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: The purpose of this study was to evaluate whether nedocromil sodium benefits urban asthmatic children showing seasonal bronchial hyper-reactivity to ultrasonic nebulization of distilled water ( UNDW ) . A prospect i ve , r and omized , placebo-controlled , parallel-group , double-blind study was carried out at the outpatient pulmonology service at a tertiary-care teaching hospital . Twelve children living in Milan , who were 7–17 years of age , who were SPT and RAST-negative to perennial allergens , who were suffering from episodic asthma , and showing seasonal bronchial hyper-reactivity to UNDW during winter , participated in this study . All the children received either placebo or nedocromil sodium , 4 mg every 6 h for 6 weeks . Spirometry and UNDW challenge were done at the following times : day−7 ; day 0 ; day 1 ; day 7 ; day 14 ; day 28 ; day 42 . No differences were found in the basal spirometric parameters , which were normal in both nedocromil and placebo groups . Bronchial reactivity to UNDW was found to be significantly decreased in the group treated with nedocromtl starting from day 7 . It is therefore concluded that nedocromil sodium can reverse bronchial hyper-reactivity caused by seasonal factors such as cold , viral infections and atmospheric pollutants in children suffering from asthma Nedocromil sodium in a dose of 4 mg b.i.d . or q.i.d . by inhalation was used to treat asthmatic patients in a double-blind , placebo-controlled , r and omized , parallel study . 80 patients ( 39 active drug and 41 placebo ) received q.i.d . dosage and 87 patients ( 45 active drug and 42 placebo )  received b.i.d .  dosage . The patients selected were not on oral or inhaled steroids but required oral sustained-release theophylline with or without an inhaled beta-agonist aerosol . There was a significant reduction in daytime asthma symptoms ( p = 0.04 ) and asthma severity ( p less than 0.01 ) 6 weeks after the onset of therapy in the nedocromil sodium q.i.d . treated group as compared with placebo . In the nedocromil sodium b.i.d . treated group , the following variables showed statistically significant improvements compared with placebo : daytime and night-time asthma ( p = 0.002 in both instances ) , wheezing assessed by auscultation ( p = 0.03 ) and overall asthma severity ( p less than 0.01 ) . All these variables showed improvements within 2 weeks of the onset of therapy and became statistically significant at 6 weeks . Side-effects were minor and occurred only in a small number of patients . It can be concluded from this study that nedocromil sodium is a safe and effective drug in the management of asthma Background : While increases in body mass index ( BMI ) have been associated with the incidence and prevalence of asthma , the mechanisms behind this association are unclear . Methods : We hypothesised that BMI would be independently associated with measures of asthma severity in a population of children with mild to moderate asthma enrolled in the Childhood Asthma Management Program ( CAMP ) . A multivariable baseline cross sectional analysis of BMI with our outcomes of interest was performed . Results : BMI was generally not associated with symptoms , nor was it associated with atopy . While BMI was positively associated with the methacholine concentration that causes a 20 % fall in forced expiratory volume in 1 second ( PC20FEV1 ) , this association did not persist after adjustment for FEV1 . Increasing BMI was associated with increasing FEV1 ( β = 0.006 l , 95 % CI ( 0.001 to 0.01 ) ) and forced vital capacity ( FVC ) ( β = 0.012 l , 95 % CI ( 0.007 to 0.017 ) ) . However , decrements in the FEV1/FVC ratio were noted with increasing BMI ( β = −0.242 , 95 % CI ( −0.118 to −0.366 ) ) . Thus , an increase in BMI of 5 units was associated with a decrease in FEV1/FVC of over 1 % . Conclusions : Although the association of FEV1 and FVC with BMI did not support our initial hypothesis , the decrease noted in the FEV1/FVC ratio has potential relevance in the relationship between BMI and asthma severity The present study examines the relationship between hypothalamic-pituitary-adrenal ( HPA ) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma . The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH ) stimulation when assessed as area under the curve . Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program ( CAMP ) during the pre-r and omization phase of the CAMP trial . At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center . Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present . Results further indicated significant associations between cortisol production and measures of child neuropsychological function . Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender , working memory , and arousal maintenance , providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma . In contrast , cortisol production was not associated with child reports of psychological functioning . Limitations to the methods employed in this study are discussed BACKGROUND Declining protocol adherence can threaten the validity of a clinical trial . OBJECTIVE We sought to explore patient and family factors important for protocol adherence in the 133 patients followed at one of the 8 Childhood Asthma Management Program ( CAMP ) clinical centers . Difficulties with timely return of diary cards (  diary card  problem ) , with keeping or frequently rescheduling appointments ( appointment problem ) , and with commitment to all aspects of the trial ( commitment problem ) were tracked prospect ively during the treatment phase of CAMP , which ranged from 20 to 40 months at the time of the analysis . METHODS We performed a cross-sectional analysis . RESULTS During the course of this investigation , no St Louis CAMP patients dropped out of the study , although signs of eroding participation were observed in 44 % of patients . For this cross-sectional analysis , the percentage of patients exhibiting protocol -adherence problems was greater the longer patients had been in the trial : 33.3 % at 20 to 25 months , 39.5 % at 26 to 30 months , 51.4 % at 31 to 35 months , and 69.2 % at 36 to 40 months ( P < .01 ) . The diary card problem was present in 22.2 % of the patients enrolled in the trial for 20 to 25 months compared with 66.7 % for patients enrolled for 36 to 40 months ( P < .005 ) . Appointment and commitment problems were present in smaller percentages of patients and did not change by time in the trial ( P = .41 and .22 , respectively ) . A logistic regression analysis of demographic characteristics indicated that age at r and omization and time in the trial were significant factors : for every 2-year increase in age , a child was twice as likely to have a commitment problem ( odds ratio [ OR ] , 1.96 ; 95 % CI , 1.50 - 2.57 ) , and for each additional 5 months of participation in the study , a child was twice as likely to have a diary card problem ( OR , 1.91 ; 95 % CI , 1.76 - 2.07 ) . There was no influence of family income , patient race , or patient sex on the occurrence of any of the 3 protocol -adherence problems . A similar analysis of psychologic characteristics of the child and family indicated ( 1 ) a 2-fold increase in the risk of a diary card problem with a 10 % increase in the percentage of total commissions on the attention scale of the Gordon Diagnostic Study ( OR , 2.18 ; 95 % CI , 2.02 - 2.35 ) , ( 2 ) a 2-fold decrease in the risk of an appointment problem with a 10-unit increase in the Child Manifest Anxiety Scale ( OR , 0.46 ; 95 % CI , 0.44 - 0.49 ) , ( 3 ) a 2-fold decrease in risk of an appointment problem with a 10-unit increase in the cohesion subscale of the Family Environment Scale ( OR , 0.58 ; 95 % CI , 0.55 - 0.60 ) , and ( 4 ) a 5-fold decrease in the risk of a commitment problem with a 10-unit increase in the Child Depression Index score ( OR , 0.21 ; 95 % CI , 0.18 - 0.24 ) . CONCLUSIONS Adherence and retention problems commonly occur in longer clinical trials . CAMP patients and families were selected in part on the basis of likelihood of being able to participate in the trial to enhance the conclusions of the trial . Despite this selection process , adherence problems were noted . Problems increased with duration of participation , increasing child age , and the presence of less family cohesion or attention problems in the child . In contrast , the presence of mild emotional distress ( anxiety and depression ) in the child was associated with fewer protocol -adherence problems . Incorporating procedures that help anticipate and identify adherence problems early might improve continued participation in all aspects of a trial and even retention in long-term clinical trials The efficacy and tolerability of nedocromil sodium , 4 mg four times daily , were investigated in a 4-week , r and omized , placebo-controlled , double-blind trial in 54 asthmatic patients . Significant improvements were seen in the nedocromil sodium treated patients with respect to asthma severity ( recorded by patients on diary cards ) ; lung function ( assessed by PEFR ) ; daytime and night-time asthma ( patients ' diary cards ) , and morning and evening peak flow rates ( measured by patients at home ) . Unusual symptoms were few and of a minor nature , differing little between active and placebo treatment . Nedocromil sodium , at the dosage used in this study , was well tolerated and provided a useful addition to asthma therapy Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways , contributing to allergic inflammation . IL-4 and IL-13 are the most important factors in production of class E immunoglobulin , playing major role in childhood atopic asthma . The mechanism of effect of nedocromil , often prescribed in children , has been discussed . Our previous study on the effect of nedocromil on different inflammatory markers , showed decreased levels of IL-4 and IgE after monotherapy in 15 asthmatic children . The purpose of this study was to define the effect of treatment with nedocromil on serum level of IL-4 and IgE , clinical symptoms and bronchial hyperreactivity ( BHR ) in children with moderate atopic asthma . It was 8 week , placebo-controlled and r and omized , double blind trial of 81 children with moderate atopic asthma allergic to dust mite . Patients were r and omly allocated to receive nedocromil sodium two puffs four times daily ( 0.002 g/puff ) ( n = 34 ) or placebo ( n = 47 ) . 