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: Patients with chronic obstructive pulmonary disease ( COPD ) often subjectively benefit from inhaled R2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second ( FEV1.0 ) . A comparison between the effects of terbutaline administered via a dry powder inhaler ( Turbuhaler ® ) and via a chlorofluorocarbon ( CFC ) inhaler in conjunction with a spacer device ( Nebuhaler ® ) was performed in patients with regard to FEV1.0 , forced expiratory capacity ( FVC ) , residual volume ( RV ) , and specific conductance ( s-Gaw ) . Fifteen hospitalised patients ( 11 male ) with COPD were studied , each of whom had a diurnal variation in peak expiratory flow ( PEF ) not exceeding 15 % and with a demonstrated volume response to inhaled β2-agonists in FVC and /or RV of at least 15 % . Patients were administered each of the following five treatments on a single occasion in a r and omized order ( latin square ) in intervals of at least 2 days : placebo , terbutaline via Turbuhaler ( 1.0 and 2.5 mg ) and terbutaline via a CFC inhaler ( 1.0 mg without and 2.5 mg with Nebuhaler ) . Inhalation of terbutaline in different doses and from different devices induced a decrease in RV , an increase in FVC , and s-Gaw and a less pronounced increase in FEV1.0 . No statistically significant differences between the four terbutaline treatments were seen , but all were significantly different from the placebo . These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation , the choice of inhalation device seems to be of little importance for its efficacy We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler , the Turbuhaler , or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age . The bronchodilator response did not differ between the two inhalational devices . The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used In the near future it is to be expected that many new inhaled corticosteroids or formulations of these drugs will be compared with older ones , to discover whether they are therapeutically equivalent or not . The statistical evaluation of these trials differs from the classic methods . When two averages are similar or differ only slightly , power is very low . The regulatory bodies dem and a power of at least 80 % . This problem was initially solved by using the so-called power approach . Research ers included enough volunteers to enable them to detect a predefined difference , considered to be without any clinical significance , with a power of 80 % . This approach , however , has been shown to be incorrect and has been replaced by the two one-sided tests procedure , where a new sample size equation is derived . Important elements of this new equation are the coefficient of variation of the parameter measured , the difference between the averages of the two groups and the equivalence limit ( the difference between the means still tolerable ) . This equation was used in the present study to estimate the number of volunteers needed in a parallel inhaled corticosteroids equivalence trial . The end points chosen were the changes in FEV1 and PC20 due to the corticosteroid effect . Calculations were performed by extracting data from published placebo-controlled trials , and defining a range of equivalence limits and differences between the group averages . It was shown that a huge number of volunteers ( 500–1000 ) will be needed , as a result of the small corticosteroid effect and the high variance . In the case of inhaled corticosteroids , the equivalence limit is not known and needs defining to avoid discussion s on the outcome . Due to the high number of patients who need to be included , the trial will most probably be multicentre and take place in several countries . Such a trial will suffer from several sources of bias . For instance , the definition of asthma can differ from country to country and from research er to research er , result ing in non-comparable groups of patients . The many sources of bias will make the outcome difficult to interpret . Therefore alternative methods to establish therapeutic equivalence are proposed and discussed Two hundred and fifty eight adult patients with bronchial asthma participated in an open , parallel group study of 8 wks duration . During a 2 wk run-in period the beta 2-agonist terbutaline ( 0.5 mg q.i.d ) was delivered via a pressurized freon aerosol , Bricanyl metered dose inhaler ( MDI ) . During the following 6 wks , one third of the patients continued with MDI and two thirds with the same dose of terbutaline in the form of dry powder , Bricanyl Turbuhaler . There were no statistically significant differences in the increases in peak expiratory flow rate ( PEFR ) after inhalation between the two treatment groups . The asthma symptom scores decreased in the Turbuhaler group during the study but remained the same in the MDI group . No difference in use of extra trial medication during the day was found . During the night , the difference was statistically significant in favour of Turbuhaler ( p less than 0.05 ) . Turbuhaler was well accepted and easy to use . As compared with the MDI used during run-in , 50 % of the patients in the Turbuhaler group preferred to use  Turbuhaler and 26 % MDI , whilst 24 % had no preference . In conclusion , Turbuhaler was at least as effective as MDI during the whole Turbuhaler life-span ( 6 wks ) Metered-dose inhalers ( MDIs ) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon ( CFC ) propellants . The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry . The mean + /- SD relative lung bioavailability of albuterol  to the lung following inhalation of 400 micrograms of albuterol from an MDI , the Rotahaler and Diskhaler in 10 well-trained volunteers , was 2.83 ( 0.78 ) , 1.72 ( 0.99 ) , and 2.64 (1.23)% , respectively , expressed as a percentage of the nominal dose . The delivery of albuterol to the lungs from the MDI and Diskhaler was similar . In nine asthmatic subjects , the relative lung bioavailability of albuterol  following inhalation with the MDI and Diskhaler was 1.19 ( 0.79 ) and 2.38 (1.46)% , respectively , expressed as a percentage of the nominal dose . There was no difference in reversibility 30 min after administration of the dose by the two methods . Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique , which was absent in the asthmatic subjects . The Diskhaler does not rely on coordination during inhalation and therefore is easier to use Forty‐three children from 3‐16 years of age suffering from moderate bronchial asthma completed a double‐blind cross‐over study on the clinical effect of inhaled salbutamol ( Ventoline ® ) powder ( 0.2 mg/dosis ) compared with spray ( 0.1 mg/dosis ) over two 4‐week periods . Both administrations gave significant improvement in air flow meter ( AFM ) results . There was no significant difference between the periods on active powder or spray regarding daily symptom scores , adjuvant medication or AFM values . The powder caused cough in four children but in 12 of 28 children it was considered as easy or easier to accept as the spray ; nine of these 12 children were younger than 10 years of age . It is concluded that salbutamol inhaled as a powder is a useful alternative when using a spray is difficult or unwanted Nineteen patients with asthma completed an open , r and omized , crossover study in which 0.5 mg terbutaline sulphate was administered either via Turbuhaler or via the metered dose inhaler ( MDI ) for 2-week periods . The clinical effect of the two treatment forms was comparable ; both provided adequate bronchodilator therapy . Patients also considered  Turbuhaler and MDI equally effective , with a small preference for the MDI . Turbuhaler seems to be a valuable alternative to bronchodilator MDI therapy BACKGROUND : beta Agonists have been shown to increase mucociliary clearance in some studies but not all . Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases . METHODS : The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second ( FEV1 ) was assessed in 10 patients with asthma and 10 healthy subjects .  Terbutaline ( 1 mg ) was administered through a metered dose inhaler with a spacer ( Nebuhaler ) or a dry powder inhaler ( Turbuhaler ) , or both treatments were given , in a four way double blind , double dummy trial . Mucociliary clearance was measured by bronchoscintigraphy . RESULTS : Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32 % after terbutaline was given by metered dose inhaler and 55 % after a combined dose of 2 mg from both inhalers ( 1 mg from each ) compared with placebo but by only 9 % after 1 mg of terbutaline was given by a dry powder inhaler . In the healthy subjects  mucociliary clearance increased by 51 % when terbutaline was given by a dry powder inhaler , by 66 % when given by a metered dose inhaler , and by 66 % when given by both inhalers combined . The effect of terbutaline on FEV1 was the same with each of the inhalers . CONCLUSION : Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects . The reason for the difference in asthmatic subjects is unclear , but may be associated with differences in the deposition of terbutaline There is some concern over the environmental consequences of chlorofluorocarbons ( CFCs ) used in pressurized metered-dose inhalers ( p-MDIs ) . Turbuhaler was design ed to deliver a drug as a dry powder without administering additives directly to the airways . The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler .  Ten symptomatic , asthmatic patients , with highly reactive airways ( provocative concentration of methacholine producing a 20 % fall in forced expiratory volume in one second ( PC20 ) < 0.2 mg.ml-1 ) , inhaled , on separate days , 0.25 mg terbutaline via p-MDI or Turbuhaler . Changes in airway calibre were followed as specific airways conductance ( sGaw ) . On a third day , patients inhaled from a placebo p-MDI containing all constituents except terbutaline . The study was conducted in a single-blind fashion and in r and om order . There were no significant differences in baseline sGaw on any of the study days . Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min , reaching a mean maximum + /- SD of 17 + /- 8 % at 10 s and then returning to baseline value after 20 s , followed by a progressive increase in sGaw to a maximum of 39 + /- 45 % above baseline at 45 min . In contrast , inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction ( fall in sGaw , 3 + /- 16 % ) at 10 s and achieved a greater increase in sGaw , reaching 63 + /- 51 % at 45 min , although just failing to reach statistical significance compared to terbutaline p-MDI inhalation . ( ABSTRACT TRUNCATED AT 250 WORDS Twelve adult asthmatic patients participated in an open , r and omized , cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler ( Turbuhaler ) or via a pressurized inhaler . Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects . Both treatments produced a significant increase in pulmonary function measurements , forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) . No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments . Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of  exercise-induced bronchospasm in children . Forty-six patients aged 4 - 11 years with asthma and exercise-induced bronchospasm were enrolled in this r and omized , double-blind , single-dose , three-way crossover study comparing albuterol aerosol , albuterol powder , and placebo . Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits . Prevention of exercise-induced 
