Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial Characterisation of COPD heterogeneity in the ECLIPSE cohort Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Systemic glucocorticoids in severe exacerbations of COPD. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Comparison of two systemic steroid regimens for the treatment of COPD exacerbations. Compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AECOPD. Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease. Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to-moderate COPD exacerbations Distinct clinical phenotypes of airways disease defined by cluster analysis Two different dosages of nebulized steroid versus parenteral steroid in the management of COPD exacerbations: A randomized control trial Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Standardizing measurement of chronic obstructive pulmonary disease exacerbations. Reliability and validity of a patient-reported diary. [The effects and therapeutic duration of oral corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary diseases]. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Resource use and risk factors in high-cost exacerbations of COPD. Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial. Short versus conventional term glucocorticoid therapy in acute exacerbation of chronic obstructive pulmonary disease - the "REDUCE" trial. Characterisation and impact of reported and unreported exacerbations: results from ATTAIN Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease. Prevalence and predictors of vertebral fracture in patients with chronic obstructive pulmonary disease.
BACKGROUND The value of azithromycin for treatment of acute bronchitis is unknown , even though this drug is commonly prescribed . We have investigated this question in a r and omised , double-blind , controlled trial . METHODS Adults diagnosed with acute bronchitis , without evidence of underlying lung disease , were r and omly assigned  azithromycin ( n=112 ) or vitamin C  ( n=108 ) for 5 days ( total dose for each 1.5 g ) . All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer . The primary outcome was improvement in health-related quality of life at 7 days ; an important difference was defined as 0.5 or greater . Analysis was by intention to treat . FINDINGS The study was stopped by the data -monitoring and safety committee when 220 patients had been recruited . On day 7 , the adjusted difference in health-related quality of life was small and not significant ( difference 0.03 [ 95 % CI -0.20 to 0.26 ] , p=0.8 ) . 86 ( 89 % ) of 97 patients in the azithromycin group and 82 ( 89 % ) of 92 in the vitamin C group had returned to their usual activities by day 7 ( difference 0.5 % [ -10 % to 9 % ] , p>0.9 ) . There were no differences in the frequency of adverse effects ; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects , compared with none in the azithromycin group . Most patients ( 81 % ) reported benefit from the albuterol inhaler . INTERPRETATION Azithromycin is no better than low-dose vitamin C for acute bronchitis . Further studies are needed to identify the best treatment for this disorder BACKGROUND The role of oral corticosteroids in treating patients with exacerbations of chronic obstructive pulmonary disease ( COPD ) remains contentious . We assessed in a prospect i ve , r and omised , double-blind , placebo-controlled trial the effects of oral corticosteroid therapy in patients with exacerbations of COPD requiring hospital admission . METHODS We recruited patients with non-acidotic exacerbations of COPD who were r and omly assigned oral prednisolone 30  mg once daily  ( n=29 ) or identical placebo ( n=27 ) for 14 days , in addition to st and ard treatment with nebulised bronchodilators , antibiotics , and oxygen . We did spirometry and recorded symptom scores daily in in patients . Time to discharge and withdrawals were noted in each group . We recalled patients at 6 weeks to repeat spirometry and collect data on subsequent exacerbations and treatment . Hospital stay was analysed by intention to treat and forced expiratory volume in 1 s ( FEV1 ) according to protocol . FINDINGS FEV1 after bronchodilation increased more rapidly and to a greater extent in the corticosteroid-treated group : percentage predicted FEV1 after bronchodilation rose from 25.7 % ( 95 % CI 21.0 - 30.4 ) to 32.2 % ( 27.3 - 27.1 ) in the placebo group ( p<0.0001 ) compared with 28.2 % ( 23.5 - 32.9 ) to 41.5 % ( 35.8 - 47.2 ) in the corticosteroid-treated group ( p<0.0001 ) . Up to day 5 of hospital stay , FEV1 after bronchodilation increased by 90 mL daily ( 50.8 - 129.2 ) and by 30 mL daily ( 10.4 - 49.6 ) in the placebo group ( p=0.039 ) . Hospital stays were shorter in the corticosteroid-treated group . Groups did not differ at 6-week follow-up . INTERPRETATION These data provide evidence to support the current practice of prescribing low-dose oral corticosteroids to all patients with non-acidotic exacerbations of COPD requiring hospital admission Background Chronic obstructive pulmonary disease ( COPD ) is a complex condition with pulmonary and extra-pulmonary manifestations . This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort ( ECLIPSE ) . Methods We studied 2164 clinical ly stable COPD patients , 337 smokers with normal lung function and 245 never smokers . In these individuals , we measured clinical parameters , nutritional status , spirometry , exercise tolerance , and amount of emphysema by computed tomography . Results COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function . Co-morbidities were more prevalent in COPD patients than in controls , and occurred to the same extent irrespective of the GOLD stage . The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness , health status , presence of co-morbidity , exercise capacity and number of exacerbations reported in the year before the study . The distribution of these variables within each GOLD stage was wide . Even in subjects with severe airflow obstruction , a substantial proportion did not report symptoms , exacerbations or exercise limitation . The amount of emphysema increased with GOLD severity . The prevalence of bronchiectasis was low ( 4 % ) but also increased with GOLD stage . Some gender differences were also identified . Conclusions The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease Recommendation of the use of systemic steroids in chronic obstructive disease ( COPD ) exacerbation rely on trials that excluded patients requiring ventilatory support . In an open-label , r and omised evaluation of oral prednisone administration , 217 patients with acute COPD exacerbation requiring ventilatory