human
***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 IL-5 , a mediator of eosinophil activity , is an important potential treatment target in patients with uncontrolled asthma . The efficacy of reslizumab , a humanized anti-human IL-5 monoclonal antibody , has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma , particularly those with eosinophils < 400 cells/μL. METHODS Patients were r and omly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks . The primary end point was the change in FEV1 from baseline to week 16 . Secondary measures included Asthma Control Question naire-7 ( ACQ-7 ) scores , use of short-acting β-agonists ( SABAs ) , and FVC . RESULTS Four hundred ninety-two patients received ≥ 1 dose of placebo ( n = 97 ) or reslizumab ( n = 395 ) . In the overall population , mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo , and no significant relationship was detected between treatment , baseline blood eosinophils and change in FEV1 . In the subgroup of patients with baseline eosinophils < 400 cells/μL , patients treated with reslizumab showed no significant improvement in FEV1 compared with those receiving placebo . In the subgroup with eosinophils ≥ 400 cells/μL , however , treatment with reslizumab was associated with much larger improvements in FEV1 , ACQ-7 , rescue SABA use , and FVC compared with the placebo group . Reslizumab was well tolerated , with fewer overall adverse events compared with placebo ( 55 % vs 73 % ) . CONCLUSIONS Reslizumab was well tolerated in patients with inadequately controlled asthma . Clinical ly meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01508936 ; URL : www . clinical trials.gov Background : Restrictive , very low-energy diets focused on rapid weight loss have proven to be effective in improving asthma outcome in obese patients , but their use in children and pubescents is controversial due its potential consequences in growth . More conservative , normocaloric schemes are suggested as a more suitable dietary approach for these patients . Methods : A r and omized clinical trial was run of 51 pubertal adolescents with asthma and obesity , who were allocated to either an  interventional 28-week  program  of normocaloric diet based on normal requirements for height and meal planning ( n = 26 ) or a non-interventional ( free diet ) control group ( n = 25 ) . Asthma-related quality of life ( AR-QOL , assessed by the St and ardized Pediatric Asthma Quality of Life Question naire , PAQLQ[S ] ) and clinical indicators of asthma control were measured before and after the intervention period . Results : Diet intervention was associated with a significant improvement in AR-QOL in relation to baseline ( Δ PAQLQ[S ] scores ) compared with controls , both in overall score ( p < 0.001 ) and its subdomains ( activity limitation , p < 0.001 ; symptoms , p < 0.002 ; emotional function , p < 0.001 ) . The group with normocaloric diet observed a significant decrease in body mass index z-score , which correlated positively with the improvement in AR-QOL ( Spearman 's r = 0.51 , p < 0.01 ) , in addition to have significantly fewer events of acute attacks of asthma and nighttime awakenings , plus a non-significant reduction in the use of inhaled corticosteroids . No significant changes were observed in the pulmonary function tests . Conclusion : The normocaloric dietary intervention was associated with improvement of AR-QOL and some aspects of asthma control . Such structured dietary programs could probably have a role as a complementary non-pharmacological therapeutic strategy in obese pubertal adolescents with asthma Background : Overweight/obesity ( OW ) is linked to worse asthma and poorer inhaled corticosteroid ( ICS ) response in older children and adults . Objective : We sought to describe the relationships between OW and asthma severity and response to ICS  in preschool children . Methods : This post hoc study of 3 large multicenter trials involving 2‐ to 5‐year‐old children compared annualized asthma symptom days and exacerbations among normal weight ( NW ) ( body mass index : 10th‐84th percentiles ) versus OW ( body mass index : ≥85th percentile ) participants . Participants had been r and omized to daily ICS , intermittent ICS , or daily placebo .  Simple and multivariable linear regression was used to compare body mass index groups . Results : Within the group not treated with a daily controller , OW children had more asthma symptom days ( 90.7 vs 53.2 , P = .020 ) and exacerbations ( 1.4 vs 0.8 , P = .009 ) thanNW children did . Within the ICS‐treated groups , OW and NW children had similar asthma symptom days ( daily ICS : 47.2 vs 44.0 days , P = .44 ; short‐term ICS : 61.8 vs 52.9 days , P = .46 ; as‐needed ICS : 53.3 vs 47.3 days , P = .53 ) , and similar exacerbations ( daily ICS : 0.6 vs 0.8 , P = .10 ; short‐term ICS : 1.1 vs 0.8 days , P = .25 ; as‐needed ICS : 1.0 vs 1.1 , P = .72 ) . Compared with placebo , daily ICS in OW led to fewer annualized asthma symptom days ( 90.7 vs 41.2 , P = .004 ) and exacerbations ( 1.4 vs 0.6 , P = .006 ) , while similar protective ICS effects were less apparent among NW . Conclusions : In preschool children off controller therapy , OW is associated with greater asthma impairment and exacerbations . However , unlike older asthmatic patients , OW preschool children do not demonstrate reduced responsiveness to ICS therapy Background There is increasing evidence that obesity is related to asthma development and severity . However , it is largely unknown whether weight reduction can influence asthma management , especially in children . Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with ( a high risk of developing ) asthma . Methods An 18-month weight-reduction r and omized controlled trial was conducted in 87 children with overweight/obesity and asthma . Every six months , measurements of anthropometry , lung function , lifestyle parameters and inflammatory markers were assessed . Analyses were performed with linear mixed models for longitudinal analyses . Results After 18 months , the body mass index-st and ard deviation score decreased by -0.14±0.29 points ( p<0.01 ) in the intervention group and -0.12±0.34 points ( p<0.01 ) in the control group . This change over time did not differ between groups ( p>0.05 ) . Asthma features ( including asthma control and asthma-related quality of life ) and lung function indices ( static and dynamic ) improved significantly over time in both groups . The FVC% predicted improved over time by 10.1 ± 8.7 % in the intervention group ( p<0.001 ) , which was significantly greater than the 6.1 ± 8.4 % in the control group ( p<0.05 ) . Conclusions & clinical relevance Clinical ly relevant improvements in body weight , lung function and asthma features were found in both the intervention and control group , although some effects were more pronounced in the intervention group ( FVC , asthma control , and quality of life ) . This implies that a weight reduction intervention could be clinical ly beneficial for children with asthma . Trial Registration Clinical Trials.gov Background : Adult‐onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis . The remission rate is believed to be low , and it is still obscure which factors predict remission or persistence of the disease . Objective : This study sought to determine the remission rate and identify predictors of persistence and remission of adult‐onset asthma . Methods : Two hundred adult patients with recently diagnosed ( < 1 year ) asthma were recruited from secondary and tertiary pulmonary clinics and prospect ively followed for 5 years . Clinical , functional , and inflammatory parameters were assessed at baseline and at yearly visits . Asthma remission was defined as absence of asthma symptoms for ≥1 year and no asthma medication use for ≥1 year . Descriptive statistics and logistic regression analysis were performed . Results : Five‐year follow‐up data of 170 patients ( 85 % ) was available . Of these , 27 patients ( 15.9 % ) experienced asthma remission . Patients with asthma persistence were older , had worse asthma control , required higher doses of inhaled corticosteroids , had more severe airway hyperresponsiveness , more often nasal polyps , and higher levels of blood neutrophils as compared to patients who experienced clinical remission . In a multivariable logistic regression analysis , only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence . Patients with these 2 characteristics had < 1 % chance of asthma remission . Conclusions : One in 6 patients with adult‐onset asthma  experiences remission within the first 5 years of the disease . In patients with moderate to severe bronchial hyperresponsiveness and nasal polyposis , the chance of remission is close to zero RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms Studies on the effects of weight loss in patients with asthma are scarce . No studies have been performed in patients with severe asthma . Therefore , the aim of the present study was to assess the impact of weight loss  in patients with severe asthma associated with obesity . This was an open , prospect i ve , r and omised study of two parallel groups , in patients with severe uncontrolled asthma and moderate obesity . The primary outcome was the level of asthma control 6 months after initiation of the  weight reduction programme  , quantified using the Asthma Control Question naire ( ACQ ) . We evaluated clinical parameters , lung function , markers of airway inflammation and circulating cytokines .  22 patients were r and omised to undergo treatment for obesity and 11 to the control group .  The weight reduction programme was associated with significant improvements in asthma control ( mean±se ACQ score 3.02±0.19 to 2.25±0.28 in the treatment group versus 2.91±0.25 to 2.90±0.16 in the controls , p=0.001 ) . This improvement was not accompanied by changes in markers of airway inflammation or bronchial reactivity , but by an increase in forced vital capacity . Our results suggest  that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation . Weight loss improves outcomes in severely asthmatic obese patients ; poor control results from obesity-related factors It was recently shown that 30 % of adults with a physician diagnosis of asthma did not have ast 
    Output:
    
