Value of serial peak expiratory flow measurements in assessing treatment response in chronic airflow limitation. The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease. Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate. Effects of long-term treatment with corticosteroids in COPD. Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response. A controlled trial of prednisone, in low dosage, in patients with chronic airways obstruction Effect of steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease. Steroid response in stable chronic obstructive pulmonary disease. A double-blind comparison of oral prednisolone 40 mg/day with inhaled beclomethasone dipropionate 1500 ug/day in patients with adult onset chronic obstructive airways disease. The effect of oral corticosteroids on bronchodilator responses in COPD. Oral corticosteroid trials in the management of stable chronic obstructive pulmonary disease. Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Response to oral corticosteroids in chronic airflow obstruction. Treatment of chronic obstructive pulmonary disease with corticosteroids. Comparison of daily vs alternate-day therapy. Time course of response to prednisolone in chronic airflow obstruction. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction. The use of the 12 minute walking test in assessing the effect of oral steroid therapy in patients with chronic airways obstruction. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease. Time course of response to oral and inhaled corticosteroids in non-asthmatic chronic airflow obstruction. Prediction of nonresponse to corticosteroids in stable chronic airflow limitation. EFFECTS OF PREDNISOLONE IN CHRONIC AIRFLOW LIMITATION Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease. A comparison of oral and inhaled steroids in patients with chronic airways obstruction: features determining response. Response to corticosteroids in chronic bronchitis. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. Corticosteroids in COPD. A clinical trial and reassessment of the literature. Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine. Comparison of Oral and Depot Intra‐muscular Steroids in Assessing Steroid‐Responsiveness in COPD Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial
A double blind , r and omised , placebo controlled , crossover trial of prednisolone ( 40 mg/day for 14 days ) was carried out in 33 patients with chronic airflow limitation ( mean age 62 years , mean FEV1 1.01 litres , mean FEV1/FVC ratio 44 % ) , to assess the value of serial peak expiratory flow ( PEF ) measurements , taken five times daily in evaluating treatment response by comparison with other objective measurements and with measurements of symptoms . The mean serial PEF after a one week run in period was 189 1 min-1 , during the second week of placebo 193 1 min-1 , and during the second week on prednisolone 231 1 min-1 . The difference in mean PEF values between placebo and prednisolone was significant ( p less than 0.01 ) . With regard to the response to steroids of the individual patients , 13 of the 33 had a detectable trend of improvement on visual inspection of serial PEF measurements during prednisolone treatment but only one during placebo administration . Of all the objective measurements made after the run in and after each treatment phase ( 12 minute walking distance , FEV1 , forced vital capacity ( FVC ) , serial PEF ) , the serial PEF chart provided the best discrimination between placebo and prednisolone treatment . There was no statistically significant association between steroid induced improvement in serial PEF measurements and in breathlessness , partly because of placebo improvements in symptoms in those who had no improvement in serial PEF values . This study indicates the importance of making objective measurements to identify a genuine steroid response rather than relying on symptomatic improvement alone . The best simple measurement to make is serial PEF during steroid trials . This is more sensitive in detecting a steroid response than are the 12 minute walking distance , FEV1 , or FVC , and is also less likely than these measurements to show spurious placebo responses BACKGROUND A significant minority of patients with COPD have favourable response to corticosteroid treatment . In addition , the benefit of corticosteroid treatment may be outweighed by the side-effects . Long-term administration of inhaled steroids is a safe means of treatment . However , only a few studies have addressed the role of inhaled steroids in patients with COPD , with conflicting results . METHODS Forty-four patients with stable COPD were defined as ' responders to bronchodilators ' ( increase in FEV1 > or = 20 % following administration of  beta 2-agonist ) ( group A ) , and 124 as ' non-responders to bronchodilators ' ( group B ) . All patients were r and omized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo , separated by 4 weeks when no medication was taken ; were r and omized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide , or 800 micrograms day-1 of inhaled budesonide plus placebo ; and were r and omized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo . All stages were performed in a double-blind cross-over design . RESULTS Following administration of 800 micrograms day-1 of inhaled budesonide , there was an increase in the mean FEV1 from 1.40 + /- 0.20 to 1.92 + /- 0.22 L ( P < 0.001 ) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment . The mean FEV1 did not change during the placebo period , or in group B in either treatments . CONCLUSIONS Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD , and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation . There was no additional benefit in using a higher dose of inhaled budesonide or prednisone Background : A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease ( COPD ) , with the subsequent “ response ” determining the treatment selected . This approach assumes that patients can be reliably divided into responder and non-responder groups . We have assessed whether such a separation is statistically valid , which factors influence the change in forced