Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Effect of an inhaled glucocorticoid on reactive oxygen species production by bronchoalveolar lavage cells from smoking COPD patients. Inhaled corticosteroids in stable COPD patients: do they have effects on cells and molecular mediators of airway inflammation? Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. Inhaled Corticosteroids May Reduce Neutrophilic Inflammation in Patients with Stable Chronic Obstructive Pulmonary Disease
BACKGROUND Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for  plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD 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 The aim of this double-blind single center study ( the COPE study ) was to investigate the effect of discontinuation of the inhaled corticosteroid fluticasone propionate ( FP ) on exacerbations and health-related quality of life in patients with chronic obstructive pulmonary disease . After 4 months of treatment with FP ( 1,000 microg/day ) , 244 patients were r and omized to either continue FP or to receive placebo for 6 months : 123 patients continued FP ( FP group ) , and 121 received placebo ( placebo group ) . In the FP group , 58 ( 47 % ) patients developed at least one exacerbation compared with 69 ( 57 % ) in the placebo group . The hazard ratio of a first exacerbation in the placebo group compared with the FP group was 1.5 ( 95 % confidence interval [ CI ] 1.1 - 2.1 ) . In the placebo group 26 patients ( 21.5 % ) experienced rapid recurrent exacerbations and were subsequently unblinded and prescribed FP compared with 6 patients ( 4.9 % ) in the FP group ( relative risk = 4.4 ; 95 % CI 1.9 - 10.3 ) . Over a 6-month period , a significant difference in favor of the FP group was observed in the total score ( + 2.48 95 % CI 0.37 - 4.58 ) , activity domain ( + 4.64 95 % CI 1.60 - 7.68 ) , and symptom domain ( + 4.58 95 % CI 1.05 - 8.10 ) of the St. George 's Respiratory Question naire . This study indicates that discontinuation of FP in patients with chronic obstructive pulmonary disease is associated with a more rapid onset and higher recurrence-risk of exacerbations and a significant deterioration in aspects of Health-Related Quality of Life Oxidative stress in the lung is important in the pathogenesis of COPD . Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species ( ROS ) . We investigated the effect of Fluticasone propionate ( FP ) on the ROS production capabilities of pulmonary cells . Bronchoalveolar lavage ( BAL ) was performed in smoking COPD patients , before and after a six month , placebo-controlled treatment with FP . BAL cells were stimulated with phorbol myristrate acetate ( PMA ) alone , and together with superoxide dismutase ( SOD ) . From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production : V(max ) . We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants . Paired results were obtained from 6 FP- and 9 placebo-treated patients . No significant change of V(max ) was found in both patient groups . Also BAL cellularity was unchanged . Correlation analyses showed a significant ( inverse ) association of V(max ) with the number of cigarettes smoked per day . We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients . Apparently , heavy smoking impaired the ability of alveolar macrophages to produce ROS , which was not further decreased by FP STUDY OBJECTIVE To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients . DESIGN Six-week open preliminary prospect i ve study . SETTING A university respiratory disease clinic . PATIENTS : Stable COPD patients with mild disease . INTERVENTION Six-week treatment with inhaled beclomethasone ( 1.5 mg die ) . MEASUREMENTS The levels of interleukin (IL)-8 , myeloperoxidase , eosinophilic cationic protein and tryptase , and cell numbers in bronchial lavage specimens were determined , and the symptom score , the endoscopic bronchitis index , and functional parameters were recorded . RESULTS After treatment there were significant reductions in the lavage levels of IL-8 ( [ mean + /- SEM ] 1,603.4 + /- 331.2 vs 1,119.2 + /- 265.3 pg/mL , respectively ; p = 0 . 01 ) and myeloperoxidase ( 1,614.5 + /- 682.3 vs 511.2 + /- 144.2 microg/L , respectively ; p = 0.05 ) , in cell numbers ( 250.6 + /- 27.7 vs 186.3 + /- 11.5 cells x 10(3)/mL , respectively ; p = 0.04 ) , neutrophil proportion ( 59.7 + /- 14.3 % vs 31.5 + /- 10.1 % ; p = 0.01 ) , symptom score ( 4.5 + /- 0.6 vs 1.4 + /- 0.5 ; p = 0.01 ) , and bronchitis index ( 8.5 + /- 0.8 vs 5.5 + /- 0.7 ; p = 0.007 ) . CONCLUSIONS In stable patients with COPD , inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease ( COPD ) , despite lack of proven efficacy . Because COPD involves airway inflammation and probable protease-antiprotease imbalance , we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms . Thirteen patients with COPD were treated with fluticasone propionate ( 500 microg twice a day ) for 4 wk , delivered via MDI and spacer , in a double-blind crossover study . There was no clinical benefit in terms of lung function or symptom scores , and induced sputum inflammatory cells , percentage neutrophils , and IL-8 levels were unchanged . Sputum supernatant elastase activity , matrix metalloproteinase (MMP)-1 , MMP-9 , and the antiproteases secretory leukoprotease inhibitor ( SLPI ) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment . These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD . Furthermore , inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction The effects of fluticasone propionate ( FP ) on sputum chemotactic activity , elastase inhibitory potential , albumin concentrations , and peripheral neutrophil function were studied in a group of patients with clinical ly stable , smoking-related chronic bronchitis and emphysema . Seventeen patients ( 50 to 75 yr of age ) were entered into a double-blind , placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk . Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group ( p < 0.01 ) . Values fell from a mean of 21.75 ( + /- 1.58 ) during the run-in period to 18.37 ( + /- 1.46 ; p < 0.01 ) after 4 wk and 17.63 ( + /- 1.86 ; p < 0.05 ) after 8 wk treatment returning to 22.08 ( + /- 1.26 ) cell/field after the washout period . The neutrophil elastase inhibitory capacity of the sputum sol phase increased ( p < 0.025 ) with treatment from a mean of 0.177 microM elastase inhibited/L ( + /- 0.05 ) pretreatment to 0.413 microM ( + /- 0.054 ) after 4 wk and 0.415 microM ( + /- 0.054 ) after 8 wk returning to 0.270 microM ( + /- 0.07 ) after the washout period . Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations . The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung , and also by directly affecting the proteinase/antiproteinase balance , in favor of antiproteinases , within lung secretions BACKGROUND The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease ( COPD ) remains controversial because of a lack of placebo-controlled studies . We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD . METHODS We used a r and omised , double-blind , placebo-controlled design . We enrolled from 13 European countries , New Zeal and , and South Africa , 281 outpatient current or ex-smokers , aged between 50 and 75 years . They had a forced expiratory volume in 1 s ( FEV1 ) of between 35 % and 90 % of predicted normal values , a ratio of FEV1 to forced vital capacity of 70 % or less and bronchodilator reversibility of less than 15 % , as well as a history of chronic bronchitis . Patients were r and omly assigned fluticasone propionate 500 microg ( n=142 ) or placebo ( n=139 ) twice daily via a metered-dose inhaler for 6 months . The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment , the number and severity of exacerbations , clinic lung function , diary card symptoms and peak expiratory flow and 6 min walking distance . FINDINGS 51 ( 37 % ) patients in the placebo group compared with 45 ( 32 % ) in the fluticasone propionate group had had at least one exacerbation by the end of treatment ( p=0.449 ) . Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group ( 86 % vs 60 % , p<0.001 ) . Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group ( p<0.001 , p=0.048 , respectively ) , as did clinic FEV1 ( p<0.001 ) , forced vital capacity ( p<0.001 ) , and mid-expiratory flow ( p=0.01 ) . Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo ( p=0.004 and p=0.016 , respectively ) . At the end of treatment , patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo ( p=0.032 ) . Fluticasone propionate was tolerated as well as placebo , with few adverse effects and without a clinical ly important effect on mean serum cortisol concentration . INTERPRETATION Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months .  Inhaled corticosteroids may have an important role in the long-term treatment of COPD 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 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 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 Although patients with chronic obstructive pulmonary disease ( COPD ) should stop smoking , some do not . In a double-blind , placebo-controlled study , we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking . After a six-month run-in period , we r and omly assigned 1277 subjects ( mean age , 52 years ; mean forced expiratory volume in one second [ FEV1 ] , 77 percent of the predicted value ; 73 percent men ) to twice-daily treatment with 400 microg of budesonide or placebo , inhaled from a dry-powder inhaler , for three years . RESULTS Of the 1277 subjects , 912 ( 71 percent ) completed the study . Among these subjects , the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group ( P=0.05 ) , or 4.3 percent and 5.3 percent of the predicted value , respectively . During the first six months of the study , the FEV1 improved at the rate of 17 ml per year in the budesonide group , as compared with a decline of 81 ml per year in the placebo group ( P<0.001 ) . From nine months to the end of treatment , the FEV1 declined at similar rates in the two groups ( P=0.39 ) . Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising ( P<0.001 ) . Newly diagnosed hypertension , bone fractures , postcapsular cataracts , myopathy , and diabetes occurred in less than 5 percent of the subjects , and the diagnoses were equally distributed between the groups . CONCLUSIONS In patients with mild COPD who continue smoking , the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline Inhaled corticosteroids ( ICS ) are effective in the treatment of asthma and markedly reduce the numbers of inflammatory cells in bronchial biopsies . However , the effect of ICS on the inflammatory profile of biopsies in smokers with chronic obstructive pulmonary disease ( COPD ) is unknown . We have performed a double-blind , placebo-controlled , r and omized study to compare fluticasone propionate ( FP ) 500 microg twice daily via a dry powder inhaler and placebo ( P ) over a 3-month period in subjects with COPD .  