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: Abstract Study objective : This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers , both given via their respective pressurised metered dose inhaler ( pMDI ) devices at high doses within the manufacturers recommended dose range . Design : We used a single ( investigator ) blind , r and omised , crossover design comparing a total daily dose of 1.625 mg fluticasone propionate delivered via a pMDI , 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer , or placebo pMDI ; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period . Each drug treatment was separated by a 1-week washout . Patients : Twelve normal subjects mean age 27.5 years were studied . Measurements : Blood sample s were taken for 0800 hours plasma cortisol , i.e. 10 h following the second dose . Ten hour urine collection s ( 2200 hours until 0800 hours ) were taken for urinary cortisol and creatinine excretion . Results : For the 0800 hours plasma cortisol ( geometric mean , nmol · l−1 ) compared with placebo ( 353 ) fluticasone propionate ( 138 ) produced significant ( P<0.05 ) suppression ( 2.57-fold difference ) , whereas triamcinolone acetonide ( 263 ) did not ( 1.34-fold difference ) . Fluticasone propionate produced a 1.91-fold greater adrenal suppression than triamcinolone acetonide ( 95 % CI 1.10 to 3.33 ) . Individual subjects with abnormally low 0800 hours cortisol values < 150 nmol · l−1 ( < 5.4 μg/dl ) were n=4 for fluticasone propionate and n=0 for triamcinolone acetonide . Overnight urinary cortisol/creatinine ratio ( geometric mean , nmol/mmol ) did not show any difference between fluticasone propionate ( 1.48 ) and triamcinolone acetonide ( 1.60 ) , with both producing significant suppression versus placebo ( 4.01 ) : triamcinolone acetonide 2.50-fold difference ( 95 % CI 1.45–4.24 ) ; fluticasone propionate 2.71-fold difference ( 95 % CI 1.57–4.69 ) . Conclusion : Fluticasone propionate 1.625 mg/day ( pMDI ) produced an approximately two-fold greater adrenal suppression of 0800 hours plasma cortisol than triamcinolone acetonide 1.60 mg per day ( Oral Inhaler ) when given twice daily , and one third of subjects with fluticasone had abnormally low 0800 hours cortisol values < 150 nmol · l−1 ( < 5.4 μg · dl−1 ) . There were no differences between the drugs for urinary cortisol excretion . Further dose-ranging studies are required at steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose – response curve for both plasma and urinary cortisol suppression BACKGROUND Inhaled corticosteroids have dose related systemic effects determined by oral ( swallowed or oropharyngeal absorption ) and lung bioavailability . A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate . METHODS Sixteen healthy volunteers of mean age 29.3 years were studied using an open r and omised , placebo controlled , four way crossover design . Treatments were : ( a ) fluticasone metered dose inhaler ( pMDI ) 250 μg , 8 puffs ; ( b ) fluticasone pMDI 250 μg , 8 puffs + mouth rinsing/gargling ( water ) ; ( c ) fluticasone pMDI 250 μg , 8 puffs + mouth rinsing/gargling ( charcoal ) ; and ( d ) placebo pMDI , 8 puffs + mouth rinsing/gargling ( water ) . Overnight ( ONUC ) and early morning ( EMUC ) urinary cortisol/creatinine ratios and 8 am serum cortisol ( SC ) levels were measured . RESULTS Significant ( p<0.05 ) suppression of ONUC , EMUC , and SC occurred with each active treatment compared with placebo . The mean values ( 95 % CI for difference from placebo ) were : ( a ) ONUC ( nmol/mmol ) : fluticasone ( 2.8 , 95 % CI 3.6 to 7.9 ) , fluticasone + water ( 3.1 , 95 % CI 3.3 to 7.7 ) , fluticasone + charcoal ( 2.3 , 95 % CI 4.1 to 8.5 ) ; placebo ( 8.6 ) ; ( b ) EMUC ( nmol/mmol ) : fluticasone ( 5.6 , 95 % CI 8.4 to 24.5 ) , fluticasone + water ( 7.6 , 95 % CI 6.6 to 22.4 ) ; fluticasone + charcoal ( 5.6 , 95 % CI 8.7 to 24.5 ) ; placebo ( 22.1 ) . There were no significant differences between active treatments . The numbers of subjects with an overnight urinary cortisol of < 20 nmol/10 hours were 0 ( placebo ) , 11 ( fluticasone ) , 12 ( fluticasone + water ) , and 13 ( fluticasone + charcoal ) . CONCLUSIONS Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression . In view of almost complete hepatic first pass inactivation with fluticasone , there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral c and idiasis Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids  have reduced bone mass . This prospect i ve 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids . Patients ( n = 33 ) ( males aged 18 - 50 yrs , females aged 18 - 40 yrs ) on inhaled corticosteroids 1,000 - 2,000 microg x day(-1 ) , were r and omized in a double-blind fashion to either fluticasone propionate ( FP ) 1,000 microg x day(-1 ) or beclomethasone dipropionate ( BDP ) 2,000 microg x day(-1 ) . In parallel , three open control groups of the same age range were studied : asthmatics ( n = 8) receiving low dose inhaled corticosteroids ( < or = 400 microg x day(-1 ) ) ( group A ) ; chronic , severe asthmatics ( n = 8) receiving oral