Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease

OBJECTIVE: To define the role of antimicrobial therapy in the treatment of acute bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through review of placebo-controlled clinical trials. Specificalty, to determine the benefit of antimicrobial therapy on patient outcome. DATA SOURCES: Placebo-controlled dinical trials identified by MEDLINE search (1957-December 1999). STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled clinical trials that included COPD patients with no evidence of pneumonia or underlying asthma were included in the evaluation. DATA SYNTHESIS: The role of antimicrobial agents in the treatment of acute exacerbations of COPD is controversial. Patients with COPD are often chronically colonized with bacteria, and many exacerbations are due to nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis have demonstrated significant improvements in outcome for patients treated with an antibiotic versus placebo. In contrast, six studies failed to demonstrate statistical differences, possibly due to the small sample size and the subjectivity of outcome measures. Overall, the data suggest that the benefit of antimicrobial therapy in acute exacerbations of COPD may be related to exacerbation severity. CONCLUSIONS: Antimicrobial agents may have a beneficial effect in the treatment of acute exacerbations of COPD in certain patients. Pending further research in this area, we recommend antimicrobial therapy only for COPD patients with acute bronchitic exacerbations characterized by increased dyspnea, sputum volume, and purulence.     

Management of clinical failures in non-ICU patients with chronic obstructive pulmonary disease exacerbations

Clinical failure after initial treatment for exacerbations of chronic obstructive pulmonary disease (COPD) occurs in 10-25% of cases. Once the original diagnosis is confirmed, there is a need to optimise therapy, including introducing bronchodilators and corticosteroids. The use of aggressive antibiotic treatment is recommended for patients with risk factors (elderly, more than four exacerbations per year, underlying cardiopulmonary disease) and more severe disease. Fluoroquinolones are a good choice for those patients who failed initial therapy and who require antimicrobials, including those with simple exacerbations, complicated cases with comorbidity, or those with bronchiectasis. Consideration of less common pathogens, such as Pseudomonas aeruginosa infection, should also be considered. Bacteria usually associated with exacerbations are becoming increasingly resistant, and this needs to be considered when deciding on appropriate antibiotic treatment.     

Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials

Introduction: Although evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types.

Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients).

Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.     

Clinical and bacteriological efficacy and tolerability of FCE 22891 in patients with exacerbations of chronic obstructive pulmonary disease.

A beta-lactamase-stable antibiotic, the oral penem FCE 22891 (ritipenem acoxil), was investigated for use in exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen of the 15 COPD patients had a proven lower respiratory tract infection. Symptom scores and forced expiratory volumes in 1 s significantly improved during therapy with FCE 22891 in combination with bronchodilators and intravenous corticosteroids. Conversion of representative sputum to nonrepresentative sputum or eradication of the original pathogen in representative sputum was effected in 12 patients. Resistance to FCE 22891 was observed in three cases with Haemophilus influenzae. Gastrointestinal disturbances, of which one was severe, were experienced by eight patients. Although FCE 22891 has some beneficial effect in exacerbations of COPD, there are reservations about its use because of adverse effects and potential inefficacy in the treatment of infection with H. influenzae.     

Levofloxacin inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells

Respiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.     

Chronic obstructive pulmonary disease management: the evidence base.

In long-term management of stable chronic obstructive pulmonary disease (COPD), a number of medications improve pulmonary function test results. The long-term clinical benefits of those drugs would seem intuitive, but there is very little strong evidence that long-term outcomes in COPD are substantially affected by those drugs. Nevertheless, symptom improvement such as dyspnea reduction is certainly strong reason to use those agents. The 2 most compelling bodies of evidence in stable COPD are for oxygen therapy in the chronically hypoxemic patient and pulmonary rehabilitation to improve exercise tolerance and dyspnea. Inhaled corticosteroids also appear to be useful in patients at risk for frequent exacerbations. In acute exacerbations, the rationale for therapy comes in part from the large body of literature regarding acute asthma therapy. Bronchodilator therapy and corticosteroids both seem to reduce the severity and the duration of exacerbations. Moreover, routine antibiotic use seems beneficial, and the role of noninvasive positive-pressure ventilation with patients suffering impending respiratory failure from acute COPD exacerbations is well supported by the literature.     

Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a meta-analysis

What is Known and Objective: Inhaled long‐acting beta‐agonists have been licensed for the treatment of chronic obstructive pulmonary disease (COPD) since the late 1990s, and they improve lung function and symptoms of dyspnoea. However, the evidence that long‐acting beta‐agonists alone can reduce the rate of COPD exacerbations is not conclusive. This meta‐analysis was performed to evaluate their effect on the frequency of exacerbations. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for the review. Randomized controlled trials of greater than or equal to 24 weeks’ treatment duration comparing long‐acting beta‐agonists (LABAs) with placebo were reviewed. Studies were pooled to yield odds ratios (ORs) with 95% confidence intervals (CIs). Results and Discussion: Seventeen randomized controlled trials (11871 randomized subjects) met the inclusion criteria and were selected for analysis. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol significantly reduced COPD exacerbations with both study arms exposed or not exposed to inhaled corticosteroids (ICS). The summary ORs were 0·79 (95% CI: 0·67–0·92; P < 0·01) and 0·80 (95% CI: 0·65–0·99; P = 0·04), respectively. However, when both arms were not exposed to ICS, there was no significant reduction in exacerbations with formoterol compared with placebo. The 'summary OR was 0·93 (95% CI: 0·75–1·15; P = 0·50). What is New and Conclusion: Long‐acting beta‐agonists reduce the frequency of COPD exacerbations. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol but not formoterol decreased exacerbations significantly in the absence of ICS.     

Clinical efficacy and safety of Chinese herbal medicine versus placebo for the treatment of chronic obstructive pulmonary disease: A systematic review and meta-analysis

ObjectiveRandomized clinical trials and published meta-analyses assessing the clinical effectiveness of Chinese herbal medicine (CHM) on the treatment of stable chronic obstructive pulmonary disease (COPD) yielded inconsistent results in terms of disease outcomes, in which the design of placebo-controlled studies can contribute to the heterogeneity. This study aimed to evaluate the efficacy and safety of CHM compared to placebo on the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD.MethodsNine electronic databases were searched from inception to October 1, 2019 to identify placebo controlled randomized trials of CHM for the treatment of stable COPD and studies in English or Chinese were included. The primary outcomes were symptom score (CAT score), quality of life (SGRQ) and frequency of acute exacerbations. The secondary outcomes included lung function, clinical total effective rate and adverse events. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies were conducted by two reviewers independently. Mean difference (MD) was used to analyze continuous variable and relative risk ratio (RR) for dichotomous data.ResultsA total of eleven studies involving 1223 patients were included. While maintaining routine western pharmacotherapies (WP), CHM had significant advantage over the treatment of placebo in improving CAT score (MD -3.93; 95 %CI -6.01 to -1.85) and SGRQ score (MD -6.20; 95 %CI -10.13 to -2.28), reducing the frequency of acute exacerbations (MD -0.78; 95 %CI -1.40 to -0.16) and improving clinical effective rate (RR 1.29; 95 %CI 1.14 to 1.45), but had no significant effect on improving FEV₁%pred (MD 8.18; 95 %CI -4.22 to 20.58). High heterogeneity was found for the changes in exacerbation frequency and FEV₁%pred. No serious adverse events related to CHM were reported.ConclusionsThis meta-analysis of placebo-controlled RCTs demonstrated that the use of CHM in addition to WP could alleviate clinical symptoms, improve quality of life and clinical efficiency and reduce the frequency of exacerbations, which could be an alternative approach for treatment adjustment of COPD. CHM was a relatively safe treatment. These findings need to be verified in future with high-quality clinical trials.     

Heliox and noninvasive positive-pressure ventilation: a role for heliox in exacerbations of chronic obstructive pulmonary disease?

Evidence-based respiratory therapy for exacerbations of chronic obstructive pulmonary disease (COPD) includes oxygen, inhaled bronchodilators, and noninvasive positive-pressure ventilation. Examining the physics of gas flow, a case can be made either for or against the use of helium-oxygen mixture (heliox) in the care of patients with COPD. The evidence for the use of heliox in patients with COPD exacerbation is not strong at present. Most of the peer-reviewed literature consists of case reports, case series, and physiologic studies in small samples of carefully selected patients. Some patients with COPD exacerbation have a favorable physiologic response to heliox therapy, but predicting who will be a responder is difficult. Moreover, the use of heliox is hampered by the lack of widespread availability of an approved heliox delivery system. Appropriately designed randomized controlled trials with patient-important outcomes, such as avoidance of intubation, decreased intensive-care-unit and hospital days, and decreased cost of therapy, are sorely needed to establish the role of heliox in patients with COPD exacerbation, including those receiving noninvasive positive-pressure ventilation. Lacking such evidence, the use of heliox in patients with COPD exacerbation cannot be considered standard therapy.     

Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

Introduction

Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.

Method

Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org.Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.

Results

Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis.Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups.Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.

Conclusion

Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care.Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.     

Optimizing maintenance therapy for chronic obstructive pulmonary disease: strategies for improving patient-centered outcomes

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality. Published practice guidelines and treatment algorithms for COPD are designed to increase awareness of the problem and improve patient care; however, <40% of subjects diagnosed with COPD are receiving appropriate maintenance therapy. OBJECTIVE: This paper reviews the use of maintenance therapy in COPD and examines the optimal timing for initiating such therapy based on the available literature. METHODS: Relevant publications were identified through a search of MEDLINE (1995-May 2007) using the terms COPD, guidelines, treatment, maintenance therapy, bronchodilator, ipratropium, tiotropium, beta-agonist, salmeterol, and inhaled corticosteroid. English-language publications discussing pharmacologic maintenance therapy for COPD, including practice statements/guidelines, randomized controlled clinical trials, systematic reviews, and meta-analyses, with a focus on agents currently approved for use in the United States, were selected for inclusion. RESULTS: Although guidelines and algorithms agree on the importance of regularly scheduled maintenance therapy to reduce symptoms of COPD, minimize activity limitations, and improve health status, the timing of the initiation of such therapy is debatable. In most instances, maintenance medications, which include long-acting beta(2)-agonists, long-acting anticholinergics, and combination products, are prescribed late in the disease process and mainly for patients with severe disease. However, there is increasing evidence that the use of maintenance therapy early in the disease process may be associated with improvements in such outcomes as lung function, symptoms, exercise tolerance, exacerbations of COPD, and quality of life. CONCLUSION: The high burden associated with COPD highlights the need to initiate maintenance therapy before a substantial decline in lung function has occurred.     

Noninvasive positive pressure ventilation for respiratory failure caused by exacerbations of chronic obstructive pulmonary disease: a standard of care?

This editorial comments on a meta-analysis of the use of noninvasive positive pressure ventilation to treat patients with acute respiratory failure caused by chronic obstructive pulmonary disease (COPD) exacerbations published in the British Medical Journal earlier this year. Based on its analysis of seven randomized controlled trials that met pre-specified criteria, the meta-analysis demonstrated highly significant benefits of noninvasive positive pressure ventilation in COPD patients, including a reduction in a combined end-point consisting of death and endotracheal intubation. The editorial argues that, based on the strength of this and other evidence, noninvasive positive pressure ventilation to treat selected patients with acute respiratory failure due to COPD exacerbations should now be considered a standard of care.     

Echinacea purpurea along with zinc, selenium and vitamin C to alleviate exacerbations of chronic obstructive pulmonary disease: results from a randomized controlled trial

What is known and objective: Upper respiratory tract infections (URTI) frequently cause exacerbations of chronic‐obstructive pulmonary disease (COPD). Stimulation of the innate immune system may provide an early defence against such infections. The objective of this study was to determine whether Echinacea purpurea (EP) along with micronutrients may alleviate COPD exacerbations caused by acute URTI. Methods: This was a double‐blind, randomized, placebo‐controlled trial in COPD patients with acute URTI. Patients were given ciprofloxacin for 7 days and additionally one tablet per day of EP, of EP along with zinc, selenium and ascorbic acid (EP+), or of placebo until day 14. Serum levels of TNF α and interleukins 1β, 6 and 10 were measured before and after treatment. Until week 4 post‐end of treatment, all patients had to daily report on COPD symptoms in diaries. Results and Discussion: In total, 108 mostly male patients with a mean age of 65·8 years (40–81 years) were enrolled. Patients of the three treatment arms did not vary significantly in baseline characteristics. EP+, but not EP resulted in significantly less severe and shorter exacerbation episodes following URTI as compared with placebo suggesting a synergistic effect of Echinacea and micronutrients. Large variations in biomarkers in‐between and within groups were unrelated to treatment. Study medication was safe and well tolerated with overall 15 adverse events one of which was serious. Among those, sleeping disorders were most frequent and likely related to the underlying disease. What is new and Conclusion: The combination of EP, zinc, selenium and vitamin C may alleviate exacerbation symptoms caused by URTI in COPD. Further studies are warranted to investigate the interactions among Echinacea, zinc, selenium and vitamin C.     

