Realistic and possible abilities in prevention of COPD exacerbation


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  • AbstractContext Guidelines recommend antibiotic therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD), but the evidence is based on small, heterogeneous trials, few of which include hospitalized patients.Objective To compare the outcomes of patients treated with antibiotics in the first 2 hospital days with those treated later or not at all.Design, Setting, and Patients Retrospective cohort of patients aged 40 years or older who were hospitalized from January 1, 2006, through December 31, 2007, for acute exacerbations of COPD at 413 acute care facilities throughout the United States.Main Outcome Measures A composite measure of treatment failure, defined as the initiation of mechanical ventilation after the second hospital day, inpatient mortality, or readmission for acute exacerbations of COPD within 30 days of discharge; length of stay, and hospital costs.Results Of 84 621 patients, 79% received at least 2 consecutive days of antibiotic treatment. Treated patients were less likely than nontreated patients to receive mechanical ventilation after the second hospital day (1.07%; 95% confidence interval [CI], 1.06%-1.08% vs 1.80%; 95% CI, 1.78%-1.82%), had lower rates of inpatient mortality (1.04%; 95% CI, 1.03%-1.05% vs 1.59%; 95% CI, 1.57%-1.61%), and had lower rates of readmission for acute exacerbations of COPD (7.91%; 95% CI, 7.89%-7.94% vs 8.79%; 95% CI, 8.74%-8.83%). Patients treated with antibiotic agents had a higher rate of readmissions for Clostridium difficile (0.19%; 95% CI, 0.187%-0.193%) than those who were not treated (0.09%; 95% CI, 0.086%-0.094%). After multivariable adjustment, including the propensity for antibiotic treatment, the risk of treatment failure was lower in antibiotic-treated patients (odds ratio, 0.87; 95% CI, 0.82-0.92). A grouped treatment approach and hierarchical modeling to account for potential confounding of hospital effects yielded similar results. Analysis stratified by risk of treatment failure found similar magnitudes of benefit across all subgroups.Conclusion Early antibiotic administration was associated with improved outcomes among patients hospitalized for acute exacerbations of COPD regardless of the risk of treatment failure.JAMA:2010; 303(20); 2035-2042
  • AbstractExacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations.Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results.Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.Obstructive lung diseases, particularly chronic obstructive pulmonary disease (COPD) are one of the main causes of morbidity and mortality in developed countries. It is estimated that more than 15 million people in the USA have COPD and more than 12 million have chronic bronchitis [1], with these numbers having increased over recent decades. The age-adjusted mortality rate from COPD doubled from 1970 to 2002 in the USA, whereas mortality rates from stroke and heart disease decreased by 63% and 52%, respectively [2].The prevalence of COPD in Spain is 10.2% in adults between 40–80 yrs of age, although only 27% are diagnosed [3]. This prevalence may even increase in the future. In fact, an international survey showed that up to 11.8% of subjects aged between 20–44 yrs had chronic bronchitis, characterised by chronic respiratory symptoms of cough and sputum production and 3.6% had Global Initiative for Chronic Obstructive Lung Diseases stages I to III COPD with impairment in lung function [4], which is remarkable considering the young age of the participants.The chronic and progressive course of COPD is often aggravated by short periods of increasing symptoms, particularly increasing cough, dyspnoea and sputum production which can become purulent. Exacerbations have been demonstrated to have a negative impact on the quality of life of patients with COPD [5, 6]. Furthermore, acute exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic lung disease [7]. Therefore, strategies aimed at reducing the frequency of exacerbations are a cornerstone of the treatment of COPD.
  • AbstractBACKGROUNDSmoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations.OBJECTIVEWe sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations.DESIGNWe assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation.PARTICIPANTSWe performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US.MEASUREMENTS AND MAIN RESULTSIn comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75–0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit<1 year, 1.04; 95% CI 0.87–1.26; 1–5 years 0.93, 95% CI 0.79–1.08; 5–10 years 0.84, 95% CI 0.70–1.00; ≥10 years 0.65, 95% CI 0.58–0.74; linear trend<0.001).CONCLUSIONSSmoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence.