support were r and omised ( with stratification on the type of ventilation ) to usual care ( n=106 ) or to receive a daily dose of prednisone ( 1 mg·kg−1 ) for up to 10 days ( n=111 ) . There was no difference regarding the primary end-point , intensive care unit mortality , which was 17 ( 15.3 % ) deaths versus 15 ( 14 % ) deaths in the steroid-treated and control groups , respectively ( relative risk 1.08 , 95 % CI 0.6–2.05 ) . Analysis according to ventilation modalities showed similar mortality rates . Noninvasive ventilation failed in 15.7 % and 12.7 % ( relative risk 1.25 , 95 % CI 0.56–2.8 ; p=0.59 ) , respectively . Both study groups had similar median mechanical ventilation duration and intensive care unit length of stay , which were 6 ( interquartile range 6–12 ) days versus 6 ( 3.8–12 ) days and 9 ( 6–14 ) days versus 8 ( 6–14 ) days , respectively . Hyperglycaemic episodes requiring initiation or alteration of current insulin doses occurred in 55 ( 49.5 % ) patients versus 35 ( 33 % ) patients in the prednisone and control groups , respectively ( relative risk 1.5 , 95 % CI 1.08–2.08 ; p=0.015 ) . Prednisone did not improve intensive care unit mortality or patient-centred outcomes in the selected subgroup of COPD patients with severe exacerbation but significantly increased the risk of hyperglycaemia . In COPD exacerbation needing ventilatory support , prednisone has no impact on ICU mortality or related patient outcome OBJECTIVE The aim of the study was to explore the clinical value of a step-wise application of methylprednisolone ( MP ) compared to dexamethasone ( DXM ) in acute exacerbations of COPD . METHODOLOGY One hundred and forty-two patients with an acute exacerbation of COPD were divided r and omly into two groups : 71 patients were treated with MP and the other 71 patients were treated with DXM . Otherwise each group was given the same basic treatments : antibiotics , bronchodilators , oxygen therapy as well as st and ard hospital care . The patients in the MP group were given a tapering dose of MP for 7 - 14 days , and the patients in the DXM group were given a corresponding tapering dose of DXM for 7 - 14 days . Then both groups were given a gradually reducing dose of oral prednisone for 2 - 3 weeks . Two weeks before the prednisone was tapered off , inhaled corticosteroid was introduced . The patients ' symptom scores , physical signs , per cent predicted FEV1 % , and arterial blood gases were monitored before treatment and after the seventh day of treatment . RESULTS There was an obvious improvement in symptoms after 1 - 3 days in all 71 patients in the MP group , with their wheezing being distinctly reduced or disappearing entirely . The maximum benefit that occurred in the MP group ( 90.14 % ) was considerably higher than that of the DXM group ( 25.35 % ) , P < 0.05 . The predicted FEV1 % in the MP group increased from 46.7 + /- 10.6 to 67.5 + /- 12.4 , compared with an increase in the DXM group from 50.1 + /- 7.6 to 58.9 + /- 10.8 . The difference between the two groups was significant ( P < 0.05 ) . CONCLUSIONS An adequate and tapering dose of MP used in acute exacerbations of COPD can relieve the inflammatory reaction in airways and reduce airway spasm more promptly than DXM Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations . The aim of this study was to investigate whether these are related . Methods : Over 4 years ,  peak expiratory flow ( PEF ) and symptoms were measured at home daily by 109 patients with COPD ( 81 men ; median ( IQR ) age 68.1 ( 63–74 ) years ; arterial oxygen tension ( Pao2 ) 9.00 ( 8.3–9.5 ) kPa , forced expiratory volume in 1 second ( FEV1 ) 1.00 ( 0.7–1.3 ) l , forced vital capacity ( FVC ) 2.51 ( 1.9–3.0 ) l ) ; of these , 32 ( 29 men ) recorded daily FEV1 . Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations ( > or < 2.92 per year ) on lung function decline was examined using cross sectional , r and om effects models . Results : The 109 patients experienced 757 exacerbations . Patients with frequent exacerbations had a significantly faster decline in FEV1 and peak expiratory flow ( PEF ) of –40.1 ml/year ( n=16 ) and –2.9 l/min/year ( n=46 ) than infrequent exacerbators in whom FEV1 changed by –32.1 ml/year ( n=16 ) and PEF by –0.7 l/min/year ( n=63 ) . Frequent exacerbators also had a greater decline in FEV1 if allowance was made for smoking status . Patients with frequent exacerbations were more often admitted to hospital with longer length of stay . Frequent exacerbations were a consistent feature within a patient , with their number positively correlated ( between years 1 and 2 , 2 and 3 , 3 and 4 ) . Conclusions : These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD BACKGROUND In this r and omized , double-blind , placebo-controlled trial , we studied the effectiveness of prednisone in reducing the risk of relapse after outpatient exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS We enrolled 147 patients who were being discharged from the emergency department after an exacerbation of COPD and r and omly assigned them to 10 days of treatment with 40 mg of oral prednisone once daily or identical-appearing placebo . All patients received oral antibiotics for 10 days , plus inhaled bronchodilators . The primary end point was relapse , defined as an unscheduled visit to a physician 's office or a return to the emergency department because of worsening dyspnea , within 30 days after r and omization . RESULTS The overall rate of relapse at 30 days was lower in the prednisone group than in the placebo group ( 27 percent vs. 43 percent , P=0.05 ) , and the time to relapse was prolonged in those taking prednisone ( P=0.04 ) . After 10 days of therapy , patients in the prednisone group had greater improvements in forced expiratory volume in one second than did patients in the placebo group ( mean [ + /-SD ] increase from base line , 34+/-42 percent vs. 15+/-31 percent ; P=0.007 ) . Patients in the prednisone group also had significant improvements in dyspnea , as measured by the transitional dyspnea index ( P=0.04 ) and by the dyspnea domain of the Chronic Respiratory Disease Index Question naire ( P=0.02 ) , but not in health-related quality of life ( P=0.14 ) . CONCLUSIONS Outpatient treatment with oral prednisone offers a small advantage over placebo in treating patients who are discharged from the emergency department with an exacerbation of COPD BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often present with severe acute exacerbations requiring hospital treatment . However , little is known about the prognostic consequences of these exacerbations . A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality . METHODS Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital ( visits to the emergency service and admissions ) , patient age , smoking , body mass index , co-morbidity , long term oxygen therapy , forced spirometric parameters , and arterial blood gas tensions in a prospect i ve cohort of 304 men with COPD followed up for 5 years . The mean ( SD ) age of the patients was 71 ( 9 ) years and forced expiratory volume in 1 second was 46 (17)% . RESULTS Only older age ( hazard ratio ( HR ) 5.28 , 95 % CI 1.75 to 15.93 ) , arterial carbon dioxide tension ( HR 1.07 , 95 % CI 1.02 to 1.12 ) , and acute exacerbations of COPD were found to be independent indicators of a poor prognosis . The patients with the greatest mortality risk were those with three or more acute COPD exacerbations ( HR 4.13 , 95 % CI 1.80 to 9.41 ) . CONCLUSIONS This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis . Mortality increases with the frequency of severe exacerbations , particularly if these require admission to hospital OBJECTIVE This study aim ed to compare the efficacies of 3-day and 10-day courses of methylprednisolone ( MP ) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure . DESIGN Prospect i ve , r and omized , single-blind study . SETTING Tertiary-care center . PATIENTS AND METHODS Thirty-six patients were included in the study and r and omized into two groups : group 1 received MP , 0.5 mg/kg q6h for 3 days , and group 2 was administered the same dosage of MP for the first 3 days , after which it was tapered and terminated on the tenth day . There was no difference between the groups for age , baseline FEV(1 ) , PaO(2 ) , PaCO(2 ) , and pH levels . One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study . RESULTS Both groups showed significant improvements in PaO(2 ) and FEV(1 ) levels , but these were more marked in group 2 ( p = 0.012 and p = 0.019 , respectively ) . There was a significant increase in FVC levels in group 2 only ( p = 0.003 ) . Group 2 also had a more marked improvement in dyspnea on exertion . There was no difference between the two groups with regards to other parameters , including pH , PaCO(2 ) levels , and other symptom scores . Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months . Hyperglycemia occurred in two patients in each group . CONCLUSION In severe COPD exacerbations , a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome , but has no benefit in reducing exacerbation rates BACKGROUND Treatment with systemic corticosteroids for exacerbations of COPD results in improvement in clinical outcomes . On hospitalization , corticosteroids are generally administered IV . It has not been established whether oral administration is equally effective . We conducted a study to demonstrate that therapy with oral prednisolone was not inferior to therapy with IV prednisolone using a double-blind , double-dummy design . METHODS Patients hospitalized for an exacerbation of COPD were r and omized to receive 5 days of therapy with prednisolone , 60 mg IV or orally . Treatment failure , the primary outcome , was defined as death , admission to the ICU , readmission to the ICU because of COPD , or the intensification of pharmacologic therapy during a 90-day follow-up period . RESULTS A total of 435 patients were referred for a COPD exacerbation warranting hospitalization ; 107 patients were r and omized to receive IV therapy , and 103 to receive oral therapy .  Overall treatment failure within 90 days was similar , as follows : IV prednisolone , 61.7 % ; oral prednisolone , 56.3 % ( one-sided lower bound of the 95 % confidence interval [ CI ] , -5.8 % ) . There were also no differences in early ( ie , within 2 weeks ) treatment failure ( 17.8 % and 18.4 % , respectively ; one-sided lower bound of the 95 % CI , -9.4 % ) , late ( ie , after 2 weeks ) treatment failure ( 54.0 % and 47.0 % , respectively ; one-sided lower bound of the 95 % CI , -5.6 % ) , and mean ( + /- SD ) length of hospital stay ( 11.9 + /- 8.6 and 11.2 + /- 6.7 days , respectively ) . Over 1 week , clinical ly relevant improvements were found in spirometry and health-related quality of life , without significant differences between the two treatment groups . CONCLUSION Therapy with oral prednisolone is not inferior to IV treatment in the first 90 days after starting therapy . We suggest that the oral route is preferable in the treatment of COPD exacerbations . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00311961 RATIONALE Systemic steroids shorten recovery time , improve lung function and hypoxemia in COPD exacerbations . Although several studies have shown that both parenteral and oral steroids are effective and GOLD guideline recommends use of oral steroids at a dose of 30 - 40 mg/day , very little data exists as to whether any route of admininstration ( parenteral vs oral ) or any dose is more effective and /or safer . METHODS This was a r and omized , parallel-group study aim ing to compare the effectiveness and safety of orally administered lower dose of steroids with parenteral administration of higher doses . Thus , a total of 40 patients were included ; one group ( Group 1 , n = 20 ) received methylprednisolone ( MP ) as recommended by the GOLD guideline ( PO 32 mg/day for seven days ) and the other ( Group 2 , n = 20 ) was given IV MP at 1 mg/kg/day for four days and 0.5 mg/kg/day for three days . RESULTS The two groups were similar with regards to age ( 69.0 ± 10.5 vs 67.1 ± 8.4 years ) , duration of COPD ( 11.8 ± 8.3 vs 9.7 ± 7.7 years ) , FEV1 ( 41.3 ± 17.3 vs 34.0 ± 12.0 % ) , PaO2 levels ( 55.5 ± 9.9 vs 59.1 ± 11.0 mmHg ) and dyspnea scores ( 9.4 ± 1.1 vs 10.0 ± 1.0 ) . Worsening hypercapnic respiratory failure developed in two patients from Group 1 on days 1 and 2 , these were intubated and thus excluded from the study . At day 7 , both groups showed significant improvements in FEV1 levels ( 50.8 ± 19.4 and 43.8 ± 21.4 % , respectively ) ( Table 2 ) , PaO2 levels ( 66.5 ± 12.5 and 65.3 ± 10.6 mmHg , respectively ) ( Table 3 ) and dyspnea scores ( 3,5 ± 2,8 and 4.2 ± 2.8 ) ( Fig. 1 ) . The length of hospital stay was similar for the two groups ( 11.0 ± 3.9 vs 12.7 ± 6.4 ) . Regarding adverse events , four patients in Group 1 vs 11 patients in group 2 developed hyperglycemia . Besides , three patients in group 2 had worsening of previously controlled hypertension . All events were treated and controlled with administration of proper medications . All patients were followed up for three months . Eight patients in group 1 and 15 patients in group 2 had unplanned visits to their physicians or to the emergency rooms for recurring exacerbations . Four patients in group 1 and five patients in group 2 