expiratory volume in 1 second ( FEV1 ) after prednisolone , and whether the prednisolone response predicts 3 year changes in FEV1 , health status , or number of exacerbations during placebo or fluticasone propionate treatment . Methods : Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before r and omised treatment for 3 years with fluticasone propionate or placebo . Factors relating to change in FEV1 after prednisolone were investigated using multiple regression . The response to prednisolone was entered into separate mixed effects models of decline in FEV1 and health status during the 3 years of the study . Results : The post-bronchodilator FEV1 increased by a mean 60 ml ( CI 46 to 74 ) after prednisolone with a wide unimodal distribution . Current smoking was the factor most strongly associated with the change in FEV1 after prednisolone , with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers ( p<0.001 ) . There was no relationship between the change in FEV1 after prednisolone  and the response to inhaled bronchodilators , baseline FEV1 , atopic status , age , or sex . The response to prednisolone  , however expressed , was unrelated to the subsequent change in FEV1 over the following 3 years on either placebo or fluticasone propionate . Regression to the mean effects explained much of the apparent prednisolone response . The significant effect of treatment on decline in health status was not predicted by the prednisolone response . Conclusion : Patients with COPD can not be separated into discrete groups of corticosteroid responders and non-responders . Current smoking reduces the FEV1 response to prednisolone . Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients 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 STUDY OBJECTIVE To determine the effectiveness of treatment with corticosteroids in patients with COPD . METHODS In this study , we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD . Subjects were treated in a double-blind , r and omized , placebo-controlled , parallel way with inhaled budesonide ( bud ) , 1,600 micrograms/d ; inhaled budesonide , 1,600 micrograms/d , plus oral prednisolone , 5 micrograms/d ( bud + pred ) ; or placebo ( plac ) .  Clinical assessment ( history , physical examination , and spirometry ) was carried out every 2 months . The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject . RESULTS Eleven patients dropped out . The number of withdrawals due to pulmonary problems was significantly higher in the plac group ( n = 5 out of 18 ) than in the actively treated groups ( n = 2 out of 40 ) . Treatment with corticosteroids significantly reduced pulmonary symptoms . Median decline of FEV1 was 60 mL/yr in the plac group , 40 mL/yr in the bud + pred group , and 30 mL/yr in the bud group . Variation was large and differences were not statistically significant . No treatment effect was found on frequency or duration of exacerbations , possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group . Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone . Morning plasma cortisol levels remained within the normal range in all three groups . CONCLUSIONS Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems . Lung function decline tends to decrease during treatment with inhaled corticosteroids . The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease ( COLD ) . Emphysema dominated the clinical picture in 38 , rest being chronic bronchitis with varying degrees of air trapping . None of the patients had clinical asthma . All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study . Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets . Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy . Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions . In 20 others only subjective response was observed . A good objective response was predicted by a pre- study variability in FEV1 , disease duration of less than 10 years and a history of smoking less than 50 pack years Evans , J. A. , Morrison , I. M. , and Saunders , K. B. (1974).Thorax , 29 , 401 - 406 . A controlled trial of prednisone , in low dosage , in patients with chronic airways obstruction . Ten men with chronic airways obstruction took part in a double-blind controlled cross-over trial of 5 mg prednisone , daily for a week , versus placebo .  All patients had breathlessness as their main complaint , and chronic cough with sputum for 2 to 30 years ; five had evidence of emphysema on the chest radiograph . None had a personal or family history of asthma . For the group , mean forced expiratory volume in one second was 1·11 1 . , and mean forced vital capacity was 2·28 1 . Six patients had abnormally high levels of arterial Pco2 ( 46 - 52 mmHg ) . When the ` placebo ' and ` prednisone ' measurements were compared there was no significant change in forced expiratory volumes , bronchodilator effect on forced expiratory volumes , or blood gas tensions . Inspiratory airways resistance measured by body plethysmography was significantly higher , or ` worse ' , on prednisone ( mean 4·2 cmH2O per 1/sec ) than on placebo ( mean 3·2 ) Many patients with irreversible chronic obstructive pulmonary disease ( COPD ) cl aim symptomatic improvement with steroid therapy , despite a lack of objective improvement in their spirometric data . To determine if steroids actually increase the exercise capacity of these individuals , 13 clinical ly stable patients ( mean age , 63 + /- 4 years ; 12 male patients ) were given methylprednisolone ( 32 mg once daily ) or placebo in a r and omized double-blind crossover fashion . Spirometric data and minute ventilation , oxygen consumption ( VO2 ) , carbon dioxide production , and heart rate during incremental exercise were measured at each visit . Methylprednisolone did not produce a significant change in any of the measured parameters . Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone , while two experienced a decline in maximal VO2 of similar magnitude . The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients ( r = 0.08 ) . We conclude that in the absence of any improvement in the usual tests of airway mechanics , steroid therapy does not improve exercise performance in patients with COPD We compared a 2-week course of 32 mg/d methylprednisolone with placebo in a double-blind crossover trial in 46 well-characterized patients with stable chronic obstructive pulmonary disease .  