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: Theophylline is commonly prescribed for chronic obstructive pulmonary disease ( COPD ) , although controlled studies do not exist to support this use . We administered theophylline and placebo orally to 40 ambulatory COPD patients in a double-blind , crossover manner . Pulmonary function tests were conducted before and after isoproterenol nebulization on the final day of each four-week study period . Theophylline therapy produced small , but significant , increases over placebo in mean values . However , only the forced expiratory volume in 1 s was " improved , " according to published criteria . There were no significant differences in subjective effects between treatment periods . Six patients were identified as " responders " ; responder status could be predicted on the basis of improvement in flow rates after isoproterenol nebulization . Theophylline therapy is not beneficial to most COPD patients , and potential responders should be given carefully monitored therapeutic trials rather than arbitrarily being given maintenance therapy We studied ventilatory , hemodynamic , and subjective responses to different plasma theophylline concentrations in 10 patients with " irreversible " airflow obstruction . Subjects received theophylline at doses that produced low ( 9.0 to 12.5 micrograms/mL ) and high ( 17 to 22 micrograms/mL ) peak plasma concentrations ; subjects also received placebo . A significant ( P less than 0.05 ) dose-related difference in pulmonary function was observed between each treatment . The mean maximal increase in forced expiratory volume at 1 second over placebo was 21.3 % for high-dose theophylline and 6.0 % for low dose . Both treatments were well tolerated with respect to hemodynamic changes and other adverse effects . Despite improved findings in pulmonary function tests patients were unable to distinguish either treatment from placebo in terms of improvement in breathlessness Summary In order to measure the plasma levels of interleukin-4 ( IL-4 ) . cyclic adenosine monophosphate ( cAMP ) and cyclic guanosine monophosphate ( cGMP ) in patients with chronic obstructive pulmonary disease ( COPD ) and observe the effects of oral theophylline on them , we divided 28 COPD patients into COPD experimental group and COPD control group .  Plasma levels of IL-4 , cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline ( Protheo , 400 mg , qd ) or placebo .  Plasma levels of IL-4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P < 0 . 05 ) , while cAMP and cAMP/cGMP were significantly lower than those in controls ( P < 0 . 01 ) . Plasma level of IL-4 was inversely correlated with forced expiratory volume at the first second ( FEV1 ) and with maximum expiratory flow rate at 50 % of forced vital capacity ( V50 ) ( bothr= −0.46,P < 0.05 ) while it was directly correlated with the scores of the clinical manifestations ( r=0.57,P < 0.05 ) in COPD patients . Two weeks after treatment with theophylline , IL-4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/ cGMP increased significantly ( P < 0 . 05 ) . The change of IL-4 was inversely correlated with the changes of FEV1 , and V50(r=−0.53 and -0.54 , respectively , P < 0 . 05 ) . Two weeks after placebo treatment , the COPD control group did not show such changes . We are led to conclude that IL-4 might play a role in the pathogenesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline ’s therapeutic efrects of attenuating air-flow limitation may partially depend on its anti-inflammatory effects on the airways which , in turn , is dependent on its inhibitory effects on some inflammatory mediators such as IL-4 The bronchodilator , respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease ( COLD ) . The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day , serum theophylline concentration was negligible . Initial pulmonary function tests were performed . Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day . Ten of the patients were given placebo . On day 7 , serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated . Bronchodilator effect was assessed by spirometry , flow-volume loops and measuring airway resistance ( Raw ) . Respiratory muscle function was assessed by measuring maximal inspiratory ( PImax ) and expiratory pressures ( PEmax ) and the effect on respiratory center was evaluated by minute ventilation , mouth occlusion pressure index and inspiratory duty ratio . Forced vital capacity in one second ( p less than 0.001 ) , maximal mid expiratory flow rate ( p less than 0.05 ) , maximal expiratory flow at 50 percent of vital capacity ( p less than 0.001 ) , maximal inspiratory pressure ( p less than 0.01 ) increased , while airway resistance ( p less than 0.05 ) decreased significantly . Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy . In placebo group , there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures . It is therefore , concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease , increases respiratory muscle function , but in therapeutic doses has no effect on respiratory center This study evaluated the effectiveness of oral bronchodilator therapy using theophylline in patients with nonreversible chronic obstructive pulmonary dis ease . Twelve chronic obstructive pulmonary disease patients were entered into a doubleblind crossover study using either active drug theophylline in 200 mg capsules ( Elixophyllin ) or placebo for 3 months , followed by 3 months of the alternate capsule . At baseline and monthly visits , data were recorded , including history , physical examination , and pulmonary function testing . Clinical ly , 7 of 11 patients responded favorably to theophylline , 3 were unchanged , and 1 improved on placebo . Comparison of each sign and symptom individually revealed no statistically significant differences . Pulmonary function ( FEV1 and FVC ) showed slight deterioration with placebo , but not with active drug therapy . These findings suggest that nonasthmatic patients may improve clinical ly during theophylline therapy whereas their pulmonary function may deteriorate during placebo therapy STUDY OBJECTIVE To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol , 400 micrograms , and ipratropium bromide , 80 micrograms , four times daily administered with a metered-dose inhaler . DESIGN Twenty-four male patients with stable COPD ( FEV1 , 0.96 + /- 0.43 L ; 36.8 + /- 17.0 percent predicted [ % pred ] ) completed a r and omized , double-blind , placebo-controlled crossover trial with oral theophylline for 4 weeks . MEASUREMENTS AND RESULTS The average serum theophylline level was 15.0 + /- 5.5 micrograms/mL during treatment . On the whole , without inhalation of bronchodilators , FEV1 was 0.93 + /- 0.42 L during the placebo period and 1.00 + /- 0.43 L ( significantly different from placebo ; p < 0.01 ) during the theophylline period . At 15 and 60 min after inhalation of salbutamol , 400 micrograms , and ipratropium , 80 micrograms , the FEV1 with placebo was 1.12 + /- 0.43 L and 1.14 + /- 0.46 L , respectively , and the FEV1 with theophylline was 1.18 + /- 0.45 L ( p < 0.01 ) and 1.20 + /- 0.47 L ( p < 0.01 ) , respectively . Daily peak expiratory flow rate also improved . Daily symptom scores were not significantly different between theophylline and placebo periods . Nevertheless , eight patients reported a subjective benefit during the theophylline administration period , and they were thus considered subjective responders . While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders ( change in FEV1 between theophylline and placebo treatment 15 min after inhalation , 3.1 % pred ; 60 min , 3.5 % pred ) , postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders ( 15 min , 1.7 % pred ; 60 min , 1.6 % pred ) . CONCLUSIONS On the whole , theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD . However , one third of patients with COPD may respond subjectively to theophylline . The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders OBJECTIVE --To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline .  DESIGN -- Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data . This was followed by r and om assignment to four consecutive two month treatment periods -- placebo and low , medium , and high dose , as assessed by serum concentrations of theophylline .  Respiratory function and exercise performance was assessed at the end of each two month period . SETTING --Chest unit in district hospital . PATIENTS --Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited ; 33 aged 53 - 73 years completed the study . INTERVENTIONS --Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted , when 400 mg was given . Targets for the steady state serum theophylline concentrations were 5 - 10 mg/l in the low dose period , 10 - 15 mg/l in the medium dose , and 15 - 20 mg/l in the high dose period . ENDPOINTS -- Respiratory function as measured by forced expiratory volume in one second , forced vital capacity , peak expiratory flow rate , slow vital capacity , and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived . Exercise performance assessed by six minute walking test and diary cards using visual analogue scale . MEASUREMENTS AND MAIN RESULTS --The forced expiratory volume in one second , forced vital capacity , and peak expiratory flow rate changed only slightly ( about 13 % ) over the range of doses . There was a linear dose dependent fall of trapped gas volume from 1.84 l ( SE 0.157 ) to 1.42 l ( 0.152 ) , 1.05 l ( 0.128 ) , and 0.67 l ( 0.102 ) during the placebo and low , medium , and high dose treatment periods . Mean walking distance increased by up to 55.6 m ( 20 % ) . There was a modest improvement in dyspnoea as the dose of theophylline was increased . Side effects were mostly minor but they became more frequent as the dose was increased . CONCLUSION --The fall in trapped gas volume may reflect an improvement in peripheral ventilation ( associated with treatment with theophylline ) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease ( COPD ) , but its relevance to exercise capacity and symptoms is uncertain . Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients . We studied 32 patients with stable COPD , mean age 65 yrs , in a double-blind , placebo-controlled , cross-over trial of the inhaled anticholinergic drug , oxitropium bromide . From the within and between day placebo spirometry , we derived the spontaneous variation in forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) of this population ( FEV1 140 ml ; FVC 390 ml ) and considered responses beyond this to be significant . Oxitropium bromide increased baseline FEV1 from 0.70 ( 0.28 ) l ( mean ( SD ) ) to 0.88 ( 0.36 ) l. The 6 min walking distance increased by 7 % compared with placebo , whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug . Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC , indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients BACKGROUND --Theophylline is a well known bronchodilator which has been used for more than 50 years in the treatment of ob 
