.0005 , respectively ) . No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity . No significant changes in serum cortisol were observed from the baseline to the study end . Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups , which , due to the large patient numbers , were statistically significant ( p<0.05 ) ; however , no dose-response effect was seen and the difference between groups was not significant ( p=0.7892 ) . CONCLUSION CIC640 was superior to CIC160 for time to first exacerbation , % predicted FEV1 , morning PEF , asthma symptom score sum and RMU in patients with severe asthma ; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group BACKGROUND In 2010 , the Canadian Thoracic Society ( CTS ) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older , and adults , including an up date d Asthma Management Continuum . The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline up date process , focusing , in this first iteration , on topics of controversy and ⁄or gaps in the previous guidelines . METHODS Four clinical questions were identified as a focus for the up date d guideline : the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy ; the initiation of adjunct therapy to inhaled corticosteroids ( ICS ) for uncontrolled asthma ; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever , and as a reliever and a controller ; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan . The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics . In addition , literature search es were performed to identify relevant systematic review s and r and omized controlled trials . The panel formally assessed and grade d the evidence , and made 34 recommendations . RESULTS The up date d guideline recommendations outline a role for inclusion of assessment of sputum eosinophils , in addition to st and ard measures of asthma control , to guide adjustment of controller therapy in adults with moderate to severe asthma . Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations . New recommendations for the adjustment of controller medication within written action plans are provided . Finally , priority areas for future research were identified . CONCLUSIONS The present clinical practice guideline is the first up date of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee 's new guideline development process . Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide up date s reflecting new evidence OBJECTIVE To assess the long-term safety of hydrofluoroalkane 134a (HFA)-beclomethasone dipropionate ( BDP ) extrafine aerosol administered by the Autohaler compared with chlorofluorocarbon (CFC)-BDP administered by a press- and -breathe metered-dose inhaler ( pMDI ) and spacer ( + S ) in the treatment of children with asthma . METHODS This 12-month , open-label , r and omized , multicenter study enrolled 300 children who were aged 5 to 11 years and had well-controlled asthma on inhaled CFC-BDP or budesonide ; 256 patients were using doses within the recommended range ( 200 - 400 microg ) and were analyzed separately . Patients were r and omized in a 1:3 ratio to continue on CFC-BDP+S at approximately the same dose as they were using before study entry or switch to HFA-BDP at half the daily dose . RESULTS Asthma control was well maintained in the HFA-BDP group as evidence d by lung function tests and asthma symptoms compared with CFC-BDP+S at approximately twice the dose . There were no significant differences between the HFA-BDP 100 to 200 microg and CFC-BDP+S 200 to 400 microg treatment groups in mean change from baseline in height ( 5.23 cm vs 5.66 cm at month 12 , respectively ) or mean growth velocity from day 1 to month 12 ( 5.27 cm/y vs 5.71 cm/y , respectively ) . There were no significant differences between groups in adrenal function tests or markers of bone metabolism . CONCLUSIONS In this long-term study in children with asthma , extrafine HFA-BDP provided long-term maintenance of asthma control at approximately half the dose compared with CFC-BDP+S. There were no clinical ly meaningful differences between HFA-BDP extrafine aerosol and conventional CFC-BDP+S with regard to growth or other systemic effects The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects ( microgram dose producing equal systemic cortisol suppression ) of inhaled corticosteroids ( ICS ) .  Steroid naive asthma subjects ( n = 156 ) were enrolled at six centers . A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses . Systemic effect was evaluated by hourly plasma cortisol concentrations ( 8 P.M. to 8 A.M. ) , 12- and 24-hour urine cortisol concentrations , and a morning blood osteocalcin . The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect . For the six ICS and matching placebos ( beclomethasone-chlorofluorocarbon [ CFC ] , budesonide dry powder inhaler [ DPI ] , fluticasone DPI , fluticasone-CFC metered dose inhaler [ MDI ] , flunisolide-CFC , and triamcinolone-CFC ) , only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect . Thus microgram comparison of all ICS could only be performed at a 10 % cortisol suppression : flunisolide-CFC - 936 ; triamcinolone-CFC - 787 ; beclomethasone-CFC - 548 ; fluticasone DPI - 445 ; budesonide DPI - 268 ; fluticasone-CFC MDI - 111 . This study represents the first step in evaluation of ICS efficacy based on equisystemic ( cortisol suppression ) effects of a given ICS , rather than doses judged arbitrarily to be comparable on a microgram basis OBJECTIVE To compare the safety of budesonide inhalation suspension ( BIS ) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze . STUDY DESIGN In this multicenter , r and omized , double-blinded , parallel-group , placebo-controlled study , 141 patients received 0.5 mg BIS ( n = 48 ) , 1.0 mg BIS ( n = 44 ) , or placebo ( n = 49 ) once daily for 12 weeks . The primary variable was adrenal function , based on cosyntropin-stimulated plasma cortisol levels . Spontaneous adverse events and clinical laboratory findings also were monitored . RESULTS Overall , the types and frequencies of adverse events reported during the study were comparable across treatment groups . The response to cosyntropin stimulation was similar across treatment groups , with no significant difference between BIS treatment and placebo . CONCLUSIONS The safety profile of BIS was similar to that of placebo , with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze BACKGROUND An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children . The role of long-acting beta2-adrenergic-receptor agonists , such as salmeterol , needs to be defined . METHODS We conducted a r and omized , double-blind , placebo-controlled , parallel-group , one-year study of 241 children ( mean [ + /-SD ] age , 9.3+/-2.4 years ) with clinical ly stable asthma and less than one month of prior glucocorticoid use . We compared inhaled beclomethasone dipropionate ( 200 microg twice daily ) with salmeterol xinafoate ( 50 microg twice daily ) and placebo ( lactose ) . The primary outcome measure , airway responsiveness ( as assessed with a methacholine challenge ) was evaluated before treatment ; after 3 , 6 , 9 , and 12 months of treatment ( 12 and 36 hours after study medications had been withheld ) ; and 2 weeks after the end of treatment . Spirometry , symptoms , use of rescue medication ( 200 microg of albuterol inhaled as needed ) , and adverse effects were also assessed . RESULTS During months 1 through 12 overall , beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol ( P= 0.003 ) or placebo ( P<0.001 ) . This effect was lost two weeks after treatment had been stopped . As compared with placebo , beclomethasone was associated with less variability between morning and evening in the peak expiratory flow ( P=0.002 ) , as was salmeterol ( P=0.02 ) . Beclomethasone was also associated with a reduced need for albuterol as rescue therapy ( P<0.001 ) and fewer withdrawals because of asthma exacerbations ( P=0.03 ) , but salmeterol was not ( P=0.09 and 0.55 , respectively ) . During months 1 through 12 , linear growth was 3.96 cm in the children receiving beclomethasone , as compared with 5.40 cm in the salmeterol group ( P=0.004 ) and 5.04 cm in the placebo group ( P=0.018 ) . Height was not measured after treatment ended . CONCLUSIONS Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma , but it was associated with decreased linear growth . Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms ; however , it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness , masking of symptoms , or adverse effects Betamethasone valerate aerosol is a new compound for the treatment of asthma . Its clinical effectiveness was established in a double-blind cross-over trial in non-steroid-dependent asthmatic patients . At a dosage of 400 to 800 μg/day for three months there was no evidence of suppression of hypothalamic-pituitary-adrenal function , as assessed by tetracosactrin and insulin stress tests . A 12-month follow-up study of 120 patients using steroid aerosols ( betamethasone valerate or beclomethasone dipropionate )  indicated that tolerance does not develop and that a daily maintenance dose of 200 μg/day was adequate in most patients . Temporary lack of response was observed during episodes of sputum production or of heavy exposure to antigen . There were no observed side effects other than fungal infections of the respiratory tract . However , the incidence of c and idiasis of the pharynx ( 13 % ) and particularly of the larynx ( 5 % ) in apparently immunologically normal patients was disturbing . These infections were not seen in patients taking 200 μg/day . Though there is yet no evidence that fungal infections associated with steroid aerosols may penetrate the trachea and bronchi the possibility of this indicates that caution should be exercised in their use , particularly in long-term high dosage BACKGROUND It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma . METHODS We r and omly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate ( at a dose of 88 mug twice daily ) or masked placebo for two years , followed by a one-year period without study medication . The primary outcome was the proportion of episode-free days during the observation year . RESULTS During the observation year , no significant differences were seen between the two groups in the proportion of episode-free days , the number of exacerbations , or lung function . During the treatment period , as compared with placebo use , use of the inhaled corticosteroid was associated with a greater proportion of episode-free days ( P=0.006 ) and a lower rate of exacerbations ( P<0.001 ) and of supplementary use of controller medication ( P<0.001 ) . In the inhaled-corticosteroid group , as compared with the placebo group , the mean increase in height was 1.1 cm less at 24 months ( P<0.001 ) , but by the end of the trial , the height increase was 0.7 cm less ( P=0.008 ) . During treatment , the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth , albeit temporarily and not progressively . CONCLUSIONS In preschool children at high risk for asthma , two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third , treatment-free year . These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued . ( Clinical Trials.gov number , NCT00272441 . ) In sensitive asthmatic children , the exposure to relevant allergens causes a deterioration of lung function and symptoms associated with an increase of inflammatory indices . The aim of this single-blind r and omized add-on study was to compare the effects of montelukast or formoterol added to low-dose budesonide in asthmatic allergic children exposed to relevant allergens . Twenty children ( 5 female subjects and 15 male subjects , aged 6 - 12 years ) were enrolled .  Lung function and airway inflammatory indices ( exhaled nitric oxide [ eNO ] and sputum eosinophils ) were evaluated at T0 when children were not exposed to relevant allergens and at T1 after 15 days of natural effective allergen exposure . At T1 , pulmonary function tests and sputum eosinophils remained stable in both of the groups , without significant differences in comparison with T0 at baseline . Furthermore , formoterol plus budesonide was effective in preventing the expected increase in eNO from 26.46 + /- 2.62 ppb at T0 to 29.33 + /- 9.28 ppb at T1 ( not significant ) . However , in the group receiving montelukast plus budesonide , there was a significant decrease of eNO from baseline ( 30.78 + /- 6.87 ppb ) to T1 ( 18.17 + /- 6.60 ppb ) ( p < .05 ) . In allergic asthmatic children , the use of montelukast or formoterol combined with budesonide could offer a durable protective effect on symptoms , lung function , and inflammatory indices Dose-dependent effects of inhaled corticosteroids have been described . Although it has been advised to start treatment with inhaled corticosteroids with a high dose tapering off subsequently ( stepdown approach ) , no clinical studies have assessed this strategy . We compared two different dosage schedules of inhaled fluticasone propionate ( FP ) in chronic persistent childhood asthma with respect to efficacy ( airways hyperresponsiveness [ PD(20 ) ] , lung function , exhaled nitric oxide [ eNO ] ) and safety ( height ) . During this double-blind study , children with asthma ( aged 6 - 10 yr ) were r and omized to receive either FP 200 microg/d ( constant dose approach ) or to start with 1000 microg/d with two monthly reductions to 500 , 200 , and 100 microg/d ( stepdown approach ) . PD(20 ) improved in both approaches during treatment with FP , with a significantly better PD(20 ) after 2 mo of 1000 microg/d followed by 500 microg/d in the stepdown approach versus 200 microg/d in the constant dose approach . No significant differences in PD(20 ) or other efficacy parameters were found after 1 yr . Changes in st and ing height were similar in both treatment approaches . This study showed no superior clinical effect of a stepdown approach compared with a constant dose strategy of FP for 1 yr in children with chronic persistent asthma In a r and omized double-blind multicenter clinical study , 116 children with asthma were r and omly assigned to treatment with an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus an inhaled corticosteroid ( budesonide 0.2 mg ) three times a day ( BA+CS ) or to an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus a placebo three times a day ( BA+PL ) . After a median follow-up time of 22 months , 26 patients receiving BA+PL ( 45 % ) had withdrawn from r and omized treatment , mainly because of asthma symptoms , compared with three withdrawals in the patients receiving BA+CS ( p less than 0.0001 ) . The FEV1 , expressed as a percentage of the predicted value for age , sex , and height , showed an absolute increase of 7.0 % after 2 months of BA+CS compared with a decrease of 4.0 % after 2 months of BA+PL . This 11 % difference in percent predicted FEV1 ( 95 % confidence interval , 7 to 15 % ; p less than 0.0001 ) was then maintained after a median follow-up period of 22 months . Postbronchodilator FEV1 showed an absolute increase of 3.7 % predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1 % predicted in children receiving BA+PL ( p = 0.0005 ) . Thereafter , this difference between the two treatment groups was maintained . Average peak expiratory flow rate ( PEFR ) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group ( p = 0.003 ) . This difference then remained for the median follow-up time of 22 months . ( ABSTRACT TRUNCATED AT 250 WORDS Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma . To evaluate whether prolonged treatment can bring about full recovery , this double-blind , r and omized , controlled trial examined the effect of budesonide , 400 micrograms daily for 1 yr , on airway hyperresponsiveness . The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated . Thirty-two stable adult asthmatics , requiring bronchodilators alone , were selected . Before and monthly throughout the study , airway responsiveness to methacholine was measured and clinical asthma severity assessed by question naire , daily bronchodilator use , and number of asthma exacerbations . Patients receiving budesonide  showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo ( p less than 0.0005 ) , whose responsiveness remained very stable . Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range . Largest improvements occurred during the first 3 months but , in some , were still progressing slowly at 1 yr . Improvements in responsiveness were accompanied by significant improvements in asthma symptoms , bronchodilator use , and number of asthma exacerbations . The results show that regular , prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness , sometimes with full resolution , and these improvements are accompanied by clinical ly significant improvements in clinical asthma This study is an extended follow‐up for 24 months of a 12‐week trial to study the long‐term clinical efficacy of low‐dose inhaled budesonide ( BUD ) once or twice daily in children with mild asthma . A total of 122 children ( mean age 9.7 years , girls/boys ; 42/80 ) with mild asthma ( FEV1 103.7 % of predicted , reversibility in FEV1 3.5 % , and fall in FEV1 afterexercise 12.2 % ) , not previously treated with inhaled steroids , were included in a double‐blind , r and omized , parallel‐group study . The children were treated with inhaled BUD 100 or 200 µg administered via Turbuhaler ® once daily in the morning , 100 µg twice daily , or placebo for 27 months . Exercise and methacholine challenges were performed at 3‐month intervals the first year and at 6‐month intervals the second year , in a total of seven visits . A significant dose‐response effect favoring BUD 200 µg daily ( vs 100 µg daily ) was found when comparing changes in FEV1 , FEF25 % , and FEV50 % ; the fall in FEV1 after an exercise test ; and the effect on blood eosinophils . Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 µg daily compared to placebo . Growth rate was not significantly affected except in children aged 7–11 years at baseline after 12 months of treatment . In conclusion , 100 or 200 µg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise‐induced asthma and achieving nearly normal lung function . Baseline lung function was not significantly affected in this group of children with mild asthma BACKGROUND Preliminary evidence is equivocal about the role of exhaled nitric oxide ( NO ) in clinical asthma management . We aim ed to assess whether measurement of exhaled NO , as a biomarker of airway inflammation , could increase the effectiveness of asthma treatment , when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults . METHODS We did a r and omised , double-blind , parallel-group trial at ten centres in the USA . We screened 780 inner-city patients , aged 12 - 20 years , who had persistent asthma . All patients completed a run-in period of 3 weeks on a regimen based on st and ard treatment .  546 eligible participants who adhered to treatment during this run-in period were then r and omly assigned to 46 weeks of either st and ard treatment , based on the guidelines of the National Asthma Education and Prevention Program ( NAEPP ) , or st and ard treatment modified on the basis of measurements of fraction of exhaled NO . The primary outcome was the number of days with asthma symptoms . We analysed patients on an intention-to-treat basis . This trial is registered with clinical trials.gov , number NCT00114413 . FINDINGS During the 46-week treatment period , the mean number of days with asthma symptoms did not differ between the treatment groups ( 1.93 [ 95 % CI 1.74 to 2.11 ] in the NO monitoring group vs 1.89 [ 1.71 to 2.07 ] in the control group ; difference 0.04 [ -0.22 to 0.29 ] , p=0.780 ) . Other symptoms , pulmonary function , and asthma exacerbations did not differ between groups . Patients in the NO monitoring group received higher doses of inhaled corticosteroids ( difference 119 mug per day , 95 % CI 49 to 189 , p=0.001 ) than controls . Adverse events did not differ between treatment groups ( p>0.1 for all adverse events ) . INTERPRETATION Conventional asthma management result ed in good control of symptoms in most participants . The addition of fraction of exhaled NO as an indicator of control of asthma result ed in higher doses of inhaled corticosteroids , without clinical ly important improvements in symptomatic asthma control BACKGROUND Antiinflammatory therapies , such as inhaled corticosteroids or nedocromil , are recommended for children with asthma , although there is limited information on their long-term use . METHODS We r and omly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide ( 311 children ) , 8 mg of nedocromil ( 312 children ) , or placebo ( 418 children ) twice daily . We treated the participants for four to six years . All children used albuterol for asthma symptoms . RESULTS There was no significant difference between either treatment and placebo in the primary outcome , the degree of change in the forced expiratory volume in one second ( FEV1 , expressed as a percentage of the predicted value ) after the administration of a bronchodilator . As compared with the children assigned to placebo , the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity ( FVC , expressed as a percentage ) before the administration of a bronchodilator ( decline in FEV1:FVC , 0.2 percent vs. 1.8 percent ) . The children given budesonide also had lower airway responsiveness to methacholine , fewer hospitalizations ( 2.5 vs. 4.4 per 100 person-years ) , fewer urgent visits to a caregiver ( 12 vs. 22 per 100 person-years ) , greater reduction in the need for albuterol for symptoms , fewer courses of prednisone , and a smaller percentage of days on which additional asthma medications were needed . As compared with placebo , nedocromil significantly reduced urgent care visits ( 16 vs. 22 per 100 person-years ) and courses of prednisone . The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group ( 22.7 vs. 23.8 cm , P=0.005 ) ; this difference was evident mostly within the first year . The height increase was similar in the nedocromil and placebo groups . CONCLUSIONS In children with mild-to-moderate asthma , neither budesonide nor nedocromil is better than placebo in terms of lung function , but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil . The side effects of budesonide are limited to a small , transient reduction in growth velocity In a double-blind , parallel-group study , we examined the effect of short-term treatment with inhaled fluticasone propionate ( FP ) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms . We administered FP ( 250 microg twice daily ) or matched placebo for 6 wk . Methacholine challenge was performed before treatment , after 3 wk , and at the end of treatment . Each patient underwent bronchoscopy with bronchoalveolar lavage ( BAL ) and bronchial biopsy before and after treatment . Eight patients in the placebo group and nine patients in the FP group completed the study .  Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP ( p < 0.05 ) . When we compared the FP group with the placebo group , we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 ( ICAM-1 ) and MAC-1 ( p < 0.04 and p < 0.03 , respectively ) . Moreover , we saw that the tryptase level in BAL decreased ( p < 0.001 ) , whereas the eosinophil cationic protein ( ECP ) level did not change significantly . Additionally , the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group ( p < 0.02 and p < 0.01 , respectively ) . Additionally , in the FP group , we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group ( p < 0.05 ) . In conclusion , our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens . Moreover , short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma 1 . Beclomethasone dipropionate aerosol has been shown to be a highly effective treatment for asthma in childhood , with virtual absence of side effects at this age . 2 . When treatment is unsuccessful , this is usually due to failure to take it correctly and regularly . 3 . A good response is usually associated with an improvement in ventilatory function and a marked increase in growth velocity BACKGROUND Inhaled corticosteroids are recommended as first-line therapy for persistent asthma . OBJECTIVE We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma . METHODS An integrated analysis of 2 identical , multicenter , double-blind , r and omized , parallel-group , placebo-controlled trials was conducted . Patients ( n = 1015 ; aged > or = 12 years ) with mild-to-moderate asthma ( FEV1 of 60 % to 85 % of predicted value ) were r and omized to ciclesonide 80 microg ( CIC80 ) , 160 microg ( CIC160 ) , or 320 microg ( CIC320 ) , once daily ( exactuator doses ) in the morning or placebo for 12 weeks . RESULTS All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group ( CIC80 , 0.12 L [ P = .0007 ] ; CIC160 , 0.13 L [ P = .0004 ] ; and CIC320 , 0.14 L [ P < .0001 ] ) . Likewise , FEV1 percent predicted , morning and evening peak expiratory flow , 24-hour asthma symptom score , daily albuterol use , and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group . Overall  ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group . Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events , and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group . No suppression of hypothalamic-pituitary-adrenal-axis function ( as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [ 1 microg ] cosyntropin ) was observed with any dose of ciclesonide . CONCLUSIONS In this integrated analysis , ciclesonide once daily administered in the morning is effective and well tolerated Forty-five steroid-dependent asthmatic out patients were treated twice daily for 51 weeks with a new inhalation steroid , budesonide ( BUD ) , using a 750 ml spacer . During the initial 15 weeks the prednisone-sparing effects of a high daily dose ( 1600 micrograms ) and a conventional dose ( 400 micrograms per day ) were compared in a double-blind r and omized trial including 50 patients . During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily . All patients used other antiasthmatic drugs which were maintained throughout the study , except for inhalations of beta-2 agonists that could be used whenever needed . All patients but 2 were able to reduce the daily dose of oral prednisone . The mean daily dose decreased from 13.9 mg to 5.3 mg . Eighteen patients ( 40 % ) were able to discontinue oral prednisone . Adrenal gl and function improved considerably as prednisone intake decreased . Oropharyngeal thrush frequency showed no change . No severe side effects were observed Serum concentrations of growth hormone – dependent insulin – like growth factor I ( IGF – I ) and insulinlike growth factor binding protein–3 ( IGFBP–3 ) , the carboxy terminal propeptide of type I procollagen ( PICP ) , the carboxy terminal pyridinoline cross – linked telopeptide of type I collagen ( ICTP ) and the amino terminal propeptide of type III procollagen ( PIIINP ) were studied in 14 prepubertal children with asthma ( mean age 9.7 years ) during treatment with inhaled budesonide .  The study design was a r and omized , crossover trial with two double – blind treatment periods ( 200 and 800 μg ) and one open , non – r and omized treatment period ( 400 μg ) . All periods were 18 days ’ duration . Budesonide treatment was associated with a dose – related suppressive trend in serum concentrations of PIIINP when the 400 μg period was included ( p < 0.01 ; z = –2.7 ) and when it was excluded from the calculations ( p < 0.01 ; z = –2.6 ) , indicating reduced synthesis of type III collagen . A similar trend was observed in ICTP levels when the 400 μg period was excluded from the calculations ( p= 0.05 ; z = –1.9 ) . No other statistically significant variations were seen OBJECTIVE To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma . STUDY DESIGN In a double-blind , r and omized , parallel-group , multicenter study , 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year . Growth was evaluated monthly , whereas other safety variables and pulmonary function were evaluated periodically . RESULTS The prepubescent patients showed no statistically significant differences in mean height , mean growth velocity , or mean skeletal age between any of the treatment groups at any time . Over a period of 1 year , mean height ( + /- SE ) increased 6.15 + /- 0.17 cm in the placebo group , 5.94 + /- 0.16 cm in the fluticasone propionate 50 microg group , and 5.73 + /- 0.13 cm in the fluticasone propionate 100 microg group ( p = 0.308 , overall ) . CONCLUSIONS Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age RATIONALE For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids , evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids . OBJECTIVE To evaluate whether salmeterol/fluticasone propionate ( SFP ) , 50/100 μg twice a day , is noninferior regarding symptom control compared with fluticasone propionate ( FP ) , 200 μg twice a day Diskus in children with symptomatic asthma . METHODS A multicenter , r and omized , parallel-group , double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function . MEASUREMENTS AND MAIN RESULTS A total of 158 children , 6 - 16 years old , still symptomatic on FP , 100 μg twice a day , during a 4-week run-in period , were included .  Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups ( per protocol analysis : adjusted mean difference [ FP minus SFP ] 2.6 % ; 95 % confidence interval , -8.1 to 13.4 ) . Both groups showed substantial improvements of about 25 percent points in symptom-free days ( both P < 0.001 from baseline ) . Lung function measurements ( FEV(1 ) , FVC , PEF rate , and maximal expiratory flow ) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week . No differences were found between FP and SFP regarding exacerbation rates , adverse events , or growth . CONCLUSIONS In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid RATIONALE Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma , but no formulation suitable for administration to infants and young children is available in the United States . METHODS This was a 12-week , multicenter , double-blind , r and omized , parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension ( BIS ) or placebo in 480 asthmatic infants and children ( 64 % boys ) , ages 6 months to 8 years , with moderate persistent asthma . Approximately 30 % of children were previously on inhaled corticosteroids that were discontinued before the study . Active treatments were comprised of BIS 0.25 mg once daily ( QD ) , 0.25 mg twice a day ( BID ) , 0.5 mg BID , or 1.0 mg QD . Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication , and discontinuation from the study because of worsening asthma and /or a requirement for systemic steroids . Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests . Safety was assessed by reported adverse events and by cortisol testing ( adrenocorticotropic hormone stimulation ) in a subset of patients . RESULTS Patients enrolled had an average duration of asthma of 34 months ; the mean asthma symptom score was approximately 1.3 ( scale of 0 - 3 ) . All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo . The lowest dose used , 0.25 mg QD , was efficacious but with fewer efficacy parameters than seen with the other doses administered . Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens . A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing . All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo . Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo . CONCLUSION Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range , and that QD dosing is an important option to be considered by the prescribing physician 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 Twenty-six children with asthma were treated with beclomethasone dipropionate aerosol in a dose adjusted to their symptoms for 13 to 20 months . 18 children in the group had been taking systemic steroids at the start of the trial and all were successfully weaned off them , mostly within 2 months . All but 1 of the children were satisfactorily controlled by beclomethasone , but 15 children needed short courses of oral steroids at times of severe exacerbations . There was no evidence of either suppression or acceleration of growth , nor was there any adrenal suppression as assessed at intervals by the estimation of the resting level of plasma cortisol and the response to tetracosactrin . No other side effects were encountered apart from exacerbations of eczema or rhinitis in some children previously on systemic steroids Fluticasone propionate ( FP ) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma . To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler ( Diskhaler ) , a multicenter , double-blind , r and omized , placebo-controlled , parallel-group study was conducted in adolescent and adult patients ( n = 331 ) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone . Patients received FP powder 50 , 100 , or 250 micrograms or placebo twice daily for 12 weeks . FP-treated patients compared with placebo-treated patients had significantly ( p < 0.001 ) greater improvements in morning predose forced expiratory volume in 1 sec ( 21 - 22 % increase vs. 9 % ) . Improvement in morning peak flow rate were also significantly ( p < 0.001 ) greater with FP than with placebo ( 8 - 10 % increase vs. 2 % increase ) . There was also a significant overall treatment difference in the frequency of inhaled albuterol use ( p < 0.001 ) and number of nighttime awakenings due to asthma ( p = 0.005 ) . There were no statistically significant difference among the FP treatment groups in any outcome measure . Physicians ' global assessment s also indicated significant ( p < 0.001 ) differences in efficacy , with 67 - 74 % of FP-treated patients rated as having " effective " or " very effective " treatment compared with 41 % of placebo-treated patients . Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment . Adverse events were similar across treatment groups and primarily related to local irritation . Effect on hypothalamic-pituitary-adrenal axis function was minimal . In summary , all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables . Improvements in pulmonary function , beyond those achieved with beta 2-agonist therapy alone , were maintained for the duration of the 12-week study BACKGROUND Treatment guidelines for asthma recommend inhaled corticosteroids ( ICS ) as first-line therapy for children with persistent asthma . Although ICS treatment is generally considered safe in children , the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern , especially the effects on linear growth . OBJECTIVES To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments ( molecule , dose , length of exposure , inhalation device ) and of treated children ( age , disease severity , compliance with treatment ) . SEARCH METHODS We search ed the Cochrane Airways Group Specialised Register of trials ( CAGR ) , which is derived from systematic search es of bibliographic data bases including CENTRAL , MEDLINE , EMBASE , CINAHL , AMED and PsycINFO ; we h and search ed respiratory journals and meeting abstract s. We also conducted a search of Clinical Trials.gov and manufacturers ' clinical trial data bases to look for potential relevant unpublished studies . The literature search was conducted in January 2014 . SELECTION CRITERIA Parallel-group r and omised controlled trials comparing daily use of ICS , delivered by any type of inhalation device for at least three months , versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma . DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection , data extraction and assessment of risk of bias in included studies . We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0 . We used the r and om-effects model for meta-analyses . We used mean differences ( MDs ) and 95 % CIs as the metrics for treatment effects . A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls . We performed a priori planned subgroup analyses to explore potential effect modifiers , such as ICS molecule , daily dose , inhalation device and age of the treated child . MAIN RESULTS We included 25 trials involving 8471 ( 5128 ICS-treated and 3343 control ) children with mild to moderate persistent asthma . Six molecules ( beclomethasone dipropionate , budesonide , ciclesonide , flunisolide , fluticasone propionate and mometasone furoate ) given at low or medium daily doses were used during a period of three months to four to six years . Most trials were blinded and over half of the trials had drop out rates of over 20 % . Compared with placebo or non-steroidal drugs , ICS produced a statistically significant reduction in linear growth velocity ( 14 trials with 5717 participants , MD -0.48 cm/y , 95 % CI -0.65 to -0.30 , moderate quality evidence ) and in the change from baseline in height ( 15 trials with 3275 participants ; MD -0.61 cm/y , 95 % CI -0.83 to -0.38 , moderate quality evidence ) during a one-year treatment period . Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment ( Chi(2 ) = 26.1 , degrees of freedom ( df ) = 5 , P value < 0.0001 ) . The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone . Subgroup analyses did not show a statistically significant impact of daily dose ( low vs medium ) , inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period . However , head-to-head comparisons are needed to assess the effects of different drug molecules , dose , inhalation device or patient age . No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment ( five trials with 3174 participants ; MD -0.19 cm/y , 95 % CI -0.48 to 0.11 , P value 0.22 ) . Of two trials that reported linear growth velocity in the third year of treatment , one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups ( 5.34 cm/y vs 5.34 cm/y ) , and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group ( MD -0.33 cm/y , 95 % CI -0.52 to -0.14 , P value 0.0005 ) . Among four trials reporting data on linear growth after treatment cessation , three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation . One trial showed accelerated linear growth velocity in the fluticasone group at 12 months after treatment cessation , but there remained a statistically significant difference of 0.7 cm in height between the fluticasone and placebo groups at the end of the three-year trial . One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 μg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm ( 95 % CI -1.90 to -0.50 ) in adult height compared with those treated with placebo . AUTHORS ' CONCLUSIONS Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma . The effect size of  ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose ( low to medium dose range ) .  ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment . However , additional studies are needed to better characterise the molecule dependency of growth suppression , particularly with newer molecules ( mometasone , ciclesonide ) , to specify the respective role of molecule , daily dose , inhalation device and patient age on the effect size of ICS , and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma . PLAIN LANGUAGE SUMMARY Do inhaled corticosteroids reduce growth in children with persistent asthma ? Review question : We review ed the evidence on whether inhaled corticosteroids ( ICS ) could affect growth in children with persistent asthma , that is , a more severe asthma that requires regular use of medications for control of symptoms . BACKGROUND Treatment guidelines for asthma recommend ICS as first-line therapy for children with persistent asthma . Although ICS treatment is generally considered safe in children , parents and physicians always remain concerned about the potential negative effect of ICS on growth . Search date : We search ed trials published until January 2014 . Study characteristics : We included in this review trials comparing daily use of corticosteroids , delivered by any type of inhalation device for at least three months , versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma . KEY RESULTS Twenty-five trials involving 8471 children with mild to moderate persistent asthma ( 5128 treated with ICS and 3343 treated with placebo or non-steroidal drugs )  were included in this review . Eighty percent of these trials were conducted in more than two different centres and were called multi-centre studies ; five were international multi-centre studies conducted in high-income and low-income countries across Africa , Asia-Pacifica , Europe and the Americas . Sixty-eight percent were financially supported by pharmaceutical companies . Meta- analysis ( a statistical technique that combines the results of several studies and provides a high level of evidence ) suggests that children treated daily with ICS  may grow approximately half a centimeter per year less than those not treated with these medications during the first year of treatment . The magnitude of ICS-related  growth reduction may depend on the type of drug . Growth reduction seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment . Evidence provided by this review allows us to conclude that daily use of ICS can cause a small reduction in height in children up to 18 years of age with persistent asthma ; this effect seems minor compared with the known benefit of these medications for asthma control . QUALITY OF EVIDENCE Eleven of 25 trials did not report how they guaranteed that participants had an equal chance of receiving ICS or placebo or non-steroidal drugs . All but six trials did not report how research ers were kept unaware of the treatment assignment list . However , this method ological limitation may not significantly affect the quality of evidence because the results remained almost unchanged when we excluded these trials from the analysis We set out to evaluate lung deposition , systemic availability , and basic pharmacokinetic parameters of beclomethasone dipropionate ( BDP ) in children with chronic asthma .  Plasma levels of BDP , 17 and 21 beclomethasone monopropionate ( 17-BMP and 21-BMP )  , and beclomethasone  were measured after an intravenous infusion of 60 microg BDP and after inhalation of A ) 100 microg HFA-BDP , B ) 200 microg HFA-BDP , C ) 200 microg HFA-BDP after ingestion of charcoal to block gastrointestinal ( GI ) absorption of drug , and D ) 400 microg CFC-BDP . A breath-actuated pMDI ( Autohaler ) was used for HFA inhalations , and a pMDI with a large volume spacer ( Volumatic ) for CFC inhalations . Treatments A-D were given in a r and omized , cross-over design . Fourteen patients aged 10 - 14 years completed all 5 study days . The mean systemic bioavailabilities in percent of dose leaving the canister valve ( ex-valve ) were 70 % ( 100 HFA ) , 74 % ( 200 HFA ) , 60 % ( 200 HFA + charcoal ) , and 27 % ( 400 microg CFC ) . After HFA treatment , 82 % of the systemically available dose was absorbed through the lungs , and 18 % from the gastrointestinal tract . The estimated bioavailability of BDP from the GI tract was 68 % . BDP was metabolized to 17-BMP within minutes . Mean steady-state volume of distribution of 17-BMP was 84 L , and the mean terminal half-life ( T((1/2 ) ) ) after the four inhalations was 2.7 hr ( range , 2.2 - 3.7 hr ) . Mean T((1/2 ) ) and clearance after i.v . administration were 1.7 hr and 0.9 L/min , respectively . The HFA Autohaler delivers approximately three times as much BDP to the intrapulmonary airways as a CFC-pMDI with a large volume spacer BACKGROUND Ciclesonide is a new lung-activated inhaled corticosteroid ( ICS ) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma . It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability . OBJECTIVE This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma . METHODS This 12-week , r and omized study was conducted at 62 study sites across Europe . Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled . This study was double blind with respect to the ciclesonide dose and open label for budesonide , as placebofor budesonide was not available . Patients were r and omly assigned to receive inhaled ciclesonide 80 or 320 microg QD ( morning ) or budesonide 200 microg BID for 12 weeks . Efficacy and tolerability assessment s were performed at weeks 0 ( baseline ) , 4 , 8 , and 12 . The primary end point was the change from baseline in forced expiratory volume in 1 second ( FEV1 ) at 12 weeks . Secondary end points were changes from baseline in morning peak expiratory flow ( PEF ) , asthma symptom scores , and rescue medication use . Tolerability was assessed throughout the study by monitoring of st and ard laboratory variables ( hematology and biochemistry ) ; physical examination , including vital signs ; reporting of adverse events ( AEs ) ; and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function . RESULTS Five hundred fifty-four patients were r and omized ( 301 men , 253 women ; mean age , 41.3 years ; ciclesonide 80 microg QD , 182 patients ; ciclesonide 320 microg QD , 195 ; budesonide 200 microg BID , 177 ) . Demographic and baseline clinical characteristics , including age , sex , weight , and ( FEV1 ) were similar between the 3 groups . Compared with baseline values , week-12 FEV1 ( least squares mean [ LSM ] [ SEM ] A , + 0.267 [ 0.035 ] , + 0.256 [ 0.033 ] , and + 0.355 [ 0.034 ] L , respectively ; all , P<0.001 ) and morning PEF ( LSM [ SEM ] Delta , + 12 [ 5 ] , + 17 [ 4 ] , and + 21 [ 4 ] L/min , respectively ; all , P < or=0.008 ) were significantly improved with ciclesonide 80 and 320 microg QD and budesonide 200 microg BID . At 12 weeks , ciclesonide was found to be noninferior to budesonide with regard to mean changes from baseline in ( FEV1 ) ( intent to treat [ ITT ] : 97.5 % CI for ciclesonide 80 microg QD vs budesonide 200 microg BID , -0.192 to 0.015 ; 97.5 CI for ciclesonide 320 microg QD vs budesonide 200 microg BID , -0.200 to 0.001 ) and morning PEF ( ITT . 97.5 % CI for ciclesonide 80 microg QD vs budesonide 200 microg BID , -22 to 5 ; 97.5 % CI for ciclesonide 320 microg QD vs budesonide 200 microg BID , -17 to 10 ) . Similar findings were seen in the per- protocol population . Week-12 daily , daytime , and nighttime asthma symptom scores and rescue medication use were significantly decreased from baseline in all 3 treatment groups ( all , P<0.001 ) . The prevalences of AEs were similar across all 3 treatment groups . Week-12 mean urinary cortisol excretion was statistically similar to baseline with both ciclesonide doses ( Delta , -0.54 and + 0.16 nmol/mmol creatinine with ciclesonide 80 and 320 microg QD , respectively ) but was significantly reduced from baseline with budesonide ( Delta , -1.42 nmol/mmol creatinine ; P<0.05 ) . CONCLUSIONS The results of this study in patients with primarily mild to moderate asthma suggest that ciclesonide 80 and 320 microg QD were similar to budesonide 200 microg BID in improving pulmonary function , controlling asthma symptoms , and reducing the need for rescue medication use . Unlike budesonide , ciclesonide was not associated with significant urinary cortisol suppression in these patients OBJECTIVES --To assess bone and collagen turnover in asthmatic children treated with dry powder budesonide from the Turbuhaler and dry powder beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day . SUBJECTS -- Thirteen prepubertal children with asthma . DESIGN --Open crossover study with two treatment periods and treatment free run-in and wash-out periods . All periods were of two weeks ' duration . At day 14 in each period blood sample s were taken for assessment of serum osteocalcin , the carboxyterminal propeptide of type I collagen ( PICP ) , and the aminoterminal propeptide of type III collagen ( PIIINP ) . At the same time urine was collected for assessment of creatinine corrected pyridinoline ( uPYR/cr ) and deoxypyridinoline ( udPYR/cr ) crosslinks . RESULTS --Osteocalcin concentrations were not influenced by any of the treatments . During budesonide treatment mean ( SEM ) PICP was reduced by 18 % ( 8 % ) ( p = 0.03 ) , PIIINP by 24 % ( 3 % ) ( p = 0.0002 ) , uPYR/cr by 16 % ( 6 % ) ( p = 0.03 ) , and udPYR/cr by 21 % ( 13 % ) ( p = 0.12 ) . During treatment with beclomethasone dipropionate  mean ( SEM ) PICP was reduced by 20 % ( 6 % ) ( p = 0.01 ) , PIIINP by 36 % ( 3 % ) ( p = 0.0002 ) , uPYR/cr by 18 % ( 4 % ) ( p = 0.004 ) , and udPYR by 13 % ( 5 % ) ( p = 0.02 ) . The suppressive effect of beclomethasone dipropionate on PIIINP was more marked than that of budesonide ( p = 0.001 ) . CONCLUSION --Treatment with dry powder budesonide and beclomethasone dipropionate 800 micrograms/day is associated with suppression of bone and collagen turnover . The suppression seems to be more marked during treatment with beclomethasone dipropionate . Long term effects and effects of lower doses of budesonide and beclomethasone dipropionate on bone and collagen markers needs further study BACKGROUND Inhaled glucocorticosteroids ( GCS ) are the most effective long-term controller medications for the treatment of persistent asthma . Currently , however , available delivery devices limit their use in young children . A nebulized formulation of budesonide has been developed to address the needs of infants and young children . OBJECTIVE To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS . METHODS Three hundred fifty-nine children were r and omized to receive once-daily budesonide inhalation suspension ( 0.25 mg , 0.50 mg , or 1.0 mg ) or placebo via a Pari LC-Jet Plus nebulizer for 12 weeks . Efficacy assessment s included nighttime/daytime asthma symptoms , pulmonary function ( subset of patients ) , rescue medication use , and treatment discontinuations . Safety was based on adverse events and assessment of HPA-axis function . RESULTS Demographics , baseline characteristics , asthma symptoms , and pulmonary function were similar across treatment groups . Mean nighttime/daytime asthma symptom scores were 1.19 + /- 0.63 and 1.34 + /- 0.53 , respectively . Mean duration of asthma was 36.3 months and mean FEV1 was 81.3 % of predicted with 27.7 % reversibility . Following 12 weeks of treatment , all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms ( P < or = .049 ) and significant decreases in rescue medication use ( P < or = .038 ) compared with placebo . Significant improvements ( P < or = .044 ) in FEV1 were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups . There were no differences between doses of budesonide inhalation suspension . Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups . CONCLUSION Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments OBJECTIVE To evaluate the effects of treatment with fluticasone propionate vs placebo on bone , hypothalamic-pituitary-adrenal ( HPA ) axis function , and the eyes in patients with asthma . PATIENTS AND METHODS This r and omized , double-blind , placebo-controlled study of 160 patients with asthma who had minimal previous exposure to corticosteroids was conducted from July 1994 through June 1997 . Patients received fluticasone at 88 microg twice daily , fluticasone at 440 microg twice daily , or placebo twice daily for 2 years . Bone mineral density ( BMD ) was evaluated every 6 months by lumbar spine , proximal femur , and total body scans . Measurements of HPA axis function and ophthalmic evaluations were conducted at similar intervals . RESULTS Among the 3 groups , no significant differences were observed in BMD at week 104 ( at any anatomical site ) . Mean percent change from baseline in the lumbar spine was less than 1 % for all 3 groups . At all time points , HPA axis function was similar in the 88-microg fluticasone group compared with the placebo group . For mean change from baseline in corticotropin-stimulated peak cortisol ( P = .003 and P = .02 at weeks 24 and 52 , respectively ) and area under the stimulated plasma cortisol vs time curve ( P = .002 and P = .02 at weeks 24 and 52 , respectively ) , statistically significant reductions from baseline were observed in the 440-microg fluticasone group compared with the placebo group . These reductions of 10 % to 13 % from baseline were not accompanied by other signs of systemic effect and did not persist with continued treatment ( at weeks 76 and 104 ) . No important ocular changes were observed . CONCLUSION Long-term treatment with 88 microg of fluticasone twice daily was comparable to placebo in all skeletal , ophthalmic , and HPA axis function assessment s. Treatment with fluticasone at 440 microg twice daily result ed in no significant effects on BMD and a statistically significant but not clinical ly important temporary reduction in cortisol production Background and objective : The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination ( SFC ) therapy have been well established in the treatment of adults and adolescents with asthma . Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma . This study aim ed to investigate whether once-daily SFC 50 μg/100 μg was at least as effective as fluticasone propionate ( FP ) 100 μg twice daily , and more effective than twice-daily placebo , over 52 weeks as initial maintenance therapy in patients with mild persistent asthma . Methods : This was a r and omized , double-blind , double-dummy , placebo-controlled , multicentre , parallel-group study carried out in primary and secondary care . Patients aged between 12 and 79 years with a documented clinical history of asthma for ≥6 months who were currently receiving inhaled short-acting β2-adrenoceptor agonists only were enrolled . Patients were r and omized to receive either once-daily inhaled SFC 50 μg/100 μg , twice-daily inhaled FP 100 μg ( i.e. twice the dose of FP compared with SFC ) or placebo for 52 weeks . The primary efficacy endpoints were mean morning peak expiratory flow ( PEF ) , as recorded by patients prior to the use of bronchodilator or study medication , and the rate of investigator-recorded asthma exacerbations . Results : Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo ( FP , difference in means 20.1 L/min ; 95 % CI 14.7 , 25.5 ; p < 0.001 ; SFC , difference in means 14.8 L/min ; 95 % CI 9.4 , 20.2 ; p < 0.001 ) . The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was —5.3 L/min ( 95 % CI −9.1,−1.6 ) . PEF results showed that once-daily SFC was non-inferior to twice-daily FP . Over 52 weeks , there was a 35 % reduction in exacerbation rates with once-daily SFC , which in this respect demonstrated superiority over placebo ( p < 0.001 ) . Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown . Once-daily SFC significantly improved clinic forced expiratory flow between 25 % and 75 % of forced vital capacity ( difference in means 0.129 L/s ; p < 0.001 ) and clinic PEF ( difference in means 10.8 L/min ; p < 0.001 ) compared with twice-daily FP . Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo . Conclusion : In patients with mild persistent asthma not previously receiving maintenance therapy , once-daily SFC 50 μg/100 μg is an effective treatment compared with placebo , and was non-inferior to twice-daily FP 100 μg with respect to mean morning PEF . However , in this study , once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates . This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma BACKGROUND Current asthma guidelines recommend inhaled glucocorticoids administered via pressurized metered-dose inhaler ( MDI ) with a holding chamber as the preferred therapy for young children with asthma . OBJECTIVE To evaluate the efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in preschool-aged children with asthma . METHODS R and omized , double-blind , placebo-controlled , parallel-group study of 332 children aged 24 to 47 months with asthma .  Fluticasone propionate chlorofluorocarbon , 44 or 88 microg twice daily , or placebo ( chlorofluorocarbon propellant alone ) administered for 12 weeks via MDI with a valved holding chamber and an attached face mask . The primary efficacy measure was average change in 24-hour daily asthma symptom scores . Safety assessment s included adverse events , 12-hour urinary cortisol excretion , and growth . RESULTS Treatment failure ( ie , asthma exacerbation ) occurred in approximately half as many fluticasone propionate-treated patients ( 13%-14 % ) as placebo-treated patients ( 24 % ) . Compared with placebo users , patients treated with fluticasone propionate , 88 microg twice daily , had a 13 % greater improvement in the mean proportion of symptom- and albuterol-free days ( P = .02 ) ; asthma symptom scores and albuterol use were also significantly reduced . Patients treated with fluticasone propionate , 44 microg twice daily , had greater improvements than placebo-treated patients ; however , differences did not reach statistical significance . At end point , the growth velocities of fluticasone propionate-treated patients were within the range of those of placebo-treated patients . No clinical ly relevant changes in 12-hour overnight urinary cortisol excretion were observed . CONCLUSION Compared with placebo use , fluticasone propionate , 88 microg administered twice daily , significantly reduced asthma exacerbations , asthma symptoms , and rescue albuterol use and was well tolerated , with no clinical ly relevant systemic effects , as measured by growth velocity or 12-hour urinary cortisol excretion levels BACKGROUND More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children . OBJECTIVE The Pediatric Asthma Controller Trial ( PACT ) compared the effectiveness of 3 regimens in achieving asthma control . METHODS A total of 285 children ( ages 6 - 14 years ) with mild-moderate persistent asthma on the basis of symptoms , and with FEV(1 ) > or= 80 % predicted and methacholine FEV(1 ) PC(20 ) < or= 12.5 mg/mL , were r and omized to 1 of 3 double-blind 48-week treatments : fluticasone 100 microg twice daily ( fluticasone monotherapy ) , fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening ( PACT combination ) , and montelukast 5 mg in the evening . Outcomes included asthma control days ( primary outcome ) , exacerbations , humanistic measurements , and pulmonary function measurements . RESULTS Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes , including percent of asthma control days , but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity ( P = .015 ) , maximum bronchodilator response ( P = .009 ) , exhaled nitric oxide ( P < .001 ) , and PC(20 ) ( P < .001 ) . Fluticasone monotherapy was superior to montelukast for asthma control days ( 64.2 % vs 52.5 % ; P = .004 ) and for all other control outcomes . Growth over 48 weeks was not statistically different ( fluticasone , 5.3 cm ; PACT combination , 5.3 cm ; montelukast , 5.7 cm ) . CONCLUSION Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast . However , fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control . Growth was similar in all groups . CLINICAL IMPLICATION S Therefore , of the regimens tested , the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1 ) > or= 80 % predicted , confirming current guideline recommendations 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 Our objective was to evaluate the efficacy and safety of two doses of fluticasone propionate ( FP ) in young children with recurrent wheezing and risk factors for asthma . Our study design was a r and omized , double-blind , placebo-controlled comparison of inhaled FP 50 mcg twice daily ( FP 100 ) and 125 mcg twice daily ( FP 250 ) , for 6 months . Outcome measures included number of wheezing episodes , days on albuterol , height st and ard deviation score ( height SDS ) , osteocalcin ( OC ) , bone alkaline phosphatase fraction ( AKP ) , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , and serum levels of cortisol ( SC ) .  Our subjects were 30 patients , aged 7 - 24 months .  