Placebo and steroid trials were separated by 2 weeks when no tablets were given . Response was assessed by measuring forced expiratory volume in 1 second ( FEV1.0 ) .  Placebo responses were normally distributed ( mean , 0.8 % change in FEV1.0 ; range , -30 % to 33 % ) . Six patients showed a greater than 50 % increase of FEV1.0 in response to steroid ; a seventh showed a 36 % increase and an eighth , a 29 % increase . Because of these patients the group as a whole showed a significantly greater FEV1.0 after steroid than after placebo . The eight steroid responders did not differ from nonresponders in age , sex , smoking history , or duration and intensity of symptoms including wheeze . Baseline lung function and eosinophilia of blood or sputum did not differ between the two groups . Patients who responded to steroids also responded to inhaled beta agonists : Acute bronchodilator response averaged 25 % in steroid responders and 13 % in nonresponders , a difference that was statistically significant although there was overlap between the two groups A double-blind cross-over trial was carried out on 83 sequential out- patients presenting with adult onset chronic airflow obstruction who were not clearly asthmatic . The study consisted of three treatment phases each lasting two weeks with a two week interval between each phase . The treatment phases were prednisolone 40 mg daily , beclomethasone dipropionate 500 ug three times a day and placebo , administered in a r and om order . FEV1 and FVC were measured at the end of each of the treatment phases and peak expiratory flow rate five times a day throughout . Over the study period 25 ( 30 % ) patients responded with an improvement of greater than or equal to 20 % in at least one of the parameters measured as compared with the best of either baseline or placebo measurements . A further eight patients were classified as partial responders with an improvement of greater than 15 % in any single parameter or greater than 10 % in any two parameters . A similar number responded to  beclomethasone  [ 15 ] as responded to prednisolone [ 16 ] . Only six patients , however , responded fully to both forms of steroid therapy . A number of patients responded to one form of steroid treatment only which was also comparable between the two groups ( prednisolone 10 , beclomethasone 9 ) . For full and partial responders mean improvement in FEV1 , FVC and PEFR was greater during the prednisolone phase than during the beclomethasone phase , however , the difference did not achieve statistical significance There have been suggestions that corticosteroid treatment might improve bronchodilator responses in chronic obstructive pulmonary disease ( COPD ) . We have studied bronchodilator responses to salbutamol and to oxitropium bromide in 20 patients with stable moderate to severe COPD . Dose responses to the two bronchodilators were tested before and after 3 week courses of placebo and 30 mg prednisolone .  Thirteen patients were taking inhaled corticosteroids .  There were no significant changes in numbers of responses or maximum bronchodilator effects from either bronchodilator , although there was a trend towards higher maximum levels after 3 weeks of prednisolone .  Spirometry measured at home each morning before and after oxitropium bromide showed no difference between prednisolone and placebo periods . This study provides no evidence for a significant effect on bronchodilator responses to beta-agonists or anticholinergic agents from 3 weeks of oral prednisolone in moderately severe COPD Although recent guidelines for managing chronic obstructive pulmonary disease ( COPD ) recommend a trial of oral corticosteroids in the initial assessment , its prognostic value remains unclear . We prospect ively studied 127 adults ( 64 % men ) with stable COPD ( FEV1/FVC < 60 % ) over 1 year . At entry , we measured lung volumes , gas transfer factor , respiratory symptoms ( by question naire ) , and peripheral blood eosinophil count .  Skin-prick testing was done , and spirometry after nebulized 5 mg salbutamol and , after 2 weeks , oral prednisolone . Physician A gave all patients inhaled beclomethasone dipropionate ( 800 mcg/day ) , whereas physician B prescribed this only to those with a positive oral corticosteroid trial . At 1 year , spirometry and respiratory question naire were repeated , with an estimate of overall symptom severity on a visual analogue scale . Follow-up data were available in 104 ( 82 % ) patients . Of these , 32 ( 31 % ) were unresponsive to salbutamol and prednisolone ; 48 ( 46 % ) were responsive to beta agonists but not to corticosteroids , and 24 ( 23 % ) responded to corticosteroids and salbutamol . Patients in all groups were comparable , except that the prednisolone responders had a higher mean eosinophil count ( p < 0.001 ) and more were  ex-smokers  ( p < 0.001 ) . Only the response to oral prednisolone correlated with the change in prebronchodilator FEV1 over 1 year . Oral prednisolone responders had higher FEV1 at 1 year ( p < 0.02 ) and significantly lower symptom scores ( p < 0.02 ) . In COPD , corticosteroid trials contribute information additional to that gained from nebulized bronchodilator reversibility testing . Patients with a positive response to a corticosteroid trial are more likely to have improved symptomatically and spirometrically at 1 year Systemic corticosteroids are often administered in COPD patients . The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) was retrospectively analysed . Baseline characteristics of the patients , in stable clinical condition , were collected on admission to a pulmonary rehabilitation centre . Overall mortality was asessed at the end of follow-up . The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use , distinguishing administration route ( oral/inhalation ) and oral dose , and overall mortality , adjusted for the influence of age , sex , smoking , lung function , resting arterial blood gases