69 children completed the study . After treatment with nedocromil the levels of IL-4 and IgE in blood serum in study group significantly decreased , and all clinical parameters improved . Mean levels of IL-4 in serum before and after treatment with nedocromil were 0.13 pg/ml + /- 0.01 and 0.12 pg/ml + /- 0.02 respectively ( p < 0.01 ) . Mean serum levels of IgE before and after treatment with nedocromil were 556.83 IU/ml + /- 201.3 and 485 IU/ml + /- 200.5 respectively ( p < 0.02 ) . This study demonstrate that one possible way by which nedocromil contribute to inhibition of allergic inflammation is by decreasing IL-4 and IgE levels BACKGROUND Beta2-adrenergic receptor ( B2AR ) polymorphisms have been associated with a variety of asthma-related phenotypes , but association results have been inconsistent across different studies . OBJECTIVE We sought to apply family-based association methods to individual single nucleotide polymorphisms ( SNPs ) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes . METHODS DNA sample s were obtained from 707 Childhood Asthma Management Program participants , representing 650 sibships , as well as their parents .  Genotyping was performed at 8 B2AR SNPs . Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT ; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test . RESULTS Several SNPs , including SNP -654 and SNP + 46 , demonstrated significant associations ( P < .05 ) to postbronchodilator FEV1 as both a qualitative ( < 80 % of predicted value ) and quantitative phenotype . Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP + 523 with bronchodilator responsiveness expressed as a percentage of baseline FEV1 ( P = .012 ) or a percentage of predicted FEV1 ( P = 
    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: The purpose of this study was to evaluate whether nedocromil sodium benefits urban asthmatic children showing seasonal bronchial hyper-reactivity to ultrasonic nebulization of distilled water ( UNDW ) . A prospect i ve , r and omized , placebo-controlled , parallel-group , double-blind study was carried out at the outpatient pulmonology service at a tertiary-care teaching hospital . Twelve children living in Milan , who were 7–17 years of age , who were SPT and RAST-negative to perennial allergens , who were suffering from episodic asthma , and showing seasonal bronchial hyper-reactivity to UNDW during winter , participated in this study . All the children received either placebo or nedocromil sodium , 4 mg every 6 h for 6 weeks . Spirometry and UNDW challenge were done at the following times : day−7 ; day 0 ; day 1 ; day 7 ; day 14 ; day 28 ; day 42 . No differences were found in the basal spirometric parameters , which were normal in both nedocromil and placebo groups . Bronchial reactivity to UNDW was found to be significantly decreased in the group treated with nedocromtl starting from day 7 . It is therefore concluded that nedocromil sodium can reverse bronchial hyper-reactivity caused by seasonal factors such as cold , viral infections and atmospheric pollutants in children suffering from asthma Nedocromil sodium in a dose of 4 mg b.i.d . or q.i.d . by inhalation was used to treat asthmatic patients in a double-blind , placebo-controlled , r and omized , parallel study . 80 patients ( 39 active drug and 41 placebo ) received q.i.d . dosage and 87 patients ( 45 active drug and 42 placebo )  received b.i.d .  dosage . The patients selected were not on oral or inhaled steroids but required oral sustained-release theophylline with or without an inhaled beta-agonist aerosol . There was a significant reduction in daytime asthma symptoms ( p = 0.04 ) and asthma severity ( p less than 0.01 ) 6 weeks after the onset of therapy in the nedocromil sodium q.i.d . treated group as compared with placebo . In the nedocromil sodium b.i.d . treated group , the following variables showed statistically significant improvements compared with placebo : daytime and night-time asthma ( p = 0.002 in both instances ) , wheezing assessed by auscultation ( p = 0.03 ) and overall asthma severity ( p less than 0.01 ) . All these variables showed improvements within 2 weeks of the onset of