COPD: Reversing the Reversible in

2014Donald 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

COPD80%PURE EMPHYSEMA

10%

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

DMP-2000

Short Acting Beta 2 Agonist

BRONCHODILATORMedication Dose

DurationIsuprel Isoproterenol 130mcg/p 2pq3-4h

.5-2hBronkosol Isoetharine 3-40mcg/p 2pq4h

2-4hAlupent Metaproterenol 65mcg/p 2pq4-

6h 4-6hBrethine Terbutaline 200mcg/p 2pq4-6h

4-6hProventil Albuterol 90mcg/p 2pq4-6h

4-6hMaxair Pirbuterol 200mcg/p 2pq4-

6h 4-6hTornolate Bitolterol 370mcg/p 2pq4-6h

5-8h

Lancet, Feb 2003

Long Acting Beta 2 Agonist

BRONCHODILATORMedication Dose

DurationSerevent Diskus Inhale 1 BID

12hForadil (Fomoterol) Inhale 1 BID

12hAdvair 50/500 Inhale 1 BID

12hSymbicort160/4.5 Inhale 2 BID

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%

StatinsVast improvement in

lung transplant survival91% vs 54%

Johnson Am J Crit Care Med (167), 1271-1278 2003

StatinsMarked reduction in

number of exacerbationsby 2/3

ACE InhibitorsAdditional 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 No

StatinPneumonia 11 18 94COPD 8 5 84Influenza 8 16 80All statin users RR.23 for COPDNo COPD, moderate dose RR .54

Floyd & Foster, Chest (131), 1006-1012

Effects of statins Hospitalized patient deaths due to

influenza/pneumonia Pneumonia All statins 73, Low dose 89, High dose

49 COPDAll 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) 265-273 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

groupBlamoun 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.