were readmitted to hospital for recurrence ( p = NS ) . During the follow-up two patients from group 1 died . CONCLUSION These data show that oral administration of MP at a dose 32 mg/day for seven days significantly improves lung function , symptom scores and oxygenation in patients admitted to the hospital for COPD exacerbation and is as effective as and possibly safer than parenteral admininistration of higher doses BACKGROUND Corticosteroids have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . However , whether inhaled corticosteroids ( IC ) alone have similar effects with systemic corticosteroid ( SCS ) is still unclear . OBJECTIVES To compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AE COPD . METHODS 30 AE COPD patients were r and omly divided into two group . Budesonide group ( 15 cases ) were treated with inhaled budesonide ( 3 mg Bid ) ; methylprednisolone group ( 15 cases ) were treated with systemic methylprednisolone ( methylprednisolone acetate injectable suspension 40 mg Qd for three days and then methylprednisolone tablets 8 mg Bid ) . Observe symptoms , lung function , blood gas analysis and adverse effects of the patients in two groups . Peripheral blood sample s were collected before and after treatment for 1 day , 4 days and 7 days . Interleukin-8 ( IL-8 ) and TNF-α levels were determined by an enzyme linked immunosorbent assay ( ELISA ) . Hs-CRP levels were detected by automatic biochemical analyzer . Western blotting was used to determine histone deacetylase 2 ( HDAC2 ) protein expression . MEASUREMENTS AND MAIN RESULTS Symptoms , pulmonary function and blood gas analysis were significantly improved after treatment in the two groups ( P < 0.05 ) and no significant differences between the two groups ( P > 0.05 ) . There were no significant differences of IL-8 , TNF-α and hs-CRP levels in the two groups ( P > 0.05 ) . Besides , the levels of HDAC2 protein expression before treatment were significantly lower comparing to that after treatment for 4 and 7 days . Incidence of adverse events ( heart rate , blood pressure , glycemic , sleep condition , gastrointestinal symptoms ) in budesonide group was lower than methylprednisolone group ( P < 0.05 ) . CONCLUSIONS Inhaled budesonide and systemic methylprednisolone have the same effects on systemic inflammation of AE COPD . Inhaled corticosteroid alone could instead systemic corticosteroid in AE COPD treatment RATIONALE The EXAcerbations of Chronic Pulmonary Disease Tool ( EXACT ) is a patient-reported outcome measure to st and ardize the symptomatic assessment of chronic obstructive pulmonary disease exacerbations , including reported and unreported events . The instrument has been vali date d in a short-term study of patients with acute exacerbation and stable disease ; its performance in longer-term studies has not been assessed . OBJECTIVES To test the EXACT 's performance in three r and omized controlled trials and describe the relationship between re source -defined medically treated exacerbations ( MTEs ) and symptom (EXACT)-defined events . METHODS Prespecified secondary analyses of data from phase II r and omized controlled trials testing new drugs for the management of chronic obstructive pulmonary disease : one 6-month trial ( United States ) ( n = 235 ) and two 3-month , multinational trials ( AZ 1 [ n = 749 ] , AZ 2 [ n = 597 ] ) . In each case , the experimental drugs were found to be ineffective , permitting assessment of the EXACT 's performance in three independent studies of moderate to severe high-risk patients on maintenance therapies . MEASUREMENTS AND MAIN RESULTS The mean age of subjects was 62 to 64 years ; 48 to 76 % were male . Mean FEV1 % predicted was 42 to 59 % . EXACT scores exhibited internal consistency ( Cronbach 's α ≥ 0.90 ) , reproducibility ( intraclass correlation ≥ 0.70 ) , correlation with St. George 's Respiratory Question naire ( Spearman rho [ rs ] = 0.62 , 0.46 , 0.46 in the three trials ; P < 0.001 ) , and Breathlessness Cough and Sputum Scale ( AZ 1 , rs = 0.83 ; AZ 2 , rs = 0.83 ; P < 0.001 ) . EXACT-defined events had a high correspondence with alternative indicators of worsening ( 94 , 88 , and 93 % ) . In each trial , unreported events were similar in severity ( mean EXACT score , 56 , 57 , 61 vs. 53 , 54 [ P < 0.05 ] , 57 [ P < 0.05 ] , respectively ; 100-point scale ) and longer ( median , 9 , 8 , 7 vs. 8 , 7 [ P < 0.01 ] , 6 days , respectively ) than moderate MTEs . CONCLUSIONS Data generated through the EXACT offers insight into the symptomatic nature of MTEs and the frequency , severity , and duration of unreported symptom-defined events . Clinical trials registered with www . clinical trials.gov ( MPEX : NCT00739648 ; AZ 1 : NCT00949975 ; AZ 2 : NCT01023516 ) Background The effectiveness of antibiotics in chronic obstructive pulmonary disease ( COPD ) exacerbations is still a matter of debate , especially in out patients with an intermediate probability of bacterial infection . Methods In this study , 35 COPD out patients diagnosed by their chest physician with moderately severe COPD exacerbation , but without pneumonia , were r and omised in a double blind , placebo-controlled study . Patients had one or two of the following characteristics : a positive Gram 's stain of the sputum , 2 or more exacerbations in the previous year , a decrease in lung function of > 200 mL and > 12 % . Patients received amoxicillin clavulanic acid ( 500/125 mg three times daily ) or placebo for 7 days , always combined with a course of prednisolone ( 30 mg/day ) for 7 days . Primary outcome was duration of the exacerbation . Additionally , we measured severity of the exacerbation , health-related quality of life , sputum parameters , number of relapses within 28 days and the number of re-exacerbations within 4 months after the study . Results There was no difference observed in time to resolution of the exacerbation between the two groups ( HR=1.12 ; ( 95 % CI 0.5 to 2.3 ; p=0.77 ) ) , nor in any other treatment parameter . Conclusions We detected no evidence for the effectiveness of addition of antibiotics to prednisolone for COPD exacerbations of moderate severity and with intermediate probability of bacterial infection in this underpowered study . More placebo-controlled studies are needed to properly define subgroups of COPD out patients in which antibiotics are of additional value . Trials registration number clinical trial registered with http://www.trialregister.nl/(NTR351 ) Airways disease is currently classified using diagnostic labels such as asthma , chronic bronchitis and emphysema . The current definitions of these classifications may not reflect the phenotypes of airways disease in the community , which may have differing disease processes , clinical features or responses to treatment . The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease . A r and om population sample of 25–75-yr-old adults underwent detailed investigation , including a clinical question naire , pulmonary function tests , nitric oxide measurements , blood tests and chest computed tomography . Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results . Subjects with a complete data set ( n = 175 ) were included in the cluster analysis . Five clusters were identified with the following characteristics : cluster 1 : severe and markedly variable airflow obstruction with features of atopic asthma , chronic bronchitis and emphysema ; cluster 2 : features of emphysema alone ; cluster 3 : atopic asthma with eosinophilic airways inflammation ; cluster 4 : mild airflow obstruction without other dominant phenotypic features ; and cluster 5 : chronic bronchitis in nonsmokers . Five distinct clinical phenotypes of airflow obstruction were identified . If confirmed in other population s , these findings may form the basis of a modified taxonomy for the disorders of airways obstruction Background The study aim ed to compare the efficacy and safety of nebulized steroid ( NS ) with systemic corticosteroids ( SC ) and to determine optimal NS dose in the treatment of patients with COPD exacerbations requiring hospitalization . Material / Methods The study was a r and omized , parallel design trial . Eligible patients ( n=86 ) were r and omly allocated to 1 of the 3 treatment groups : parenteral corticosteroid ( PS ) ( n=33 ) , 4 mg ( NB ) ( n=27 ) , or 8 mg NB ( n=26 ) . Partial pressure of arterial oxygen ( PaO2 ) , carbon dioxide ( PaCO2 ) , pH , and oxygen saturation ( SaO2 ) were evaluated at baseline , 24 h , 48 h , and discharge . Airway obstruction ( forced vital capacity [ FVC ] and forced expiratory volume 1 s [ FEV1 ] ) was evaluated at admission and discharge . Results There were no significant differences between the groups for all parameters at all time periods , except for higher FEV1 value in the 8-mg NB group at baseline . In groups , significant differences were determined for FVC , FEV1 , PaO2 , and SaO2 ( p<0.001 ) , but not for PaCO2 and pH , in comparison to their baseline values . As adverse events , hyperglycemia and oral moniliasis were observed in the PS group ( n=4 ) and in the NB groups ( n=5 ) , respectively , and treatment change was required in 9 patients ( 2 patients in the PS group and 7 patients in the NB groups ) ( p=0.57 ) . Conclusions Nebulized budesonide may be used as an alternative to SC because of its equal effectiveness and lesser systemic adverse effects . The choice of optimal dosage needs to be evaluated carefully because adverse effect and dropout rates varied according to dosage . However , there is a need for further studies including more severe cases and evaluating long-term outcomes or relapses comparing the 3 arms The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic .  The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic .  Peak flow recovered more rapidly with antibiotic treatment than with placebo .  Side effects were uncommon and did not differ between antibiotic and placebo RATIONALE Although exacerbations are an important problem in chronic obstructive pulmonary disease ( COPD ) and a target of intervention , there is no valid , st and ardized tool for assessing their frequency , severity , and duration . OBJECTIVES This study tested the properties of the Exacerbations of Chronic Pulmonary Disease Tool ( EXACT ) , a new patient-reported outcome diary . METHODS A prospect i ve , two-group , observational study was conducted in patients with COPD . The acute group ( n = 222 ) was enrolled during a clinic visit for exacerbation with follow-up visits on Days 10 , 29 , and 60 . The stable group ( n = 188 ) , recruited by telephone or during routine visits , was exacerbation free for at least 60 days . MEASUREMENTS AND MAIN RESULTS Acute patients completed the diary on Days 1 - 29 and 60 - 67 ; stable patients for 7 days . All patients provided stable-state spirometry and completed the St. George Respiratory Question naire- COPD ( SGRQ-C ) . Acute patient assessment s included clinician and patient global ratings of exacerbation severity and recovery .  Mean age of the sample ( n = 410 ) was 65 ( ± 10 ) years ; 48 % were male ; stable FEV₁ was 51 % predicted ( ± 20 ) .  Internal consistency ( Pearson separation index ) for the EXACT was 0.92 , 1-week reproducibility ( stable patients ; intraclass correlation ) was 0.77 . EXACT scores correlated with SGRQ-C ( r = 0.64 ; P < 0.0001 ) and differentiated acute and stable patients ( P < 0.0001 ) . In acute patients , scores improved over time ( P < 0.0001 ) and differentiated between degrees of clinician-rated exacerbation severity ( P < 0.05 ) . EXACT change scores differentiated responders and nonresponders on Day 10 , as judged by clinicians or patients ( P < 0.0001 ) . CONCLUSIONS Results suggest the EXACT is reliable , valid , and sensitive to change with exacerbation recovery OBJECTIVE To observe the clinical efficacy and therapeutic duration of oral corticosteroids in patients with acute exacerbations of chronic obstructive pulmonary diseases ( AE COPD ) . METHODS A r and omized , double-blinded , placebo-controlled clinical study was design ed . One hundred and thirty hospitalized patients with AE COPD were r and omly divided into three groups : group 1 ( n = 44 ) received 30 mg/d of prednisone for 7 days and then placebo for another 7 days ; group 2 ( n = 43 ) received 30 mg/d of prednisone for 10 days , then tapered to 15 mg/d for 4 days ; group 3 ( n = 43 ) received placebo for 14 days . The lung functions , arterial blood gas , length of stay , symptom scores , failure rate of treatment , side-effect of corticosteroids and the rate of relapse were evaluated before and after treatments . The results were analyzed by statistical package for social science ( SPSS version 11.0 ) . Measurement data were expressed by ( -x ) + /- s , and t test was used for the comparison of the data before and after treatments . Chi-square test was used for the comparison of count data . Analysis of variance was applied to test for differences between the three groups . Multiple comparison was analyzed by SNK test . Fisher exact test was used for the comparison of the failure rate of treatment , the rate of relapse and safety evaluation . RESULTS Compared with the placebo group [ group 3 , ( 0.74 + /- 0.32)L ] , the FEV(1 ) in [ group 1 ( 0.87 + /- 0.23 ) L and in group 2 ( 0.93 + /- 0.30 ) L ] were significantly increased ( F = 4.53 , P < 0.05 ) . The PaO(2 ) in group 1 ( 79 + /- 9 ) mm Hg ( 1 mm Hg = 0.133 kPa ) and in group 2 ( 80 + /- 10 ) mm Hg were also increased significantly [ group 3 was ( 73 + /- 12 ) mm Hg ] ( F = 3.98 , P < 0.05 ) . The length of stay ( LOS ) in group 1 ( 12.5 + /- 3.5 ) d and in group 2 ( 12.4 + /- 4.1 ) d were shortened [ group 3 was ( 13.5 + /- 3.6 ) d ] ( F = 3.82 , P < 0.05 ) . However , no difference of FEV(1 ) , PaO(2 ) and LOS was found between 7-day and 14-day duration s of corticosteroids therapy . There were no differences in symptom scores , failure rate of treatment , side-effect of corticosteroids and the rate of relapse among the 3 groups . CONCLUSIONS Oral prednisone results in improvement of FEV(1 ) , PaO(2 ) and LOS in hospitalized patients with AE COPD . A 7-day or 14-day duration of oral prednisone is of the same clinical efficacy . From these results , we recommend that 30 mg/d of prednisone for a 7-day duration is appropriate for the treatment of AE COPD To evaluate the role of corticosteroids as treatment for acute exacerbations of chronic obstructive pulmonary disease , we conducted a double-blind , r and omized , placebo-controlled trial in 44 consecutive patients with chronic bronchitis and severe airflow obstruction . All were hospitalized with acute respiratory insufficiency from acute bronchitis . Patients with asthma , atopy , or pneumonia were excluded . Treatment consisted of intravenous aminophylline , inhaled isoproterenol , antibiotics , and either methylprednisolone , 0.5 mg/kg of body weight , or placebo every 6 h intravenously for 72 h. Bedside spirometry  was done before and after bronchodilator inhalation three times daily . The methylprednisolone-treated group had a greater improvement in both prebronchodilator and postbronchodilator forced expiratory volume in 1 second ( P less than 0.001 ) . More patients with large improvements in their prebronchodilator or postbronchodilator flow rates , or both ( greater than or equal to 40 % by 72 h ) , received methylprednisolone ( P less than 0.01 ) . Methylprednisolone improved airflow more than placebo when added to st and ard therapy in patients with chronic bronchitis and acute respiratory insufficiency Patients hospitalised for exacerbations contribute significantly to the total chronic obstructive pulmonary disease ( COPD ) -related healthcare costs . This study aim ed to determine the re source use and costs of exacerbations by exacerbation-severity and to identify risk factors for hospitalisation . Exacerbations and the details of all associated healthcare utilisation were recorded as part of a prospect i ve cost-effectiveness analysis linked to two r and omised controlled trials comparing tiotropium with ipratropium in 519 patients with stable COPD at study entry in the Netherl and s and Belgium .  Exacerbation-severity was rated by the physician . A Cox proportional hazards analysis was performed to identify independent risk factors of hospitalisation . Covariates that entered this analysis were smoking status , pack-years , body mass index , number of concomitant diseases , number of concomitant medications , use of inhaled steroids , physician visits prior to trial , FEV1 % predicted , quality of life , baseline dyspnea index ( BDI ) and treatment arm . The mean number of exacerbations per patient was 0.70 ( 95%-CI:0.60 , 0.81 ) . About 10 % of the exacerbations was severe , 47 % moderate and 43 % was mild . The mean costs of these exacerbations were Euro 4007 ( 95%-CI:2004 , 6011 ) , Euro 579 ( 390 , 768 ) and Euro 86 ( 49 , 124 ) , respectively . In addition to treatment arm , a body mass index below 18.5 ( RR:3.62 ) , each additional concomitant diagnosis ( RR:1.40 ) and a decrease of 1 point in the baseline dyspnea index ( RR:1.18 ) were significant risk factors of hospitalisation . Exacerbations that were associated with a hospitalisation accounted for 90 % of the total costs of exacerbations . Underweight , history of concomitant diseases and increased dyspnea ( BDI score ) are factors that are likely to identify patients who are at increased risk for generating high costs due to hospitalisation OBJECTIVE To analyze prospect ively the hypothalamic-pituitary-adrenal ( HPA ) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve observational study . SUBJECTS AND METHODS Patients presenting to the emergency department were r and omized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner . The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline , on day 6 before blinded treatment , at hospital discharge , and for up to 180 days of follow-up . Prednisone was stopped abruptly , irrespective of the test results . Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment . RESULTS A total of 311 patients were included in the analysis . Mean basal and stimulated serum total cortisol levels were highest on admission ( 496±398 and 816±413 nmol/l respectively ) and lowest on day 6 ( 235±174 and 453±178 nmol/l respectively ) . Pathological stimulation tests were found in 63 , 38 , 9 , 3 , and 2 % of patients on day 6 , at discharge , and on days 30 , 90 , and 180 respectively , without significant difference between treatment groups . Clinical indicators of hypocortisolism did not correlate with stimulation test results , but cortisol levels were inversely associated with re-exacerbation risk . There were no hospitalizations or deaths as a result of adrenal crisis . CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD . In hypocortisolemic patients who were provided with instructions about stress prophylaxis , the abrupt termination of prednisone appeared safe BACKGROUND International guidelines advocate a 10 to 14-day course of systemic glucocorticoid therapy in the management of COPD exacerbations . The optimal duration of therapy is unknown and glucocorticoids have serious adverse effects . The aim of this trial is to demonstrate non-inferiority of a five-day compared to a 14-day course of systemic glucocorticoids with respect to COPD outcome , thereby significantly reducing steroid exposure and side effects in patients with COPD exacerbations . METHODS This is a r and omised , placebo-controlled , non-inferiority multicentre trial . Patients with acute COPD exacerbation are r and omised to receive 40 mg of prednisone-equivalent daily for 14 days ( conventional arm ) or glucocorticoid treatment for 5 days , followed by placebo for another 9 days ( intervention arm ) . Follow-up is 180 days . The primary endpoint is time to next exacerbation . Secondary endpoints include cumulative glucocorticoid dose , time to open-label glucocorticoid therapy , glucocorticoid-associated side effects and complications , duration of hospital stay , death , change in FEV1 , need for assisted ventilation , clinical outcome assessed by st and ardised question naires , and suppression of the hypothalamic-pituitary-adrenal axis . RESULTS Mean age ( ± SD ) of patients who finished the study was 70 ± 11 years . 