and body mass index . On multivariate analysis , oral glucocorticoid use at a ( prednisone equivalent ) dose of 10 mg x day(-1 ) without inhaled glucocorticoids , was associated with an increased risk ( RR=2.34 , 95 % confidence interval ( CI ) 1.24 - 4.44 ) while 15 mg x day(-1 ) carried a relative risk of 4.03 , CI = 1.99 - 8.15 ) . A significant interaction was observed between inhaled and oral glucocorticoid use . Combined with inhaled glucocorticoids , the relative risk of oral glucocorticoid use appeared to be significantly smaller . It is concluded that in severe chronic obstructive pulmonary disease , maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner . Since the present study design can not exclude the possibility of bias by indication , further prospect i ve studies are indicated using a broader patient characterization The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease ( COPD ) is controversial . We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 ( IL-8 ) and tumor necrosis factor-alpha ( TNF-alpha ) , and of the cell activation markers eosinophil cationic protein ( ECP ) , eosinophil peroxidase ( EPO ) , myeloperoxidase ( MPO ) , and human neutrophil lipocalin ( HNL ) in COPD patients as compared with controls , and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD . We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum . Initially , we studied the effect of a 2-wk course of inhaled budesonide ( 800 mg twice daily for 2 wk ) in 13 patients with severe COPD ( mean FDV1 : 35 % predicted ) . There was no clinical benefit in either lung function or symptom scores , and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO , and neutrophil activation markers MPO and HNL . Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation , we undertook a study examining the antiinflammatory effect of oral prednisolone ( 30 mg daily for 2 wk ) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma .  Sputum eosinophil numbers , ECP , and EPO were significantly reduced in the asthmatic patients but were not modified in COPD . This confirms the clinical impression that inhaled steroids have little antiinflammatory effect , at least in the short term in this group of patients , and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids Sixteen Chinese patients with chronic fixed airflow obstruction ( mean age 62.5 years ; mean forced expiratory volume in 1 second ( FEV1 ) of 0.85 litres , and mean ratio FEV1/forced vital capacity ( FVC ) of 0.45 ) entered a r and omized double-blind crossover trial comparing prednisolone 40 mg orally daily for 2 weeks with placebo . Nine of the 16 patients ( 56 % ) had an increase in FEV1 of 15 % or more after prednisolone . Compared with placebo , prednisolone significantly improved objective measurements ( mean FEV1 by 21.4 % , mean FVC by 11.9 % , mean daily peak expiratory flow rate by 22.6 % ) , subjective measurement ( mean dyspnoea score by 16 % ) and exercise performance assessed by the distance walked in 12 minutes ( 12MD , by 5.5 % ) . Objective improvements in FEV1 and PEFR were correlated with subjective upgrading of the dyspnoea score , but were not paralleled by an improvement in 12MD . Changes in FVC correlated with neither . FEV1 was thus the best index of objective measurement . The following characteristics were examined for reliability in predicting steroid responsiveness : variability of symptoms , wheezing score , prick skin test positivity , initial bronchodilator response , peripheral blood and sputum eosinophilia , and serum and sputum immunoglobulin E ( IgE ) level . None was found to be useful . A therapeutic trial of oral corticosteroid should be considered in patients with chronic fixed airflow obstruction on an individual basis We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease . In this double-blind study , 44 patients with moderate to severe COPD ( mean FEV1 740 + /- 310 ml ) were hospitalized and r and omly allocated to receive methylprednisolone , 8 mg qid , 64 mg qod , or placebo for a ten-day period . The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups , but not in the placebo-treated group . Eight of the 29 steroid-treated patients ( 28 percent ) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients . Those in the qod group also had notable improvement in SaO2 . Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant , some patients had more than a 25 percent improvement in their FEV1 with corticosteroids , but less than a 10 percent improvement after nebulized bronchodilators . We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration . Since the response to a qod regimen is comparable to that of a qid regimen , and since the qod regimen is associated with fewer side effects , we recommend that a qod regimen be tried initially Nineteen patients with chronic airflow obstruction measured their morning and evening peak expiratory flow ( PEF ) daily for 28 days . A placebo was taken for the first week and prednisolone 20 mg twice daily was taken for the last three weeks . The mean PEF in 13 patients who responded to prednisolone reached a maximum after eight days ' treatment . The majority of the 19 patients had asthma and were thought to represent a typical cross section of patients who would be considered for a trial of oral corticosteroids . Most responsive patients will achieve a maximum response within eight days BACKGROUND Some patients with chronic obstructive pulmonary disease ( COPD ) respond to corticosteroid therapy . Whether these patients have different airway pathology from other COPD patients is unclear . We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation . METHODS We did a r and omised , double-blind , crossover trial . Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each , in a r and om order , separated by a 4-week washout period . Before and after each treatment period , we assessed patients with spirometry , symptom scores , the chronic respiratory disease question naire ( CRQ ) , incremental shuttle walk test , and induced sputum .  