  • BackgroundAlthough current performance measures recommend smoking cessation counseling at the time of acute myocardial infarction (AMI), the American College of Cardiology/American Heart Association guidelines recommend pharmacotherapy as well. The aim of this study was to describe the prevalence and correlates of smoking cessation pharmacotherapy in hospitalized patients with AMI.MethodsIn the 24-center TRIUMPH registry, 4,340 AMI patients underwent detailed interviews; and 1,631 reported smoking within 30 days of admission. Prescription of first-line smoking cessation medications at discharge was assessed by medical record review. All patient-related factors associated with smoking cessation treatment, based on literature review, were included in hierarchical modified log Poisson models.ResultsOnly 14% (222/1,631) of AMI patients who smoked were prescribed smoking cessation medication at discharge. After multivariable adjustment for patient characteristics, there was significant variation across sites (range 0%-28%, median rate ratio 1.41, 95% CI 1.23-2.67). Independent factors associated with smoking cessation pharmacotherapy included older age (rate ratio 0.81 per 10-year increment, 95% CI 0.71-0.93), high school graduation (rate ratio 1.37, 95% CI 1.10-1.66), heavy cigarette usage (>20/d) (rate ratio 3.08, 95% CI 2.20-4.12), in-hospital revascularization (rate ratio 1.41, 95% CI 1.0-1.94), and instructions on smoking cessation (rate ratio 2.37, 95% CI 1.40-4.01).ConclusionsSmokers surviving an AMI are infrequently prescribed guideline-recommended smoking cessation treatments, and there is considerable variation across hospitals. Older, less educated, and lighter smokers are less likely to receive aggressive smoking cessation treatment. Novel strategies to augment current practice are needed.
  • Authors’ conclusionsIt appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.
  • AbstractTo determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV + IV group (n = 87) or an IV group (n = 80). The number of patients with CLD experiencing infectious acute exacerbation (P = 0.022), but not pneumonia (P = 0.284), was significantly lower in the PV + IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P = 0.037). In patients with CLD, the Kaplan–Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P = 0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P = 0.019), but not during the second year (P = 0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.
  • AbstractBACKGROUND:Pulmonary rehabilitation has become a cornerstone in the management of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic reviews have shown large and important clinical effects of pulmonary rehabilitation in these patients. However, in unstable COPD patients who have recently suffered an exacerbation, the effects of pulmonary rehabilitation are less established.OBJECTIVES:To assess the effects of pulmonary rehabilitation after COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity).SEARCH STRATEGY:Trials were identified from searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Airways Group Register of Trials. Searches were current as of March 2010.SELECTION CRITERIA:Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care. Pulmonary rehabilitation programmes needed to include at least physical exercise. Control groups received conventional community care without rehabilitation.DATA COLLECTION AND ANALYSIS:We calculated pooled odds ratios and weighted mean differences (MD) using random-effects models. We requested missing data from the authors of the primary studies.MAIN RESULTS:We identified nine trials involving 432 patients. Pulmonary rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.22 [95% CI 0.08 to 0.58], number needed to treat (NNT) 4 [95% CI 3 to 8], over 25 weeks) and mortality (OR 0.28; 95% CI 0.10 to 0.84), NNT 6 [95% CI 5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference when measured by the Chronic Respiratory Questionnaire (MD for dyspnea, fatigue, emotional function and mastery domains between 0.81 (fatigue; 95% CI 0.16 to 1.45) and 0.97 (dyspnea; 95% CI 0.35 to 1.58)) and the St. Georges Respiratory Questionnaire total score (MD -9.88; 95% CI -14.40 to -5.37); impacts domain (MD -13.94; 95% CI -20.37 to -7.51) and for activity limitation domain (MD -9.94; 95% CI -15.98 to -3.89)). The symptoms domain of the St. Georges Respiratory Questionnaire showed no significant improvement. Pulmonary rehabilitation significantly improved exercise capacity and the improvement was above the minimally important difference (six-minute walk test (MD 77.70 meters; 95% CI 12.21 to 143.20) and shuttle walk test (MD 64.35; 95% CI 41.28 to 87.43)). No adverse events were reported in three studies.AUTHORS' CONCLUSIONS:Evidence from nine small studies of moderate methodological quality, suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients who have recently suffered an exacerbation of COPD.
