1 Acute Care of COPD: Gaps in our knowledge Robert A. Wise, M.D. May 20, 2010
2 Outline of talk Importance of COPD exacerbations Current treatments Areas for improvement Significant knowledge gaps Strategies for improving care
3 Importance of COPD exacerbations
4 Outcome of Exacerbations Room for In outpatients Improvement Treatment failure rate 13%-33% In ER patients In hospitalized patients In ICU patients Relapse (repeat ER visit) Hospital mortality Hospital mortality 22%-32% 5%-10% 20%-24% Seneff et al. JAMA. 1995; 274: ; Murata et al. Ann Emerg Med. 1991;20: ; Adams et al. Chest. 2000;117:
5 Exacerbations Affect Quality of Life SGRQ Score * Total * * * 48 SymptomsActivities Impacts Activities 0-2 Exacerbations 3-8 Exacerbations * P<0.05 versus lower exacerbation rate Seemungal TA, et al. Am J Respir Crit Care Med. 2000;161:
6 Baseline Rate of Change in SGRQ (control group) and Exacerbation Frequency During the UPLIFT Trial Rate of change in SGRQ total score (units/yr) >0 to 1 >1 to 2 >2 Exacerbation Rate (per patient-year) SGRQ, St George s Respiratory Questionnaire
7 High Mortality Following Emergency Department Visit for COPD Exacerbation Percent Mortality 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 5% 9% 11% 16% 23% 32% 39% 30 Days 60 Days 90 Days 180 Days 1 Year 2 Years 3 Years Time Following Visit Kim S, et al. COPD. 2006;3:
8 Effects of Repeated Exacerbations on Survival 1.0 Prospective study Cohort of 304 males Exacerbations requiring hospital treatment during the year Follow-up over 5 years Probability of surviving No exacerbation p< exacerbations p= exacerbations Soler-Cataluña JJ et al. Thorax 2005;64: Time (months)
9 2010 projected Health Care Costs for COPD Long-term Care, $3.7 Home Health Care, $1.3 Prescriptions, $5.8 Hospital Care, $13.2. Cost in Billions Total = $29.5 Physican Fees, $5.5 Hospital Care Physican Fees Prescriptions Home Health Care Long-term Care
10 Recurrence of Exacerbations 27% of first exacerbations associated with second exacerbation in 8 weeks 34% of 1,221 hospitalized patients in UK readmitted within 3 months (range 5-65%) C M Roberts et al.thorax 2002;57: Hurst et al. Am J Respir Crit Care Med 2009; 179:369
11 Effects of Repeated Exacerbations on Recovery of QoL 60 N=133 6-month prospective study SGRQ total score N=299 N=133 N=280 N=116 N=233 N=115 N=221 After one exacerbation treated with antibiotics Followed for 26 weeks. 31% had recurrent exacerbation N =Patients remaining in the study at that time point With a further exacerbation 30 Presentation 4 weeks 12 weeks 26 weeks No new exacerbation Spencer S. et al. Thorax 2003;58:589
12 Recurrent admissions after hospital discharge the critical issue for COPD in % of patients account for 70% of costs Medicare reimbursement schedule makes hospitals interested High mortality in frequent exacerbators Wide range of readmissions at hospitals (5-65%) Event rate high enough to study easily Outcome measure easy to count We can probably do something about it
13 Triple therapy Fewer hospitalizations % Pts with 1 or more exacerbation(s) Tiotropium (n=156) Tiotropium + Salmeterol (n=148) Tiotropium + Salmeterol + Fluticasone (n=145) 62.8 % 64.8% 60.0% Total Exacerbations Exacerbations with Hosp * Aaron et. al. Ann Int Med. 2007
14 Checklist for Acute Coronary Syndrome Discharge ASA ACE / ARB Beta-blocker Statin Rehabilitation / Exercise prescription Smoking cessation treatment / adjuncts Hypertension treated
15 Checklist for AE-COPD Discharge Has he got a way to get home?
16 Checklist for AE-COPD Discharge ICS / LABA LAMA Inhaler instruction with actual devices Oxygen instruction Steroid taper instruction and monitoring Rehabilitation / Exercise prescription Self-management care plan Follow-up care plan Drug affordability
18 Need for economic analyses?
19 Cost-Utility Analyses - TORCH Salmeterol-Fluticasone $33,865 / QALY Salmeterol alone $20,792 / QALY Fluticasone null Salmeterol-Fluticasone $52,046 / QALY Salmeterol alone $56,519 / QALY Salmeterol-Fluticasone $43,600 / QALY Salmeterol alone $197,000 / QALY Earnshaw et al. Cost-effectiveness of fluticasone propionate/salmeterol (500/50 microg) in the treatment of COPD. Respir Med Jan;103(1): Oba Y.et al. Cost-effectiveness of salmeterol, fluticasone, and combination therapy for COPD. Am J Manag Care. 2009;15: Briggs A et al. Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study. Eur Respir J. 2010;35:532-9
20 Etiology of Exacerbations of COPD Non-infectious e.g., air pollution. climate change, noncompliance,etc. Bacteria Virus Obaji A, Sethi S. Drugs and Aging. 2001;18:1-11 Bacteria and virus
21 Immunization Influenza vaccination Pneumococcal vaccination
22 Pneumococcal Vaccine Dec-March Relative Risk of Death P = Pneumococcal vaccine I = Influenza vaccine n = 177, * 0.53 * 1 * 0 I+/P- I+/P+ I-/P- I-/P+ Vaccination status Schembri S. et al. Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD. Thorax. 2009;64: Adjusted for age, gender, Co-morbidities
23 Pneumococcal Vaccine Apr-Nov Relative Risk of Death P = Pneumococcal vaccine I = Influenza vaccine n = 177, * I+/P- I+/P+ I-/P- I-/P+ Vaccination status Schembri S. et al. Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD. Thorax. 2009;64: Adjusted for age, gender, Co-morbidities
24 Key questions Is it harmful to give pneumococcal vaccine? Is it beneficial to give influenza vaccine for hospitalized COPD patients on steroids?