corticosteroids ( > or = 10 mg x day(-1 ) ( group B ) ; and healthy untreated volunteers ( n = 7 ) ( group C ) . Bone densitometry scans ( quantitative computed tomography ( QCT ) of spine ; dual X-ray absorptiometry of spine , femoral neck , and single photon absorptiometry of forearm ) were performed at baseline and after 6 , 12 and 24 months of treatment . Biochemical bone marker measurements ( serum osteocalcin , bone alkaline phosphatase , pro-collagen type 1 carboxy terminal propeptide , deoxypyridinoline and C-telopeptide of type 1 collagen ) were collected every 3 months . Fifteen FP ( mean age 36 yrs , six male ) and 9 BDP patients ( mean age 33 yrs , five male ) ; completed the study . At 0 months , mean bone mineral density ( BMD ) was lower in patients receiving inhaled corticosteroids ( both low dose and high dose ) than in normal volunteers . In the FP-treated group , mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline , whereas there was some decline in the BDP-treated group . The treatment difference between FP  and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months ( p = 0.006 ) and 24 months ( p = 0.004 ) . This study suggests that over 24 months , changes in bone density are minimal in patients on high-dose inhaled corticosteroids BACKGROUND Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma , prospect i ve , long-term , placebo-controlled trials characterizing their systemic safety with chronic use are lacking . OBJECTIVE This study was design ed to prospect ively evaluate the long-term safety of inhaled fluticasone propionate therapy . METHODS Fluticasone propionate powder , 500 microgram , or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a r and omized , double-blind , parallel-group study . Primary safety variables were measured at baseline and every 6 months thereafter . Although evaluation of efficacy was not an objective of this study , pulmonary function testing was performed at monthly intervals . RESULTS Two years of treatment with fluticasone propionate had no significant effects on the skeletal system . No clinical ly significant changes were observed in ophthalmic parameters ( glaucoma and posterior subcapsular cataracts ) . Mean change from baseline in lumbar spine ( L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate ( -0.006 + /- 0.008 g/cm2 ) and placebo ( -0.007 + /- 0.010 g/cm2 ) . Markers of bone formation ( serum osteocalcin ) and resorption ( urinary N-telopeptide ) did not differ significantly between treatment groups . The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal , with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations ( P = .021 ) and 8-hour plasma cortisol area under the curve values ( P = .020 ) at week 104 . Drug-related adverse events were primarily topical effects of inhaled corticosteroids . Pulmonary function improved significantly during 2 years of fluticasone propionate treatment . CONCLUSION Fluticasone propionate powder , 500 microgram twice daily for up to 2 years , was efficacious and well tolerated , with no clinical ly relevant effects on the hypothalamic-pituitary-adrenal axis , bone density , or ophthalmic parameters in adults with mild asthma Inhaled corticosteroids are the cornerstone of the modern therapy for asthma . In recent years , inhaled corticosteroids have been used in higher doses than previously . This has caused concern about possible osteoporotic side-effects . We studied bone mineral densities ( BMDs ) in 19 non-smoking women ( mean age 53 years , range 40 - 63 ) with newly diagnosed bronchial asthma and 19 voluntary healthy non-smoking women ( mean age 53 years , range 43 - 67 ) . In both groups , 13 subjects were postmenopausal . Patients started beclomethasone dipropionate from the spacer 500 micrograms twice daily as the sole corticosteroid therapy . BMDs were measured with dual-energy x-ray absorptiometry ( DEXA ) at the lumbar spine ( L2 - 4 ) and at the left proximal femur ( the neck , Ward 's triangle and the trochanteric region ) . The measurements were made at baseline and 6 and 12 months thereafter . No significant changes were observed in the measured BMDs in either study group . The results show that inhaled beclomethasone dipropionate therapy 1000 micrograms/day for one year does not affect BMD . Further studies are needed to assess the effects of inhaled corticosteroid on BMD during a longer treatment period In a controlled prospect i ve study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide  and compared these findings with those obtained from children not treated with corticosteroids . Two hundred and sixteen children were followed at 6 monthly intervals for 1 - 2 years without inhaled budesonide and then for 3 - 6 years on inhaled budesonide .  Sixty-two children treated with theophylline , beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3 - 7 years ( controls ) . During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms ( P < 0.01 ) and no signs of tachyphylaxis to the treatment were seen . Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma ( from 0.03 to 0.0 