Antibiotic therapy for common infections

Several important points regarding the treatment of urinary tract infections should be made. Single-dose and short-course antibiotic therapy is appropriate only for women with acute bacterial cystitis due to E. coli. Studies comparing single-dose to full-course therapy have not been sufficiently designed to draw valid statistical conclusions, and only TMP/SMX is recommended at this time. Recurrent UTI in women is almost always due to reinfection, which is best managed by prophylactic antibiotics. Acute bronchitis and acute exacerbations of chronic bronchitis are often due to viral infections, and therefore antibiotic therapy is not always needed. In acute exacerbations of chronic bronchitis, the clearest success rates for antibiotic therapy have been in patients, who have all three of the following symptoms: increased dyspnea, increased sputum production, and sputum purulence. Mupirocin is an important addition to the agents used to treat bacterial skin infections due to streptococcal and staphylococcal strains. In impetigo, mupirocin has been demonstrated to be as effective or superior to oral erythromycin. In prostatitis, data on the fluoroquinolones appears impressive, but further comparative trials are needed. They may become first-line, empiric therapy. The newer oral antibiotics are not recommended as initial, empiric therapy in the outpatient management of common infections, with the possible exception of the treatment of prostatitis. These newer agents may be more important in the treatment of recurrent or resistant infections.     

Faropenem: review of a new oral penem

Faropenem medoxomil is a new orally administered penem antibiotic. Its chiral tetrahydrofuran substituent at position C2 is responsible for its improved chemical stability and reduced CNS effects, compared with imipenem. Faropenem demonstrates broad-spectrum in vitro antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes, and is resistant to hydrolysis by nearly all β-lactamases, including extended-spectrum β-lactamases and AmpC β-lactamases. However, faropenem is not active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, Pseudomonas aeruginosa or Stenotrophomonas maltophilia. Prospective, multicenter, randomized, double-blind, comparative (not vs placebo) clinical trials of acute bacterial sinusitis (ABS), acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP) and uncomplicated skin and skin structure infections (uSSSIs) have demonstrated that faropenem medoxomil has equivalent efficacy and safety compared with cefuroxime, clarithromycin, azithromycin, amoxicillin, cefpodoxime and amoxicillin–clavulanate. The evidence supports faropenem medoxomil as a promising new oral β-lactam with proven efficacy and safety for the treatment of a variety of community-acquired infections. However, the US FDA recently rejected faropenem for all four indications stating that the clinical trials in ABS and AECB should have been performed versus a placebo. In the CAP studies, the FDA stated that they could not be certain of the validity of the study population actually having the disease and for uSSSI, the FDA stated that only a single trial was not adequate evidence of efficacy for this indication.     

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5–10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.     

COPD: management of acute exacerbations and chronic stable disease

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are treated with oxygen (in hypoxemic patients), inhaled beta2 agonists, inhaled anticholinergics, antibiotics and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators. Antibiotic therapy is directed at the most common pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Mild to moderate exacerbations of COPD are usually treated with older broad-spectrum antibiotics such as doxycycline, trimethoprim-sulfamethoxazole and amoxicillin-clavulanate potassium. Treatment with augmented penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides may be considered in patients with more severe exacerbations. The management of chronic stable COPD always includes smoking cessation and oxygen therapy. Inhaled beta2 agonists, inhaled anticholinergics and systemic corticosteroids provide short-term benefits in patients with chronic stable disease. Inhaled corticosteroids decrease airway reactivity and reduce the use of health care services for management of respiratory symptoms. Preventing acute exacerbations helps to reduce long-term complications. Long-term oxygen therapy, regular monitoring of pulmonary function and referral for pulmonary rehabilitation are often indicated. Influenza and pneumococcal vaccines should be given. Patients who do not respond to standard therapies may benefit from surgery.     

Clinical efficacy of inhaled corticosteroids in COPD

The use of inhaled corticosteroids in asthma is regarded as first-line therapy. But the efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial. However data from some large studies provide the evidence that regular treatment with inhaled glucocorticosteroids is appropriate for symptomatic COPD patients with an FEVi<50% predicted and repeated exacerbations. In these studies glucocorticosteroids combined with a long-acting beta-agonist was more effective than the individual components. However, additional studies are needed to clarify the effects of inhaled corticosteroids on mortality and to define their long-term adverse effects.