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Effect of Treatment of Comorbidities on COPD Esen KIYAN Istanbul University, Istanbul Medical Faculty Department of Resp

Effect of Treatment of Comorbidities on COPD Esen KIYAN Istanbul University, Istanbul Medical Faculty Department of Respiratory Diseases. Importance of treatment of co-morbidities in COPD. Severity of COPD Exacerbations Hospitalization In-hospital mortality Quality of life

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Effect of Treatment of Comorbidities on COPD Esen KIYAN Istanbul University, Istanbul Medical Faculty Department of Resp

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  1. Effect of Treatment of Comorbidities on COPD Esen KIYAN Istanbul University, Istanbul Medical Faculty Department of Respiratory Diseases

  2. Importance of treatment of co-morbidities in COPD • Severity of COPD • Exacerbations • Hospitalization • In-hospital mortality • Quality of life • Health expenses Foster TS, COPD 2006 Barnes PJ, Celli BR, Eur Respir J 2009 Pei-Jung L, Respir Med 2009 Morbidity Mortality

  3. 2962 inpatient and outpatient COPD (71y) with FEV1 %49.3+14.8 %51 with at least one comorbidity (%61 MS, %24 heart disease) Improvement in exercise tolerance and quality of life after PR may be reduced depending on comorbidity • Crisafulli E et al. Efficacy of standart rehabilitation in COPD outpatients with co-morbidities, Eur Respir J 2010 • 360 COPD and 62% with comorbidities (HT 35%, DM 12%, CAD 11%, dyslipidemia 13%) • Patient disability and osteoporosis were independently associated with poorer rehabilitation outcomes

  4. Mortality in COPD patients with two chronic disease or one severe disease at least 2 fold higher (OR52.2; 95% CI 1.26–3.84) • Almagro P et al. Mortality after hospitalization for COPD. Chest 2002 • Charlson Index score correlated with in-hospital mortality (if index score≥5, mortality at least 5 fold higher • Patil SP, In-hospital mortality following acute • exacerbations of chronic obstructive pulmonary disease. Arch Intern Med 2003 (Holguin F, Comorbidity and mortality in COPD-related hospitalizations in the US, 1979 to 2001. Chest 2005)

  5. COPD and Co-morbidities • KVD (MI, HT, heart failure, CAD) • Sleep apnea • Anxiety and Depression • Osteoporosis • Diabetes • Pulmonary hypertension • GER • Skeletal muscle dysfunction

  6. Mancini GBJ et al. Reduction of Morbidity and Mortality by Statins, ACE Inhibitors, and Angiotensin Receptor Blockers in Patients With COPD, J Am Coll Cardiol 2006 • Retrospective analysis of Canadian database: combination of statins and either ACE inhibitors or ARBs associated with a reduction in COPD hospitalization and total mortality (both high and low CV risk cohort) • Combination also reduced MI in high CV risk cohort • Benefits similar when ICS users included.

  7. Soyseth V et al. Statin use is associated with reduced mortality in COPD (Eur Respir J 2007) • retrospective cohort (854 COPD, follow-up 1.9) • improved survival (regardless of IHD) after COPD-AE • use of ICS with seems to increase survival mortality among ICS users only, statin users only, statin+ICS users was 0.75 (95% CI 0.58–0.98), 0.69 (95% CI 0.36–1.3), and 0.39 (95% CI 0.22–0.67), respectively, compared with patients receiving none of these treatments HR (95% CI) P value

  8. Risk reduction associated with statin therapy in observational studies compared with primary prevention randomised controlled trials in CAD

  9. Keddissi JI, The use of statins and lung function in current and former smokers. Chest 2007 • Statin group had a significantly reduced annual FEV1 decline • Statin group had 37% reduction in COPD related hospitalisation.

  10. Khurana V et al. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest 2007 • Of the 483,733 patients, 163,662 (33.8%) were receiving statins and 7,280 patients (1.5%) had a primary diagnosis of lung cancer. • Statin use > 6 months was associated with a risk reduction of lung cancer of 55%

  11. Statins • observational studies • reduced hospitalisation for COPD exacerbations • lower mortality from exacerbations • lower cardiovascular mortality • also reduces FEV1 decline and lung cancer risk • Two RCTs 1-reduced respiratory death (30%reduction) and COPD exacerbations (20%) • Heart Protection Study collaborative Group. BMC Med 2005 2-six months pravastatin had a 54% increase in exercise tolerance (125 COPD ptns) • Lee TM, Am J Cardiol 2008

  12. Lee TM, et al. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension.Clin Sci (Lond) 2009 • 53 COPD ptns with PH (either placebo or pravastatin-40 mg/day-for 6m. • exercise time increased 52% (P<0.0001) in pravastatin group • systolic PAP decreased significantly from (47±8 to 40±6mmHg) in pravastatin group.

