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 : A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported . This paper presents additional information on exacerbations of asthma and trends in lung function , airways hyperresponsiveness to methacholine , and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment . METHODS : Subjects undertook a year long r and omised , double blind crossover study of regular upsilon as needed inhaled beta agonist treatment . Fenoterol ( 400 micrograms ) or matching placebo was inhaled as a dry powder four times daily for 24 weeks , then subjects crossed over to the alternative regimen . Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study . Symptoms , peak expiratory flow rates , and drug use were recorded daily , spirometry was performed every four weeks , and methacholine and bronchodilator responsiveness were measured every eight weeks . RESULTS : Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment . Prebronchodilator forced expiratory volume in one second ( FEV1 ) was on average 0.15 litres lower ( 95 % confidence interval ( 95 % CI ) 0.11 - 0.19 ) and vital capacity ( VC ) 0.12 litres lower ( 95 % CI 0.08 - 0.16 ) than during the placebo period . Morning peak flow rates were significantly lower and evening peak flow rates significantly higher , with an increase in diurnal variation from 9.8 % ( 95 % CI 6.9 - 12.8 ) to 17.5 % ( 95 % CI 13.8 - 21.3 ) during regular treatment . Geometric mean concentration of methacholine causing a 20 % fall in FEV1 from the value after saline ( PC20 ) decreased significantly from 1.63 to 1.15 mg/ml , indicating increased bronchial hyperresponsiveness during regular treatment . Response to bronchodilator , as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1 , was maintained with no evidence for tachyphylaxis . CONCLUSION : Chronic use of inhaled fenoterol result ed in more exacerbations , a significant decline in baseline lung function , and an increase in airway responsiveness to methacholine in asthmatic subjects , but did not alter bronchodilator responsiveness . These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma BACKGROUND The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial . Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine ( Arg/Arg ) , rather than glycine ( Gly/Gly ) , at aminoacid residue 16 of the beta2-adrenergic receptor . However , the existence of any genotype-dependent difference has not been tested in a prospect i ve clinical trial . METHODS Patients with mild asthma , not using a controller medication , were enrolled in pairs matched for forced expiratory volume in 1 s ( FEV1 ) according to whether they had the Arg/Arg ( n=37 ; four of 41 matches withdrew before r and omisation ) or Gly/Gly ( n=41 ) genotype . Regularly scheduled treatment with albuterol or placebo was given in a masked , cross-over design , for 16-week periods . During the study , as-needed albuterol use was discontinued and ipratropium bromide was used as needed . Morning peak expiratory flow rate ( PEFR ) was the primary outcome variable . The primary comparisons were between treatment period for each genotype ; the secondary outcome was a treatment by genotype effect . Analyses were by intention to treat . FINDINGS During the run-in period , when albuterol use was kept to a minimum , patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min ( p=0.0162 ) ; the change in patients with the Gly/Gly genotype was not significant ( 2 L/min ; p=0.8399 ) . During r and omised treatment , patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo ( 14 L/min [ 95 % CI 3 to 25 ] ; p=0.0175 ) . By contrast , patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period , when albuterol use was limited ( -10 L/min [ -19 to -2 ] ; p=0.0209 ) . The genotype-attributable treatment difference was therefore -24 L/min ( -37 to -12 ; p=0.0003 ) . There were similar genotype-specific effects in FEV1 , symptoms , and use of supplementary reliever medication . INTERPRETATION Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use . Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype AIMS Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect . The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma . METHODS Twenty-one otherwise healthy adults with persistent asthma , mean age 25 years , completed treatment with maximum tolerated doses of placebo ( P ) , nifedipine ( N ) , and diltiazem ( D ) in a double-blind , r and omized , three-treatment , three-period , crossover manner , each for 4 weeks . Frequency and severity of asthmatic symptoms were recorded twice daily , as well as peak expiratory flow and frequency of ' prn ' use of inhaled  terbutaline .  