25 Helium-Oxygen Mixtures Improves exercise tolerance and dynamic hyperinflation in COPD Does not improve bronchodilator response as carrier for nebulizer Question: Can Heliox by inhalation or by NIPPV prevent intubation or improve outcomes compared with NIPPV alone? Rodrigo G, Pollack C, Rodrigo C, Rowe B. Heliox for treatment of exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;(2):CD
26 Heliox and PPV reduces work of breathing during COPD exacerbations Jaber S, et al. Noninvasive ventilation with helium-oxygen in acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:
27 Heliox and PPV decrease PaCO2 during COPD exacerbations Jaber S, et al. Noninvasive ventilation with helium-oxygen in acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:
28 Self Management / Case Management Can t hurt, can it?
29 Self Management Cochrane Systematic Review because of heterogeneity in interventions, study populations, follow-up time, and outcome measures, data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD. There is an evident need for more large RCTs with a long-term follow-up, before more conclusions can be drawn. Effing et al. Self-Management education for patients with COPD. Cochrane Review :CD002990
30 Care Management in COPD N = 743 pts Usual Care vs Disease Management 1.5 hr education Action plan for self treatment Monthly f/u calls from case manager Results: All cause hospitalizations decreased 28% Rice KL, Disease Management Program for Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. Am J Respir Crit Care Med Jan 21. Epub.
31 Mucolytics Meta-analysis of 28 trials with 7,042 pts. 21% reduction in exacerbation rate 44% reduction in days of disability 1.93 OR of remaining exacerbation free Possibly increased benefit in patients NOT on ICS Poole P, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Reviews 2010, CD
32 Carbocysteine PEACE Trial Carbocysteine exac/yr Placebo 1.35 exac/yr P = No effect for 3 months No interaction with ICS, smoking status Zheng JP.. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet. 2008;371::2013-8
33 Corticosteroids for COPD exacerbation in hospital Hospital days Decreased from 9.7 to 8.5 in steroid group Niewoehner DE, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. VA Study Group. N Engl J Med. 1999;340:1941-7
34 Oral steroids after ER visit for COPD Aaron SD, et al.. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003;348:
35 Steroid Resistance in COPD Induced by oxidative / nitrosative stress on HDAC2 Reduced by theophylline, anti-oxidant treatments Can adjuvants be used to augment corticosteroid efficacy? Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med ;200:689-95
36 Etiology of Exacerbations of COPD Non-infectious e.g., air pollution. climate change, noncompliance,etc. Bacteria Virus Obaji A, Sethi S. Drugs and Aging. 2001;18:1-11 Bacteria and virus
37 Inhalation during swallowing in COPD 14% 12% 10% 8% 6% 4% 2% 0% O.R. = 4.4, p < O.R. = 1.23, p = 0.44 Cookie Pudding COPD Control Gross RD et al. The coordination of breathing and swallowing in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179:559-65
38 Can we prevent exacerbations with aspiration precautions, swallowing training, or dietary modification?
39 Etiology of Exacerbations of COPD Non-infectious e.g., air pollution. climate change, noncompliance,etc. Bacteria Virus Obaji A, Sethi S. Drugs and Aging. 2001;18:1-11 Bacteria and virus
40 Antibiotics Zpak is a simple prescription to write because it comes in a selfexplanatory packet. --- Indiana School of Optometry
41 Erythromcycin decreases frequency, severity and time to first exacerbation N = 109 pts Erythromycin 250mg bid 36% reduction in exacerbations Seemungal TA, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178:
42 Clinical trial of doxycycline in COPD flares treated with corticosteroids No difference in 30 day outcomes Improved efficacy at day 10 Daniels JM, et. al.. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181:150-7
43 Impaired macrophage clearance of bacteria in COPD reversed with sulforaphane % Inoculated CFUs Vehicle PA * Sulforaphane P1 250 P2 200 P3 P4 150 P5 100 P6 P7 50 P8 P9 0 % Inoculated CFUs Vehicle NTHI * Sulforaphane P6 P7 P8 P9 P10 P11 P12 P13 P14 Courtesy of C. Harvey, S. Biswal
44 Key Messages Recurrent hospital admissions are a major lever point for improving COPD care The future probably lies with real-world studies of combined therapies Both administrative and pharmacological strategies need to be explored conjointly
45 Thank you!