Mean wheezing episodes were 6.0 + /- 1.9 , 1.9 + /- 1.9 , and 2.8 + /- 1.2 ; mean days of albuterol use were 24.3 + /- 1.3 , 6.5 + /- 0.8 , and 9.1 + /- 0.8 , per patient for placebo , FP100 , and FP250 groups , respectively . There was a significant reduction in clinical outcome in the two FP groups compared to placebo ( P < 0.01 ) . No significant correlations were found between FP dosage and height SDS , OC , AKP , IGFBP-3 , and SC . In conclusion , in young children with asthmatic symptoms , FP at 50 and 125 mcg b.i.d . for 6 months significantly improved respiratory symptoms without causing significant side effects on growth and bone metabolism OBJECTIVE To evaluate the efficacy and safety of three doses of ciclesonide ( with or without spacer ) in children with persistent asthma . PATIENTS AND METHODS This was a multicentre , double-blind , placebo-controlled , 12-week study of ciclesonide 40 , 80 or 160 μg ( once daily pm ) . Children ( 6 - 11 years ) were r and omised 1:1 to treatment via a metered dose inhaler ( MDI ) or MDI plus spacer . The primary variable was change from baseline in mean morning peak expiratory flow ( PEF ) . Secondary variables included : time to first lack of efficacy ( LOE ) , asthma control , forced expiratory volume in 1 s ( FEV(1 ) ) , asthma symptom score and quality of life ( QoL ) . Safety assessment s included : adverse events ( AEs ) , urinary cortisol excretion and body height . RESULTS In total , 1073 children received treatment . At endpoint , mean morning PEF significantly improved with all doses of ciclesonide vs. placebo . There was no difference over placebo in time to first LOE , but ciclesonide was superior to placebo on asthma control , symptom score , FEV(1 ) and QoL. There were no differences between the spacer or non-spacer subgroups . The incidences of AEs were comparable between treatment groups ( approximately 35 % ) and there were no between-group differences in body height or urinary cortisol . CONCLUSIONS Ciclesonide 40 - 160 μg once daily is effective and well tolerated in children with persistent asthma ; its efficacy and safety are unaffected by the use of a spacer . clinical trials.gov registration number : NCT00384189 BACKGROUND Few large-scale studies have examined inhaled corticosteroid treatment in preschool children with recurrent wheeze . We assessed the effects of ciclesonide in preschool children with recurrent wheeze . METHODS We included children 2 - 6 yrs with recurrent wheeze and a positive asthma predictive index or aeroallergen sensitization to , excluding patients with episodic viral wheezing . After a 2 - 4-week baseline period , patients with ongoing symptoms or rescue medication use were r and omised to once-daily ciclesonide 40 , 80 , 160 μg or placebo for 24 weeks . RESULTS The number of wheeze exacerbations requiring systemic corticosteroids  was unexpectedly low in all groups : 25 ( 10.2 % ) in placebo group , as compared to 11 ( 4.4 % ) , 18 ( 7.3 % ) , and 17 ( 6.7 % ) in ciclesonide 40 , 80 , and 160 μg , respectively . The difference in time to first exacerbation was not significantly different between groups ( p = 0.786 ) , but the difference in exacerbation rates between placebo and the pooled ciclesonide groups was ( p = 0.03 ) . Large and significant ( p < 0.0001 ) improvements in symptom scores and rescue medication use occurred in all groups , including placebo . Improvements in FEV(1 ) and FEF(25 - 75 ) ( measured in 284 4 - 6 yr olds ) were larger in the ciclesonide than in the placebo group . No differences in safety parameters ( adverse events , height growth , serum and urinary cortisol levels ) between ciclesonide and placebo were observed . CONCLUSIONS In preschool children with recurrent wheeze and a positive asthma predictive index  , ciclesonide modestly reduces wheeze exacerbation rates and improves lung function . A large placebo response and unexpected selection of patients with mild disease may have affected outcomes , highlighting the heterogeneity of preschool wheezing disorders BACKGROUND Inhaled corticosteroid ( ICS ) nonadherence is common among patients with asthma ; however , interventions to improve adherence have often been complex and not easily applied to large patient population s. OBJECTIVE To assess the effect of supplying patient adherence information to primary care providers . METHODS Patients and providers were members of a health system serving southeast Michigan . Providers ( 88 intervention ; 105 control ) and patients ( 1335 intervention ; 1363 control ) were r and omized together by practice . Patients were age 5 to 56 years , had a diagnosis of asthma , and had existing prescriptions for ICS medication . Adherence was estimated by using prescription and fill data . Unlike clinicians in the control arm , intervention arm providers could view up date d ICS adherence information on their patients via electronic prescription software , and further details on patient ICS use could be viewed by selecting that option . The primary outcome was ICS adherence in last 3 months of the study period . RESULTS At the study end for the intention-to-treat analysis , ICS adherence was not different among patients in the intervention arm compared with those in the control arm ( 21.3 % vs 23.3 % , respectively ; P = .553 ) . However , adherence was significantly higher among patients whose clinician elected to view their detailed adherence information ( 35.7 % ) compared with both control arm patients ( P = .026 ) and intervention arm patients whose provider did not view adherence data ( P = .002 ) . CONCLUSIONS Overall , providing adherence information to clinicians did not improve ICS use among patients with asthma . However , patient use may improve when clinicians are sufficiently interested in adherence to view the details of this medication use Correlations between knemometric ( lower leg length ) growth rates and urine free cortisol excretion , respectively , and serum concentrations of IGF-I , IGF binding protein-3 , osteocalcin , carboxy terminal propeptide of type I collagen(PICP ) , carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen ( ICTP ) , and amino terminal propeptide of type III procollagen(PIIINP ) were investigated in 17 asthmatic children aged 7 - 14 y during treatment with fluticasone propionate , 200 μg , and beclomethasone dipropionate , 400 and 800 μg/d , taken from dry powder inhalers . The study was a double blind , crossover trial with three active treatment periods and two wash-out periods . All periods were 15 d long . Overnight urine free cortisol/creatinine × 106 did not correlate with knemometric growth rates or any of the serum markers . Significant correlations ( Pearson 's correlation coefficient , P ) between knemometric growth rates and IGF-I ( 0.41 ; 0.006 ) , IGFBP-3 ( 0.35 ; 0.02 ) , PICP ( 0.44 ; 0.003 ) , ICTP ( 0.35 ; 0.001 ) , and PIIINP ( 0.46 ; 0.002 ) were found . Compared with fluticasone propionate , 200 μg , beclomethasone dipropionate , 400 and 800 μg , caused significant suppression of lower leg growth rate ( F = 12.41;p = 0.002 , and F = 23.30 ; p = 0.0001 , respectively ) and of urine free cortisol/creatinine × 106(F = 10.52 ; p = 0.003 , and F = 13.74;p = 0.001 ) . Beclomethasone , 800 μg , caused suppression of PICP compared with fluticasone propionate , 200 μg ( F = 8.31;p = 0.008 ) , and beclomethasone , 400 μg ( F = 7.53;p = 0.01 ) . Both low ( F = 6.82 ; p = 0.02 ) and high ( F = 23.35 ; p = 0.0001 ) doses of beclomethasone were associated with reduced concentrations of ICTP , the high dose being the most suppressive ( F = 4.42 ; p = 0.05 ) . Beclomethasone 400(F = 9.75 ; p = 0.004 ) and 800 μg ( F = 23.61;p = 0.0001 ) result ed in reduced levels of PIIINP . Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover
BACKGROUND Inhaled corticosteroids ( ICS ) are the first-line treatment for children with persistent asthma .
Their potential for growth suppression remains a matter of concern for parents and physicians .
OBJECTIVES To assess whether increasing the dose of ICS is associated with slower linear growth , weight gain and skeletal maturation in children with asthma .
In view of prevailing parents ' and physicians ' concerns about the growth suppressive effect of ICS , lack of or incomplete reporting of growth velocity in more than 86 % ( 19/22 ) of eligible paediatric trials , including those using beclomethasone and budesonide , is a matter of concern .
PLAIN LANGUAGE SUMMARY Does altering the dose of inhaled corticosteroids make a difference in growth among  children with asthma ?
BACKGROUND Asthma guidelines recommend inhaled corticosteroids ( ICS ) as the first choice of treatment for children with persistent asthma that is not well controlled when only a reliever inhaler is used to treat symptoms .
Steroids work by reducing inflammation in the lungs and are known to control underlying symptoms of asthma .
However , parents and physicians remain concerned about the potential negative effect of ICS on growth .
REVIEW QUESTION Does altering the dose of inhaled corticosteroids make a difference in the growth of children with asthma ?
We studied whether a difference could be seen in the growth of children with persistent asthma who were using different doses of the same ICS molecule and the same delivery device .