agent
***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 IL-5 , a mediator of eosinophil activity , is an important potential treatment target in patients with uncontrolled asthma . The efficacy of reslizumab , a humanized anti-human IL-5 monoclonal antibody , has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma , particularly those with eosinophils < 400 cells/μL. METHODS Patients were r and omly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks . The primary end point was the change in FEV1 from baseline to week 16 . Secondary measures included Asthma Control Question naire-7 ( ACQ-7 ) scores , use of short-acting β-agonists ( SABAs ) , and FVC . RESULTS Four hundred ninety-two patients received ≥ 1 dose of placebo ( n = 97 ) or reslizumab ( n = 395 ) . In the overall population , mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo , and no significant relationship was detected between treatment , baseline blood eosinophils and change in FEV1 . In the subgroup of patients with baseline eosinophils < 400 cells/μL , patients treated with reslizumab showed no significant improvement in FEV1 compared with those receiving placebo . In the subgroup with eosinophils ≥ 400 cells/μL , however , treatment with reslizumab was associated with much larger improvements in FEV1 , ACQ-7 , rescue SABA use , and FVC compared with the placebo group . Reslizumab was well tolerated , with fewer overall adverse events compared with placebo ( 55 % vs 73 % ) . CONCLUSIONS Reslizumab was well tolerated in patients with inadequately controlled asthma . Clinical ly meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01508936 ; URL : www . clinical trials.gov Background : Restrictive , very low-energy diets focused on rapid weight loss have proven to be effective in improving asthma outcome in obese patients , but their use in children and pubescents is controversial due its potential consequences in growth . More conservative , normocaloric schemes are suggested as a more suitable dietary approach for these patients . Methods : A r and omized clinical trial was run of 51 pubertal adolescents with asthma and obesity , who were allocated to either an  interventional 28-week  program  of normocaloric diet based on normal requirements for height and meal planning ( n = 26 ) or a non-interventional ( free diet ) control group ( n = 25 ) . Asthma-related quality of life ( AR-QOL , assessed by the St and ardized Pediatric Asthma Quality of Life Question naire , PAQLQ[S ] ) and clinical indicators of asthma control were measured before and after the intervention period . Results : Diet intervention was associated with a significant improvement in AR-QOL in relation to baseline ( Δ PAQLQ[S ] scores ) compared with controls , both in overall score ( p < 0.001 ) and its subdomains ( activity limitation , p < 0.001 ; symptoms , p < 0.002 ; emotional function , p < 0.001 ) . The group with normocaloric diet observed a significant decrease in body mass index z-score , which correlated positively with the improvement in AR-QOL ( Spearman 's r = 0.51 , p < 0.01 ) , in addition to have significantly fewer events of acute attacks of asthma and nighttime awakenings , plus a non-significant reduction in the use of inhaled corticosteroids . No significant changes were observed in the pulmonary function tests . Conclusion : The normocaloric dietary intervention was associated with improvement of AR-QOL and some aspects of asthma control . Such structured dietary programs could probably have a role as a complementary non-pharmacological therapeutic strategy in obese pubertal adolescents with asthma Background : Overweight/obesity ( OW ) is linked to worse asthma and poorer inhaled corticosteroid ( ICS ) response in older children and adults . Objective : We sought to describe the relationships between OW and asthma severity and response to ICS  in preschool children . Methods : This post hoc study of 3 large multicenter trials involving 2‐ to 5‐year‐old children compared annualized asthma symptom days and exacerbations among normal weight ( NW ) ( body mass index : 10th‐84th percentiles ) versus OW ( body mass index : ≥85th percentile ) participants . Participants had been r and omized to daily ICS , intermittent ICS , or daily placebo .  Simple and multivariable linear regression was used to compare body mass index groups . Results : Within the group not treated with a daily controller , OW children had more asthma symptom days ( 90.7 vs 53.2 , P = .020 ) and exacerbations ( 1.4 vs 0.8 , P = .009 ) thanNW children did . Within the ICS‐treated groups , OW and NW children had similar asthma symptom days ( daily ICS : 47.2 vs 44.0 days , P = .44 ; short‐term ICS : 61.8 vs 52.9 days , P = .46 ; as‐needed ICS : 53.3 vs 47.3 days , P = .53 ) , and similar exacerbations ( daily ICS : 0.6 vs 0.8 , P = .10 ; short‐term ICS : 1.1 vs 0.8 days , P = .25 ; as‐needed ICS : 1.0 vs 1.1 , P = .72 ) . Compared with placebo , daily ICS in OW led to fewer annualized asthma symptom days ( 90.7 vs 41.2 , P = .004 ) and exacerbations ( 1.4 vs 0.6 , P = .006 ) , while similar protective ICS effects were less apparent among NW . Conclusions : In preschool children off controller therapy , OW is associated with greater asthma impairment and exacerbations . However , unlike older asthmatic patients , OW preschool children do not demonstrate reduced responsiveness to ICS therapy Background There is increasing evidence that obesity is related to asthma development and severity . However , it is largely unknown whether weight reduction can influence asthma management , especially in children . Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with ( a high risk of developing ) asthma . Methods An 18-month weight-reduction r and omized controlled trial was conducted in 87 children with overweight/obesity and asthma . Every six months , measurements of anthropometry , lung function , lifestyle parameters and inflammatory markers were assessed . Analyses were performed with linear mixed models for longitudinal analyses . Results After 18 months , the body mass index-st and ard deviation score decreased by -0.14±0.29 points ( p<0.01 ) in the intervention group and -0.12±0.34 points ( p<0.01 ) in the control group . This change over time did not differ between groups ( p>0.05 ) . Asthma features ( including asthma control and asthma-related quality of life ) and lung function indices ( static and dynamic ) improved significantly over time in both groups . The FVC% predicted improved over time by 10.1 ± 8.7 % in the intervention group ( p<0.001 ) , which was significantly greater than the 6.1 ± 8.4 % in the control group ( p<0.05 ) . Conclusions & clinical relevance Clinical ly relevant improvements in body weight , lung function and asthma features were found in both the intervention and control group , although some effects were more pronounced in the intervention group ( FVC , asthma control , and quality of life ) . This implies that a weight reduction intervention could be clinical ly beneficial for children with asthma . Trial Registration Clinical Trials.gov Background : Adult‐onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis . The remission rate is believed to be low , and it is still obscure which factors predict remission or persistence of the disease . Objective : This study sought to determine the remission rate and identify predictors of persistence and remission of adult‐onset asthma . Methods : Two hundred adult patients with recently diagnosed ( < 1 year ) asthma were recruited from secondary and tertiary pulmonary clinics and prospect ively followed for 5 years . Clinical , functional , and inflammatory parameters were assessed at baseline and at yearly visits . Asthma remission was defined as absence of asthma symptoms for ≥1 year and no asthma medication use for ≥1 year . Descriptive statistics and logistic regression analysis were performed . Results : Five‐year follow‐up data of 170 patients ( 85 % ) was available . Of these , 27 patients ( 15.9 % ) experienced asthma remission . Patients with asthma persistence were older , had worse asthma control , required higher doses of inhaled corticosteroids , had more severe airway hyperresponsiveness , more often nasal polyps , and higher levels of blood neutrophils as compared to patients who experienced clinical remission . In a multivariable logistic regression analysis , only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence . Patients with these 2 characteristics had < 1 % chance of asthma remission . Conclusions : One in 6 patients with adult‐onset asthma  experiences remission within the first 5 years of the disease . In patients with moderate to severe bronchial hyperresponsiveness and nasal polyposis , the chance of remission is close to zero RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms Studies on the effects of weight loss in patients with asthma are scarce . No studies have been performed in patients with severe asthma . Therefore , the aim of the present study was to assess the impact of weight loss  in patients with severe asthma associated with obesity . This was an open , prospect i ve , r and omised study of two parallel groups , in patients with severe uncontrolled asthma and moderate obesity . The primary outcome was the level of asthma control 6 months after initiation of the  weight reduction programme  , quantified using the Asthma Control Question naire ( ACQ ) . We evaluated clinical parameters , lung function , markers of airway inflammation and circulating cytokines .  22 patients were r and omised to undergo treatment for obesity and 11 to the control group .  The weight reduction programme was associated with significant improvements in asthma control ( mean±se ACQ score 3.02±0.19 to 2.25±0.28 in the treatment group versus 2.91±0.25 to 2.90±0.16 in the controls , p=0.001 ) . This improvement was not accompanied by changes in markers of airway inflammation or bronchial reactivity , but by an increase in forced vital capacity . Our results suggest  that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation . Weight loss improves outcomes in severely asthmatic obese patients ; poor control results from obesity-related factors It was recently shown that 30 % of adults with a physician diagnosis of asthma did not have ast 
    Output:
    