therapy and became statistically significant at 6 weeks . Side-effects were minor and occurred only in a small number of patients . It can be concluded from this study that nedocromil sodium is a safe and effective drug in the management of asthma Background : While increases in body mass index ( BMI ) have been associated with the incidence and prevalence of asthma , the mechanisms behind this association are unclear . Methods : We hypothesised that BMI would be independently associated with measures of asthma severity in a population of children with mild to moderate asthma enrolled in the Childhood Asthma Management Program ( CAMP ) . A multivariable baseline cross sectional analysis of BMI with our outcomes of interest was performed . Results : BMI was generally not associated with symptoms , nor was it associated with atopy . While BMI was positively associated with the methacholine concentration that causes a 20 % fall in forced expiratory volume in 1 second ( PC20FEV1 ) , this association did not persist after adjustment for FEV1 . Increasing BMI was associated with increasing FEV1 ( β = 0.006 l , 95 % CI ( 0.001 to 0.01 ) ) and forced vital capacity ( FVC ) ( β = 0.012 l , 95 % CI ( 0.007 to 0.017 ) ) . However , decrements in the FEV1/FVC ratio were noted with increasing BMI ( β = −0.242 , 95 % CI ( −0.118 to −0.366 ) ) . Thus , an increase in BMI of 5 units was associated with a decrease in FEV1/FVC of over 1 % . Conclusions : Although the association of FEV1 and FVC with BMI did not support our initial hypothesis , the decrease noted in the FEV1/FVC ratio has potential relevance in the relationship between BMI and asthma severity The present study examines the relationship between hypothalamic-pituitary-adrenal ( HPA ) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma . The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH ) stimulation when assessed as area under the curve . Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program ( CAMP ) during the pre-r and omization phase of the CAMP trial . At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center . Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present . Results further indicated significant associations between cortisol production and measures of child neuropsychological function . Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender , working memory , and arousal maintenance , providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma . In contrast , cortisol production was not associated with child reports of psychological functioning . Limitations to the methods employed in this study are discussed BACKGROUND Declining protocol adherence can threaten the validity of a clinical trial . OBJECTIVE We sought to explore patient and family factors important for protocol adherence in the 133 patients followed at one of the 8 Childhood Asthma Management Program ( CAMP ) clinical centers . Difficulties with timely return of diary cards (  diary card  problem ) , with keeping or frequently rescheduling appointments ( appointment problem ) , and with commitment to all aspects of the trial ( commitment problem ) were tracked prospect ively during the treatment phase of CAMP , which ranged from 20 to 40 months at the time of the analysis . METHODS We performed a cross-sectional analysis . RESULTS During the course of this investigation , no St Louis CAMP patients dropped out of the study , although signs of eroding participation were observed in 44 % of patients . For this cross-sectional analysis , the percentage of patients exhibiting protocol -adherence problems was greater the longer patients had been in the trial : 33.3 % at 20 to 25 months , 39.5 % at 26 to 30 months , 51.4 % at 31 to 35 months , and 69.2 % at 36 to 40 months ( P < .01 ) . The diary card problem was present in 22.2 % of the patients enrolled in the trial for 20 to 25 months compared with 66.7 % for patients enrolled for 36 to 40 months ( P < .005 ) . Appointment and commitment problems were present in smaller percentages of patients and did not change by time in the trial ( P = .41 and .22 , respectively ) . A logistic regression analysis of demographic characteristics indicated that age at r and omization and time in the trial were significant factors : for every 2-year increase in age , a child was twice as likely to have a commitment problem ( odds ratio [ OR ] , 1.96 ; 95 % CI , 1.50 - 2.57 ) , and for each additional 5 months of participation in the study , a child was twice as likely to have a diary card problem ( OR , 1.91 ; 95 % CI , 1.76 - 2.07 ) . There was no influence of family income , patient race , or patient sex on the occurrence of any of the 3 protocol -adherence problems . A similar analysis of psychologic characteristics of the child and family indicated ( 1 ) a 2-fold increase in the risk of a diary card problem with a 10 % increase in the percentage