    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: Theophylline is commonly prescribed for chronic obstructive pulmonary disease ( COPD ) , although controlled studies do not exist to support this use . We administered theophylline and placebo orally to 40 ambulatory COPD patients in a double-blind , crossover manner . Pulmonary function tests were conducted before and after isoproterenol nebulization on the final day of each four-week study period . Theophylline therapy produced small , but significant , increases over placebo in mean values . However , only the forced expiratory volume in 1 s was " improved , " according to published criteria . There were no significant differences in subjective effects between treatment periods . Six patients were identified as " responders " ; responder status could be predicted on the basis of improvement in flow rates after isoproterenol nebulization . Theophylline therapy is not beneficial to most COPD patients , and potential responders should be given carefully monitored therapeutic trials rather than arbitrarily being given maintenance therapy We studied ventilatory , hemodynamic , and subjective responses to different plasma theophylline concentrations in 10 patients with " irreversible " airflow obstruction . Subjects received theophylline at doses that produced low ( 9.0 to 12.5 micrograms/mL ) and high ( 17 to 22 micrograms/mL ) peak plasma concentrations ; subjects also received placebo . A significant ( P less than 0.05 ) dose-related difference in pulmonary function was observed between each treatment . The mean maximal increase in forced expiratory volume at 1 second over placebo was 21.3 % for high-dose theophylline and 6.0 % for low dose . Both treatments were well tolerated with respect to hemodynamic changes and other adverse effects . Despite improved findings in pulmonary function tests patients were unable to distinguish either treatment from placebo in terms of improvement in breathlessness Summary In order to measure the plasma levels of interleukin-4 ( IL-4 ) . cyclic adenosine monophosphate ( cAMP ) and cyclic guanosine monophosphate ( cGMP ) in patients with chronic obstructive pulmonary disease ( COPD ) and observe the effects of oral theophylline on them , we divided 28 COPD patients into COPD experimental group and COPD control group .  Plasma levels of IL-4 , cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline ( Protheo , 400 mg , qd ) or placebo .  Plasma levels of IL-4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P < 0 . 05 ) , while cAMP and cAMP/cGMP were significantly lower than those in controls ( P < 0 . 01 ) . Plasma level of IL-4 was inversely correlated with forced expiratory volume at the first second ( FEV1 ) and with maximum expiratory flow rate at 50 % of forced vital capacity ( V50 ) ( bothr= −0.46,P < 0.05 ) while it was directly correlated with the scores of the clinical manifestations ( r=0.57,P < 0.05 ) in COPD patients . Two weeks after treatment with theophylline , IL-4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/ cGMP increased significantly ( P < 0 . 05 ) . The change of IL-4 was inversely correlated with the changes of FEV1 , and V50(r=−0.53 and -0.54 , respectively , P < 0 . 05 ) . Two weeks after placebo treatment , the COPD control group did not show such changes . We are led to conclude that IL-4 might play a role in the pathogenesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline ’s therapeutic efrects of attenuating air-flow limitation may partially depend on its anti-inflammatory effects on the airways which , in turn , is dependent on its inhibitory effects on some inflammatory mediators such as IL-4 The bronchodilator , respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease ( COLD ) . The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day , serum theophylline concentration was negligible . Initial pulmonary function tests were performed . Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day . Ten of the patients were given placebo . On day 7 , serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated . Bronchodilator effect was assessed by spirometry , flow-volume loops and measuring airway resistance ( Raw ) . Respiratory muscle function was assessed by measuring maximal inspiratory ( PImax ) and expiratory pressures ( PEmax ) and the effect on respiratory center was evaluated by minute ventilation , mouth occlusion pressure index and inspiratory duty ratio . Forced vital capacity in one second ( p less than 0.001 ) , maximal mid expiratory flow rate ( p less than 0.05 ) , maximal expiratory flow at 50 percent of vital capacity ( p less than 0.001 ) , maximal inspiratory pressure ( p less than 0.01 ) increased , while airway resistance ( p less than 0.05 ) decreased significantly . Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy . In placebo group , there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures . It is therefore , concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease , increases respiratory muscle function , but in therapeutic doses has no effect on respiratory center This study evaluated the effectiveness of oral bronchodilator therapy using theophylline in patients with nonreversible chronic obstructive pulmonary dis ease . Twelve chronic obstructive pulmonary disease patients were entered into a doubleblind crossover study using either active drug theophylline in 200 mg capsules ( Elixophyllin ) or placebo for 3 months , followed by 3 months of the alternate capsule . At baseline and monthly visits , data were recorded , including history , physical examination , and pulmonary function testing . Clinical ly , 7 of 11 patients responded favorably to theophylline , 3 were unchanged , and 1 improved on placebo . Comparison of each sign and symptom individually revealed no statistically significant differences . Pulmonary function ( FEV1 and FVC ) showed slight deterioration with placebo , but not with active drug therapy . These findings suggest that nonasthmatic patients may improve clinical ly during theophylline therapy whereas their pulmonary function may deteriorate during placebo therapy STUDY OBJECTIVE To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol , 400 micrograms , and ipratropium bromide , 80 micrograms , four times daily administered with a metered-dose inhaler . DESIGN Twenty-four male patients with stable COPD ( FEV1 , 0.96 + /- 0.43 L ; 36.8 + /- 17.0 percent predicted [ % pred ] ) completed a r and omized , double-blind , placebo-controlled crossover trial with oral theophylline for 4 weeks . MEASUREMENTS AND RESULTS The average serum theophylline level was 15.0 + /- 5.5 micrograms/mL during treatment . On the whole , without inhalation of bronchodilators , FEV1 was 0.93 + /- 0.42 L during the placebo period and 1.00 + /- 0.43 L ( significantly different from placebo ; p < 0.01 ) during the theophylline period . At 15 and 60 min after inhalation of salbutamol , 400 micrograms , and ipratropium , 80 micrograms , the FEV1 with placebo was 1.12 + /- 0.43 L and 1.14 + /- 0.46 L , respectively , and the FEV1 with theophylline was 1.18 + /- 0.45 L ( p < 0.01 ) and 1.20 + /- 0.47 L ( p < 0.01 ) , respectively . Daily peak expiratory flow rate also improved . Daily symptom scores were not significantly different between theophylline and placebo periods . Nevertheless , eight patients reported a subjective benefit during the theophylline administration period , and they were thus considered subjective responders . While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders ( change in FEV1 between theophylline and placebo treatment 15 min after inhalation , 3.1 % pred ; 60 min , 3.5 % pred ) , postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders ( 15 min , 1.7 % pred ; 60 min , 1.6 % pred ) . CONCLUSIONS On the whole , theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD . However , one third of patients with COPD may respond subjectively to theophylline . The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders OBJECTIVE --To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline .  DESIGN -- Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data . This was followed by r and om assignment to four consecutive two month treatment periods -- placebo and low , medium , and high dose , as assessed by serum concentrations of theophylline .  Respiratory function and exercise performance was assessed at the end of each two month period . SETTING --Chest unit in district hospital . PATIENTS --Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited ; 33 aged 53 - 73 years completed the study . INTERVENTIONS --Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted , when 400 mg was given . Targets for the steady state serum theophylline concentrations were 5 - 10 mg/l in the low dose period , 10 - 15 mg/l in the medium dose , and 15 - 20 mg/l in the high dose period . ENDPOINTS -- Respiratory function as measured by forced expiratory volume in one second , forced vital capacity , peak expiratory flow rate , slow vital capacity , and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived . Exercise performance assessed by six minute walking test and diary cards using visual analogue scale . MEASUREMENTS AND MAIN RESULTS --The forced expiratory volume in one second , forced vital capacity , and peak expiratory flow rate changed only slightly ( about 13 % ) over the range of doses . There was a linear dose dependent fall of trapped gas volume from 1.84 l ( SE 0.157 ) to 1.42 l ( 0.152 ) , 1.05 l ( 0.128 ) , and 0.67 l ( 0.102 ) during the placebo and low , medium , and high dose treatment periods . Mean walking distance increased by up to 55.6 m ( 20 % ) . There was a modest improvement in dyspnoea as the dose of theophylline was increased . Side effects were mostly minor but they became more frequent as the dose was increased . CONCLUSION --The fall in trapped gas volume may reflect an improvement in peripheral ventilation ( associated with treatment with theophylline ) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease ( COPD ) , but its relevance to exercise capacity and symptoms is uncertain . Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients . We studied 32 patients with stable COPD , mean age 65 yrs , in a double-blind , placebo-controlled , cross-over trial of the inhaled anticholinergic drug , oxitropium bromide . From the within and between day placebo spirometry , we derived the spontaneous variation in forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) of this population ( FEV1 140 ml ; FVC 390 ml ) and considered responses beyond this to be significant . Oxitropium bromide increased baseline FEV1 from 0.70 ( 0.28 ) l ( mean ( SD ) ) to 0.88 ( 0.36 ) l. The 6 min walking distance increased by 7 % compared with placebo , whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug . Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC , indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients BACKGROUND --Theophylline is a well known bronchodilator which has been used for more than 50 years in the treatment of ob 
    Output:
    