***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: Small airways disease plays an important role in the pathogenesis of asthma , but assessment of small airways impairment is not easy in everyday clinical practice . The small airways can be examined by several invasive and noninvasive methods , most of which can at present be used only in the experimental setting . Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways . Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation , ie , on dysfunction in both the central and distal airways in asthmatics , and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes , including nocturnal asthma , severe steroid-dependent or difficult-to-treat asthma , asthma complicated by smoking , elderly asthmatic patients and /or patients with fixed airflow obstruction , and asthmatic children . The relevant r and omized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints , but there are certain clinical ly important endpoints for which the extrafine formulations show additional benefits Purpose : Results of r and omized controlled trials may not predict effectiveness of inhaled corticosteroids ( ICS ) in real-world clinical practice , where inhaler technique and device characteristics can influence effectiveness . We compared asthma outcomes for ICS delivered via three different inhaler devices : pressurized metered-dose inhaler ( pMDI ) , breath-actuated MDI ( BAI ) , and dry powder inhaler ( DPI ) . Patients and methods : This retrospective data base study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS ( initiation population ) by pMDI ( n = 39,746 ) , BAI ( n = 9809 ) , or DPI ( n = 6792 ) , or their first ICS dose increase ( step-up population ) by pMDI ( n = 6245 ) , BAI ( n = 1388 ) , or DPI ( n = 1536 ) . Co- primary outcome measures were composite proxy measures of asthma control ( no hospital attendance for asthma , oral corticosteroids , or antibiotics for lower respiratory infection ) and severe exacerbations ( unscheduled hospital admission , emergency room attendance , or oral corticosteroids ) . Outcomes were adjusted for potential confounding factors identified during a baseline year . Results : In the initiation population , adjusted odds ratios ( 95 % confidence intervals [ CI ] ) for asthma control , as compared with pMDIs , were significantly better for BAIs ( 1.08 [ 1.02–1.14 ] ) and DPIs ( 1.13 [ 1.06–1.21 ] ) , while adjusted exacerbation rate ratios ( 95 % CI ) were 1.00 ( 0.93–1.08 ) and 0.88 ( 0.81–0.95 ) , respectively . In the step-up population , adjusted odds of asthma control were 1.21 ( 1.05–1.39 ) for BAIs and 1.13 ( 0.99–1.29 ) for DPIs ; adjusted exacerbation rate ratios were 0.83 ( 0.71–0.98 ) for BAIs and 0.85 ( 0.74–0.98 ) for DPIs , compared with pMDIs . Conclusion : Inhaler device selection may have a bearing on clinical outcomes . Differences in real-world effectiveness among these devices require closer evaluation in well- design ed prospect i ve trials Chronic bronchitis is associated with airways obstruction and inflammation . In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction , subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage ( BAL ) before and after receiving 6 wk of therapy ( five puffs four times a day ) with either aerosolized beclomethasone ( n = 20 ) or placebo ( n = 10 ) in a double-blinded , r and omized fashion . All subjects received aerosolized albuterol before each use of the study medications . Before BAL , the airways were visually assessed for the appearance of inflammation and assigned a score , the bronchitis index . BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a " bronchial sample . " The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis . The fluid was prepared for cytologic examination by cytocentrifugation . Albumin ( as a measure of epithelium permeability ) and lactoferrin and lysozyme ( as measures of serous cell activity ) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay , and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution . After treatment , the beclomethasone group , but not the placebo group , showed improvement in FVC ( p = 0.02 ) , FEV1 ( p = 0.002 ) , and 25 to 75 % forced expiratory flow ( p = 0.006 ) . Associated with the improvement in spirometry , the bronchitis index fell ( 13.5 + /- 1.0 versus 10.75 + /- 1.1 , p = 0.02 ) in the beclomethasone-treated group , but not the placebo-treated group . ( ABSTRACT TRUNCATED AT 250 WORDS Bone mass and biochemical bone markers were prospect ively studied in 33 patients with chronic obstructive pulmonary disease treated for 1 year with inhaled beclomethasone 200 micrograms/q.i.d . ( group A , 8 men and 4 women ) , inhaled budesonide 200 micrograms/q.i.d . ( group B , 6 men and 5 women ) ,  or not requiring steroids  ( group C , 6 men and 4 women ) . Both inhaled corticosteroids decreased serum concentrations of the osteoblastic markers , osteocalcin and carboxy-terminal propeptide of type I collagen ( PICP ) . The osteoclastic marker cross-linked carboxy-terminal telopeptide of type I collagen ( ICTP ) increased significantly more in patients on beclomethasone than in those on budesonide . The decrease in bone mineral density was more pronounced in patients