Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.

Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown. COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 microg b.i.d.) and oral prednisolone (30 mg o.d.) for 2 weeks. After this time, patients were randomised to b.i.d. inhaled budesonide/formoterol 320/9 microg, budesonide 400 microg, formoterol 9 microg or placebo for 12 months. Postmedication FEV1 improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254 versus 96 days) and maintained higher FEV1 (99% versus 87% of baseline), both primary variables versus placebo. They had fewer exacerbations (1.38 versus 1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQ versus placebo (-7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables. Budesonide/formoterol in a single inhaler (Symbicort) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.     

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.     

Does negative expiratory pressure influence performances of spirometry in older patients?

The aim of this study is to assess the influence of the negative expiratory pressure (NEP) technique on the performance of maximal expiratory manoeuvre in elderly patients. Firstly, the authors studied how NEP (at 5 and 10 cmH2O, NEP5 and NEP10) influences forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 60 young healthy volunteers, in order to assess the fluctuations of the method. In the second part of the study, 65 successive elderly inpatients (>70 yrs old) were examined. In this group, 15 elderly patients were unable to perform the manoeuvre, 27 had a normal function, 14 had a lung function with obstructive pattern and nine with restrictive pattern. In young subjects, FVC during NEP5 and NEP10 compared to baseline values was 101+/-5%, and 103+/-5%, respectively, and FEV1 was 100+/-4% and 101+/-5%, respectively. In elderly patients with normal function, FVC during NEP5 and NEP10 compared to baseline values was 99+/-14% and 109+/-23%, respectively, and FEV1 was 97+/-9% and 104+/-13%, respectively. There were no relevant effects of the NEP application on FVC or FEV1 values in elderly patients with an obstructive or restrictive pattern. In elderly patients, the use of the negative expiratory pressure technique during maximal expiratory manoeuvres provides little complementary information compared to a classical manoeuvre. The negative expiratory pressure technique did not modify the initial diagnosis when compared with the classical manoeuvre.     

Assessing response to treatment of exacerbations of bronchiectasis in adults

The present study aimed to assess the effect of intravenous antibiotic therapy on clinical and laboratory end-points in exacerbations of noncystic fibrosis bronchiectasis and to determine whether the outcomes were influenced by the pathogenic organism isolated. A prospective cohort study was conducted from November 2006 to March 2008 of exacerbations requiring intravenous antibiotics. End-points included 24-h sputum volume, forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test, qualitative sputum microbiology, white cell count, erythrocyte sedimentation rate, C-reactive protein (CRP) and St George's Respiratory Questionnaire (SGRQ). Exacerbations due to Pseudomonas aeruginosa were compared with exacerbations due to other potential pathogenic organisms. In total, 32 exacerbations were studied. Following 14 days of intravenous antibiotics, all outcomes significantly improved independent of a pathogenic organism, except FEV(1) and FVC. The most responsive markers were: 24-h sputum volume (reduced in all patients and 80% had >/=50% reduction); sputum bacterial clearance (78.1%); CRP (>/=75% reduction in 62.5%) and SGRQ (>/=4 unit improvement in 89.7%). CRP, 24-h sputum volume and SGRQ improved independent of microbial clearance. In the current study, 24-h sputum volume, microbial clearance, C-reactive protein and St George's Respiratory Questionnaire were the most useful parameters to assess response to treatment of exacerbations of bronchiectasis. Outcomes were similar independent of the pathogenic organism with the exception of forced expiratory volume in one second and forced vital capacity.     

Physiological changes during symptom recovery from moderate exacerbations of COPD.

Acute exacerbations of chronic obstructive disease (AECOPD) are characterised by worsening dyspnoea that is variably prolonged. In this study, physiological changes during moderate AECOPD were examined and the factors associated with dyspnoea resolution over time were determined. In total, 20 patients experiencing an AECOPD were evaluated within 72 h of initial worsening of symptoms (day 0) with pulmonary function testing, metabolic testing and symptom assessment using the dyspnoea domain of the Chronic Respiratory Disease Questionnaire (CRQ). Treatment was optimised and testing was repeated after 7, 14, 30 and 60 days. At day 0, patients were very short of breath (CRQ-dyspnoea mean+/-SEM 2.4+/-0.3) and showed significant airflow obstruction (forced expiratory volume in one second (FEV1) 41+/-3% predicted) and lung hyperinflation (forced residual capacity (FRC) 164+/-7% pred). By day 60 CRQ-dyspnoea improved to 4.6+/-0.5 (some shortness of breath); FRC and residual volume decreased by 5 and 11%, respectively; inspiratory capacity (IC) and slow vital capacity increased by 18 and 17%, respectively; and FEV1 increased by 18% with no change in FEV1/FVC. Total lung capacity did not change during AECOPD, and thus, changes in IC reliably reflected changes in end-expiratory lung volume. In conclusion, moderate acute exacerbation of chronic obstructive pulmonary disease is characterised by worsening airflow obstruction and lung hyperinflation. Improvement of dyspnoea following acute exacerbations of chronic obstructive pulmonary disease was associated with reduction in lung hyperinflation and consequent increase in expiratory flow rates.     

