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: RATIONALE The treatment effect of golimumab , a human monoclonal antibody against tumor necrosis factor (TNF)-alpha , in severe persistent asthma is unknown . OBJECTIVES To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled , severe persistent asthma . METHODS From 2004 to 2006 , 309 patients with severe and uncontrolled asthma , despite high-dose inhaled corticosteroids and long-acting beta(2 ) agonists , were r and omized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab ( 50 , 100 , or 200 mg ) through Week 52 . Co primary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1 ) and the number of severe asthma exacerbations through Week 24 . MEASUREMENTS AND MAIN RESULTS No significant differences were observed for the change in percent-predicted FEV1 ( least squares mean : placebo , 2.44 [ 95 % confidence interval ( CI ) -0.574 to 5.461 ] ; combined 100-mg and 200-mg , 2.91 [ 0.696 - 5.116 ] ) or severe exacerbations ( mean + /- SD : placebo , 0.5 + /- 1.07 vs. combined 100-mg and 200-mg 0.5 + /- 0.97 ) through week 24 . Through Week 24 , 2.6 % of patients treated with placebo vs. 19.5 % of those treated with golimumab discontinued the study agent , and 1.3 % and 7.8 % discontinued study participation , respectively . An unfavorable risk-benefit profile led to early discontinuation of study -agent administration after the Week-24 data base lock . Through Week 76 , 20.5 % of patients treated with placebo and 30.3 % of patients treated with golimumab experienced serious adverse events , with serious infections occurring more frequently in golimumab-treated patients . One death and all eight malignancies occurred in the active groups . CONCLUSIONS Overall , treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma . Clinical trial registered with www . clinical trials.gov ( NCT00207740 ) BACKGROUND AND OBJECTIVE There seems to be a strong causal relationship between allergy and the origins of asthma . Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines . Nearly 90 % of affected children have positive skin tests indicating the presence of specific immunoglobulin E ( IgE ) , with sensitivity to house dust mite , Alternaria , cockroach , cat , and dog most closely linked to the disease . Greater exposure to house dust mite during infancy leads to earlier onset of wheezing , and elevated serum IgE levels correlate with the appearance of asthma symptoms . Specific IgE binds to high-affinity ( FcepsilonRI ) receptors on mast cells and basophils . The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are design ated early- and late-phase asthmatic responses ( EAR and LAR ) . EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure . It is often followed by LAR , an infiltration of the airways by inflammatory cells associated with an episode of more prolonged , and usually more severe airflow obstruction , 4 to 8 hours after antigen exposure . Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure . IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity . IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling , with permanent loss in pulmonary function .  Omalizumab ( rhuMAb-E25 ) is a recombinant , humanized , monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases . Omalizumab binds to free IgE at the same site as the high-affinity receptor . Although it attaches to free IgE , it does not bind to IgA , IgG , or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE , which would lead to the release of allergic mediators . It has been reported to decrease serum IgE levels in a dose-dependent manner , inhibit EAR and LAR , and cause a down-regulation of FcepsilonRI receptors on basophils . Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids . This double-blind , r and omized , placebo-controlled study evaluated the safety , steroid-sparing effects , and impact on disease exacerbations of omalizumab in the treatment of childhood asthma . Methods . Participants were 334 males and premenarchal females aged 6 to 12 years , with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids .  During a run-in phase , all children were switched to equivalent doses of beclomethasone dipropionate ( BDP ) , and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment . Children were r and omized to subcutaneously administered placebo ( N = 109 ) or omalizumab ( N = 225 ) at a dose based on body weight and initial serum IgE ( 0.016 mg/kg/IgE [ IU/mL ] per 4 weeks ) . BDP dose ( initial range 168 - 420 microg/d ) was kept stable for 16 weeks ( stable-steroid phase ) , reduced over 8 weeks to the minimum effective dose ( steroid-reduction phase ) , and maintained constant for the final 4 weeks . RESULTS More participants in the omalizumab group decreased their BDP dose , and their reduction was greater than that of the placebo group ( median reduction 100 % vs 66.7 % ) . BDP was withdrawn completely in 55 % of the omalizumab group versus 39 % of the placebo group . The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group . The treatment differences were statistically significant during the steroid-reduction phase , during which fewer participants in the omalizumab group had asthma exacerbation episodes ( 18.2 % vs 38.5 % ) , and the mean number of episodes per patient was smaller than with placebo ( 0.42 vs 2.72 ) . Five asthma exacerbations requiring hospitalization all occurred in the placebo group . Participants ' and investigators ' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo .  Investigators rated effectiveness excellent for 31.5 % of the omalizumab group versus 16.3 % of the placebo group and good for 44.7 % of the omalizumab group versus 32.7 % of the placebo group . There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase , with minimal differences between the treatment groups . The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline . At week 28 , the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group . The change from baseline was significant in favor of omalizumab . ( ABSTRACT TRUNCATED BACKGROUND Allergic bronchopulmonary aspergillosis ( ABPA ) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s , causing an intense systemic immune response and progressive lung damage . OBJECTIVE We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA . METHODS A r and omized , double-blind , placebo-controlled trial was performed in stable subjects with ABPA ( n = 29 ) . Subjects received 400 mg of itraconazole per day ( n = 15 ) or placebo ( n = 14 ) for 16 weeks . All subjects were review ed monthly with history , spirometry , and sputum induction to measure airway inflammation , serum total IgE and IgG levels to A fumigatu s , and blood eosinophil counts . RESULTS By using regression analysis in a r and om-effects model , subjects receiving itraconazole had a decrease in sputum eosinophils of 35 % per week , with no decrease seen in the placebo arm ( P < .01 ) . Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42 % per week compared with 23 % in the placebo group ( P < .01 ) . Itraconazole reduced systemic immune activation , leading to a decrease in serum IgE levels ( 310 IU/mL ) compared with levels seen in the placebo group ( increase of 18 IU/mL , P < .01 ) and a decrease in IgG levels to A fumigatu s ( 15.4 IU/mL ) compared with levels seen in the placebo group ( increase of 3.7 IU/mL , P = .03 ) . There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group ( P = .03 ) . CONCLUSION Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation , systemic immune activation , and exacerbations . These results imply that itraconazole is a potential adjunctive treatment for ABPA OBJECTIVE To evaluate the long-term effects of the anti-IgE antibody omalizumab in children with asthma . METHODS This was a 28-week , double-blind , r and omized , placebo-controlled trial with a 24-week open-label extension . In the core trial 225 children ( ages 6 to 12 years ) with moderate-to-severe allergic asthma requiring inhaled beclomethasone dipropionate ( BDP ) received omalizumab every 2 or 4 weeks , and 109 received placebo .  BDP dosage was stable for weeks 1 to 16 , then reduced during weeks 17 to 24 using strict safety criteria . The lowest dose for optimal asthma control was maintained for 4 more weeks . During the 24-week extension , all patients ( n = 309 ) received open-label omalizumab in addition to other asthma medications . One-year safety data were analyzed . RESULTS The incidence of adverse events in patients treated with omalizumab for 52 weeks was similar to those treated for 28 weeks in the core trial , which was generally comparable with placebo . In the 52-week omalizumab group , upper respiratory tract infection and headache were the most frequently reported adverse events ( 47.1 % and 42.7 % , respectively ) . Eleven patients ( 4.9 % ) reported urticaria , which resolved spontaneously or with antihistamine , except for 1 patient who was discontinued because of severe urticaria . No anaphylactic reactions or adverse events suggestive of serum sickness or immune complex formation occurred . No anti-omalizumab antibodies were detected in any of the children . There is no evidence that new or more serious adverse events occur with long-term omalizumab treatment . CONCLUSIONS Long-term treatment with omalizumab is safe and well tolerated in children with allergic asthma BACKGROUND Eosinophilic inflammation , which may be a consequence of interleukin-5 action , is a characteristic feature of some forms of asthma . However , in three previous clinical trials involving patients with asthma , blockade of this cytokine did not result in a significant improvement in outcomes . We studied the prednisone-sparing effect of mepolizumab , a monoclonal antibody against interleukin-5 , in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone . Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood , symptoms , and airflow limitation . METHODS In this r and omized , double-blind , parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment , we assigned 9 patients to receive mepolizumab ( administered in five monthly infusions of 750 mg each ) and 11 patients to receive  placebo . RESULTS There were 12 asthma exacerbations in 10 patients who received placebo , 9 of whom had sputum eosinophilia at the time of exacerbation . In comparison , only one patient who received mepolizumab had an asthma exacerbation , and this episode was not associated with sputum eosinophilia ( P=0.002 ) . Patients who received mepolizumab were able to reduce their prednisone dose by a mean ( + /-SD ) of 83.8+/-33.4 % of their maximum possible dose , as compared with 47.7+/-40.5 % in the placebo group ( P=0.04 ) . The use of mepolizumab was associated with 
