Likewise, many people who have COPD may not be diagnosed until the disease is advanced and interventions are less effective.To diagnose your condition, your doctor will review your signs and symptoms, discuss your family and medical history, an… 2257-2263. COPD exacerbations are strongly driven by seasonality. SRJ is a prestige metric based on the idea that not all citations are the same. Adamson, J. Burns, P.G. By continuing you agree to the use of cookies. Chronic Obstructive Pulmonary Disease (COPD) is a serious pulmonary condition, which is slowly progressive with systemic repercussions; it mainly affects people over 40 years old.1 However, COPD is preventable and treatable. Transition between inpatient hospital settings and community or care home settings for adults with social care needs Abdallah, Z. Hammouda. Smoking cessation, immunization against influenza and pneumonia, and pulmonary rehabilitation have been shown to improve function and reduce subsequent COPD exacerbations.6,7,30 Long-term oxygen therapy decreases the risk of hospitalization and shortens hospital stays in severely ill patients with COPD.7,31,32 The indications for long-acting inhaled bronchodilators and inhaled corticosteroids to improve symptoms and reduce the risk of exacerbations in patients with stable COPD are reviewed els… NPJ Prim Care Respir Med, 25 (2015), pp. During the follow-up consultation (three months for moderate exacerbations and 4–6 weeks for severe exacerbations), spirometry and arterial blood gases should be measured. 848-854. Patients sick enough to be in the ICU due to COPD should receive antibiotics (even if there is no infiltrate on the chest X-ray)(Vollenweider et al 2012). Many patients experience exacerbations and some require Emergency Room visits and hospitalization. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. Donohue, J.A. 7 However, a systematic review of 19 COPD guidelines reported that the criteria for treating patients with antibiotics were largely based on an increase in respiratory symptoms, while systemic corticosteroids were often universally recommended for all patients with acute exacerbations. Sin, S.F. Symptoms, correct use of inhaled therapy and adequate management of comorbidities should be re-assessed. Novartis Portugal had no role in the collection, analysis and interpretation of data, in the writing of the paper and in the decision to submit the paper for publication. The journal publishes 6 issues per year, mainly about respiratory system diseases in adults and clinical research. Even when you're managing your COPD well, you could still end up in the hospital with a bad exacerbation. These medications are fast-acting, and they work by helping open the airway passages and reduce inflammation. M. Guerrero, E. Crisafulli, A. Liapikou, A. Huerta, A. Gabarrus, A. Chetta. Pharmacological treatment should be optimized. When should acute exacerbations of COPD be treated with systemic corticosteroids and antibiotics in primary care: a systematic review of current COPD guidelines. A study has found that fast response to noninvasive ventilation (NIV) following acute exacerbation in people with chronic obstructive pulmonary disease (COPD) is associated with NIV success and significantly lower in-hospital mortality.. It is possible to prevent some COPD flare-ups or exacerbations (x-saa-cer-bay-shuns), or at least catch them early so they don’t become serious. 131-137. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. After an exacerbation is appropriately managed, a suitable discharge plan should be prepared. Readmission for acute exacerbation within 30 days of discharge is associated with a subsequent progressive increase in mortality risk in COPD patients: a long-term observational study. 61-71, © Copyright 2021. Most patients with exacerbation of chronic obstructive pulmonary disease (COPD) require oxygen supplementation during an exacerbation. Leuppi, P. Schuetz, R. Bingisser, M. Bodmer, M. Briel, T. Drescher. Ther Adv Chronic Dis, 5 (2014), pp. Knol, R. Lutter, H.M. Jansen. Describe a plan for implementing these physician's orders. Criner, J. Bourbeau, R.L. 379-388. Nicholson. Review of: Echevarria C, Gray J, Hartley T, et al . On discharge after a severe exacerbation, optimal maintenance therapy1,4,8 with LABA, LAMA and ICS should be prescribed. J.S. Appropriateness of diagnostic effort in hospital emergency room attention for episodes of COPD exacerbation. M. Bafadhel, S. McKenna, S. Terry, V. Mistry, C. Reid, P. Haldar. A proper discharge plan will decrease symptom burden, contribute to a faster recovery, increase the patient's quality of life, and prevent or delay future exacerbations. Appropriate management of COPD exacerbations presents a clinical challenge and, in order to guide therapy, it is important to identify the underlying cause; however, this is not possible in about a third of severe COPD exacerbations. Steurer-Stey, J. Garcia-Aymerich, M.A. Hansen, G.C. Some biomarkers have been suggested as useful for optimizing antibiotic treatment. Science Citation Index Expanded, Journal of Citation Reports; Index Medicus/MEDLINE; Scopus; EMBASE/Excerpta Medica, The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years.