  • AbstractSTUDY OBJECTIVE:To assess the comparative efficacy of pharmacologic agents for the maintenance treatment of chronic obstructive pulmonary disease (COPD).DESIGN:Traditional and mixed-treatment comparison (MTC) meta-analyses of randomized controlled trials.PATIENTS:A total of 31,020 patients with COPD from 43 trials.MEASUREMENTS AND MAIN RESULTS:A systematic literature search of various databases (through October 2007) was performed to identify randomized controlled trials of long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and/or combination therapy with an inhaled corticosteroid and a long-acting beta(2)-agonist in patients with COPD. Forty-three trials were included. Both meta-analyses were used to evaluate the occurrence of one or more episodes of COPD exacerbation, overall mortality, and patient withdrawal rates. With MTC analysis, long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and combination inhaled corticosteroid-long-acting beta(2)-agonist therapy each decreased the odds of having an exacerbation by 16%, 31%, 15%, and 24%, respectively, compared with placebo. Moreover, tiotropium use reduced the odds of having at least one exacerbation by 18% compared with long-acting beta(2)-agonists and by 19% compared with inhaled corticosteroids alone. Each of the four drug classes was associated with significant odds reductions in patient withdrawals (26-41%) compared with placebo, and both tiotropium and combination therapy significantly decreased the odds of patient withdrawals compared with long-acting beta(2)-agonists or inhaled corticosteroids alone. Only combination therapy was associated with a mortality benefit, showing a 29% reduction compared with placebo and a 25% reduction compared with long-acting beta(2)-agonists alone. Compared with combination therapy, tiotropium use reduced exacerbations by 9% and increased mortality by only 4%. These findings did not demonstrate significant changes in the sensitivity or subgroup analyses, which were performed to evaluate the effect of heterogeneity among the included studies.CONCLUSIONS:Combination inhaled corticosteroid-long-acting beta(2)-agonist therapy was associated with the greatest positive effect on outcomes in patients with COPD. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having a COPD exacerbation or withdrawal from a study compared with long-acting beta(2)-agonists.
  • Speaker notesIn each study, an additive effect of roflumilast on reducing exacerbations was shown.In studies M2-127 and M2-128, and approximately 50% of patients in M2-124/125, this effect was in addition to the benefit already achieved by COPD maintenance therapy with bronchodilators.ReferenceRabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharm2011;163:53-67.
  • Realistic and possible abilities in prevention of COPD exacerbation

    1. 1. FIFTH CONGRESS OF THE MACEDONIAN RESPIRATORY SOCIETY Ohrid, 26-29.September,2012Realistic and possible abilities in prevention of COPD exacerbation Dejan Žujović Municipal Institute for Lung Diseases and Tuberculosis Belgrade
    2. 2. DisclosureSpeaker fees from: GSK, Pfizer, Takeda-Nycomed,Merck, AstraZeneca, Boehringer Ingelheim, SanofiAventis, MSD. I have no, real or perceived, conflicts of interest that relate to this presentation.
    3. 3. Effect of acute exacerbations of COPD (AECOPD) versus myocardial infarction (MI) on survival Mortality at 12 months following hospitalization for an exacerbation of COPD is between 20% and 40%. This is much worse than the mortality observed following hospital admission with an acute MI, whether or not patients received acute reperfusion therapyHalpin D. Mortality in COPD: Inevitable or Preventable? Insights from the Cardiovascular Arena. COPD: Journal of Chronic Obstructive Pulmonary Disease, 2008;5:187–200
    4. 4. Proper treatment of AECOPD as prevention of future exacerbations?
    5. 5. AECOPD - High readmission rates2011, St. George’s HospitalN=577218 episodes with >1 admission47% readmissions within 30 days Nearly half of the patients were readmitted within 30 days
    6. 6. Quality of Care in Hospitalized COPD Patients Retrospective cohort study of 360 US hospitals involving 69,820 patients hospitalized for AECOPD 66% received all recommended Rx – O2, bronchodilatators, CS, antibiotics 45% received non-recommended Rx 33% received “ideal” careLindenaurer PK, et al. Ann Intern Med. 2006;144:894-903.