    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: RATIONALE The treatment effect of golimumab , a human monoclonal antibody against tumor necrosis factor (TNF)-alpha , in severe persistent asthma is unknown . OBJECTIVES To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled , severe persistent asthma . METHODS From 2004 to 2006 , 309 patients with severe and uncontrolled asthma , despite high-dose inhaled corticosteroids and long-acting beta(2 ) agonists , were r and omized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab ( 50 , 100 , or 200 mg ) through Week 52 . Co primary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1 ) and the number of severe asthma exacerbations through Week 24 . MEASUREMENTS AND MAIN RESULTS No significant differences were observed for the change in percent-predicted FEV1 ( least squares mean : placebo , 2.44 [ 95 % confidence interval ( CI ) -0.574 to 5.461 ] ; combined 100-mg and 200-mg , 2.91 [ 0.696 - 5.116 ] ) or severe exacerbations ( mean + /- SD : placebo , 0.5 + /- 1.07 vs. combined 100-mg and 200-mg 0.5 + /- 0.97 ) through week 24 . Through Week 24 , 2.6 % of patients treated with placebo vs. 19.5 % of those treated with golimumab discontinued the study agent , and 1.3 % and 7.8 % discontinued study participation , respectively . An unfavorable risk-benefit profile led to early discontinuation of study -agent administration after the Week-24 data base lock . Through Week 76 , 20.5 % of patients treated with placebo and 30.3 % of patients treated with golimumab experienced serious adverse events , with serious infections occurring more frequently in golimumab-treated patients . One death and all eight malignancies occurred in the active groups . CONCLUSIONS Overall , treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma . Clinical trial registered with www . clinical trials.gov ( NCT00207740 ) BACKGROUND AND OBJECTIVE There seems to be a strong causal relationship between allergy and the origins of asthma . Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines . Nearly 90 % of affected children have positive skin tests indicating the presence of specific immunoglobulin E ( IgE ) , with sensitivity to house dust mite , Alternaria , cockroach , cat , and dog most closely linked to the disease . Greater exposure to house dust mite during infancy leads to earlier onset of wheezing , and elevated serum IgE levels correlate with the appearance of asthma symptoms . Specific IgE binds to high-affinity ( FcepsilonRI ) receptors on mast cells and basophils . The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are design ated early- and late-phase asthmatic responses ( EAR and LAR ) . EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure . It is often followed by LAR , an infiltration of the airways by inflammatory cells associated with an episode of more prolonged , and usually more severe airflow obstruction , 4 to 8 hours after antigen exposure . Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure . IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity . IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling , with permanent loss in pulmonary function .  Omalizumab ( rhuMAb-E25 ) is a recombinant , humanized , monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases . Omalizumab binds to free IgE at the same site as the high-affinity receptor . Although it attaches to free IgE , it does not bind to IgA , IgG , or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE , which would lead to the release of allergic mediators . It has been reported to decrease serum IgE levels in a dose-dependent manner , inhibit EAR and LAR , and cause a down-regulation of FcepsilonRI receptors on basophils . Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids . This double-blind , r and omized , placebo-controlled study evaluated the safety , steroid-sparing effects , and impact on disease exacerbations of omalizumab in the treatment of childhood asthma . Methods . Participants were 334 males and premenarchal females aged 6 to 12 years , with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids .  During a run-in phase , all children were switched to equivalent doses of beclomethasone dipropionate ( BDP ) , and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment . Children were r and omized to subcutaneously administered placebo ( N = 109 ) or omalizumab ( N = 225 ) at a dose based on body weight and initial serum IgE ( 0.016 mg/kg/IgE [ IU/mL ] per 4 weeks ) . BDP dose ( initial range 168 - 420 microg/d ) was kept stable for 16 weeks ( stable-steroid phase ) , reduced over 8 weeks to the minimum effective dose ( steroid-reduction phase ) , and maintained constant for the final 4 weeks . RESULTS More participants in the omalizumab group decreased their BDP dose , and their reduction was greater than that of the placebo group ( median reduction 100 % vs 66.7 % ) . BDP was withdrawn completely in 55 % of the omalizumab group versus 39 % of the placebo group . The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group . The treatment differences were statistically significant during the steroid-reduction phase , during which fewer participants in the omalizumab group had asthma exacerbation episodes ( 18.2 % vs 38.5 % ) , and the mean number of episodes per patient was smaller than with placebo ( 0.42 vs 2.72 ) . Five asthma exacerbations requiring hospitalization all occurred in the placebo group . Participants ' and investigators ' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo .  Investigators rated effectiveness excellent for 31.5 % of the omalizumab group versus 16.3 % of the placebo group and good for 44.7 % of the omalizumab group versus 32.7 % of the placebo group . There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase , with minimal differences between the treatment groups . The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline . At week 28 , the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group . The change from baseline was significant in favor of omalizumab . ( ABSTRACT TRUNCATED BACKGROUND Allergic bronchopulmonary aspergillosis ( ABPA ) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s , causing an intense systemic immune response and progressive lung damage . OBJECTIVE We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA . METHODS A r and omized , double-blind , placebo-controlled trial was performed in stable subjects with ABPA ( n = 29 ) . Subjects received 400 mg of itraconazole per day ( n = 15 ) or placebo ( n = 14 ) for 16 weeks . All subjects were review ed monthly with history , spirometry , and sputum induction to measure airway inflammation , serum total IgE and IgG levels to A fumigatu s , and blood eosinophil counts . RESULTS By using regression analysis in a r and om-effects model , subjects receiving itraconazole had a decrease in sputum eosinophils of 35 % per week , with no decrease seen in the placebo arm ( P < .01 ) . Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42 % per week compared with 23 % in the placebo group ( P < .01 ) . Itraconazole reduced systemic immune activation , leading to a decrease in serum IgE levels ( 310 IU/mL ) compared with levels seen in the placebo group ( increase of 18 IU/mL , P < .01 ) and a decrease in IgG levels to A fumigatu s ( 15.4 IU/mL ) compared with levels seen in the placebo group ( increase of 3.7 IU/mL , P = .03 ) . There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group ( P = .03 ) . CONCLUSION Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation , systemic immune activation , and exacerbations . These results imply that itraconazole is a potential adjunctive treatment for ABPA OBJECTIVE To evaluate the long-term effects of the anti-IgE antibody omalizumab in children with asthma . METHODS This was a 28-week , double-blind , r and omized , placebo-controlled trial with a 24-week open-label extension . In the core trial 225 children ( ages 6 to 12 years ) with moderate-to-severe allergic asthma requiring inhaled beclomethasone dipropionate ( BDP ) received omalizumab every 2 or 4 weeks , and 109 received placebo .  BDP dosage was stable for weeks 1 to 16 , then reduced during weeks 17 to 24 using strict safety criteria . The lowest dose for optimal asthma control was maintained for 4 more weeks . During the 24-week extension , all patients ( n = 309 ) received open-label omalizumab in addition to other asthma medications . One-year safety data were analyzed . RESULTS The incidence of adverse events in patients treated with omalizumab for 52 weeks was similar to those treated for 28 weeks in the core trial , which was generally comparable with placebo . In the 52-week omalizumab group , upper respiratory tract infection and headache were the most frequently reported adverse events ( 47.1 % and 42.7 % , respectively ) . Eleven patients ( 4.9 % ) reported urticaria , which resolved spontaneously or with antihistamine , except for 1 patient who was discontinued because of severe urticaria . No anaphylactic reactions or adverse events suggestive of serum sickness or immune complex formation occurred . No anti-omalizumab antibodies were detected in any of the children . There is no evidence that new or more serious adverse events occur with long-term omalizumab treatment . CONCLUSIONS Long-term treatment with omalizumab is safe and well tolerated in children with allergic asthma BACKGROUND Eosinophilic inflammation , which may be a consequence of interleukin-5 action , is a characteristic feature of some forms of asthma . However , in three previous clinical trials involving patients with asthma , blockade of this cytokine did not result in a significant improvement in outcomes . We studied the prednisone-sparing effect of mepolizumab , a monoclonal antibody against interleukin-5 , in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone . Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood , symptoms , and airflow limitation . METHODS In this r and omized , double-blind , parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment , we assigned 9 patients to receive mepolizumab ( administered in five monthly infusions of 750 mg each ) and 11 patients to receive  placebo . RESULTS There were 12 asthma exacerbations in 10 patients who received placebo , 9 of whom had sputum eosinophilia at the time of exacerbation . In comparison , only one patient who received mepolizumab had an asthma exacerbation , and this episode was not associated with sputum eosinophilia ( P=0.002 ) . Patients who received mepolizumab were able to reduce their prednisone dose by a mean ( + /-SD ) of 83.8+/-33.4 % of their maximum possible dose , as compared with 47.7+/-40.5 % in the placebo group ( P=0.04 ) . The use of mepolizumab was associated with 
    Output:
    