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The patients with COPD and frequent exacerbations who present the highest degree of complexity are those with greater airflow obstruction and respiratory infections due to unusual PPMs such as PA, which is associated with increased mortality. Abbreviation: FEV 1 , forced expiratory volume in 1 second. Furthermore, the main risk factor associated with PA infection was the extent of bronchiectasis, followed by the number of previous courses of antibiotics.

The same strain of PA was not isolated again in the remaining patients; some acquired new strains of PA and eradicated them during the follow-up, and others showed patterns of clonal persistence or alternation but did not fulfill the criteria for CBI. In those with CBI, it was not associated with the extent of bronchiectasis, nor was any clonal transmission observed between patients with COPD. This distinction may be clinically relevant. As expected, culture-independent techniques, such as studies of the bronchial microbiome in patients with severe COPD, showed that patients colonized by PA have a higher prevalence of the genus Pseudomonas compared with patients not colonized by PA, as do conventional microbiological cultures.

In these cases, the rest of the bronchial microbiome was similar in patients colonized and noncolonized by PA. Moreover, patients with and without colonization by PA had a similar microbiome during exacerbations. In view of the above, participants in the expert panel discussion agreed that active attempts should be made to isolate PA in serial sputum cultures in patients with severe COPD and frequent infective exacerbations.

The first point to consider is the pattern of PA resistance to commonly used antibiotics. If CBI is due to a quinolone-sensitive PA, the best option would be oral ciprofloxacin at high doses mg bid over a period of 2—3 weeks. The use of parenteral antibiotics with antipseudomonal activity should be reserved for severely ill patients or those with prior treatment failures.

It should also be considered that not all the exacerbations in a patient colonized by PA are caused by this microorganism. Another empirical oral treatment option in this situation is the use of high-dose levofloxacin mg bid , which has good activity against usual microorganisms such as H. Inhaled antibiotics represent a very attractive therapeutic option, since these drugs may achieve a high concentration in the airways with low systemic exposure. As a consequence, the side effects are minor and relatively well tolerated, the most common being wheezing and local irritation, which are easily controlled with BDs.

This therapy is indicated in cystic fibrosis and also in noncystic fibrosis bronchiectasis, but scientific evidence in patients with COPD is scarce.

The expert panel did not reach agreement on this point. At present, the use of inhaled antibiotics in patients with COPD and CBI is not indicated because their efficacy has not been demonstrated and the clinical experience is very limited. A preliminary analysis also recorded a significant reduction in the number of exacerbations and emergency visits during a year of follow-up in these patients. There was consensus among participants that the only viral infection associated with COPD exacerbation that can be treated is influenza A H1N1 , for which a specific antiviral agent and a hospital-based diagnostic test are available.

Antiviral treatment should be started early, since the viral load has been reported to remain high in the first 7 days after onset of symptoms. In the case of antipneumococcal vaccine, the use of the conjugate vaccine with 13 serotypes is recommended because patients with COPD are a risk group for pneumococcal infection. The only exception are those with an additional condition, such as the continued use of corticosteroids or other pathology associated with immunosuppression.

Annual influenza vaccination is indicated for all patients with COPD. However, all authors agreed that having an effective vaccine against H. In clinical practice, the use of azithromycin in COPD has followed the example of cystic fibrosis, that is, continuous administration throughout the year. Its use in the winter months is recommended in the GesEPOC guidelines to try to reduce antibiotic exposure without loss of effectiveness, but no clear evidence exists in favor of this strategy.

The use of azithromycin should be considered when the patient continues to experience infectious exacerbations despite optimal respiratory treatment. In these circumstances, the benefits appear to outweigh the risks, although close monitoring of the patient is crucial to detect early adverse effects associated with the use of the macrolide. Some discontinue the treatment in summer, but others maintain it throughout the year if the patient does not show side effects.

At present, there is not enough evidence to support initiating ICS treatment after a single exacerbation and maintaining it chronically in all cases. The existing evidence suggests that systemic inflammation may play a key role in the development of various comorbidities associated with COPD, and may thus affect patient prognosis. However, all participants agreed that there is no specific treatment aimed at controlling systemic inflammation in COPD. All expert panel participants reported that roflumilast was poorly tolerated by a high percentage of patients, who develop gastrointestinal side effects in spite of the use of progressive doses or dose reduction in the case of an adverse event.

However, patients who tolerate roflumilast will benefit from it, with a reduction in the frequency of exacerbations and slight increase in lung function. Therefore, roflumilast should be tested in patients in whom it is indicated, that is, those with severe COPD with chronic bronchitis and frequent exacerbations despite maximum inhaled treatment. Even though the use of roflumilast is recommended in the main clinical practice guidelines, experience with its use as an anti-inflammatory agent is not comparable with that of ICS; far more is known of the safety profile of ICSs and their long-term benefits.

It has been reported that patients with COPD present sustained lung inflammation even in the stable state and may suffer a loss of lung function after ICS withdrawal. The consensus among participants was that the decision to withdraw ICSs should be individualized, after weighing up the risk of pneumonia, the possible loss of lung function, and other adverse effects, against their efficacy in reducing the frequency of exacerbations. During the process of withdrawal of ICS, patients must be closely monitored. Inflammatory mechanisms play a key role in COPD, both in the progression of the disease and during exacerbations.

The presence of inflammatory cells primarily neutrophils and macrophages increases with the severity of disease and contributes to the exacerbations and progressive loss of lung function. There are a variety of exacerbation phenotypes, which remain relatively stable over time; bacterial and viral phenotypes are the most frequent. CBI is also associated with frequent exacerbations, affecting lung function and worsening quality of life.