treated with beclomethasone ( 1.1 % in the spine 1.7 % in the hip P < 0.05 ) compared to those treated with budesonide ( 0.6 % in both spine and hip ) or in the control group . Inhaled corticosteroids affect biochemical bone markers and bone mineral density , but there is a different effect for the two corticosteroids evaluated in the present study One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a r and omised , double blind , placebo controlled , crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day , both given for two weeks . One hundred and seven patients completed the study . Response was assessed as change in FEV1 and FVC measured on the last treatment day , and as change in mean peak expiratory flow ( PEF ) over the final seven days of treatment from home PEF recordings performed five times daily . A full response to treatment was defined as an increase in FEV or FVC , or an increase in mean daily PEF over the final seven days of treatment , of at least 20 % from baseline values . An improvement in one measurement of at least 15 % , or of 10 % in any two measurements , was defined as a partial treatment response . Response to placebo showed a significant order effect , suggesting a carry over effect of active treatment of at least three weeks . Response to active treatment was therefore related to initial baseline values , and compared with placebo by considering responses in the first treatment phase only . A full response to oral prednisolone ( 16/38 ) was significantly more common than to placebo ( 3/35 ) . The number of full responses to inhaled beclomethasone ( 8/34 ) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase , though full and partial responses to inhaled beclomethasone ( 12/34 ) were significantly more common than those to placebo ( 4/35 ) . When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment , a response to prednisolone ( 39 ) occurring more frequently than to inhaled beclomethasone ( 26 ) . Only 21 of the 44 responders showed a response to both forms of treatment . Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day , but better than placebo , in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction . It was , however , an effective alternative in over half of those showing a response to prednisolone BACKGROUND --High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma . Although effective , they may cause systemic side effects .  Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses . METHODS --Fluticasone propionate , 1.5 mg per day , was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma ; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate .  The study was multicentre , double blind and of a parallel design . For the first three months patients attended the clinic every four weeks and completed daily diary cards . For the next nine months they were only seen at three monthly intervals in the clinic . RESULTS --During the first three months diary card peak expiratory flow ( PEF ) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate ( difference in morning PEF 15 l/min ( 95 % CI 6 to 25 ) ) , and these differences were apparent at the end of the first week . The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8 % compared with those receiving beclomethasone dipropionate . No significant differences between the two groups were observed in morning plasma cortisol levels , urinary free cortisol levels , or response to synthetic ACTH stimulation . In addition , both the rates of withdrawal and of adverse events were low , and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate . CONCLUSIONS --This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate , with no increase in systemic or other side effects BACKGROUND : In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms . The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate ( FP ) and budesonide ( B ) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients . METHODS : Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second ( FEV1 ) 89.0 % predicted and mid forced expiratory flow ( FEF25 - 75 ) 58.9 % predicted , on 400 micrograms/day or less of inhaled corticosteroid , were studied in a double blind , placebo controlled , crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms , 500 micrograms , and 1000 micrograms twice daily . Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing . Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours , 10 hours after the eighth dose . RESULTS : The plasma cortisol levels ( nmol/ l ) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels : F500 333.8 , B500 415.2 ( 95 % CI 28.9 to 134.0 ) ; F1000 308.3 , B1000 380.3 ( 95 % CI 10.5 to 133.5 ) ; F2000 207.3 , B2000 318.5 ( 95 % CI 5.8 to 216.7 ) ; placebo 399.9 . Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio 
    Output:
    
Participants receiving  BDP/LABA  also had a statistically significant increased rate of exacerbations leading to hospitalisation ( risk ratio ( RR ) 1.84 , 95 % CI 1.17 to 2.90 , P = 0.008 ) ( moderate quality ) , although this finding is debatable as this study 's post hoc analysis showed no statistically significant difference when accounting for country-specific differences in hospitalisation policies .