  13. Useful actions of statins in COPD: anti-inflammatory, immunomodulator, antioxidant • Statins also have (+) effects on other comorbidities of COPD (DM, cerebrovascular event, cancer, osteoporosis) ……..RCTs neededParaskevas KI, Curr Pharm Des 2007

  14. ACE inhibitors and ARBs • Widely used for HT and heart failure treatment • Reduce pulmonary hypertension • Observational studies: ACE inhibitors and ARBs decrease exacerbations and mortality in COPD (Mancini GB, J Am Coll Cardiol 2006)

  15. Beta-blockers (1st line therapy for CHF) • Reduce hospital mortality in COPD-AE and mortality in patients with COPD undergoing vascular surgery • Dransfield MT, Thorax 2008 and van Gestel YT, AJRCCM 2008 • Selective B1 blockers do not effect lung functions and can be used safely in COPD • Salpeter SR, Respir Med 2003 • Treatment of appropriate cardiac patients with BBs improves survival in COPD. • Salpeter S, Cochrane Database Syst Rev 2005 • Van Gestel YRBM, Am J Respir Crit Care 2008 • Dransfield MT, Thorax 2008 • Heart Failure Society of America: proposing beta-blockers in heart failure patients with COPD (J Card Fail 2006)

  16. COPD and sleep apnea • more severe 02 desaturation than COPD patients with the same degree of obstruction. • increased risk of hypercapnic RF and PHT compared to patietns with SAHS alone Kessler R, Chest 2001

  17. Marin JM et al. Outcomes in Patients with COPD and OSA. The Overlap Syndrome. Am J Respir Crit Care Med. 2010 • 228 OS+CPAP, 213 OS-no CPAP, 210 COPD-only • All free of HF, MI or stroke and median follow-up 9.4 yrs (3.3-12.7). • After adjustment for age, gender, body mass index, smoking status, alcohol consumption, co-morbidities, severity of COPD, AHI and daytime sleepiness, • OS without CPAP group had a higher mortality and severe COPD exacerbation leading to hospitalization versus COPD-only group. • OS+CPAP group had no increased risk for mortality and hospitalization compared to patients with COPD-only

  18. COPD and Anxiety-Depression • exacerbation • (-) effect on PR and smoking cessation • quality of life • COPD treatment compliance • exercise capacity • use of health service (esp. depression) Tze-Pin NG, Respiratory Med 2009

  19. Between 1992-2007: 24 study (drug, psychotherapy, pulmonary rehablitation for A-D) Nortriptyline, buspirone, fluoxetine, sertraline, and paroxetine improve mood and physical symptoms and function

  20. Seven studies evaluating efficacy of cognitive behavioral interventions on A or D in COPD patients………..mixed results (discrepant results) • Relaxation techniques found helpful • Pulmonary rehabilitation……….mixed results. • Some studies found overall physical improvements but no psychologic benefits • Others found significant improvements in overall health status, exercise tolerance, dyspnea, and anxiety symptoms

  21. COPD and osteoporosis • prevalence of steoporosis 2-5 fold higher • Sabit R, 2007 • vertebral fractures result in a decreased forced vital capacity • Leech JA, 1990 • (osteoporotic) hip fractures pose a greater problem because of increased operative risk • Bapoje SR, 2007 • Smetana GW, 1999 • Trayner E Jr, 2001

  22. Effective therapy • smoking cessation • calcium (1000mg/gün) and vit. D (800IU/gün) • calcitonin, bisphosponate • Current quidelines recommend bisphosphonate in patients with COPD, regardless of sex • Ebeling PR, Clinical practice.Osteoporosis in men. • N Engl J Med 2008

  23. Current status of research on osteoporosisin COPD: a systematic review, Eur Respir J 2009 • systematic review of literature (MEDLINE/PubMed, Cochrane database) • 13 studies (a total of 775 COPD) • prevalence: 9% to 69% (overall mean prevalence for 13 studies 35.1%).

  24. COPD and diabetes • DM affects 1.6-16% of COPD patients (prevalence increase as lung function deteriorates) • Mannino DM, Eur Respir J 2008 • Chatila WM Proc Am Thorac Soc 2008) • accelarate progressive lung function decline (Borst, Chest 2010) • negatively affect respiratory muscle function • increases risk of infections and CV complications. • Hyperglycemia: • associated with poor outcome in COPD-AE • predictes failure of NMV and infectious complications in patients admitted to ICU with ARFMoretti M, Thorax 2000

  25. COPD and pulmonary hypertension • Usually mild (<35mmHg) but may be moderate (35-45mmHg, 10%) and severe (>45mmHg, <%5) • Increases hospitalization(Kessler R, 1999) • Decreases survival(Weitzenblum E, 1981 and Oswald-Mammosser M, Chest 1995) • COPD with PAP<25mmHg vs COPD with PAP<25mmHg: 5 year survival 36% vs 62% (FEV1, hypoxemia and hypercapnia not prognostic) • Safety and effectiveness of drugs used for PAH?

  26. COPD and Gatroesophageal reflux • GER causes oxygen desaturations and exacerbations Casanova C-Eur Respir J 2004, Rascon-Aguilar IE-Chest 2006) • Sasaki T, A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients.J Am Geriatr Soc. 2009. • 100 COPD ptns, observed for 12 months • conventional therapies (control group) or conventional therapies plus PPI (lansoprazole 15 mg/d; PPI group) • The number of exacerbations/person in a year in PPI group lower (P<.001).

  27. Skeletal muscle dysfunction • PR improves SMD (grade A evidence) • Improves exercise capacity and quality of life • Nutritional supplementation…. Conflicting results (some showed increase in RM strength) • Passive electrical stimulation (promising) • Testesteron if hypogonadism (+)

  28. 181 COPD 135 COPD Mean follow-up 439 days Mortality for 2003-4 cohort %38.7 vs %47.7 (p=0.017) long-term survival improved in the 2nd cohort for COPD patients with HF or cancer (p<0.001). better prognosis after hospital discharge is likely to be associated with better management and treatment of COPD and co-morbidities.

  29. TÜRK TORAKS DERNEĞİ KRONİK OBSTRÜKTİF AKCİĞER HASTALIĞI TANI VE TEDAVİ UZLAŞI RAPORU (Türk Toraks Dergisi, 2010) During follow-up of mild-severe COPD recognize and treat co-morbidities

  30. randomized controlled clinical trials in this topic are needed

  31. Thankyou

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