    7. 7. Antibiotic treatment is associated with reduced risk of a subsequent AECOPD: an historical population based cohort studyRoede BM et al. Thorax. 2008;63:968-973.
    8. 8. Outcomes With Antibiotic Therapy in Patients Hospitalized With Exacerbations: Retrospective Cohort Study Early Antibiotics No/Late Antibiotics 14 P<0.001 12 10 P<0.001 8 6 4 P<0.001 2 0 In-hospital Mortality Treatment Failure Readmission Within 30 Days for COPD N= 84 621 patientsRothberg MB, et al. JAMA.2010; 303(20); 2035-2042
    9. 9. Optimizing antibiotic selection in treating COPD exacerbations N=572 5 days moxifloxacin PO 400mg od vs. 7 days amoxicillin PO 500mg tds or clarithromycin PO 500mg bd or cefuroxime-axetil PO 250mg bd Life-table analysis of time to the first composite event (treatment failure, and/or new exacerbation and/or any further antibiotic treatment) stratified according to the time of the last exacerbation prior to randomisation. AECB > 6 months AECB ≤ 6 months Moxifloxacin Moxifloxacin Comparator Comparator P=0.01Siddiqi A, Sethi S. Int J Chron Obstruct Pulmon Dis. 2008 March; 3(1): 31–44.
    10. 10. Analysis of hospitalizations for COPD exacerbation: opportunities for improving care All patients hospitalized with acute exacerbation of COPD between January 2005 and December 2006 at 5 New York City hospitals 1285 unique patients with 1653 hospitalizations systemic steroids (85%), bronchodilators (94%) and antibiotics (80%) On discharge, only 46.0% were prescribed maintenance bronchodilators and 24% were not prescribed any inhaled therapyYip NH, et al. COPD. 2010 Apr;7(2):85-92.
    11. 11. Strategies aimed at preventing exacerbations Proven efficacy Questioned efficacy Smoking cessation Theophyllines LABAs: salmeterol, formoterol Prophylactic antibiotic in selected patients Tiotropium Immunomodulators Combination therapy: LABA/ICS Mucolytic agents Anti-influenza vaccine Antioxidants Antipneumococcal vaccine# Rehabilitation Physical exercise Self-management plans #: efficacy demonstrated in prevention of pneumonia but not in the prevention of exacerbations LVRS in selected patientsMiravitlles M. Prevention of exacerbations of COPD with pharmacotherapy. Eur Respir Rev. 2010.19;116:119-126
    12. 12. Characteristics of patients with AECOPD treated in our department Demonstration of use Written instructions in Smoking of inhalation therapy case of exacerbation 12% 31% Current smoker 28% Ex-smoker 37% No No Never smoker 63% Yes Yes 57% 72% Demonstrated Influenza vaccination breathing exercises last year 28% 42% No No Yes Yes 58% 72%126 patients with AECOPD Zujovic D, Unpublished Data. 2012
    13. 13. The Effects of Smoking Cessation on the Risk of COPD Exacerbations N= 23 971 Ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75–0.87)Au DH et al. The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations. J Gen Intern Med. 2009 April; 24(4): 457–463.
    14. 14. Prevalence of smoking cessation pharmacotherapy in hospitalized smokers with acute myocardial infarction risk reduction (RR) in reinfarction of 32% all-cause mortality of 36% benefit that may exceed standard pharmacotherapy for secondary prevention N= 1 631 Only 14% (222/1,631) of AMI patients who smoked were prescribed smoking cessation medication at discharge.Katz DA et al. Prevalence and correlates of smoking cessation pharmacotherapy in hospitalized smokers with acute myocardial infarction. American Heart Journal. 2011. 162;1:74-80.