12 % had mild or moderate disease , whereas severe and very severe stages were found in 30 and 58 % , respectively . At the time of inclusion , 20 % of patients were under treatment with systemic glucocorticoids . CONCLUSIONS If the strategy of significantly reducing cumulative exposure to glucocorticoids while taking advantage of their beneficial short-term effects proves to be successful , it will warrant a change in common glucocorticoid prescription practice , thereby improving the management of COPD The frequency and impact of exacerbations identified using healthcare re source utilisation ( HCRU ) or the EXAcerbations of Chronic pulmonary disease Tool ( EXACT ) were compared prospect ively in a 24-week , phase III trial ( ATTAIN ) . Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 & mgr;g , aclidinium 400 & mgr;g or placebo . All HCRU events were reported to physicians . “ EXACT-identified ” events were categorised as “ EXACT-reported ” ( detected by EXACT and reported to the physician ) and “ EXACT-unreported ” ( detected but not reported ) . Health status was measured using the St George ’s Respiratory Question naire ( SGRQ ) . Annualised EXACT-identified event rates were higher in all study arms ( placebo 1.39 , aclidinium 200 & mgr;g 1.00 and aclidinium 400 & mgr;g 0.98 per patient per year ) versus HCRU ( placebo 0.60 , aclidinium 200 & mgr;g 0.43 and aclidinium 400 & mgr;g 0.40 per patient per year ) . Concordance between methods was low ( kappa 0.16 ) . Aclidinium reduced EXACT-identified events ( rate ratio versus placebo : aclidinium 200 & mgr;g 0.72 and aclidinium 400 & mgr;g 0.71 ; both p<0.05 ) ; HCRU events were similarly reduced . At week 24 , SGRQ scores improved ( -6.6 versus baseline ) in patients with no event during weeks 1–12 ; improvements were significantly smaller in patients with HCRU events ( -3.4 ; p=0.036 ) or EXACT-unreported events ( -3.0 ; p=0.002 ) . Unreported events were more frequent than reported events . Both had similar negative impact on health status .  Aclidinium reduced the frequency of both types of event . There are twice as many unreported exacerbation events as reported events ; both have similar impact on health status BACKGROUND Chronic lung diseases and drugs used to treat patients with chronic lung diseases may be associated with an increased fracture risk . METHODS The design was a case-control study of all patients with a fracture ( n=124,655 ) in the year 2000 in Denmark as case subjects . For each case subject , three age- and gender-matched control subjects were r and omly drawn from the general population ( n=373,962 ) . RESULTS Chronic lung diseases such as COPD ( odds ratio [ OR ] , 1.19 ; 95 % confidence interval [ CI ] , 1.13 to 1.25 ) , emphysema ( OR , 1.31 ; 95 % CI , 1.16 to 1.48 ) , and other chronic lung diseases ( OR , 1.20 ; 95 % CI , 1.00 to 1.44 ) were associated with a higher relative risk of any fracture than asthma ( OR , 1.06 ; 95 % CI , 1.01 to 1.12 ) . Oral corticosteroids were associated with a dose-dependent increased risk of fractures .  Inhaled short-acting beta-agonists were associated with an increase in fracture risk that was not dose dependent and was seen already at low doses . Oral beta-agonists were associated with an increase in fracture risk at low doses but not at higher doses . Other bronchodilators ( inhaled long-acting beta-agonists , inhaled beta-agonists plus inhaled corticosteroids , inhaled beta-agonists plus antimuscarinic substances , inhaled antimuscarinic substances , inhaled cromoglycate and cromoglycate-like substances , oral theophylline , and oral leukotriene receptor antagonists ) , and inhaled corticosteroids were not associated with fracture risk . CONCLUSIONS The increase in fracture risk seen with inhaled short-acting beta-agonists may be linked to the severity of the underlying lung disease rather than with the beta-agonists , per se , as other types of beta-agonists were not associated with fractures BACKGROUND The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial . In older studies , the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease . However , these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time . We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease . METHODS We conducted a prospect i ve study in which clinical information and sputum sample s for culture were collected monthly and during exacerbations from 81 out patients with chronic obstructive pulmonary disease .  Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae , Moraxella catarrhalis , Streptococcus pneumoniae , and Pseudomonas aeruginosa was performed . RESULTS Over a period of 56 months , the 81 patients made a total of 1975 clinic visits , 374 of which were made during exacerbations ( mean , 2.1 per patient per year ) . On the basis of molecular typing , an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen , as compared with 15.4 percent of visits at which no new strain was isolated ( P<0.001 ; relative risk of an exacerbation , 2.15 ; 95 percent confidence interval , 1.83 to 2.53 ) . Isolation of a new strain of H. influenzae , M. catarrhalis , or S. pneumoniae was associated with a significantly increased risk of an exacerbation . CONCLUSIONS The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease IMPORTANCE International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease ( COPD ) . However , the optimal dose and duration are unknown . OBJECTIVE To investigate whether a short-term ( 5 days ) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional ( 14 days ) treatment in clinical outcome and whether it decreases the exposure to steroids . DESIGN , SETTING , AND PATIENTS REDUCE : ( Reduction in the Use of Corticosteroids in Exacerbated COPD ) , a r and omized , noninferiority multicenter trial in 5 Swiss teaching hospitals , enrolling 314 patients presenting to the emergency department with acute COPD exacerbation , past or present smokers ( ≥20 pack-years ) without a history of asthma , from March 2006 through February 2011 . INTERVENTIONS Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled , double-blind fashion . The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15 % , translating to a critical hazard ratio of 1.515 for a reference event rate of 50 % . MAIN OUTCOME AND MEASURE Time to next exacerbation within 180 days . RESULTS Of 314 r and omized patients , 289 ( 92 % ) of