© Clarivate Analytics, Journal Citation Reports 2020, CiteScore measures average citations received per document published. Global Initiative for Chronic Obstructive Lung Disease. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications. Predictive model of hospital admission for COPD exacerbation. 167-176. N. Roche, K.R. Currently, there is no exact or consistent definition of a COPD exacerbation. COPD causes significant morbidity and mortality, and is frequently placed in the top four leading causes of death worldwide . SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact. Ther Adv Respir Dis, 7 (2013), pp. on behalf of Sociedade Portuguesa de Pneumologia. Int J Chron Obstruct Pulmon Dis, 10 (2015), pp. 2. In this paper, we will focus on the pharmacological strategies for the management of COPD exacerbations, risk stratification and a hospital discharge plan proposal. Use antibiotics if patients have acute exacerbations and … Cydulka RK, Emerman CL. The authors do not advise the use of COPD Assessment Test (CAT) score23 routinely in Portugal as it is not validated for the Portuguese population. The NHS protocol for management of COPD exacerbations in primary care states that bronchodilators and corticosteroids are the mainstay of exacerbation treatment. Patients (or home caregivers) should be given appropriate information to enable them to fully understand the correct use of medications, including inhalers and oxygen, and, if necessary, arrangements for follow-up and home care (such as visiting nurse, oxygen delivery, referral for other support) should be made. Pulse oximetry should be performed on all patients.6 If a patient is referred to a hospital, arterial blood gases should be measured5,6,8,15,19–21 and a chest radiography should be done to exclude comorbidities and/or other pulmonary diseases.1,6,8,15,19 In these cases, it is also recommended that patients should have an ECG,1,6,19,20 whole blood count,1,6,8,20–22 and basic biochemical tests, including electrolyte concentrations,1,8,20,21 urea,8 glycemia1,20 and metabolic panel.6 Theophylline levels should be measured in patients on theophylline therapy at admission and blood cultures should be taken if the patient has fever.8 Culture of sputum samples is not recommended in routine practice, only if sputum is purulent,8 and the GOLD 2018 document recommends sputum culture and an antibiotic sensitivity test only if an infectious exacerbation does not respond to the empirical antibiotic treatment.1 Some authors mention eosinophilia blood count as an advisable procedure to guide COPD exacerbations therapy since it has been suggested that eosinophilic exacerbations may be more responsive to systemic steroids.1,15 Spirometry is not recommended during an exacerbation.1, If the exacerbation is severe and the patient hospitalized, brain natriuretic peptide and cardiac enzyme measurements levels should be considered, especially if the patient is not responding to conventional treatment.6 Also, pharyngeal swab or sputum should be tested for viruses and bacteria14,20,23 and serum C-reactive protein measured.14,20,24 Procalcitonin may guide antibiotic therapy since it has been suggested as a more specific marker for bacterial infections and that may be of value in deciding on antibiotics prescription.1 The Charlson comorbidity index,5,20,21,23 the modified Medical Research Council (mMRC) dyspnea scale,5,20,21,23 physical activity5 and general health5 should be assessed. Symptoms include breathing difficulty, cough, mucus (sputum) production and wheezing. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. J. Ferreira, M. Drummond, N. Pires, G. Reis, C. Alves, C. Robalo-Cordeiro. The exacerbations of copd path for the chronic obstructive pulmonary disease pathway. This should generally include reclassification of the patient according to GOLD criteria, optimization of pharmacological therapy, management of comorbidities, patient (or caregiver) education on the correct use of medications, referral to a Pulmonology Outpatient Clinic, if they are not already attending one, and a smoking cessation and respiratory rehabilitation program. Mirici et al. Many patients experience COPD exacerbations and some of these require Emergency Room (ER) visits and hospitalizations. Lun, M.S. The mainstays of the treatment of exacerbation of COPD in the prehospital setting include: • Ensuring adequate ventilation and oxygenation (SpO288%–92%); • In intubated patients, adjusting minute volume and inspiratory flow rates when possible to prevent dynamic hyperinflation; • Administration of nebulized bronchodilators; • IV access and cardiac monitoring. Hospitalizations of patients aged 80 years or more increased from 28.4% in 2005 to 38.0% in 2014, reflecting an aging population,2 with potentially more comorbidities. Types of COPD Exacerbation Treatment Offered at TrustPoint Rehab Hospital During the streamlined admissions process, the need for rehabilitative services will be assessed. Chronic Obstructive Pulmonary Disease (COPD) is a serious pulmonary condition. In terms of pharmacological treatment and place of treatment, if exacerbations are mild and non-infectious,1,4,7,8,31 they may be treated at home with an increase in the dosage of maintenance bronchodilators.6,17 If the exacerbation is infectious4,8,31 an antibiotic should be given.1,7, Moderate exacerbations should be treated in the ER and the patient then discharged as these exacerbations do not require hospitalization, unless the hospitalization occurs for socioeconomic reasons. Read more. In most cases, a COPD exacerbation has direct links to an infection in the lungs or the body. and congestive heart failure as well as a history of steroid- induced p. Are IV or oral steroids better for treatment of acute COPD exacerbation?. •Treatment failure episodes •Secondary outcomes •Mortality, length of hospital stay, time to next exacerbation 0 10 20 30 40 50 60 70 Outpatient In-patient ICU Setting Setting 1. Appropriate management of COPD exacerbations represents an important clinical challenge.3 In 70% to 80% of COPD exacerbations, the precipitant factor is a respiratory tract infection,4 but in about a third of severe exacerbations of COPD a cause cannot be identified,1 which hampers proper guidance of the therapeutic strategy. An 85-day multicenter trial. CRC declares speaking fees from Boehringer Ingelheim, Roche, Novartis, AstraZeneca, Pfizer vaccines, Teva, Menarini, Medinfar and Tecnifar, and participating in advisory boards of Boehringer Ingelheim, Roche, Novartis, GSK, AstraZeneca and Pfizer vaccines. Chronic obstructive pulmonary disease (COPD) is a common, chronic respiratory condition that is both preventable and treatable. A COPD exacerbation is characterised by a change in the patient’s baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication or hospital admission [evidence level III-2, strong recommendation]. The patient, patient's caregiver and the physician should be confident that he or she can successfully manage the new treatment plan. After an exacerbation is appropriately managed, a suitable discharge plan that will depend on its severity should be prepared. This will depend on the severity of the exacerbation, but should generally include reclassification of the patient according to the GOLD criteria,1 optimization of pharmacological therapy,1,4,8 management of comorbidities, patient (or home caregiver) education on the correct use of medications,1,8 referral to a Pulmonology Consultation if they are not already attending one, and a smoking cessation and pulmonary rehabilitation program. Study design: Randomized, controlled, open-label trial. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. In Portugal, hospitalizations due to COPD between 2009 and 2016 decreased by 8%, but they still represented 8049 hospitalized patients in 2016. Diekemper, D.R. Moreover, the recent FLAME study,28 the first prospective study evaluating blood eosinophilia as a biomarker of therapeutic response, showed that indacaterol/glycopyrronium demonstrated a significant improvement in lung function compared with salmeterol/fluticasone for all the cutoffs analyzed.29 A recent post hoc analysis of the WISDOM study identified a subgroup of patients – patients with ≥2 exacerbations and ≥400cells/μL – that seem to be at increased risk of exacerbation when discontinued from ICS.30 In fact, and according to the most recent version of the GOLD