    15. 15. Potential Quality Gaps in Pharmacological Treatment for Smoking Cessation Following Hospitalization for Acute COPD Exacerbation Use of medications for tobacco dependence is uncommon in a high−risk population of smokers following hospitalization for AECOPD 18% of patients who smoked were prescribed smoking cessation medication at 30 days post discharge N= 684McBurnie et al. Am J Respir Crit Care Med. 179;2009:A2157
    16. 16. Tobacco treatment in patients with COPD 25 Complete abstinence rate at 12 months 20 15 10 5 0 None Placebo NRT patch NRT gum NRT NRT Bupropion Varenicline inhaler lozengeWu J, Sin DD. Improved patient outcome with smoking cessation: when is it too late? International Journal of COPD. 2011.6: 259–267Strassmann R et al. Smoking cessation interventions in COPD: a network meta-analysis of randomized trials. ERJ. 2009.34(3):634-640
    17. 17. Influenza vaccine and AECOPD significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo Annually for all patients with COPD (SOR: A) GOLD,2011Poole P, Chacko EE, Wood-Baker R, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 1.
    18. 18. Influenza and Pneumococcal Vaccine: An Additive Effect? 1 0,9 The proportion of COPD patients free from 0,8 inf. acute exacerbation 0,7 0,6 0,5 0,4 0,3 Pneumococcal Vaccine + Influenza Vaccine 0,2 Influenza Vaccine 0,1 P=0.037 N=167 0 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 Time (days)Furumoto A et al. Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. Vaccine 2008; 26:4284-4289.
    19. 19. Low influenza vaccine uptake in COPD 80 Influenza vaccine uptake in COPD 70% COPD patients 60 50 40 30 20 10 0 Vozoris NT. AoRM 2009
    20. 20. Low coverage rates of PPV23 vaccine Cumulative doses distributed per 10 000 persons UK 2123 Germany 1607 Ireland 1488 Spain 1280 Belgium 1220 Greece 922 Sweden 901 Iceland 721 Italy 677 Countries recommending pneumococcal vaccination for all elderly people and those Austria 652 considered „at risk‟ of pneumococcal infection Norway 587 Countries recommending pneumococcal vaccination only for those considered „at risk‟ of Switzerland 333 pneumococcal infection Finland 218 France 583 Portugal 452 Denmark 271 Netherlan… 49 In most European countries coverage rates is 20 - 30%.Fedson DS et al. Pneumococcal Polysaccharide Vaccination for Adults. Expert Rev Vaccines. 2011;10(8):1143-1167.
    21. 21. Pulmonary rehabilitation following exacerbations of COPD Pulmonary rehabilitation should be made available to all appropriate people with COPD including those who have had a recent hospitalisation for an acute exacerbation. NICE guideline, 2010 Reduction of hospital admissions NNT=4Puhan Maet al. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2011, Issue 10.
    22. 22. Pulmonary Rehabilitation Should BePrescribed in the Same Way Medications Are Prescribed “There is no drug that has beneficial effects on as many clinical variables as pulmonary rehabilitation; there is no drug with effects that are as long-lasting (up to 18 months) as those of pulmonary rehabilitation; and there is no drug with an research and development investment as low as the costs of the most sophisticated pulmonary rehabilitation program.” Alba Ramírez-Sarmiento Arch Bronconeumol. 2008;44(3):119-21
    23. 23. What is reality?1% Only 1.2% of the more than 750 000 Canadians suffering from COPD have access to PR programs Brooks D et al. Can Respir J. 2007;14(2):87-92. 615 patients with COPD, 139 GPs5% Pulmonary rehabilitation was prescribed to 5% of all patients and less than 1/3 of patients exercised regularly. Jochmann A et al. Swiss Med Wkly. 2010 Of the 69,820 patients hospitalized for6% acute exacerbations of COPD, 6% had chest physiotherapy Lindenauer PK et al. Ann Intern Med. 2006
    24. 24. Adherence in COPD: effects on survival and exacerbations rate ratio: 0.56; 95% CI: 0.48–0.65; p < 0.001 0.4 admission rates/patient-year 0.35 Nonadherent 0.3 Adherent 0.25 0.2 0.15 0.1 0.05 0 Salmeterol Fluticasone SFC Placebo 44% reduction in admissions rate N=6112 T=3 year Good adherence= adherence >80%Vestbo J, Anderson JA, Calverley PMA et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009. 64:939–943
    25. 25. Adherence in COPD: effects on survival and exacerbations hazard ratio [HR]: 0.40; 95% CI: 0.35–0.46; p < 0.001 35 Nonadherent 30 Adherent 3-year mortality rate 25 20 % 15 10 5 0 Salmeterol Fluticasone SFC Placebo 60% mortality risk reduction N=6112 T=3 year Good adherence= adherence >80%Vestbo J, Anderson JA, Calverley PMA et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009. 64:939–943
    26. 26. What is reality? (N>1500) Physicians’ knowledge of inhaler devices and inhalation techniques remains poor (~14.5%) Spain Plaza V et al. J Aerosol Med Pulm Drug Deliv. 2012;25(1):16-22 60% nonadherent 85% use their inhaler ineffectivelyRestrepo RD et al. Medication adherence issues in patients treated for COPD. Int J Chron Obstruct Pulmon Dis. 2008; 3(3): 371–384.