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.     

Anti-inflammatory effects of combined budesonide/formoterol in COPD exacerbations

Systemic corticosteroids and additional short-acting beta2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting beta2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV(1)), symptoms, health status, and adverse events. Forty-five patients not using steroids (37 male, 21/24 current/ex smoker, median packyears 38, age 65 years, FEV(1) 61% predicted), experiencing a COPD exacerbation, were treated at home with budesonide/formoterol (320/9 microg 4 times daily), prednisolone (30 mg daily), or placebo for 14 days. Sputum eosinophils were significantly reduced by budesonide/formoterol (-57%) compared to placebo (+24%) (p = 0.01). Budesonide/formoterol reduced total symptom scores significantly (p = 0.01) compared to placebo. The increase in FEV(1) by 2 weeks of treatment with budesonide/formoterol (125 ml) was not significantly different from that of placebo (43 ml) (p = 0.07). Budesonide/ formoterol treatment did not suppress morning serum cortisol compared to placebo (-16%; p = 0.50). In conclusion, budesonide/formoterol reduces sputum eosinophils and improves symptoms in the treatment of out-patient COPD exacerbations.     

Effects of corticosteroids on lung function in asthma and chronic obstructive pulmonary disease

Both oral and inhaled corticosteroids have clinically significant effects on symptoms, exacerbations, health status, and lung function in asthma, and to a lesser extent in chronic obstructive pulmonary disease (COPD). Change in FEV(1) does not correlate well with functional tests in COPD and may not be the best measure of response to treatment. Inhaled corticosteroids may be beneficial when added to a beta-agonist for treatment of acute asthma, and the efficacy of oral corticosteroids in this setting is well established. Oral corticosteroids inconsistently improve lung function in stable outpatients with COPD. Individual inhaled corticosteroids do not have a marked effect, but the combination of fluticasone propionate and salmeterol and the combination of budesonide plus formoterol seem to improve FEV(1) over treatment with the individual components. In addition, there is convincing evidence for the use of systemic corticosteroids during acute exacerbations of COPD. Some evidence suggests that patients with COPD who respond to corticosteroids have eosinophilic inflammation and other attributes of an asthma phenotype.     

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma

BACKGROUND: The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. METHODS: Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. RESULTS: In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. CONCLUSION: Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.     

Comparison of the lung function change in patients with COPD and bronchial asthma before and after treatment with budesonide/formoterol

Objective

This study investigated the rapid onset of bronchodilation effect and compared lung function changes following budesonide/formoterol (Symbicort Turbuhaler®) inhalation in Chinese patients with moderate-severe chronic obstructive pulmonary disease (COPD) and bronchial asthma.

Methods

In this open-label, parallel-group clinical study, patients eligible for study were divided into COPD group (n=62, mean age 68.16±8.75 years) and asthma group (n=30, mean age 45.80±12.35 years). Lung function tests (include FEV1, FVC, FEV1/FVC, and IC) were performed at baseline (t=0 min time point, value before inhalation of budesonide/formoterol), and then eligible patients received two inhalations of budesonide/formoterol (160/4.5 μg). Lung function tests were reassessed at t=3, 10 and 30 min time point. The primary end-point was lung function change 3 min after drug inhalation, and the secondary end-points were comparison of the gas flow rate (ΔFEV1) and volume responses (ΔFVC, ΔIC) between COPD and asthma patients after inhalation of budesonide/formoterol.

Results

Compared with the baseline, all patients significantly improved their lung function (included FEV1, FVC, FEV1/FVC, and IC) at 3 min (P<0.05). Greater bronchodilation efficacy was found in the asthma group compared with the COPD group (P<0.05). In the asthmatic patients, the curves of FEV1, FVC, FEV1/FVC, IC, showed improvement with an ascending trend at all time points from 3 to 30 min. Whereas in the COPD patients, only the curves of FEV1, FVC, IC showed similar pattern. We found that ΔFVC was significantly higher than ΔFEV1 in both groups (P<0.05), but no significant difference between ΔIC and ΔFEV1 (P>0.05). Compared with COPD group, asthma group had higher level of ΔFEV1 and ΔIC (P<0.05), but no significant difference for ΔFVC can be found.