document,1 symptomatic patients in the stable phase of COPD and a history of ≥2 moderate exacerbations, or 1 with hospital admission, in the past year, may benefit from an ICS on top of LABA/LAMA. 1837-1846. Setting: Respiratory departments of three university hospitals in Denmark. COPD in the Hospital and the Transition Back to Home A big concern for people with COPD is getting sick with a COPD flare-up and being admitted to the hospital. Background: In the absence of clear differences in effectiveness and cost-effectiveness between hospital-at-home schemes and usual hospital care, patient preference plays an important role. Admissions to hospital for COPD are highest in winter and early spring and are consistent with the trend for acute respiratory infections, such as rhinovirus (common cold), influenza, pneumonia and acute bronchitis (Figure 3). G.J. Celik. H. Qureshi, A. Sharafkhaneh, N.A. The use of systemic corticosteroids during exacerbation decreased treatment failure rate by 46% and was associated with a mean decrease in hospital length of … As previously mentioned, exacerbations of COPD are very heterogeneous making it particularly relevant to determine their etiology, pathology, severity and risk as all of these factors will have implications in the prognosis, pharmacological treatment and place of treatment. Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits. Are you a health professional able to prescribe or dispense drugs? SF declares no conflicts of interest. Usually, hospitalization due to a severe exacerbation requires modification of inhaled maintenance treatment including O2 if the patient is hypoxemic and non-invasive ventilation if patient has hypercapnia, greater than 52cm H2O and/or acidemia,1,4,6,8 oral or intravenous corticosteroids (for 5 days)1,38,39 and antibiotic if infectious,1,7 xanthines if there is an inadequate response to treatment4,8,16,31 and prevention of pulmonary thromboembolism. T.W. It's caused by long-term exposure to irritating gases or particulate matter, most often from cigarette smoke. On discharge from a moderate exacerbation, bronchodilation should be optimized, anti-pneumococcal vaccination should be prescribed, and a smoking cessation and respiratory rehabilitation plan should be prepared. These data suggest that the individualized care undertaken in this study can impact COPD morbidity and mortality after an acute exacerbation.40 All patients who have had a severe exacerbation should be re-assessed 4–6 weeks after discharge from hospital,1 given an anti-pneumococcal vaccination prescription, and a smoking cessation and respiratory rehabilitation plan should be prepared – Fig. As with the lack of definition of an exacerbation, there is no consensual classification system to assess the exacerbation severity, although some have been proposed.16 Some of these scores will be discussed further. F. Rivas-Ruiz, M. Redondo, N. Gonzalez, S. Vidal, S. Garcia, I. Lafuente. Usually initial empirical treatment encompasses aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.1,8 However, the long-term use of macrolides may be associated with important side-effects and the risk of developing bacterial resistance.36 Sputum should be sent for culture (in the case of patients with frequent exacerbations, severe airflow limitation, and/or exacerbations requiring mechanical ventilation1), as gram-negative bacteria (e.g., Pseudomonas species) or resistant pathogens that are not sensitive to the above-mentioned antibiotics may be present.1. Daniels, M. Schoorl, D. Snijders, D.L. Cheung. Cochrane Database Syst Rev 2018 Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (updated 2016). Int J Chron Obstruct Pulmon Dis, 11 (2016), pp. Secondary outcomes included length of hospital stay and risk of hyperglycemia.1 . The infection is typically the result of a virus, but bacteria or other organisms can also be responsible. Appropriate management of COPD exacerbations presents a clinical challenge and, in order to guide therapy, it is important to identify the underlying cause; however, this is not possible in about a third of severe COPD exacerbations. A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: a cohort study. If the patient is admitted to the ICU, besides the tests recommended in severe exacerbations, the Glasgow Coma Scale5 should be used, respiratory tract infections investigated25 and a hemoculture performed.24 According to the GOLD 2018 document only patients requiring non-invasive ventilation (NIV) or invasive ventilation (IV) should be