***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND A clinical model is needed to compare inhaled corticosteroids ( ICSs ) with respect to efficacy . OBJECTIVE The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs . METHODS A 24-week , parallel , open-label , multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma . Benefit was assessed by improvements in FEV(1 ) and PC(20 ) ; risk was assessed by overnight plasma cortisol suppression .  Thirty subjects were r and omized to either beclomethasone dipropionate ( BDP ) 168 , 672 , and 1344 microg/day ( n = 15 ) or fluticasone propionate ( FP ) 88 , 352 , and 704 microg/day ( n = 15 ) , both administered by means of a metered dose inhaler ( MDI ) with chlorofluorocarbon propellant via a spacer , in 3 consecutive 6-week intervals ; this was followed by 3 weeks of FP dry powder inhaler ( DPI ) 2000 microg/day . RESULTS Maximum FEV(1 ) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI . Near-maximum methacholine PC(20 ) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI . Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression . Responsiveness to ICS treatment was found to vary markedly among subjects . Good ( > 15 % ) FEV(1 ) response , in contrast to poor ( < 5 % ) response , was found to be associated with high exhaled nitric oxide ( median , 17.6 vs 11.1 ppb ) , high bronchodilator reversibility ( 25.2 % vs 8.8 % ) , and a low FEV(1)/forced vital capacity ratio ( 0.63 vs 0.73 ) before treatment . Excellent ( > 3 doubling dilutions ) improvement in PC(20 ) , in contrast to poor ( < 1 doubling dilution ) improvement , was found to be associated with high sputum eosinophil levels ( 3.4 % vs 0.1 % ) and older age at onset of asthma ( age , 20 - 29 years vs < 10 years ) . CONCLUSIONS Near-maximal FEV(1 ) and PC(20 ) effects occurred with low-medium dose for both ICSs in the subjects studied . High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated , but it did increase the systemic effect measure , overnight cortisol secretion . Significant intersubject variability in response occurred with both ICSs . It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study , such as prevention of asthma exacerbations BACKGROUND Childhood asthma clusters , or subclasses , have been developed by computational methods without evaluation of clinical utility . OBJECTIVE To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program ( SARP ) are associated with treatment responses in Childhood Asthma Research and Education ( CARE ) Network clinical trials . METHODS A cluster assignment model was determined by using SARP participant data . A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters .  Primary and secondary outcomes were analyzed by cluster in each trial . RESULTS CARE participants were assigned to SARP clusters with high accuracy . Baseline characteristics were similar between SARP and CARE children of the same cluster . Treatment response in CARE trials was generally similar across clusters . However , with the caveat of a smaller sample size , children in the early-onset/severe-lung function cluster had best response  with fluticasone/salmeterol ( 64 % vs 23 % 2.5 × fluticasone and 13 % fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial ; P = .011 ) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments ( eg , -0.076 % change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial ) . CONCLUSIONS In this study , we replicated SARP pediatric asthma clusters by using a separate , large clinical trials network . Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy , respectively . Further prospect i ve study of therapeutic response by cluster could provide new insights into childhood asthma treatment BACKGROUND A subset of children with asthma respond better to leukotriene receptor antagonists than to inhaled corticosteroids . Information is needed to identify children with these preferential responses . OBJECTIVE We sought to determine whether the ratio of urinary leukotriene E(4 ) ( LTE(4 ) ) to fractional exhaled nitric oxide ( FE(NO ) ) delineates children with preferential responsiveness to montelukast compared with fluticasone propionate ( FP ) therapy . METHODS Data from 318 children with mild-to-moderate asthma enrolled in 2 National Heart , Lung , and Blood Institute Childhood Asthma Research and Education Network studies ( Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid [ CLIC ] and the Pediatric Asthma Controller Trial [ PACT ] ) were analyzed . The association between LTE(4)/FE(NO ) ratios at baseline and improved lung function or asthma control days ( ACDs ) with montelukast and FP therapy was determined , and phenotypic characteristics related to high ratios were assessed . RESULTS LTE(4)/FE(NO ) ratios were associated with a greater response to montelukast than FP therapy for FEV(1 ) measurements ( 2.1 % increase per doubling of ratio , P = .001 ) and for ACDs per week ( 0.3-ACD increase , P = .009 ) in the CLIC study . In PACT the ratio was associated with greater ACD responsiveness to MT than FP therapy ( 0.6 ACD increase , P=.03 ) [ corrected ] . In a combined study analysis , LTE(4 ) : FE(NO ) ratios were associated with greater response to MT than FP therapy for FEV(1 ) ( 1.8 % increase , P = .0005 ) and ACDs ( 0.4 increase , P = .001)[corrected].Children with LTE(4)/FE(NO ) ratios at or above the 75th percentile were likely ( P < .05 ) to be younger and female and exhibit lower levels of atopic markers and methacholine reactivity . CONCLUSION LTE(4)/FE(NO ) ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma BACKGROUND Responses to inhaled corticosteroids ( ICSs ) and leukotriene receptor antagonists ( LTRAs ) vary among asthmatic patients . OBJECTIVE We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other . METHODS Children 6 to 17 years of age with mild-to-moderate persistent asthma were r and omized to one of 2 crossover sequences , including 8 weeks of an ICS , fluticasone propionate ( 100 microg twice daily ) , and 8 weeks of an LTRA , montelukast ( 5 - 10 mg nightly depending on age ) , in a multicenter , double-masked , 18-week trial . Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers . RESULTS Defining response as improvement in FEV 1 of 7.5 % or greater , 17 % of 126 participants responded to both medications , 23 % responded to fluticasone alone , 5 % responded to montelukast alone , and 55 % responded to neither medication . Compared with those who responded to neither medication , favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide , total eosinophil counts , levels of serum IgE , and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20 ) and pulmonary function ; favorable response to montelukast alone was associated with younger age and shorter disease duration . Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use , bronchodilator response , exhaled nitric oxide levels , and eosinophil cationic protein levels and lower methacholine PC(20 ) and pulmonary function values . CONCLUSIONS Response to fluticasone and montelukast vary considerably . Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy . Other children could receive either ICSs or LTRAs BACKGROUND Maintenance inhaled corticosteroid ( ICS ) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits . However , determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment . OBJECTIVE To determine if demographic and atopic features predict response to ICS in preschool children at high risk for asthma . METHODS Two years of treatment with an ICS , fluticasone propionate ( 88 microg twice daily ) , was compared with matching placebo in a double-masked , r and omized , multicenter study of 285 children 2 and 3 years old at high risk for asthma development . Baseline demographic and atopic features were related to clinical outcomes in a post hoc subgroup analysis . RESULTS Multivariate analysis demonstrated significantly greater improvement with fluticasone than placebo in terms of episode-free days among boys , white subjects , participants with an emergency department ( ED ) visit or hospitalization within the past year , and those who experienced more symptomatic days at baseline . Children with aeroallergen sensitization experienced greater benefits in terms of oral corticosteroid use , urgent care and ED visits , and use of supplemental controller medications . CONCLUSIONS More favorable responses to ICS than placebo in high-risk preschool children over a 2-year period were more likely in those with a ED visit or hospitalization for asthma within the past year , children with aeroallergen sensitization , boys , and white subjects BACKGROUND Although inhaled corticosteroids ( ICSs ) generally protect against severe exacerbations in asthma , they may result in elevated IgE levels , which are associated with exacerbations . OBJECTIVE To determine whether variation in the low-affinity IgE receptor gene , FCER2 , is associated with severe exacerbations defined as emergency department visits and /or hospitalizations in patients with asthma on ICSs . METHODS We resequenced , then genotyped 10 FCER2 single nucleotide polymorphisms ( SNPs ) in 311 children r and omized to inhaled budesonide as part of the Childhood Asthma Management Program . We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial . We also evaluated differences in cellular expression of the novel FCER2 SNP , T2206C . RESULTS In white subjects , 3 FCER2 SNPs were significantly associated ( P < .05 ) with elevated 4-year IgE level ; each was also associated with increased severe exacerbations . Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children ( hazard ratio , 3.95 ; 95 % CI , 1.64 - 9.51 ; and hazard ratio , 3.08 ; 95 % CI , 1.00 - 9.47 ) , despite ICS use . Interaction models supported a true gene-environment effect in white subjects ( interaction P = .004 ) . T2206C was also associated with decreased FCER2 expression ( P = .02 ) . CONCLUSION FCER2 predicts the likelihood of treatment protocol success in asthma . The associations of T2206C with IgE level , severe exacerbations , and FCER2 expression may provide a mechanistic basis for the observed findings . CLINICAL IMPLICATION S Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma AIMS To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy  for asthma , based independently on lung function changes or asthma exacerbations . MATERIAL S & METHODS We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children ( aged 5 - 12 years ) r and omized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program ( CAMP ) . RESULTS Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response . A history of prior asthma exacerbations , younger age and a higher IgE level ( p < 0.05 ) are associated with recurrent exacerbations . By contrast , lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206 
    Output:
    
For patients that remain symptomatic , white Hispanics were more likely to respond to LTRA , blacks to ICS , white non-Hispanics to LTRA or LABA , and children without a history of eczema , regardless of race or ethnicity to LABA set-up therapy .
In severe persistent asthma , those with atopy and body mass index greater than or equal 25 were more likely to benefit from omalizumab .
Several phenotypic characteristics , biomarkers , or pharmacogenomics markers could be useful for predicting the best drug for asthma treatment