Fiberoptic bronchoscopy and bronchial biopsy was carried out at baseline and after the 3 months of treatment . Thirty-one subjects completed the trial and 30 paired biopsies were available for analysis . Compared with P ( n = 14 ) , subjects on inhaled FP ( n = 16 ) had no significant reductions in the primary endpoints : CD8 + , CD68 + cells , or neutrophils , considered to be of importance in COPD . However , there was a reduction in the CD8:CD4 ratio in the epithelium and of the numbers of subepithelial mast cells in the FP group . CD4 + cells were significantly raised in the P group in both subepithelium and epithelium . Symptoms significantly improved , and there were significantly fewer exacerbations in subjects on FP , compared to subjects on P. The data indicate that inhaled fluticasone does affect selected aspects of airway inflammation in COPD , and this may explain , in part , the decrease in exacerbations seen in long-term studies with fluticasone propionate BACKGROUND Airways inflammation is a feature of chronic obstructive pulmonary disease ( COPD ) , but the role of corticosteroids in the management of clinical ly stable patients has yet to be established . A r and omised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate ( BDP ) administered for two months to patients with stable , smoking related COPD . Sputum induction was used to evaluate bronchial inflammation response . METHODS 34 patients ( 20 men and 14 women ) were examined on three separate occasions . At the initial clinical assessment ( visit 0 ) , spirometry and blood gas analysis were performed . On visit 1 ( within one week of visit 0 ) sputum induction was performed and each patient was r and omised to receive either BDP 500 μg three times daily ( treated group ) or nothing ( control group ) . After two months ( visit 2 ) , all patients underwent repeat clinical assessment , spirometry , and sputum induction . RESULTS There were no differences in sputum cell counts between the groups at baseline . After two months of treatment , induced sputum sample s from patients in the treated group showed a reduction in both neutrophils ( −27 % ) and total cells ( −42 % ) with respect to baseline , while the control group did not ( neutrophils + 9 % , total cells + 7 % ) . Macrophages increased in the treated group but not in the control group . The mean final value of sputum neutrophils was 52 % in the treated group and 73.3 % in the control group ( 95 % confidence interval ( CI ) −27.2 to −15.4 ) . The mean final value of sputum macrophages was 35.8 % in treated group and 19.3 % in control group ( 95 % CI 10.3 to 22.8 ) . The differences between the treated and control groups for neutrophils ( −21.3 % ) , macrophages ( + 16.5 % ) , and total cells ( −65 % ) were significant . Spirometry and blood gas data did not change from baseline in either patient group . CONCLUSIONS A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinical ly stable , smoking related COPD . Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD . In an early stage of the disease , i.e. chronic bronchitis with mild or no airflow obstruction , a trial with inhaled steroids could reveal potential benefits , particularly in terms of a modulation of airway inflammation . We therefore investigated the effect of inhaled fluticasone ( 1000 microg day(-1 ) ) on markers of airway inflammation in 19 patients with chronic bronchitis ( mean+/-SEM FEV1 , 83.4+/-3.0 % predicted ; FEV1/VC , 67.5+/-2.4 % ) in a double-blind , cross-over , placebo-controlled manner . Visits were performed before and after two 4-week treatment periods . separated by a 4-week washout period . Lung function , the concentration of exhaled nitric oxide , differential cell counts in induced sputum and the number of cells positive for iNOS , as well as the levels of LDH , ECP , neutrophil elastase and IL-8 in sputum supernatants were determined . Although the total cell number decreased significantly after fluticasone ( geometric mean 12.3 vs. 7.7 x 10(6)/ml ; P<0.05 ) it was not significantly different from the change observed after placebo ( 14.2 vs. 10.6 x 10(6)/ml ; n.s . ) . None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness . We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability 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 Background : Although both inhaled and oral corticosteroids have anti-inflammatory effects causing improvement in clinical symptoms and spirometry in the treatment of asthma , the role of corticosteroids in the management of chronic obstructive pulmonary disease ( COPD ) is controversial . Objective : To evaluate the effects of inhaled corticosteroids on sputum neutrophilia in clinical ly stable COPD patients . Methods : In total , 18 patients were enrolled in the study . During 2 months , 9 patients in group A inhaled fluticasone propionate ( FP ) 500 μg 3 times daily . In group B 9 patients received placebo . All of the patients continued to inhale both salbutamol and ipratropium bromide . In 9 patients , sustained-released theophylline was also administered . Blood sample s , spirometric tests , blood gas analyses , and either spontaneous or induced sputum cultures were evaluated on entry into the study , after a 2 months of treatment and following the 6-week washout period . Results : After the 2-month FP treatment , no significant changes in the number of peripheral blood neutrophils , blood gas and spirometry data were observed in both groups . In group A , the total cell number and the number of neutrophils decreased from a mean of 3.4 ± 1.3 × 106 cells/g and 0.6 ± 0.3 × 106 neutrophils/g on entry into study to 1.9 ± 0.6 × 106 cells/g and 0.02 ± 0.01 × 106 neutrophils/g after 8-week treatment with FP , returning to 3.3 ± 1.1 × 106 cells/g and 0.5 ± 0.3 × 106 neutrophils/g following the washout period . The percentages of neutrophils were 55.6 and 77.9 % in groups A and B after 2 months of FP treatment . There was no significant change in group B values during the study . Conclusion : These data suggest that neutrophilic inflammation in sputum may be decreased by inhaled corticosteroids in clinical ly stable COPD patients
Background Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease ( COPD ) remains controversial .
We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD .