Transcript COPD: FIXING the FIXABLES in 2003

COPD: Reversing the
Reversible in 2014
Donald M. Pell M. D., FCCP
Introduction
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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
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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
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SPUTUM
SPASM
SWELLING
Differentiating COPD and
Asthma
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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
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Mechanisms of effects
Improved efficiency of the diaphragm
Anti-inflammatory
Bronchodilator
Respiratory center stimulant
Narrow therapeutic window
Frequent drug interactions
FEV1 and Aging
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Healthy lungs lose about 20 cc@ year after age
25
COPD patients lose about 80 cc@ year
Summary of New Therapies
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Non pharmaceutical supplements (Boswellia)
Supplemental Oxygen (Oximizer)
COPD rehab
Leukotriene modifiers
Cilomilast
Tioproprium Bromide
Foradil
Statins
ACE Inhibitors
Leukotriene Modifiers and
COPD
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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
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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
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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
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Floyd & Foster, Chest (131), 1006-1012
Protection from loss of lung
function in COPD
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.