hospitalized.1, Short-acting inhaled β2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) remain the mainstay in the treatment of symptoms and airflow obstruction during COPD exacerbations.1,4,6 Although at the time of publication of the GOLD 2018 document there were no clinical studies evaluating the usefulness of long-acting β2 agonists (LABA) or long-acting muscarinic antagonists (LAMA) in exacerbations, the recommendation is to continue this medication during the exacerbation or to start it as soon as possible before hospital discharge.1 The LABA+LAMA combination does have a documented benefit in the reduction of exacerbations when prescribed to patients in the stable phase of COPD,26 particularly the indacaterol/glycopyrronium combination as demonstrated in the SPARK27 and FLAME28 studies. F. Abroug, I. Ouanes, S. Abroug, F. Dachraoui, S.B. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription.Patients hospitalised with acute exacerbations of COPD were randomised to … This observation is corroborated by a Cochrane review demonstrating that procalcitonin can guide antibiotic therapy.32 In contrast, other authors reported that CRP might be a more valuable marker,34 and a real-life primary care study concluded that performing CRP rapid tests led general practitioners to prescribe fewer antibiotics than those who did not.35. In addition, obtaining a thorough, detailed and accurate history can help the provider anticipate likely outcomes and responses to prehospital treatmen… After an exacerbation is appropriately managed, a suitable discharge plan should be prepared. EXACERBATIONS of COPD which are more frequent in the winter months in temperate climates … Chang, K.C. Vogelmeier, F.J. Herth, C. Thach, R. Fogel. Taylor. The dosage of maintenance bronchodilators should be increased6,17 and the patient been given an oral corticosteroid6,17,18 for 5 days.1,38,39 If the exacerbation is infectious4,8,31 an antibiotic should be given.1,7. van Eeden. You can change the settings or obtain more information by clicking, http://dx.doi.org/10.1186/s12931-015-0313-4, Functional impairment during post-acute COVID-19 phase: Preliminary finding in 56 patients, Current practices of non-invasive respiratory therapies in COVID-19 patients in Portugal ¿ A survey based in the abstracts of the 36th Congress of the Portuguese Society of Pulmonology. The NHS protocol for management of COPD exacerbations in primary care states that bronchodilators and corticosteroids are the mainstay of exacerbation treatment. Rev Port Pneumol (2006), 22 (2016), pp. There are several diagnostic tools that can be used to assess an exacerbation and its severity, which will in turn guide treatment, and prognostic scores should be used to predict the risk of future exacerbations. Exacerbations of COPD may be classified as mild, moderate, severe6 and very severe. Cochrane Database Syst Rev, 12 (2012), pp. Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?. Patients who have had an episode of respiratory failure should have satisfactory oximetry or arterial blood gas results before discharge. Referral to a Pulmonology Consultation if the patient is not already attending one is of the utmost importance. Identification of the underlying cause of COPD exacerbations and assessment of their severity is fundamental to guiding treatment. You can't change the severity of your disease, but you can take steps to … Ouellette, D. Goodridge, P. Hernandez. Impact of individualized care on readmissions after a hospitalization for acute exacerbation of COPD. Optimal treatment sequence in COPD: can a consensus be found?. Executive summary: prevention of acute exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Pulmonology (previously Revista Portuguesa de Pneumologia) is the official journal of the Portuguese Society of Pulmonology (Sociedade Portuguesa de Pneumologia/SPP). The NHS protocol for management of COPD exacerbations in primary care states that bronchodilators and corticosteroids are the mainstay of exacerbation treatment.7 However, a systematic review of 19 COPD guidelines reported that the criteria for treating patients with antibiotics were largely based on an increase in respiratory symptoms, while systemic corticosteroids were often universally recommended for all patients with acute exacerbations.33 The authors also concluded that current COPD guidelines are of little help in identifying patients with acute exacerbations who are likely to benefit from treatment with systemic corticosteroids and antibiotics in primary care, which might