of total commissions on the attention scale of the Gordon Diagnostic Study ( OR , 2.18 ; 95 % CI , 2.02 - 2.35 ) , ( 2 ) a 2-fold decrease in the risk of an appointment problem with a 10-unit increase in the Child Manifest Anxiety Scale ( OR , 0.46 ; 95 % CI , 0.44 - 0.49 ) , ( 3 ) a 2-fold decrease in risk of an appointment problem with a 10-unit increase in the cohesion subscale of the Family Environment Scale ( OR , 0.58 ; 95 % CI , 0.55 - 0.60 ) , and ( 4 ) a 5-fold decrease in the risk of a commitment problem with a 10-unit increase in the Child Depression Index score ( OR , 0.21 ; 95 % CI , 0.18 - 0.24 ) . CONCLUSIONS Adherence and retention problems commonly occur in longer clinical trials . CAMP patients and families were selected in part on the basis of likelihood of being able to participate in the trial to enhance the conclusions of the trial . Despite this selection process , adherence problems were noted . Problems increased with duration of participation , increasing child age , and the presence of less family cohesion or attention problems in the child . In contrast , the presence of mild emotional distress ( anxiety and depression ) in the child was associated with fewer protocol -adherence problems . Incorporating procedures that help anticipate and identify adherence problems early might improve continued participation in all aspects of a trial and even retention in long-term clinical trials The efficacy and tolerability of nedocromil sodium , 4 mg four times daily , were investigated in a 4-week , r and omized , placebo-controlled , double-blind trial in 54 asthmatic patients . Significant improvements were seen in the nedocromil sodium treated patients with respect to asthma severity ( recorded by patients on diary cards ) ; lung function ( assessed by PEFR ) ; daytime and night-time asthma ( patients ' diary cards ) , and morning and evening peak flow rates ( measured by patients at home ) . Unusual symptoms were few and of a minor nature , differing little between active and placebo treatment . Nedocromil sodium , at the dosage used in this study , was well tolerated and provided a useful addition to asthma therapy Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways , contributing to allergic inflammation . IL-4 and IL-13 are the most important factors in production of class E immunoglobulin , playing major role in childhood atopic asthma . The mechanism of effect of nedocromil , often prescribed in children , has been discussed . Our previous study on the effect of nedocromil on different inflammatory markers , showed decreased levels of IL-4 and IgE after monotherapy in 15 asthmatic children . The purpose of this study was to define the effect of treatment with nedocromil on serum level of IL-4 and IgE , clinical symptoms and bronchial hyperreactivity ( BHR ) in children with moderate atopic asthma . It was 8 week , placebo-controlled and r and omized , double blind trial of 81 children with moderate atopic asthma allergic to dust mite . Patients were r and omly allocated to receive nedocromil sodium two puffs four times daily ( 0.002 g/puff ) ( n = 34 ) or placebo ( n = 47 ) . 69 children completed the study . After treatment with nedocromil the levels of IL-4 and IgE in blood serum in study group significantly decreased , and all clinical parameters improved . Mean levels of IL-4 in serum before and after treatment with nedocromil were 0.13 pg/ml + /- 0.01 and 0.12 pg/ml + /- 0.02 respectively ( p < 0.01 ) . Mean serum levels of IgE before and after treatment with nedocromil were 556.83 IU/ml + /- 201.3 and 485 IU/ml + /- 200.5 respectively ( p < 0.02 ) . This study demonstrate that one possible way by which nedocromil contribute to inhibition of allergic inflammation is by decreasing IL-4 and IgE levels BACKGROUND Beta2-adrenergic receptor ( B2AR ) polymorphisms have been associated with a variety of asthma-related phenotypes , but association results have been inconsistent across different studies . OBJECTIVE We sought to apply family-based association methods to individual single nucleotide polymorphisms ( SNPs ) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes . METHODS DNA sample s were obtained from 707 Childhood Asthma Management Program participants , representing 650 sibships , as well as their parents .  Genotyping was performed at 8 B2AR SNPs . Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT ; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test . RESULTS Several SNPs , including SNP -654 and SNP + 46 , demonstrated significant associations ( P < .05 ) to postbronchodilator FEV1 as both a qualitative ( < 80 % of predicted value ) and quantitative phenotype . Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP + 523 with bronchodilator responsiveness expressed as a percentage of baseline FEV1 ( P = .012 ) or a percentage of predicted FEV1 ( P = 
    Output:
    