    27. 27. COPD Exacerbation
    28. 28. Self-Management Education:Reduces Hospitalization
    29. 29. Benefits of COPD Self Management Education
    30. 30. Creating a Community COPD Action Plan?
    31. 31. Active prevention of AECOPD? Patients need personalized education andencouragement to use treatment properly and act on symptoms early
    32. 32. Comorbidity and risk for exacerbations Independent effect of depression on COPD exacerbations and hospitalizations. * * * 2 Adjusted incidence ratio 1.5 HADS ≤ 7 1 HADS 8-10 HADS ≥ 11 0.5 0 Exacerbation Exacerbation Hospitalisation (self reported) (event) HADS: Hospital Anxiety and Depression ScaleXu W et al. AJRCCM 2008; 178:913-20
    33. 33. Proportion of patients with pathological cognitive deficit when fit for discharge post-exacerbation Cognitive Age-matched COPD COPD p value Domain Controls -Stable -Exacerbation Visual Memory 0.003 13% 32% 55% DR Verbal Memory <0.001 10% 24% 57% IR Trail Making 7% 40% 53% <0.001 Verbal Fluency 7% 10% 41% <0.001 Working 10% 18% 50% 0.001 Memory Processing 3% 24% 50% <0.001 Speed Visuo-Spatial 0% 30% 52% <0.001Dodd JW et al. Submitted
    34. 34. Pharmacologic treatments for COPD: a mixed-treatment comparison meta- analysis 43 RCT odds of having an exacerbation LABA TIO ICS LABA N= 31 020 + TROP ICS IUM -16% -15% -24% -31%Baker WL, Baker EL, Coleman CI. Pharmacologic treatments for chronic obstructive pulmonary disease: a mixed-treatment comparison meta-analysis. Pharmacotherapy. 2009 Aug;29(8):891-905.
    35. 35. Relative Risk of Exacerbations inCOPD Patients Treated With LABA 21% reduction (95% CI, 10%-31%) in COPD exacerbation rates Sin DD et al. JAMA. 2003;290(17):2301-2312.
    36. 36. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD N= 7376 FEV1 49% RR 0.89 Tiotropium 12 months annual rate of exacerbations P=0.002 Salmeterol RR 0.93 P=0.048 RR 0.73 P<0.001 all exacerbations moderate exacerbations severe exacerbationsVogelmeier C et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. N Engl J Med 2011;364:1093-1103.
    37. 37. LABA/ICS reduces the rate of exacerbations requiring medical intervention vs. LABA alone N=1022 5 +3% FEV1 36% 12 months 0 exacerbations/patient/year 3 Number needed to treat –5 2.1 Rate of –10 2 –12% –15 1 –20 –25 –24% 0 Bud/Form vs. formoterol * –30 Bud/Form Budesonide Formoterol NNT=2.1*P < 0.05 vs. placebo;P = 0.015 Bud/Form vs. formoterol Calverley et al. Eur Respir J 2003;22:912-9.
    38. 38. The prevention of COPD exacerbations by salmeterol/fluticasone propionate or tiotropium bromide (INSPIRE Trial) 2 1.8 N=1323 annual exacerbation rate 1.6 p = 0.656 FEV1 39% 24 months 1.4 1.2 1,28 1,32 1 0.8 0.6 0.4 0.2 0 Salmeterol/Fluticasone TiotropiumWedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. (INSPIRE Trial) Am J Respir Crit Care Med2008; 177:19-26.