Analysis was done by intention to treat . FINDINGS 83 patients were recruited , of whom 67 were r and omised . The geometric mean sputum eosinophil count fell significantly after prednisolone ( from 2.4 % to 0.4 % ; mean difference six-fold [ 95 % CI 3.1 - 11.4 ] ) but not after placebo . Other sputum cell counts did not change . After stratification into tertiles by baseline eosinophil count , postbronchodilator forced expiratory volume in 1 s ( FEV1 ) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile , compared with placebo . The mean change in postbronchodilator FEV1 , total CRQ score , and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L ( 0.06 - 0.32 ) , 0.62 ( 0.31 - 0.93 ) , and 20 m ( 5 - 35 ) , respectively . INTERPRETATION Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response . The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated BACKGROUND --The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed . Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear . METHODS --A sequential placebo controlled , blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate ( BDP ) , 750 micrograms or 1500 micrograms twice daily , and oral prednisolone , 40 mg per day , was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction ( mean age 66 years , mean forced expiratory volume in one second ( FEV1 ) 1.05 litres [ 40 % predicted ] , geometric mean PD20 0.52 mumol ) . End points assessed were FEV1 , forced vital capacity ( FVC ) , and peak expiratory flow ( PEF ) , bronchial responsiveness to inhaled histamine , and quality of life as measured by a formal quality of life question naire . RESULTS --Both doses of BDP produced equivalent , small , but significant improvements in FEV1 ( mean 48 ml ) , FVC ( mean 120 ml ) , and PEF ( mean 12.4 l/min ) . The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters . Inhaled BDP produced a treatment response in individual patients ( defined as an improvement in FEV1 , FVC , or mean PEF of at least 20 % compared with baseline values ) more commonly than placebo ( 34 % v 15 % ) . The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted . Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine . Small but significant improvements were seen in dyspnoea during daily activities , and the feeling of mastery over the disease . CONCLUSIONS --High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma . Both objective and subjective measures show improvement . Unlike asthma , no improvement in bronchial responsiveness was detected after six weeks of treatment The reproducibility of the 12 minute walking distance ( 12 MD ) was assessed in ten men with chronic airways obstruction , and the 12 MD was used , together with spirometry , transfer factor and three subjective assessment s of breathlessness to evaluate the effects on respiratory function of prednisone 30 mg daily given orally in double-blind placebo-controlled fashion for two weeks . Like others , we found the 12 MD reproducible on a single day with a mean variation of 3.1 % . Tests performed two weeks apart showed greater variability ranging from 0.2 % to 30.9 % , ( mean 9.1 % ) . During placebo and prednisone therapy the 12 MD and assessment s of breathlessness correlated significantly with each other and with TLCO , but not with spirometry . Following steroid therapy there was a significant increase in mean TLCO but no significant change in 12 MD , spirometry or subjective assessment s. Changes in 12 MD and TLCO correlated significantly with each other and with changes in subjective assessment s. Changes in FEV1 correlated with changes in breathlessness , and also with variability in FEV1 while receiving placebo . Individuals with the greatest changes in 12 MD and FEV1 were those with the greatest variability on placebo . The variability of the 12 MD and FEV1 should be measured in individuals before using these tests to assess response to steroid therapy BACKGROUND Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease ( COPD ) . We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD . METHODS We used a parallel-group , r and omised , double-blind , placebo-controlled design in a singlecentre study , nested in a continuing epidemiological survey ( the Copenhagen City Heart Study ) . Inclusion criteria were as follows : no asthma ; a ratio of forced expiratory volume in 1 s ( FEV1 ) and vital capacity of 0.7 or less ; FEV1 which showed no response ( < 15 % change ) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days . 290 patients were r and omly assigned  budesonide , 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months , or placebo for 36 months . The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86 % of predicted . The main outcome measure was rate of FEV1 decline . Analyses were by intention to treat . FINDINGS The crude rates of FEV1 decline were slightly smaller than expected ( placebo group 41.8 mL per year , budesonide group 45.1 mL per year ) . The estimated rates of decline from the regression model did not differ significantly ( 49.1 mL vs 46.0 mL per year ; difference 3.1 mL per year [ 95 % CI -12.8 to 19.0 ] ; p=0.7 ) . Before the study , the minimum relevant difference was defined as 20 mL per year ; this difference was outside the 95 % CI . No effect of inhaled budesonide was seen on respiratory symptoms . 316 exacerbations occurred during the study period , 155 in the budesonide group and 161 in the placebo group . Treatment was well tolerated . INTERPRETATION Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening . We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD BACKGROUND : Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease . We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide . METHODS : Ten non-allergic subjects with stable disease were investigated ; eight completed the r and omised , double blind , three period cross over study . Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks , 40 mg oral prednisone a day for eight days , and placebo . After each period cumulative doubling doses of salbutamol , ipratropium , a combination of salbutamol and ipratropium , and placebo were administered on separate days until a plateau in FEV1 was reached . A histamine challenge was then performed . RESULTS : At the end of placebo treatment mean FEV1 was 55.5 % predicted after inhaled placebo , 67.9 % predicted after salbutamol and 64.0 % predicted after ipratropium . Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7 % predicted after treatment with budesonide and by 0.7 % predicted after treatment with prednisone ; the FEV1 with ipratropium  increased by 0.7 % predicted after budesonide and by 4.8 % predicted after prednisone ; none of these changes was significant . After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo , 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium . Compared with the placebo period the PC20 with  salbutamol  was increased by 0.86 doubling concentrations after treatment with budesonide , and by 0.67 doubling concentrations after prednisone ; the PC20 with ipratropium  increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo ; none of these changes was significant . CONCLUSIONS : In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine . Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium One hundred and twenty one patients considered on clinical grounds to have non-asthmatic chronic airflow obstruction completed a double blind , crossover trial comparing oral prednisolone 40 mg per day with inhaled beclomethasone dipropionate 500 micrograms thrice daily , each given for 14 days , with a 14 day washout period between treatments . The time course of response was analysed for the 57 occasions where there was a significant increase in mean daily peak expiratory flow ( PEF ) over the treatment period . Mean daily PEF was still rising at day 14 on 12 occasions . After withdrawal of treatment mean daily PEF remained above pretreatments levels for more than two weeks in half the responses analysed . The peak response occurred earlier with inhaled beclomethasone ( median 9.5 ( range 3 - 14 ) days ) than with oral prednisolone ( median 12 ( range 1 - 14 ) days ) , though both treatments produced a response that was sustained for a similar period . The results suggest that a trial of treatment with corticosteroids in this group of patients should last more than 14 days , and that in a study with a crossover design the washout period should be longer than two weeks The efficacy of corticosteroids in chronic airflow limitation is variable and nonpredictable . We believe that the corticosteroid-induced improvement seen in a few subjects with chronic airflow limitation indicates coexistent bronchial asthma . Therefore , we hypothesize that by carefully excluding all features ( other than corticosteroid response ) , either objective or subjective , that might be consistent with coexisting asthma , we could predict non-response to corticosteroids . Twenty patients with chronic airflow limitation related to cigarette smoking were chosen . Features that might suggest coexisting asthma were carefully excluded ; these included rhinitis , nocturnal symptoms , atopy , large response to bronchodilator , and sputum or blood eosinophilia . Eighteen of these 20 subjects completed a double-blind r and om-order cross-over placebo-controlled trial of 30 mg of prednisone for 14 d ( with a 14 d washout between treatments ) . There were no significant differences , individually or collectively , in objective or subjective determinations . Based on a greater than or equal to 250 mL improvement in FEV1 , there were two placebo responders and two prednisone responders . Although it may be difficult to predict corticosteroid response in chronic airflow limitation , it appears that careful exclusion of ' asthmatic tendencies ' may predict nonresponse to corticosteroids A double-blind , r and omised , placebo-controlled , crossover trial of prednisolone ( 40 mg daily for 14 days ) was carried out in 43 patients with chronic airflow limitation ( mean age 60 years , mean FEV1 1.02 litres , FEV1/FVC ratio 43.7 % ) . Several subjective and objective variables for response were measured . Significant improvements occurred with prednisolone in most variables measured , but improvements also occurred with placebo in some variables . The improvements with prednisolone in general wellbeing , 12 min walk distance , peak expiratory flow , FEV1 , and relaxed vital capacity were significantly greater than those with placebo . Clinical assessment and assessment of atopic status did not reveal any feature of major predictive value for steroid responsiveness . A proportion of patients with chronic airflow limitation do improve on oral corticosteroids and the continued use of such trials in clinical practice is justified , though a placebo period should be included , and several variables for response should be measured It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids  in patients with chronic obstructive pulmonary disease ( COPD ) . To assess the additive effects of 30 mg/day prednisolone to high-dose , inhaled beclomethasone dipropionate ( BDP ) , we conducted a r and omised double-blind , placebo-controlled cross-over trial . The study population consisted of 21 men with stable COPD . The mean age of the patients was 69.1 + /- 6.8 years , and FEV(1)was 0.86 + /- 0.28 l. Seventeen out of the 21 patients ( 81 % ) were considered susceptible to steroids in a previous trial ( FEV(1)increased at least 15 % from baseline after receiving 14 days of 30 mg/day prednisolone ) . All of the patients had been on 1600 microg/day BDP for more than 3 months .  Spirometry was performed before the entry , and at the end of 3-week placebo and prednisolone periods . The peak expiratory flow ( PEF ) , symptoms , and Guyatt 's Chronic Respiratory Disease Question naire ( CRQ ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated . Although a marginal increase in PEF was found during the prednisolone period , no significant differences in FEV(1 ) , FVC , symptoms or CRQ scores were observed between the two treatment periods . We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose , inhaled corticosteroid in some patients with stable COPD A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed . In a single-blind , sequential crossover trial of placebo and prednisone ( 30 mg/day ) treatment , with each given for 2 wk , we investigated whether an increased proportion of sputum eosinophils ( > = 3 % ) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis . Patients were seen before and after each treatment . Clinical measurements were made blind to the laboratory findings and vice-versa . Eighteen of 20 patients completed the study . Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia . Only in patients with sputum eosinophilia did prednisone , as compared with placebo , produce a statistically significant and clinical ly important mean effect on effort dyspnea of 0.8 ( 95 % confidence interval [ CI ] : 0.3 to 1.2 ) , p = 0.008 , and in quality of life of 1.96 ( 95 % CI : 0.5 to 3.3 ) , p = 0.01 , associated with a small improvement in FEV1 of 0.11 L ( 95 % CI : - 0.04 to 0.23 L ) , p = 0.05 . In these patients , prednisone also produced a significant decline in the median sputum eosinophil percentage , from 9.7 % to 0.5 % ( p = 0.002 ) , eosinophil cationic protein ( ECP ) , from 6 , 000 microgram/L to 1,140 microgram/L ( p < 0.001 ) , and fibrinogen , from 25 . 3 mg/L to 5.4 mg/L ( p < 0.001 ) . These findings indicate that in smokers with severe airflow limitation , sputum eosinophilia predicts a beneficial effect of prednisone treatment . Improvement in FEV1 , after prednisone treatment in this population , is small , and may not be appreciated in clinical practice There is considerable controversy concerning the utility of inhaled corticosteroids for the long-term treatment of patients with COPD . Recent studies have suggested that although inhaled corticosteroids do not alter the rate of decline in lung function , they may reduce airway hyperresponsiveness , decrease the frequency of exacerbations , and slow the rate of decline in the patients ' health status . The relationship between inhaled corticosteroids and subsequent risk of hospitalization or mortality remains unknown . We therefore conducted a population -based cohort study using administrative data bases in Ontario , Canada ( n = 22,620 ) to determine the association between inhaled corticosteroid therapy and the combined risk of repeat hospitalization and all-cause mortality in elderly patients with COPD . Patients who received inhaled corticosteroid therapy postdischarge ( within 90 d ) had 24 % fewer repeat hospitalizations for COPD ( 95 % confidence interval [ CI ] , 22 to 35 % ) and were 29 % less likely to experience mortality ( 95 % CI , 22 to 35 % ) during 1 yr of follow-up after adjustment for various confounding factors . This cohort study has suggested that inhaled corticosteroid therapy is associated with reduced COPD -related morbidity and mortality  in elderly patients . Although not definitive , because of the observational nature of these findings , these data provide a compelling rationale for a large r and omized trial to determine the effect of inhaled corticosteroids on COPD -related morbidity and mortality Two trials comparing aerosol and oral steroid treatment were carried out in patients with chronic airways obstruction . All patients had a history of chronic productive cough and an FEV1 less than 70 % predicted but did not have episodic or seasonal breathlessness with wheezing . One trial involved 18 out patients , the other 18 in patients . Both studies involved three consecutive treatment periods , the first with placebo aerosol , the second with active aerosol ( betamethasone valerate , 800 microgram/day ) , and the third with oral prednisone or prednisolone ( 30 mg/day ) . Six patients showed a significant improvement in ventilatory capacity on steroids . Initial assessment included a comprehensive history using a question naire , skin tests , blood and sputum eosinophil counts , and chest radiography . In addition , for the in patients , response to isoprenaline , daily sputum volume , and PaCO2 were measured . Only blood eosinophilia and variability in ventilatory capacity during the placebo period seemed indicative of a likely response to steroids . However , there was a large overlap between various features on assessment in the responders and non-responders , and the management of every patient with chronic airways obstruction should include a controlled trial of steroids . The steroid aerosol produced a good improvement in ventilatory capacity in the responsive patients who were hospitalised and this was thought to be helped by supervision of aerosol technique . Such an aerosol could therefore be used for a steroid trial although oral steroids were found to give a more definitive response Corticosteroid drugs are often employed in the treatment of patients with chronic bronchitis . Although some patients respond favorably to such therapy , the characteristics of such patients are not known . Twenty-four patients with chronic bronchitis were treated with prednisone 30 mg daily or placebo for one week each in a double-blind crossover study . The following were monitored before and after each treatment period : physical examination , symptoms , peripheral blood eosinophil count , sputum cell exmination , forced vital capacity ( FVC ) , before and after isoproterenol aerosol .  Seven of 24 patients had an FEV1 increase greater than 30 % of the control value on prednisone but not on placebo .  Blood eosinophil count was elevated ( greater than or equal to 350/mm(3 ) ) in 7 patients ; 2 of these 7 improved on steroid . Sputum cell examination revealed preponderance of eosinophils in 1 , and occasional clumps of eosinophils in 8 . Seven of these 9 responded to steroid . Sputum but not blood eosinophilia is a good predictor of a favorable response to steroid therapy BACKGROUND Chronic obstructive pulmonary disease ( COPD ) results from a progressive decline in lung function , which is thought to be the consequence of airway inflammation . We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline . METHODS We enrolled 1116 persons with COPD whose forced expiratory volume in one second ( FEV1 ) was 30 to 90 percent of the predicted value in a 10-center , placebo-controlled , r and omized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily . The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator . The secondary outcome measures included respiratory symptoms , use of health care services , and airway reactivity . In a sub study of 412 participants , we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment . RESULTS The mean duration of follow-up was 40 months . The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group ( 44.2+/-2.9 vs. 47.0+/-3.0 ml per year , P= 0.50 ) . Members of the triamcinolone group had fewer respiratory symptoms during the course of the study ( 21.1 per 100 person-years vs. 28.2 per 100 person-years , P=0.005 ) and had fewer visits to a physician because of a respiratory illness ( 1.2 per 100 person-years vs. 2.1 per 100 person-years , P=0.03 ) . Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months ( P=0.02 for both comparisons ) . After three years , the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group ( P < or = 0.007 ) . CONCLUSIONS Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD , but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems . These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density A placebo-controlled , double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease ( COPD ) would benefit from orally taken corticosteroids . Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole , although one patient had small improvement in airflow . The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals . Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group . Furthermore , the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined . It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids , due to a bias result ing from the selection of severely obstructed subjects The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease ( COPD ) . Forty patients with stable COPD entered the study , and received prednisolone ( 37.5 mg o.d . ) for 2 weeks . They were subsequently divided into steroid-irreversible and steroid-irreversible , using 15 % of baseline as a dividing point . In each group patients were r and omized to receive budesonide 400 micrograms b.i.d . or placebo for 6 months . During treatment with prednisolone , three patients dropped out because of side effects . Of the remaining 37 , only two patients ( 5 % ) were reversible with prednisolone forced expiratory volume in 1s [ ( FEV1 ) > 15 % of baseline ] , and among the steroid-irreversible , 26 patients were evaluated after 6 months treatment with either placebo or budesonide . No significant differences in spirometry values , symptoms , or number of exacerbations were found between these two groups . Reversibility with prednisolone is rarely seen in COPD . In out patients with stable COPD and no signs of asthma or atopy  , 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy Non‐compliance or euphoria may limit the usefulness of prednisolone tablets in assessing steroid‐responsiveness in chronic obstructive pulmonary disease ( COPD ) .  Depot intra‐muscular methyl‐prednisolone ( imMP ) , producing a plateau steroid effect over two weeks , may be more reliable . Following two weeks of placebo , twenty‐seven COPD patients ( mean FEV1 43 % predicted ) participated in a two‐week r and omised , double‐blind , placebo‐controlled , parallel‐ design trial taking either 120 mg imMP with placebo tablets or placebo injection with prednisolone 30 mg daily . After each period , post‐bronchodilator FEV1 , forced vital capacity ( FVC ) , inspiratory capacity ( IC ) and six‐minute walking distance ( 6MWD ) were assessed and patients completed both quality ‐of‐life scores ( St. George 's 30 and Short Form 36 ) and mood scores ( Hospital Anxiety and Depression scores and Altman 's Self‐rating Mania Scale ) . There were no significant changes in 6MWD , quality of life or mood scores after either type of steroids and no change in lung function  after imMP . By contrast , there were small mean improvements in lung function on oral prednisolone  ( mean FEV1 , FVC and IC increased by 100 , 320 and 150 ml , respectively ) . Only the improvement in FVC was significantly greater after prednisolone compared with imMP . Single depot intra‐muscular injections of steroids have no advantage over oral daily prednisolone in testing steroid‐responsiveness in COPD patients Abstract Objectives : To determine the effect of long term inhaled corticosteroids on lung function , exacerbations , and health status in patients with moderate to severe chronic obstructive pulmonary disease . Design : Double blind , placebo controlled study . Setting : Eighteen UK hospitals . Participants : 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second ( FEV1 ) 50 % of predicted normal . Interventions : Inhaled fluticasone propionate 500 μg twice daily from a metered dose inhaler or identical placebo . Main outcome measures : Efficacy measures : rate of decline in FEV1 after the bronchodilator and in health status , frequency of exacerbations , respiratory withdrawals . Safety measures : morning serum cortisol concentration , incidence of adverse events . Results : There was no significant difference in the annual rate of decline in FEV1 ( P=0.16 ) . Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo ( P<0.001 ) . Median exacerbation rate was reduced by 25 % from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate ( P=0.026 ) . Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate ( P=0.0043 ) . Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group ( 25 % v 19 % , P=0.034 ) . Conclusions : Fluticasone propionate 500 μg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1 . Patients on fluticasone propionate  had fewer exacerbations and a slower decline in health status . These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease
BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is a common chronic lung disorder , usually related to cigarette smoking , representing a major and increasing cause of morbidity and mortality .
It is defined " as a disease state characterized by airflow limitation that is not fully reversible .
The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases " .
The use of corticosteroids for their anti-inflammatory effects has been suggested .
OBJECTIVES To assess the effects of oral corticosteroids on the health status of patients with stable COPD .