    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: Patients with chronic obstructive pulmonary disease ( COPD ) often subjectively benefit from inhaled R2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second ( FEV1.0 ) . A comparison between the effects of terbutaline administered via a dry powder inhaler ( Turbuhaler ® ) and via a chlorofluorocarbon ( CFC ) inhaler in conjunction with a spacer device ( Nebuhaler ® ) was performed in patients with regard to FEV1.0 , forced expiratory capacity ( FVC ) , residual volume ( RV ) , and specific conductance ( s-Gaw ) . Fifteen hospitalised patients ( 11 male ) with COPD were studied , each of whom had a diurnal variation in peak expiratory flow ( PEF ) not exceeding 15 % and with a demonstrated volume response to inhaled β2-agonists in FVC and /or RV of at least 15 % . Patients were administered each of the following five treatments on a single occasion in a r and omized order ( latin square ) in intervals of at least 2 days : placebo , terbutaline via Turbuhaler ( 1.0 and 2.5 mg ) and terbutaline via a CFC inhaler ( 1.0 mg without and 2.5 mg with Nebuhaler ) . Inhalation of terbutaline in different doses and from different devices induced a decrease in RV , an increase in FVC , and s-Gaw and a less pronounced increase in FEV1.0 . No statistically significant differences between the four terbutaline treatments were seen , but all were significantly different from the placebo . These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation , the choice of inhalation device seems to be of little importance for its efficacy We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler , the Turbuhaler , or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age . The bronchodilator response did not differ between the two inhalational devices . The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used In the near future it is to be expected that many new inhaled corticosteroids or formulations of these drugs will be compared with older ones , to discover whether they are therapeutically equivalent or not . The statistical evaluation of these trials differs from the classic methods . When two averages are similar or differ only slightly , power is very low . The regulatory bodies dem and a power of at least 80 % . This problem was initially solved by using the so-called power approach . Research ers included enough volunteers to enable them to detect a predefined difference , considered to be without any clinical significance , with a power of 80 % . This approach , however , has been shown to be incorrect and has been replaced by the two one-sided tests procedure , where a new sample size equation is derived . Important elements of this new equation are the coefficient of variation of the parameter measured , the difference between the averages of the two groups and the equivalence limit ( the difference between the means still tolerable ) . This equation was used in the present study to estimate the number of volunteers needed in a parallel inhaled corticosteroids equivalence trial . The end points chosen were the changes in FEV1 and PC20 due to the corticosteroid effect . Calculations were performed by extracting data from published placebo-controlled trials , and defining a range of equivalence limits and differences between the group averages . It was shown that a huge number of volunteers ( 500–1000 ) will be needed , as a result of the small corticosteroid effect and the high variance . In the case of inhaled corticosteroids , the equivalence limit is not known and needs defining to avoid discussion s on the outcome . Due to the high number of patients who need to be included , the trial will most probably be multicentre and take place in several countries . Such a trial will suffer from several sources of bias . For instance , the definition of asthma can differ from country to country and from research er to research er , result ing in non-comparable groups of patients . The many sources of bias will make the outcome difficult to interpret . Therefore alternative methods to establish therapeutic equivalence are proposed and discussed Two hundred and fifty eight adult patients with bronchial asthma participated in an open , parallel group study of 8 wks duration . During a 2 wk run-in period the beta 2-agonist terbutaline ( 0.5 mg q.i.d ) was delivered via a pressurized freon aerosol , Bricanyl metered dose inhaler ( MDI ) . During the following 6 wks , one third of the patients continued with MDI and two thirds with the same dose of terbutaline in the form of dry powder , Bricanyl Turbuhaler . There were no statistically significant differences in the increases in peak expiratory flow rate ( PEFR ) after inhalation between the two treatment groups . The asthma symptom scores decreased in the Turbuhaler group during the study but remained the same in the MDI group . No difference in use of extra trial medication during the day was found . During the night , the difference was statistically significant in favour of Turbuhaler ( p less than 0.05 ) . Turbuhaler was well accepted and easy to use . As compared with the MDI used during run-in , 50 % of the patients in the Turbuhaler group preferred to use  Turbuhaler and 26 % MDI , whilst 24 % had no preference . In conclusion , Turbuhaler was at least as effective as MDI during the whole Turbuhaler life-span ( 6 wks ) Metered-dose inhalers ( MDIs ) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon ( CFC ) propellants . The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry . The mean + /- SD relative lung bioavailability of albuterol  to the lung following inhalation of 400 micrograms of albuterol from an MDI , the Rotahaler and Diskhaler in 10 well-trained volunteers , was 2.83 ( 0.78 ) , 1.72 ( 0.99 ) , and 2.64 (1.23)% , respectively , expressed as a percentage of the nominal dose . The delivery of albuterol to the lungs from the MDI and Diskhaler was similar . In nine asthmatic subjects , the relative lung bioavailability of albuterol  following inhalation with the MDI and Diskhaler was 1.19 ( 0.79 ) and 2.38 (1.46)% , respectively , expressed as a percentage of the nominal dose . There was no difference in reversibility 30 min after administration of the dose by the two methods . Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique , which was absent in the asthmatic subjects . The Diskhaler does not rely on coordination during inhalation and therefore is easier to use Forty‐three children from 3‐16 years of age suffering from moderate bronchial asthma completed a double‐blind cross‐over study on the clinical effect of inhaled salbutamol ( Ventoline ® ) powder ( 0.2 mg/dosis ) compared with spray ( 0.1 mg/dosis ) over two 4‐week periods . Both administrations gave significant improvement in air flow meter ( AFM ) results . There was no significant difference between the periods on active powder or spray regarding daily symptom scores , adjuvant medication or AFM values . The powder caused cough in four children but in 12 of 28 children it was considered as easy or easier to accept as the spray ; nine of these 12 children were younger than 10 years of age . It is concluded that salbutamol inhaled as a powder is a useful alternative when using a spray is difficult or unwanted Nineteen patients with asthma completed an open , r and omized , crossover study in which 0.5 mg terbutaline sulphate was administered either via Turbuhaler or via the metered dose inhaler ( MDI ) for 2-week periods . The clinical effect of the two treatment forms was comparable ; both provided adequate bronchodilator therapy . Patients also considered  Turbuhaler and MDI equally effective , with a small preference for the MDI . Turbuhaler seems to be a valuable alternative to bronchodilator MDI therapy BACKGROUND : beta Agonists have been shown to increase mucociliary clearance in some studies but not all . Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases . METHODS : The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second ( FEV1 ) was assessed in 10 patients with asthma and 10 healthy subjects .  Terbutaline ( 1 mg ) was administered through a metered dose inhaler with a spacer ( Nebuhaler ) or a dry powder inhaler ( Turbuhaler ) , or both treatments were given , in a four way double blind , double dummy trial . Mucociliary clearance was measured by bronchoscintigraphy . RESULTS : Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32 % after terbutaline was given by metered dose inhaler and 55 % after a combined dose of 2 mg from both inhalers ( 1 mg from each ) compared with placebo but by only 9 % after 1 mg of terbutaline was given by a dry powder inhaler . In the healthy subjects  mucociliary clearance increased by 51 % when terbutaline was given by a dry powder inhaler , by 66 % when given by a metered dose inhaler , and by 66 % when given by both inhalers combined . The effect of terbutaline on FEV1 was the same with each of the inhalers . CONCLUSION : Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects . The reason for the difference in asthmatic subjects is unclear , but may be associated with differences in the deposition of terbutaline There is some concern over the environmental consequences of chlorofluorocarbons ( CFCs ) used in pressurized metered-dose inhalers ( p-MDIs ) . Turbuhaler was design ed to deliver a drug as a dry powder without administering additives directly to the airways . The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler .  Ten symptomatic , asthmatic patients , with highly reactive airways ( provocative concentration of methacholine producing a 20 % fall in forced expiratory volume in one second ( PC20 ) < 0.2 mg.ml-1 ) , inhaled , on separate days , 0.25 mg terbutaline via p-MDI or Turbuhaler . Changes in airway calibre were followed as specific airways conductance ( sGaw ) . On a third day , patients inhaled from a placebo p-MDI containing all constituents except terbutaline . The study was conducted in a single-blind fashion and in r and om order . There were no significant differences in baseline sGaw on any of the study days . Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min , reaching a mean maximum + /- SD of 17 + /- 8 % at 10 s and then returning to baseline value after 20 s , followed by a progressive increase in sGaw to a maximum of 39 + /- 45 % above baseline at 45 min . In contrast , inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction ( fall in sGaw , 3 + /- 16 % ) at 10 s and achieved a greater increase in sGaw , reaching 63 + /- 51 % at 45 min , although just failing to reach statistical significance compared to terbutaline p-MDI inhalation . ( ABSTRACT TRUNCATED AT 250 WORDS Twelve adult asthmatic patients participated in an open , r and omized , cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler ( Turbuhaler ) or via a pressurized inhaler . Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects . Both treatments produced a significant increase in pulmonary function measurements , forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) . No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments . Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of  exercise-induced bronchospasm in children . Forty-six patients aged 4 - 11 years with asthma and exercise-induced bronchospasm were enrolled in this r and omized , double-blind , single-dose , three-way crossover study comparing albuterol aerosol , albuterol powder , and placebo . Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits . Prevention of exercise-induced 
    Output:
    