    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: Abstract Study objective : This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers , both given via their respective pressurised metered dose inhaler ( pMDI ) devices at high doses within the manufacturers recommended dose range . Design : We used a single ( investigator ) blind , r and omised , crossover design comparing a total daily dose of 1.625 mg fluticasone propionate delivered via a pMDI , 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer , or placebo pMDI ; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period . Each drug treatment was separated by a 1-week washout . Patients : Twelve normal subjects mean age 27.5 years were studied . Measurements : Blood sample s were taken for 0800 hours plasma cortisol , i.e. 10 h following the second dose . Ten hour urine collection s ( 2200 hours until 0800 hours ) were taken for urinary cortisol and creatinine excretion . Results : For the 0800 hours plasma cortisol ( geometric mean , nmol · l−1 ) compared with placebo ( 353 ) fluticasone propionate ( 138 ) produced significant ( P<0.05 ) suppression ( 2.57-fold difference ) , whereas triamcinolone acetonide ( 263 ) did not ( 1.34-fold difference ) . Fluticasone propionate produced a 1.91-fold greater adrenal suppression than triamcinolone acetonide ( 95 % CI 1.10 to 3.33 ) . Individual subjects with abnormally low 0800 hours cortisol values < 150 nmol · l−1 ( < 5.4 μg/dl ) were n=4 for fluticasone propionate and n=0 for triamcinolone acetonide . Overnight urinary cortisol/creatinine ratio ( geometric mean , nmol/mmol ) did not show any difference between fluticasone propionate ( 1.48 ) and triamcinolone acetonide ( 1.60 ) , with both producing significant suppression versus placebo ( 4.01 ) : triamcinolone acetonide 2.50-fold difference ( 95 % CI 1.45–4.24 ) ; fluticasone propionate 2.71-fold difference ( 95 % CI 1.57–4.69 ) . Conclusion : Fluticasone propionate 1.625 mg/day ( pMDI ) produced an approximately two-fold greater adrenal suppression of 0800 hours plasma cortisol than triamcinolone acetonide 1.60 mg per day ( Oral Inhaler ) when given twice daily , and one third of subjects with fluticasone had abnormally low 0800 hours cortisol values < 150 nmol · l−1 ( < 5.4 μg · dl−1 ) . There were no differences between the drugs for urinary cortisol excretion . Further dose-ranging studies are required at steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose – response curve for both plasma and urinary cortisol suppression BACKGROUND Inhaled corticosteroids have dose related systemic effects determined by oral ( swallowed or oropharyngeal absorption ) and lung bioavailability . A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate . METHODS Sixteen healthy volunteers of mean age 29.3 years were studied using an open r and omised , placebo controlled , four way crossover design . Treatments were : ( a ) fluticasone metered dose inhaler ( pMDI ) 250 μg , 8 puffs ; ( b ) fluticasone pMDI 250 μg , 8 puffs + mouth rinsing/gargling ( water ) ; ( c ) fluticasone pMDI 250 μg , 8 puffs + mouth rinsing/gargling ( charcoal ) ; and ( d ) placebo pMDI , 8 puffs + mouth rinsing/gargling ( water ) . Overnight ( ONUC ) and early morning ( EMUC ) urinary cortisol/creatinine ratios and 8 am serum cortisol ( SC ) levels were measured . RESULTS Significant ( p<0.05 ) suppression of ONUC , EMUC , and SC occurred with each active treatment compared with placebo . The mean values ( 95 % CI for difference from placebo ) were : ( a ) ONUC ( nmol/mmol ) : fluticasone ( 2.8 , 95 % CI 3.6 to 7.9 ) , fluticasone + water ( 3.1 , 95 % CI 3.3 to 7.7 ) , fluticasone + charcoal ( 2.3 , 95 % CI 4.1 to 8.5 ) ; placebo ( 8.6 ) ; ( b ) EMUC ( nmol/mmol ) : fluticasone ( 5.6 , 95 % CI 8.4 to 24.5 ) , fluticasone + water ( 7.6 , 95 % CI 6.6 to 22.4 ) ; fluticasone + charcoal ( 5.6 , 95 % CI 8.7 to 24.5 ) ; placebo ( 22.1 ) . There were no significant differences between active treatments . The numbers of subjects with an overnight urinary cortisol of < 20 nmol/10 hours were 0 ( placebo ) , 11 ( fluticasone ) , 12 ( fluticasone + water ) , and 13 ( fluticasone + charcoal ) . CONCLUSIONS Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression . In view of almost complete hepatic first pass inactivation with fluticasone , there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral c and idiasis Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids  have reduced bone mass . This prospect i ve 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids . Patients ( n = 33 ) ( males aged 18 - 50 yrs , females aged 18 - 40 yrs ) on inhaled corticosteroids 1,000 - 2,000 microg x day(-1 ) , were r and omized in a double-blind fashion to either fluticasone propionate ( FP ) 1,000 microg x day(-1 ) or beclomethasone dipropionate ( BDP ) 2,000 microg x day(-1 ) . In parallel , three open control groups of the same age range were studied : asthmatics ( n = 8) receiving low dose inhaled corticosteroids ( < or = 400 microg x day(-1 ) ) ( group A ) ; chronic , severe asthmatics ( n = 8) receiving oral corticosteroids ( > or = 10 mg x day(-1 ) ( group B ) ; and healthy untreated volunteers ( n = 7 ) ( group C ) . Bone densitometry scans ( quantitative computed tomography ( QCT ) of spine ; dual X-ray absorptiometry of spine , femoral neck , and single photon absorptiometry of forearm ) were performed at baseline and after 6 , 12 and 24 months of treatment . Biochemical bone marker measurements ( serum osteocalcin , bone alkaline phosphatase , pro-collagen type 1 carboxy terminal propeptide , deoxypyridinoline and C-telopeptide of type 1 collagen ) were collected every 3 months . Fifteen FP ( mean age 36 yrs , six male ) and 9 BDP patients ( mean age 33 yrs , five male ) ; completed the study . At 0 months , mean bone mineral density ( BMD ) was lower in patients receiving inhaled corticosteroids ( both low dose and high dose ) than in normal volunteers . In the FP-treated group , mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline , whereas there was some decline in the BDP-treated group . The treatment difference between FP  and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months ( p = 0.006 ) and 24 months ( p = 0.004 ) . This study suggests that over 24 months , changes in bone density are minimal in patients on high-dose inhaled corticosteroids BACKGROUND Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma , prospect i ve , long-term , placebo-controlled trials characterizing their systemic safety with chronic use are lacking . OBJECTIVE This study was design ed to prospect ively evaluate the long-term safety of inhaled fluticasone propionate therapy . METHODS Fluticasone propionate powder , 500 microgram , or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a r and omized , double-blind , parallel-group study . Primary safety variables were measured at baseline and every 6 months thereafter . Although evaluation of efficacy was not an objective of this study , pulmonary function testing was performed at monthly intervals . RESULTS Two years of treatment with fluticasone propionate had no significant effects on the skeletal system . No clinical ly significant changes were observed in ophthalmic parameters ( glaucoma and posterior subcapsular cataracts ) . Mean change from baseline in lumbar spine ( L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate ( -0.006 + /- 0.008 g/cm2 ) and placebo ( -0.007 + /- 0.010 g/cm2 ) . Markers of bone formation ( serum osteocalcin ) and resorption ( urinary N-telopeptide ) did not differ significantly between treatment groups . The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal , with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations ( P = .021 ) and 8-hour plasma cortisol area under the curve values ( P = .020 ) at week 104 . Drug-related adverse events were primarily topical effects of inhaled corticosteroids . Pulmonary function improved significantly during 2 years of fluticasone propionate treatment . CONCLUSION Fluticasone propionate powder , 500 microgram twice daily for up to 2 years , was efficacious and well tolerated , with no clinical ly relevant effects on the hypothalamic-pituitary-adrenal axis , bone density , or ophthalmic parameters in adults with mild asthma Inhaled corticosteroids are the cornerstone of the modern therapy for asthma . In recent years , inhaled corticosteroids have been used in higher doses than previously . This has caused concern about possible osteoporotic side-effects . We studied bone mineral densities ( BMDs ) in 19 non-smoking women ( mean age 53 years , range 40 - 63 ) with newly diagnosed bronchial asthma and 19 voluntary healthy non-smoking women ( mean age 53 years , range 43 - 67 ) . In both groups , 13 subjects were postmenopausal . Patients started beclomethasone dipropionate from the spacer 500 micrograms twice daily as the sole corticosteroid therapy . BMDs were measured with dual-energy x-ray absorptiometry ( DEXA ) at the lumbar spine ( L2 - 4 ) and at the left proximal femur ( the neck , Ward 's triangle and the trochanteric region ) . The measurements were made at baseline and 6 and 12 months thereafter . No significant changes were observed in the measured BMDs in either study group . The results show that inhaled beclomethasone dipropionate therapy 1000 micrograms/day for one year does not affect BMD . Further studies are needed to assess the effects of inhaled corticosteroid on BMD during a longer treatment period In a controlled prospect i ve study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide  and compared these findings with those obtained from children not treated with corticosteroids . Two hundred and sixteen children were followed at 6 monthly intervals for 1 - 2 years without inhaled budesonide and then for 3 - 6 years on inhaled budesonide .  Sixty-two children treated with theophylline , beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3 - 7 years ( controls ) . During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms ( P < 0.01 ) and no signs of tachyphylaxis to the treatment were seen . Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma ( from 0.03 to 0.0 
    Output:
    