Blood pressure , heart rate , P-R interval of the ECG and spirometry  were measured biweekly . At the end of each treatment , airway responsiveness to exercise was measured . RESULTS The mean ( s.e . mean)% of days with wheeze was 69plus minus7 % during P , 75plus minus6 % during N and 72plus minus6 % during D ( P=0.7 ) . FEV1 was 79plus minus2 % of predicted during P , 81plus minus2 % during N and 79plus minus2 % during D ( P=0.6 ) . The decrease in FEV1 after exercise was 32plus minus4 % during P , 32plus minus5 % during N and 27plus minus4 % during D ( P=0.5 ) . Heart rate was elevated during N ( P=0.0002 ) whereas P-R interval was prolonged during D ( P=0.0001 ) . CONCLUSIONS Maintenance therapy with calcium channel blockers , at doses that produce cardiovascular effects , do not suppress the signs and symptoms of persistent asthma . Previous bronchoprovocation studies did not predict these results We compared the efficacy of inhaled formoterol , a long-acting beta 2-agonist , with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial . Patients were allocated in r and omized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications . Patients were allowed to use " rescue " 100-micrograms albuterol puffs on an as-needed basis . Mean baseline FEV , in the morning before bronchodilator was 2.14 + /- 0.76 L and 1.98 + /- 0.71 L for the formoterol and albuterol groups , respectively , these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1 . Measured at each clinic visit , morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group , the greatest difference being in Week 8 ( 2.40 + /- 0.77 versus 1.92 + /- 0.66 L , p less than 0.001 ) . Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8 , the trend not reaching statistical significance at other times . Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial ( 17 versus 42 L/min at Week 12 , p less than 0.0001 ) . The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4 , 8 , and 12 as were the number of sleep disruptions during Weeks 2 , 4 , 6 , 8 , and 12 . Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study . ( ABSTRACT TRUNCATED AT 250 WORDS Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed . Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans , we determined the symptoms and alterations in pulmonary function result ing from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber . The protocol consisted of r and omized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days . Twenty-two healthy normal subjects engaged in intermittent heavy exercise ( VE = 65 L/min ) and 16 asthmatic subjects performed intermittent moderate exercise ( VE = 37 L/min ) .  Symptoms and pulmonary function were assessed during the time course of exposure ; nonspecific airway reactivity was assessed after exposure . Both groups exhibited similar , significant ( p less than 0.01 ) increases in perceived odor , nose/throat irritation , and eye irritation throughout the exposure . The normal group had the following statistically significant ( p less than 0.02 ) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air : 3.8 % in FEV1 , 2.6 % in FVC , and 2.8 % in FEV3 . The asthmatic group showed no statistically significant decrements in pulmonary function . Five of 38 subjects studied had decrements in FEV1 greater than 10 % . In conclusion , acute exposure to 3 ppm HCHO produced : consistent irritant symptoms in both normal and asthmatic subjects , small decreases in pulmonary function in normal subjects engaging in heavy exercise , and clinical ly significant responses ( defined here as decrements in FEU1 greater than 10 ) in 13 % of the study population . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present study was to compare the effectiveness , safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada . After 2 weeks of usual therapy , 1,538 patients were r and omised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 μg twice daily and as needed , or to guideline -based conventional best practice  . Severe asthma exacerbations , reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub- study of 115 patients . No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate . There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy ( 4.4 versus 7.5 events per 100 patients · yr−1 , 41 % reduction ) ; however , this did not reach statistical significance . Mean total inhaled corticosteroid dose , reliever use , asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy . Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups . In conclusion , budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice , with significantly lower total inhaled corticosteroid dose and lower cost , while maintaining similar control of eosinophilic inflammation SUMMARY Objective : The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season . Methods : This was a multicenter study of 831 patients ( ages 15 years–85 years ) with seasonal allergen sensitivity , active symptoms of seasonal allergic rhinitis , and active asthma . Following a single-blind , placebo run-in period of 3 days–5 days , patients were r and omized to oral montelukast 10 mg ( n = 415 ) or placebo ( n = 416 ) daily during the 2-week , double-blind , active-treatment period . Main outcome measures : The primary endpoint was Daily Rhinitis Symptoms score , average 