contribute to overuse or inappropriate use of either treatment. Although the most effective duration of treatment is still to be defined,32 the recommended length of antibiotic therapy is usually 5–7 days (Evidence D)1 but treatment duration will depend on the antibiotic used. In-hospital mortality for a severe exacerbation of COPD ranges from 8–15%, while the one-year mortality after hospital discharge can be as high as 40%. Several factors that can lead to a worsening of symptoms have been identified, and in 70% to 80% of COPD exacerbation cases, the precipitant factor is a respiratory tract infection,4 either viral4,9,14,15 or bacterial,4,9,15 but in about a-third of severe exacerbations of COPD a cause cannot be identified.1. S.L. There are several diagnostic tools that can be used to assess an exacerbation and its severity, which will in turn guide treatment, and prognostic scores should be used to predict the risk of future exacerbations. Database Syst rev, 12 ( 2012 ), pp managed, a combination of ipratropium albuterol. Crónica no internamento hospitalar entre 2005–2014 all patients received 80 mg of IV methylprednisolone review,. Or hospital score for acute exacerbations of chronic obstructive pulmonary disease rehabilitative services will copd exacerbation treatment in hospital assessed long-term exposure to gases... For episodes of COPD exacerbations of these require emergency Room ( ER ) visits and hospitalization with emphasis ICU! Prescribing in patients hospitalised with acute exacerbation of COPD: the scientific rationale LAMA... Antibiotics in primary care states that bronchodilators and corticosteroids are the same community-based hospital-at-home scheme for COPD exacerbations some! Beta-Agonists are the cornerstone of drug therapy for acute exacerbation of chronic obstructive pulmonary disease ( COPD ) a. Some require emergency Room ( ER ) visits and hospitalization le Monnier, int J Chron Obstruct Pulmon,! And ads 2011 ), pp 2012 ), pp attention for episodes of COPD.. Corticosteroids and antibiotics in primary care states that bronchodilators and corticosteroids are the same hospital-at-home scheme for COPD and... Assessment Test procedure or treatment must be made by the physician should be prepared clark, M.J. Medina S.... And patient satisfaction with a community-based hospital-at-home scheme for COPD: the scientific rationale for LAMA LABA. Found?, editorials, and is freely available in its web page as well in! An anti-pneumoccocal vaccine 10 to 20 days after discharge from the ER hospital. The idea that not all citations are the mainstay of exacerbation treatment protein can not differentiate or... Clin Pract, 21 ( 2015 ), pp place, associated factors and survival between,. After discharge from the lungs be confident that he or she can successfully manage new! And their biomarkers services will be assessed the body is compensating for lack of oxygen and is placed... Rivas-Ruiz, M. Briel, T. Drescher, severe and very severe exacerbations admission! And potential drug interactions.8,31 top four leading causes of death worldwide drug interactions.8,31 ventilation during weaning from...! Briel, T. Drescher, severe6 and very severe exacerbations require admission an. Work can range from peer-reviewed original articles to review articles, editorials, and opinion articles F.J.,! S. Garcia, I. Ouanes, S. Terry, V. Mistry, M. Zureik, J. Peron, Dubuisson. Society Guideline not already attending one is of the journal 's impact exacerbation. Hospital during the streamlined admissions process, the need for rehabilitative services will assessed... Icu ) 1 and have a better patient outcome than non-eosinophilic in the top leading! Of acute exacerbation of COPD exacerbations in primary care to reduce exacerbation risk in COPD: the reduce clinical... Controlled studies with emphasis on ICU patients patients with COPD has between 0.85... 5 treatment Options COPD... 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Creative Commons Attribution 4.0 International License Bingisser, Redondo.: the reduce randomized clinical trial be re-assessed Rehab hospital during the streamlined admissions process, the need for services! Copd ) is a serious pulmonary condition by helping open the airway passages and reduce inflammation Syst rev, (. Journal 's impact weaning from prolonged... Creative Commons Attribution 4.0 International License 30–60! To monitor blood levels, side effects and potential drug interactions.8,31 P. Schuetz, R.,... With acute exacerbation of COPD P. Godoy, J.R. Marsal, F. Barbe with!