    39. 39. Optimal Therapy of COPD To Prevent Exacerbations and Improve Quality of Life (OPTIMAL) study p = n.s. 100 N=449 90 FEV1 40% % patients with exacerbation 12 months 80 70 62.8 64.8 60.0 60 (1 year ) 50 40 30 20 10 0 Tiotropium (N=156) Tiotropium + Salmeterol (N=148) Tiotropium + Salmeterol/Fluticasone (N=145)Aaron SD, Vandemheen KL, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2007;146:545-555.
    40. 40. Efficacy and Tolerability of Budesonide/Formoterol Added to Tiotropium in Patients with COPD Rate of severe exacerbations reduced by 62% 0.4 Budesonide/formoterol + tiotropium N= 660 FEV1 38% Exacerbations/patient Placebo + tiotropium 12 weeks 0.3 Cox-proportional hazards: rate ratio 0.38 (95% CI 0.25, 0.57, p<0.001) 0.2 0.1 0.0 0 15 30 45 60 75 90 Days since randomisationWelte T et al. Efficacy and Tolerability of Budesonide/Formoterol Added to Tiotropium in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2009; 180: 741–750
    41. 41. The impact of triple therapy on mortality and exacerbations in COPDretrospective cohort study1857 patients LABA/ICS+Tio vs. 996 patients LABA/ICSMean follow-up 4.65 years Short PM et al. CHEST. 2012;141(1):81-86
    42. 42. Roflumilast reduced exacerbations when added to bronchodilators
    43. 43. Roflumilast reduced exacerbation rate when added to ICS M2-111 and M2-112 pooled post hoc analysis of sub-group with chronic bronchitis +/- ICSRennard SI, Calverley PMA, Goehring UM, et al. Respiratory Research 2011; 12: 18. ICS = Inhaled corticosteroids
    44. 44. Effects of roflumilast in highly symptomatic COPD patientsN=743395 patients mMRC≥ 2Tio18 mcg + roflumilast500mcg OD vs. Tio18mcg + placebo OD24 weeks 0.45 Δ= -23.2% Δ= -45.5% Rate ratio=0.768 Rate ratio=0.545 0.4 95%Cl 0.515,1.146 95%Cl 0.311,0.955 Annual rate of mod/severe exacerbation per patient 0.35 p=0.196 p=0.0338 0.3 0.25 Placebo + Tio 0.2 Roflumilast + Tio 0.15 0.1 0.05 0 Total population mMRC ≥ 2 subgroupTio= TiotropiummMRC= Modified Medical Research Council Dyspnea ScaleFabbri LM, et al. Effects of roflumilast in highly symptomatic COPD patients [abstract]. In: European Respiratory Societys 22nd Annual Congress; 2012 Sept 1-5; Vienna, Austria: ERS; 2012. Abstract P742.
    45. 45. Morbidity and mortality benefits with statin use in COPD Dobler CC et al. BMC Pulmonary Medicine 2009, 9:32
    46. 46. STATCOPE Study – Phase II  The STATCOPE study is funded by the National Heart Lung & Blood Institute and is being conducted to determine if an FDA approved statin drug called simvastatin might reduce swelling in the lungs in patients with COPD.  If it is found that this statin drug reduces lung inflammation, there is a possibility that the statin drug could also limit the number or the severity of flare-ups, called exacerbations, in patients with COPD.
    47. 47. Effect of β blockers in treatment of COPD Retrospective cohort study N=5977 4.35 years follow-up Adjusted hazard ratios for hospital admissions due to respiratory disease among patients with COPD in reference to the control group (who received only inhaled therapy with short acting β agonists or antimuscarinics).Short PM et al. BMJ 2011;342:bmj.d2549
    48. 48. Effect of β blockers in treatment of COPD β blockers may reduce mortality and COPD exacerbations when added toestablished inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. Short PM et al. BMJ 2011;342:bmj.d2549
    49. 49. TOO COMPLICATED?
    50. 50. Realistic and possible abilities inprevention of COPD exacerbation Dejan Žujović Municipal Institute for Lung Diseases and Tuberculosis Belgrade