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COPD: Reversing the Reversible in 2014 Donald M. Pell M. D., FCCP Introduction Prevalence 5.9% of U.S. population or about 24,000,000 adults (ATS Gold Paper 2004) In 2000 there were 122,000 deaths (CDC data) For the first time more women than men 2nd to heart disease as a cause of disability Annual cost 2002 est. $32.1 billion 70% of the patients were less than 65 Introduction By 2005, there were 126,000 deaths and the number of male deaths had increased by 8%. The number of female deaths had increased by 11% (CDC data) Spectrum of COPD PURE EMPHYSEMA 10% COPD 80% CHRONIC BRONCHITIS 10% REVERSIBLE COMPONENTS of COPD SPUTUM SPASM SWELLING Differentiating COPD and Asthma No diagnostic test for either is conclusive Frequent coexistence of both problems 10% overlap Autonomic Effects on Respiratory Tract Short Acting Beta 2 Agonist BRONCHODILATOR Medication Dose Isuprel Isoproterenol 130mcg/p Bronkosol Isoetharine 3-40mcg/p Alupent Metaproterenol 65mcg/p Brethine Terbutaline 200mcg/p Proventil Albuterol 90mcg/p Maxair Pirbuterol 200mcg/p Tornolate Bitolterol 370mcg/p DMP-2000 Duration 2pq3-4h .5-2h 2pq4h 2-4h 2pq4-6h 4-6h 2pq4-6h 4-6h 2pq4-6h 4-6h 2pq4-6h 4-6h 2pq4-6h 5-8h Long Acting Beta 2 Agonist BRONCHODILATOR Medication Serevent Diskus Foradil (Fomoterol) Advair 50/500 Symbicort160/4.5 Dose Inhale 1 BID Inhale 1 BID Inhale 1 BID Inhale 2 BID Lancet, Feb 2003 Duration 12h 12h 12h 12h Theophylline Mechanisms of effects Improved efficiency of the diaphragm Anti-inflammatory Bronchodilator Respiratory center stimulant Narrow therapeutic window Frequent drug interactions FEV1 and Aging Healthy lungs lose about 20 cc@ year after age 25 COPD patients lose about 80 cc@ year Summary of New Therapies Non pharmaceutical supplements (Boswellia) Supplemental Oxygen (Oximizer) COPD rehab Leukotriene modifiers Cilomilast Tioproprium Bromide Foradil Statins ACE Inhibitors Leukotriene Modifiers and COPD Reports at international and national meetings Proposed mechanism Local experience 18 patients with severe COPD 2 week trial LM Average response to SABA before trial 9% After trial 40% Statins Vast improvement in lung transplant survival 91% vs 54% Johnson Am J Crit Care Med (167), 1271-1278 2003 Statins Marked reduction in number of exacerbations by 2/3 ACE Inhibitors Additional improvements when added to statins Proposed Pathophysiology Barnes, NEJM, 2000 Barnes, NEJM, 2000 Barnes, NEJM, 2000 Mancini, JACC, vol 27, 2006 Effects of statins on COPD and Influenza mortality 150,000 patients, 90 days of statins minimum Low dose group <4 mg/day Moderate dose group >4 mg/day Usual dose 10 mg/day 2 year USA HMO study Floyd& Foster, Chest (131), 1006-1012 Effects of statins on COPD and Influenza mortality Deaths by disease category Low Moderate Pneumonia 11 18 COPD 8 5 Influenza 8 16 All statin users RR.23 for COPD No COPD, moderate dose RR .54 Floyd & Foster, Chest (131), 1006-1012 No Statin 94 84 80 Effects of statins Hospitalized patient deaths due to influenza/pneumonia Pneumonia All statins 73, Low dose 89, High dose 49 COPD All statins 29, Low dose 58, High dose 17 Floyd & Foster, Chest (131), 1006-1012 Protection from loss of lung function in COPD Decrease in FEV1 85 cc/ year in COPD Decrease in FEV1 5 cc/ year in statin group with or without smoking cessation Keddissi, Chest (132) 1764-1771 Effect of statin on COPD Mortality Norwegian study 854 patients mean age 70.8 Follow up 1.9 years 51.5% females Soyseth European Resp J (29) 279-283 2007 Effects of statin on COPD Mortality 333 died all with severe COPD Statin group 110 died Non-statin group 191 died Hazard reduction statin vs nonstatin 57% Statins alone 69% Statins plus ICS 39% Soyseth European Resp J (29) 279-283 2007 Effect of statins on COPD deaths Japanese study All cause mortality results 65 years and older COPD deaths 152/100,000 in non statin group 8/100,000 in statin group Tohoku Experimental Med (212) 265273 2007 Effects of statins Canadian study All patients over 65 High risk had been revascularized Low risk had no MI in prior 5 years and no NSAIDs Must have had 3 Rx in prior year for statin & 1 Rx in prior 60 days Mancini J Amer Col of Cardiology (47) 12 2006 Effects of statins COPD hospitalizations decreased 12-21% in both groups Death from COPD decreased 38% with satins Death or MI decreased 47% in high risk group Mancini J Amer Col of Cardiology (47) 12 2006 Effects of statins VA study from1998-2004 483,733 patients 33% on statins 7,280 Lung cancer Risk of lung cancer decreased 55% in statin group RR .45 Khurana Chest (131) 1282-1288 2007 Decreased Exacerbations and Intubations in patients on statins New Jersey community hospital 185 COPD pts 90 on statins 95 not on statins Average age 70, Duration 1 year Average FEV1 38% predicted Exacerbations reduced 90% in statin group Intubations reduced 90% in statin group Blamoun International J Clin Pract (62) 1373-78 2008 Safety of statins Study from 1985-2006 1/10,000 risk of myopathy Risk increases with fibrates Other drug interactions Hypothyroid Decreased GFR Over age 80 Lancet June 2007 SUMMARY Sputum, Spasm and Swelling all have some degree of reversibility and that becomes the basis for treating COPD. New treatments are being studied and have been reported in Europe, Canada and the US. Pell’s Pearl More than 90% of all patients with COPD have some degree of reversibility.