    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 : A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported . This paper presents additional information on exacerbations of asthma and trends in lung function , airways hyperresponsiveness to methacholine , and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment . METHODS : Subjects undertook a year long r and omised , double blind crossover study of regular upsilon as needed inhaled beta agonist treatment . Fenoterol ( 400 micrograms ) or matching placebo was inhaled as a dry powder four times daily for 24 weeks , then subjects crossed over to the alternative regimen . Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study . Symptoms , peak expiratory flow rates , and drug use were recorded daily , spirometry was performed every four weeks , and methacholine and bronchodilator responsiveness were measured every eight weeks . RESULTS : Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment . Prebronchodilator forced expiratory volume in one second ( FEV1 ) was on average 0.15 litres lower ( 95 % confidence interval ( 95 % CI ) 0.11 - 0.19 ) and vital capacity ( VC ) 0.12 litres lower ( 95 % CI 0.08 - 0.16 ) than during the placebo period . Morning peak flow rates were significantly lower and evening peak flow rates significantly higher , with an increase in diurnal variation from 9.8 % ( 95 % CI 6.9 - 12.8 ) to 17.5 % ( 95 % CI 13.8 - 21.3 ) during regular treatment . Geometric mean concentration of methacholine causing a 20 % fall in FEV1 from the value after saline ( PC20 ) decreased significantly from 1.63 to 1.15 mg/ml , indicating increased bronchial hyperresponsiveness during regular treatment . Response to bronchodilator , as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1 , was maintained with no evidence for tachyphylaxis . CONCLUSION : Chronic use of inhaled fenoterol result ed in more exacerbations , a significant decline in baseline lung function , and an increase in airway responsiveness to methacholine in asthmatic subjects , but did not alter bronchodilator responsiveness . These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma BACKGROUND The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial . Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine ( Arg/Arg ) , rather than glycine ( Gly/Gly ) , at aminoacid residue 16 of the beta2-adrenergic receptor . However , the existence of any genotype-dependent difference has not been tested in a prospect i ve clinical trial . METHODS Patients with mild asthma , not using a controller medication , were enrolled in pairs matched for forced expiratory volume in 1 s ( FEV1 ) according to whether they had the Arg/Arg ( n=37 ; four of 41 matches withdrew before r and omisation ) or Gly/Gly ( n=41 ) genotype . Regularly scheduled treatment with albuterol or placebo was given in a masked , cross-over design , for 16-week periods . During the study , as-needed albuterol use was discontinued and ipratropium bromide was used as needed . Morning peak expiratory flow rate ( PEFR ) was the primary outcome variable . The primary comparisons were between treatment period for each genotype ; the secondary outcome was a treatment by genotype effect . Analyses were by intention to treat . FINDINGS During the run-in period , when albuterol use was kept to a minimum , patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min ( p=0.0162 ) ; the change in patients with the Gly/Gly genotype was not significant ( 2 L/min ; p=0.8399 ) . During r and omised treatment , patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo ( 14 L/min [ 95 % CI 3 to 25 ] ; p=0.0175 ) . By contrast , patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period , when albuterol use was limited ( -10 L/min [ -19 to -2 ] ; p=0.0209 ) . The genotype-attributable treatment difference was therefore -24 L/min ( -37 to -12 ; p=0.0003 ) . There were similar genotype-specific effects in FEV1 , symptoms , and use of supplementary reliever medication . INTERPRETATION Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use . Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype AIMS Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect . The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma . METHODS Twenty-one otherwise healthy adults with persistent asthma , mean age 25 years , completed treatment with maximum tolerated doses of placebo ( P ) , nifedipine ( N ) , and diltiazem ( D ) in a double-blind , r and omized , three-treatment , three-period , crossover manner , each for 4 weeks . Frequency and severity of asthmatic symptoms were recorded twice daily , as well as peak expiratory flow and frequency of ' prn ' use of inhaled  terbutaline .  