percent change in age-adjusted death rates, u.s., 1965-1998 0 0 0.5 1.0 1.5 2.0 2.5 3.0 proportion...
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Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
0
0.5
1.0
1.5
2.0
2.5
3.0Proportion of 1965 Rate
1965 - 98
–59% –64% –35% +163% –7%
CoronaryHeart
Disease
Stroke Other CVD COPD All OtherCauses
COPD - PathogenesisTobacco Smoke
Chronic Inflammation*
EmphysemaChronic Bronchitis
*CD8+ T-lymphocytes Macrophages Neutrophils IL-8 and TNF
ProteinasesOxidative Stress
Host factors
Anti-oxidants Anti-proteinases
Repair Mechanisms
COPD Therapy
• Smoking Cessation• Oxygen• Reduce exacerbations• Pulmonary Rehabilitation• LVRS (selected patients)• Lung Transplantation
• MDI Therapy– SA beta-2 agonists– LA beta-2 agonists– SA and LA Anticholinergics
• Theophylline• Corticosteroids (inhaled or
oral)• Combination Preparations
– SABA and anticholinergic – LABA and corticosteroids
Prolong Life Symptomatic
Management of COPD Stage 0: At Risk
Characteristics Recommended Treatment
• Risk factors•Chronic symptoms
- cough- sputum
• No spirometric abnormalities
•Adjust risk factors•Immunizations
Management of COPD Stage I: Mild COPD
Characteristics Recommended Treatment
• FEV1/FVC < 70 %
• FEV1 > 80 % predicted• With or without symptoms
• Short-acting bronchodilator as needed
Management of COPD Stage II: Moderate COPD
Characteristics Recommended Treatment
•FEV1/FVC < 70%
•50% < FEV1< 80% predicted•With or without symptoms
•Treatment with one or more long-acting bronchodilators•Rehabilitation
Management of COPD Stage III: Severe COPD
Characteristics Recommended Treatment
•FEV1/FVC < 70%
•30% < FEV1 < 50% predicted•With or without symptoms
•Treatment with one or more long-acting bronchodilators•Rehabilitation•Inhaled glucocortico-steroids if repeated exacerbations (>3/year)
Management of COPD Stage IV: Very Severe COPD
Characteristics Recommended Treatment•FEV1/FVC < 70%
•FEV1 < 30% predicted or presence of respiratory failure or right heart failure
•Treatment with one or more long-acting bronchodilators•Inhaled glucocorticosteroids if repeated exacerbations (>3/year)•Treatment of complications•Rehabilitation•Long-term oxygen therapy if respiratory failure•Consider surgical options
Bronchodilator Therapy
• Inhaled therapy (with spacer) preferred• Long-acting preparations more convenient• Combined preparations improve effectiveness and
decrease risk of side effects – Ipratroprium-albuterol– Fluticasone-salmeterol– Budesonide-formoterol
• MDI almost always as effective as nebulizers (in equal doses)
Some General Principles
Effectiveness of BronchodilatorTherapy?
• FEV1 does not always correlate with symptoms– Concept of “dynamic hyperinflation” in COPD
• Quality of life issues are important– Chronic fatigue– Depression– Physical immobility– Dyspnea
COPD - Surgical Options• Giant Bullous Disease
– Consider bullectomy if see normal lung compression • Lung Volume Reduction Surgery*
– FEV1 (<20% pred) plus diffuse emphysema or Dlco<20% pred = high risk of surgical death
– Upper lobe emphysema and low exercise capacity = decreased mortality, increased exercise and QOL
• Lung Transplantation– FEV1<25% predicted, younger patient– 3-5 year mortality 55%
*NETT Research Group. N Eng J Med 348:2059, 2003
COPD Exacerbation
• Worsening dyspnea• Increased sputum purulence• Increase in sputum volume
• Severe - all 3 elements• Moderate - 2 elements• Mild - 1 element plus:
• URI in past 5 days• Fever without
apparent cause• Increased wheezing or
cough• Increase (+20%) of
respiratory rate or heart rate
Definition Elements Severity
Modified from Anthonisen et al. Ann Int Med 106:196, 1987
COPD Exacerbation
• 109 pts (mean FEV1 = 1.0 L over 4 years
• Frequent exacerbators:– faster decline in PEFR and
FEV1– more chronic symptoms
(dyspnea, wheeze)– no differences in PaO2 or
PaCO2
Donaldson et al. Thorax 57:847, 2002
Effects on Lung Function Decline
InfrequentFrequent
Conclusion:Frequent exacerbations accelerate decline in lung function
COPD Exacerbation
BacterialInfection
50%
Viral Infection
25%
AirPollution
5%
Unknown20%
Exacerbation
AcuteInflammation
Pathophysiology - Current Hypothesis
Chronic Inflammation
Therapy of COPD Exacerbation
Variable ACCP-ACPACCP-ACP GOLDGOLDDiagnostic CXR for admissions CXR, EKG, ABG,
sputum culture, lytes, cbcBronchodilators Ipratroprium, add B2
agonist. No methylxanthine
B2 agonist, add ipratroprium. Yes methylxanthine
Delivery system None preferred Not discussed
Antibiotics Yes, in selected (severe). Duration unclear
Yes, with purulence, Rx local sensitivities
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
Therapy of COPD Exacerbation
Variable ACCP-ACPACCP-ACP GOLDGOLDSteroids Yes, for up to two
weeksYes, oral or IV for 10-14 days
Oxygen Yes Yes - target PaO2 60 torr or Sat of 90% with ABG check
Chest PT No Maybe - for atelectasis or sputum control
Mucokinetics No Not discussed
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
Therapy of COPD Exacerbation
Variable ACCP-ACPACCP-ACP GOLDGOLDMechanical Ventilation
Yes - use NIPPV in severe exacerbation
Yes if ≥2 of:Severe dyspnea, access. muscle or paradox, pH <7.35 and PCO2 >45, RR>25
Other LMWH, fluids, diet
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
COPD Therapy - New Horizons• Newer anti-inflammatory agents
– Matrix metalloproteinase inhibitors– Specific phosphodiesterase (PDE4) inhibitors
• Cilomilast• Rofumilast• Piklanilast
• Anabolic steroids• Repair agents
– Retinoic acid• Long-acting anti-muscarinic agents
– tiotropium
Tiotropium
• 470 patients - stable COPD• 3 month, randomized, double
blind, once daily tiotropium vs. placebo
Conclusions:
Increased FEV1 and FVCNo tachyphylaxis Decreased rescue albuterolDecreased wheezing, SOBDry mouth in 9.3%Casaburi et al. CHEST 118:1294, 2000
Specific M1 and M3 Muscarinic Blockade
TiatropriumSpecific M1 and M3 Muscarinic Blockade
• 1207 patients, double blind, randomized trial,
• qd tiotropium vs. bid salmeterol vs. placebo
Conclusions: TiotropiumFewer exacerbationsIncreased time to first exacerbationFewer admissionsIncreased QOL
Brusasco et al. Thorax 58:399:2003
Lung Volumes in Obstructive DiseaseLung Volumes in Obstructive Disease
NormalNormal COPDCOPD
RVRV
RVRV
TLCTLC
FRCFRC
Room toRoom toBreatheBreathe
Room toRoom toBreatheBreathe
TLCTLC
FRCFRC
Volu
me
Volu
me
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