Long-term antibiotic treatment is effective in reducing exacerbations in carefully selected patients with COPD. It should be considered as an add-on therapy in patients with severe COPD and frequent exacerbations of infectious origin, who require multiple courses of antibiotics despite optimal pharmacological and nonpharmacological treatment. However, the indication should always be individualized, the adverse effects monitored, and strict clinical controls performed. Inhaled antibiotics are a promising alternative in patients with COPD with frequent exacerbations and CBI, particularly in cases that do not respond to oral treatment or present significant adverse events.

However, controlled studies are required to test their efficacy and safety and evaluate the possible development of antimicrobial resistance. High-resolution chest CT is useful in patients with the frequent exacerbator phenotype for the diagnosis of bron-chiectasis. In addition, serial sputum cultures will help to identify patients with CBI and specially when caused by unusual bacteria such as PA or Stenotrophomonas. The meeting was sponsored by GlaxoSmithKline. Author contributions. All authors contributed to conception, debating, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

The other authors have no conflicts of interest to report. Europe PMC requires Javascript to function effectively. Recent Activity. The snippet could not be located in the article text. This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. Published online Mar PMID: This work is published and licensed by Dove Medical Press Limited.

By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC. Keywords: COPD exacerbation, treatment, bronchial infection, anti-inflammatory treatment, antibiotics. Introduction COPD is a progressive and heterogeneous chronic entity. Significant reduction in the duration of the exacerbation with macrolide Pomares et al 59 Retrospective study of 24 patients with COPD treated with azithromycin mg three times per week for 1 year Mean age Significant delay in time to first exacerbation with macrolide Blasi et al 61 Open, randomized, noncontrolled study of 22 patients with COPD and tracheostomy: 11 receiving azithromycin mg 3 days per week for 6 months, and 11 in the usual care group Mean age 72 and 73 years.

No information on lung function. Hazard ratio for the first exacerbation associated with usual care was 5.

Management of severe acute exacerbations of COPD: an updated narrative review

Significant reduction in hospitalizations with azithromycin Albert et al 14 Randomized, double-blind, placebo-controlled clinical trial in 1, patients: received azithromycin mg daily, and received placebo Mean age 66 years. Median time to first exacerbation was significantly prolonged: days with placebo and with macrolide. Hazard ratio for time to first exacerbation was 0.

Open in a separate window. The role of inflammation and its treatment in frequent COPD exacerbations Inflammation is important not just in the context of COPD exacerbations but in the stable phase as well. Discussion Does CT have a role in the evaluation of patients with frequent exacerbations? In the light of the above, which antibiotic should be administered to a patient colonized with PA who has an infectious exacerbation? Is inhaled antibiotic therapy ever indicated in patients with COPD?

Does it make sense to treat respiratory viruses if a viral exacerbation is suspected? Are antipneumococcal and influenza vaccines recommended for all patients with COPD? What is the recommendation for the use of oral azithromycin — only in the winter months, or throughout the year? Should a patient who has required systemic corticosteroids for a single exacerbation start ICS treatment in order to prevent further exacerbations? What role does systemic inflammation play in the prognosis of these patients?

What is the experience of the efficacy and safety of roflumilast? According to current guidelines, patients with COPD without exacerbations should not use ICS, but what about those with chronic local inflammation and the resulting loss of lung function? Conclusion Inflammatory mechanisms play a key role in COPD, both in the progression of the disease and during exacerbations.

Cor pulmonale is right heart failure secondary to lung disease, and is caused by pulmonary hypertension as a consequence of hypoxia. Features of cor pulmonale include:. Inhaled bronchodilators are the first-line drugs for the treatment of chronic obstructive pulmonary disease COPD. Opportunities to review the advance care plan and discuss end-of-life issues can arise when there is a clinical event or deterioration, or when there is a change in social circumstances, such as a move into a care home. Inhaled corticosteroids should not be prescribed alone in people with chronic obstructive pulmonary disease COPD — they should always be prescribed in combination with a long-acting bronchodilator.

The recommendations relevant to primary care were mostly developed from the expert opinion of the guideline development group following narrative reviews of the evidence, where available. This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website. A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of chronic obstructive pulmonary disease.

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Last revised in August Next planned review by December Chronic obstructive pulmonary disease COPD is a treatable but not curable and largely preventable lung disease. COPD is characterized by airflow obstruction which is usually progressive, and not fully reversible. Tobacco smoking is the major risk factor for the development of COPD. Complications include disability and reduced quality of life.

A diagnosis of COPD can be made if the person meets all of the following criteria: Age older than 35 years. Presence of a risk factor, for example current smoker, history of smoking, or occupational exposure to chemicals or dust. Typical symptoms, such as exertional breathlessness, chronic cough, wheeze, regular sputum production, recurrent chest infection.

Signs of COPD include cyanosis, raised jugular venous pressure, cachexia, a hyperinflated chest, use of accessory muscles, pursed lip breathing, wheeze or quiet breath sounds, and peripheral oedema. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J Allergy Clin Immunol.

Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease - Wikipedia

National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Pulmonary Disease, Chronic Obstructive. Drug: fluticasone and salmeterol. Phase 1. Study Type :. Actual Enrollment :. Study Start Date :. Actual Primary Completion Date :. Actual Study Completion Date :. Active Comparator: 1 will start with fluticasone mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID.

Drug: fluticasone and salmeterol will start with fluticasone mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone mcg BID.