Conclusions

Budesonide/formoterol has a fast onset of bronchodilation effect in patients with moderate-severe COPD and asthma. Greater efficacy was found in the asthma group compared with the COPD group. The gas flow rate and volume responses in patients with COPD differ from those with asthma after inhalation of Budesonide/formoterol.KEY WORDS : Budesonide/formoterol, chronic obstructive pulmonary disease, bronchial asthma, lung function testChronic obstructive pulmonary disease (COPD) and bronchial asthma (asthma) have important similarities and differences. Both are chronic inflammatory diseases that cause airflow limitation (1,2). However, there are great difference between the two in terms of genetic basis, idiosyncratic reaction, airway hyper-responsiveness, inflammatory mediators and response to the treatment (3). There is neither study about the rapid onset of effect of ICS/LABA combination therapy (budesonide/formoterol) in China nor report about the differences of lung function change before and after treatment between patients with COPD and asthma all over the world.It is traditionally thought that the responses in bronchodilatation test of asthma and COPD are “gas flow rate responses” and “volume responses” respectively (1). But yet no report about the “gas flow rate responses” and “volume responses” of ICS/LABA such as budesonide/formoterol in patients with COPD and asthma is available.In this trial, we will determine the rapid onset of effect of budesonide/formoterol in patients with COPD and asthma by testing the lung function in several time points in a short time. In addition, we will discuss the differences of the gas flow rate and volume responses in patients with asthma and COPD after budesonide/formoterol inhalation.     

吸入异丙托溴铵联合布地奈德治疗哮喘-慢阻肺重叠综合征的效果探讨

目的以哮喘-慢阻肺重叠综合征患者为研究对象,探讨患者应用吸入异丙托溴铵与布地奈德联合治疗的效果。方法以90例哮喘-慢阻肺重叠综合征患者作为本次研究对象并随机分为两组,为对照组(n=45)患者实施布地奈德吸入治疗,为观察组(n=45)患者实施吸入异丙托溴铵与布地奈德联合治疗。结果治疗前患者FEV1、FEV1/FVC等肺功能指标组间差异显著(P>0.05),治疗后观察组患者FEV1、FEV1/FVC均高于对照组(P<0.05)。观察组0级及I级占比高于对照组,III级及IV级占比均低于对照组(P<0.05),两组患者III级占比差异不显著(P>0.05)。结论哮喘-慢阻肺重叠综合征患者采用异丙托溴铵与布地奈德联合吸入治疗能够使其呼吸困难症状得到有效缓解,肺功能改善效果理想。     

The effect of sleep loss on breathing in chronic obstructive pulmonary disease

We have previously shown that one night of sleep deprivation results in significant deterioration of spirometric performance and ventilatory responsiveness to inhaled carbon dioxide in normal people. Since even a small decrease in pulmonary function may be clinically important in patients with chronic limitation of airflow, we undertook the present study to assess the effects of sleep loss on breathing in patients with chronic obstructive pulmonary disease (COPD). Criteria for inclusion in this study were a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) of less than 60 percent, no hospital admission for pulmonary disease within two weeks of testing, stable (less than 30 percent variation) in tests of pulmonary function on two occasions within three months of testing, and no history of asthma. We studied 15 men (mean age, 57 +/- 3 years) on two consecutive mornings. Patients were studied with and without sleep deprivation in a randomized fashion. Patients were hospitalized for the study so that sleep deprivation, medications, smoking, and diet could be monitored and enforced. We found small but statistically significant falls in FEV1 (1.06 +/- 0.11 to 1.00 +/- 0.09 L; p less than 0.05) and in FVC (2.56 +/- 0.20 to 2.43 +/- 0.17 L; p less than 0.05) following sleep deprivation. Changes of similar magnitude which were not statistically significant occurred in maximal voluntary ventilation (MVV) and response to carbon dioxide. The arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions were not affected. Maximal expiratory pressure at the mouth increased slightly, but there was a fall in maximal inspiratory pressure (MIP) at the mouth. We conclude that sleep loss is associated with small but significant falls in FEV1 and FVC, as well as changes of similar magnitude in MVV, minute ventilation, and MIP in patients with severe COPD. Although the sleep loss which frequently accompanies exacerbations of COPD may be a slight additional stress of pulmonary reserve, a single night's loss of sleep in the patient with stable chronic airflow obstruction does not have major clinical consequences.     

Ciclesonide is more effective than budesonide in the treatment of persistent asthma

BACKGROUND: Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. METHODS: A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. RESULTS: Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels. CONCLUSION: Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.     

Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine

The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy.     

Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium.

Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18 microg once daily (n=356) compared with ipratropium 40 microg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV1) were 1.25+/-0.43 L (41.9+/-12.7% of the predicted value) (tiotropium) and 1.18+/-0.37 L (39.4+/-10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12+/-0.01 L with tiotropium and declined by 0.03+/-0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.     

Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma

Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.     

C-reactive protein levels and clinically important predictive outcomes in stable COPD patients.

The aim of this study was to determine the relationship between C-reactive protein (CRP) levels and factors known to predict outcome in stable chronic obstructive pulmonary disease (COPD) patients. The following were studied in 130 stable COPD patients: spirometry, lung volume, arterial oxygen tension (P(a,O2)), dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE (body mass index, obstruction, dyspnoea and exercise capacity), health-related quality of life, smoking status, the presence of cardiovascular risk factors or disease, corticosteroid use and number of exacerbations in the previous year. CRP levels were measured in these patients and in 65 controls. Using univariate and multivariate analyses, any possible association with the predictors of outcomes was evaluated. CRP levels were higher in COPD patients than in controls (4.1 versus 1.8 mg.L(-1), respectively). Correlation was found with the following variables: forced expiratory volume in one second (FEV1; -0.23), FEV1 % (-0.20), forced vital capacity (FVC; -0.24), FVC % (-0.24), Global Initiative for Chronic Obstructive Lung Disease stage (0.17), BODE (0.17), inspiratory capacity/total lung capacity (-0.20), P(a,O2) (-0.40) and 6MWD (-0.30). Using multivariate analysis, P(a,O2) and 6MWD manifested the strongest negative association with CRP levels. C-reactive protein levels in stable chronic obstructive pulmonary disease patients are best correlated with arterial oxygen tension and 6-min walk distance. This should be considered when C-reactive protein levels are measured in stable chronic obstructive pulmonary disease patients.     

Role of corticosteroids in stable chronic obstructive pulmonary disease

Evidence supporting or refuting the use of corticosteroids in the treatment of patients with chronic obstructive pulmonary disease (COPD) has only recently become available, and evidence is still missing for a number of important clinical issues. Results from four large studies on the long-term effects of inhaled corticosteroids on COPD and other controlled studies on the more short-term effects of inhaled corticosteroids provide evidence that regular treatment with these drugs is only appropriate for a limited group of patients with COPD. These include symptomatic COPD patients with documented spirometric response to inhaled corticosteroids or those with a forced expiratory volume in 1 second (FEV(1)) less than 50% predicted and repeated exacerbations requiring treatments with antibiotics or oral corticosteroids.     

What is the optimal treatment strategy for chronic obstructive pulmonary disease exacerbations?

The present study aims to determine whether treating chronic obstructive pulmonary disease (COPD) exacerbations with intravenous steroids and aerosol bronchodilators (group I) is superior to oral steroids and multiple dose inhaler (MDI) bronchodilators with a spacer (group II). Group I received 40 mg methylprednisolone x day(-1) intravenously with a decrease to 20 mg after 10 days and a further decrease of 4 mg x 4 days(-1). Aerosol therapy consisted of 10 mg salbutamol and 1 mg ipratropiumbromide x day(-1). Group II received 32 mg methylprednisolone orally for 1 week followed by 24 mg x day(-1) for 4 days and a subsequent decrease of 4 mg x week(-1). Duovent MDI with a spacer was given at a dose of 1.6 mg fenoterol and 640 microg ipratropiumbromide x day(-1). In group I (n=19) forced expiratory volume in one second (FEV1) rose from 0.82+/-0.46 to 0.91+/-0.47 L and average dyspnoea decreased from 6.0+/-1.9 to 4.1+/-2.6 within 10 days. The Chronic Respiratory Disease Index Questionnaire (CRQ) score increased from 78+/-24 to 90+/-24 points after 4 weeks. In group II (n=18) FEV1 increased from 0.70+/-0.27 to 0.90+/-0.29 L, dyspnoea regressed from 6.2+/-2.4 to 2.7+/-2.6 and CRQ from 67+/-17 to 86+/-20. Both groups showed similar results in dropout rate, length of hospital stay and patient satisfaction. In conclusion, the two treatment strategies appear equally effective in treating chronic obstructive pulmonary disease exacerbations, although oral steroids and metered dose inhaler bronchodilators appear associated with a higher risk of hospital re-admission.