Blood pressure , heart rate , P-R interval of the ECG and spirometry  were measured biweekly . At the end of each treatment , airway responsiveness to exercise was measured . RESULTS The mean ( s.e . mean)% of days with wheeze was 69plus minus7 % during P , 75plus minus6 % during N and 72plus minus6 % during D ( P=0.7 ) . FEV1 was 79plus minus2 % of predicted during P , 81plus minus2 % during N and 79plus minus2 % during D ( P=0.6 ) . The decrease in FEV1 after exercise was 32plus minus4 % during P , 32plus minus5 % during N and 27plus minus4 % during D ( P=0.5 ) . Heart rate was elevated during N ( P=0.0002 ) whereas P-R interval was prolonged during D ( P=0.0001 ) . CONCLUSIONS Maintenance therapy with calcium channel blockers , at doses that produce cardiovascular effects , do not suppress the signs and symptoms of persistent asthma . Previous bronchoprovocation studies did not predict these results We compared the efficacy of inhaled formoterol , a long-acting beta 2-agonist , with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial . Patients were allocated in r and omized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications . Patients were allowed to use " rescue " 100-micrograms albuterol puffs on an as-needed basis . Mean baseline FEV , in the morning before bronchodilator was 2.14 + /- 0.76 L and 1.98 + /- 0.71 L for the formoterol and albuterol groups , respectively , these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1 . Measured at each clinic visit , morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group , the greatest difference being in Week 8 ( 2.40 + /- 0.77 versus 1.92 + /- 0.66 L , p less than 0.001 ) . Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8 , the trend not reaching statistical significance at other times . Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial ( 17 versus 42 L/min at Week 12 , p less than 0.0001 ) . The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4 , 8 , and 12 as were the number of sleep disruptions during Weeks 2 , 4 , 6 , 8 , and 12 . Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study . ( ABSTRACT TRUNCATED AT 250 WORDS Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed . Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans , we determined the symptoms and alterations in pulmonary function result ing from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber . The protocol consisted of r and omized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days . Twenty-two healthy normal subjects engaged in intermittent heavy exercise ( VE = 65 L/min ) and 16 asthmatic subjects performed intermittent moderate exercise ( VE = 37 L/min ) .  Symptoms and pulmonary function were assessed during the time course of exposure ; nonspecific airway reactivity was assessed after exposure . Both groups exhibited similar , significant ( p less than 0.01 ) increases in perceived odor , nose/throat irritation , and eye irritation throughout the exposure . The normal group had the following statistically significant ( p less than 0.02 ) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air : 3.8 % in FEV1 , 2.6 % in FVC , and 2.8 % in FEV3 . The asthmatic group showed no statistically significant decrements in pulmonary function . Five of 38 subjects studied had decrements in FEV1 greater than 10 % . In conclusion , acute exposure to 3 ppm HCHO produced : consistent irritant symptoms in both normal and asthmatic subjects , small decreases in pulmonary function in normal subjects engaging in heavy exercise , and clinical ly significant responses ( defined here as decrements in FEU1 greater than 10 ) in 13 % of the study population . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present study was to compare the effectiveness , safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada . After 2 weeks of usual therapy , 1,538 patients were r and omised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 μg twice daily and as needed , or to guideline -based conventional best practice  . Severe asthma exacerbations , reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub- study of 115 patients . No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate . There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy ( 4.4 versus 7.5 events per 100 patients · yr−1 , 41 % reduction ) ; however , this did not reach statistical significance . Mean total inhaled corticosteroid dose , reliever use , asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy . Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups . In conclusion , budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice , with significantly lower total inhaled corticosteroid dose and lower cost , while maintaining similar control of eosinophilic inflammation SUMMARY Objective : The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season . Methods : This was a multicenter study of 831 patients ( ages 15 years–85 years ) with seasonal allergen sensitivity , active symptoms of seasonal allergic rhinitis , and active asthma . Following a single-blind , placebo run-in period of 3 days–5 days , patients were r and omized to oral montelukast 10 mg ( n = 415 ) or placebo ( n = 416 ) daily during the 2-week , double-blind , active-treatment period . Main outcome measures : The primary endpoint was Daily Rhinitis Symptoms score , average 
    Output:
    