whom were admitted to the hospital , 311 were included in the intention-to-treat analysis and 296 in the per- protocol analysis . Hazard ratios for the short-term vs conventional treatment group were 0.95 ( 90 % CI , 0.70 to 1.29 ; P = .006 for noninferiority ) in the intention-to-treat analysis and 0.93 ( 90 % CI , 0.68 to 1.26 ; P = .005 for noninferiority ) in the per- protocol analysis , meeting our noninferiority criterion . In the short-term group , 56 patients ( 35.9 % ) reached the primary end point ; 57 ( 36.8 % ) in the conventional group . Estimates of reexacerbation rates within 180 days were 37.2 % ( 95 % CI , 29.5 % to 44.9 % ) in the short-term ; 38.4 % ( 95 % CI , 30.6 % to 46.3 % ) in the conventional , with a difference of -1.2 % ( 95 % CI , -12.2 % to 9.8 % ) between the short-term and the conventional . Among patients with a reexacerbation , the median time to event was 43.5 days ( interquartile range [ IQR ] , 13 to 118 ) in the short-term and 29 days ( IQR , 16 to 85 ) in the conventional . There was no difference between groups in time to death , the combined end point of exacerbation , death , or both and recovery of lung function . In the conventional group , mean cumulative prednisone dose was significantly higher ( 793 mg [ 95 % CI , 710 to 876 mg ] vs 379 mg [ 95 % CI , 311 to 446 mg ] , P < .001 ) , but treatment-associated adverse reactions , including hyperglycemia and hypertension , did not occur more frequently . CONCLUSIONS AND RELEVANCE In patients presenting to the emergency department with acute exacerbations of COPD , 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure . These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N19646069 BACKGROUND This study aim ed to investigate the prevalence rate of critical illness-related corticosteroid insufficiency ( CIRCI ) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . METHODS Since January 2010 to December 2012 , 385 patients , who met the criteria of AE COPD , were enrolled in the Intensive Care Unit ( ICU ) of the First People 's Hospital and Municipal Central Hospital of Xiangtan City . The AE COPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group ( n=32 ) and a control group ( n=31 ) for a prospect i ve , r and omized and controlled clinical trial . Hydrocortisone ( 150 mg/d ) or normal saline was injected intravenously for 7 days . The patients were followed up for 28 days after injection . The endpoint included 28-day survival time , non-shock time , ICU stay and the period of non-mechanical ventilation . The markers of inflammation C-reactive protein , tumor necrosis factor-α , interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment . The variables were analyzed by Student 's t test , the non-parametric statistical test , the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software . A P value < 0.05 was considered statistically significant . RESULTS Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4 % . The shock rate of the AE COPD patients complicated with CIRCI was higher than that of the AE COPD patients without CIRCI ( 23.8 % vs. 8.7 % , P<0.01 ) . Kaplan-Meier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group ( P<0.05 ) . Compared with the control group , shock-free days within 28 days was longer in the treatment group ( 18.2±9.5 vs. 25.8±4.1 , P<0.05 ) . Treatment with low-dose glucocorticoid obviously decreased the markers of infection and inflammation ( P<0.01 ) , such as C-reactive protein ( 13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group ; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group ) , tumor necrosis factor-α ( 26.1±16.2 μg/L vs. 17.5±11.7 μg/L for the control group ; 25.0±14.8 μg/L vs. 10.4±7.8 μg/L for the treatment group ) and procalcitonin ( 3.88 μg/L vs. 2.03 μg/L for the control group ; 3.77 μg/L vs. 1.26 μg/L for the treatment group ) . Furthermore , the markers in the treatment group decreased more obviously than those in the control group ( P<0.01 ) . CONCLUSION The prevalence rate of CIRCI was higher in the patients with AE COPD in the department of critical medicine , and low-dose glucocorticoid treatment for one week reduced the 28-day mortality , shock time and markers of infection and inflammation OBJECTIVES Patients with COPD are at risk for osteoporosis-related vertebral compression fractures ( VCF ) which predispose to more fractures and worsening pulmonary function . Our objectives were to : 1 document VCF prevalence in COPD patients ; and 2 determine the independent correlates of VCF . METHODS From 2004 - 2006 , we prospect ively recruited consecutive consenting COPD patients presenting with acute exacerbation at three Canadian Emergency Departments ( ED ) . We collected clinical and pulmonary function data . Primary outcome was  radiologist documented VCF on chest radiograph . Multivariable logistic regression was used for all adjusted analyses . RESULTS Overall , 245 patients were studied ; 37 % were > or=75 years and 44 % were women .  Prevalence of VCF documented by chest radiograph was 22 of 245 ( 9 % ; 95%CI 6 - 13 % ) . Almost half ( 10 of 22 [ 43 % ] ) of VCF patients were not treated for osteoporosis and all 10 received oral steroids . Compared to patients without fractures , those with VCF were older ( p=0.014 ) , had COPD of longer duration ( p=0.09 ) and greater severity ( mean FEV(1 ) 0.9 vs 1.1L ; p=0.05 ) , and had lower body mass index [ BMI ] ( median 26 vs 28 ; p=0.01 ) . Across BMI quartiles ( from heaviest [ median 37 ] to lightest [ median 21 ] ) the prevalence of VCF progressively increased ( 2 % , 8 % , 10 % , 21 % ; p<0.001 ) . In analyses adjusted for age , sex , and COPD duration , the only independent correlate of VCF was BMI : VCF increased as BMI decreased from heaviest ( OR=1 ) to lightest ( OR=11.0 ) quartiles ( p=0.025 ) . CONCLUSIONS Almost one-tenth of COPD patients presenting with acute exacerbation have chest radiographs documenting VCF . About half of patients with VCF were not treated for osteoporosis , but all were started on oral steroids . Our findings suggest chest radiograph reports may represent an important case-finding tool for VCF , particularly in underweight patients with COPD
BACKGROUND Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease ( COPD ) should be treated with systemic corticosteroid for seven to 14 days .
Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis , hyperglycaemia and muscle weakness .
Shorter treatment could reduce adverse effects .
OBJECTIVES To compare the efficacy of short- duration ( seven or fewer days ) and conventional longer- duration ( longer than seven days ) systemic corticosteroid treatment of adults with acute exacerbations of COPD .