COPD
Objectives
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•
•
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How important is COPD?
What is COPD?
How to treat COPD?
What is the prognosis?
19.3% of US Adults Smoke – 2010
CDC, NHIS 2010
2010 Current Smokers
% of Smokers
Demographic
19.3%
US Adults
% of Smokers
Demographic
21.5%
Males
Education
17.3%
Females
45.2%
GED diploma
Race
33.8%
9-11 yrs education
31.4%
Native American/Alaska
23.8%
High school diploma
27.4%
Multiple race
9.9%
Undergraduate degree
21.0%
Caucasian
6.3%
Postgraduate degree
20.6%
African American
12.5%
Hispanic
20.1%
18-24
9.2%
Asian
22.0%
25-44
Poverty
21.1%
45-64
38.9%
Below poverty level
9.5%
65 and older
18.3%
At or above poverty
Age
CDC, NHIS 2010
Fact Sheet
• 49.9 million former smokers/46.6 million current
smokers in 2009
• 3rd leading cause of death in US in 2011
– 12.7 Million US adults have COPD
– 24 million US adults have impaired lung function
suggesting under diagnosis
• Women are more likely to have COPD and die from it
• 50% of COPD patients
have limited ability to
work
CDC, NHIS 2009, 2011
Prevalence (%) of COPD by State in
2011
CDC, NHIS 2011
Etiology of COPD
• 80-90% due to tobacco use
• 15-20% of smokers will have clinical significant
COPD
• Occupational exposures
• Bacterial/viral exposures
• -1 protease inhibitor deficiency
COPD RISK FACTORS
Genes
Exposure to particles
Tobacco smoke
Occupational dusts
Indoor air pollution
Outdoor air pollution
Lung Growth & Development
Oxidative stress
Gender
Age
Respiratory infections
Previous TB
Low SES
Poor Nutrition
Co-morbidities
Overall Mechanisms of
Cigarette Smoke-Induced Lung Damage
Inactivation of
antiproteases
Cigarette
smoke- derived
free radicals
and oxidants
Antioxidant
genes
Lipid
peroxidation
Oxidative
Stress
Depletion of
antioxidant
defenses
Neutrophil
sequestration
Epithelial
permeability
I
N
J
U
R
Y
Inflammation
‘Susceptibility’
genes
Transcription of
proinflammatory
cytokines
MacNee W. Chest. 2000;117:303S-317S.
Role of Bacterial/Viral Infections
Vicious Circle Hypothesis
Initiating factors (eg, smoking, childhood respiratory disease)
Impaired
mucociliary clearance
Airway epithelial injury
Progression
of COPD
Bacterial colonization
Bacterial products
Altered elastase
antielastase balance
Inflammatory
response
Increased
elastolytic activity
Sethi S. Chest. 2000;117:286S-291S.
Viral pathogens Associated with COPD
Exacerbations
% Exacerbations
40
30
20
10
0
Sethi S. Infect Dis Clin Pract. 1998;7:S300-S308.
Chronic Bronchitis Prevalence 2011
CDC, NHIS 2011
Emphysema Prevalence 2011
CDC, NHIS 2011
1st Hospitalization for COPD
CDC, NHIS 2011
Pulmonary Function in COPD
• Spirometry
– Decreased FEV1 more than FVC; decreased ratio
– Earliest change is a decrease in FEF25-75%
• Lung Volumes
– Increased Total Lung Capacity (TLC)
– Increased Residual Volume (RV)
– Decreased Vital Capacity (SVC)
• DLCO
– May be decreased
Spirometry in COPD
COPD Severity Classification
Severity
FEV1/FVC
Mild
≤ 0.7
FEV1 %
predicted
> 80
Moderate
≤ 0.7
50-79
Severe
≤ 0.7
30-49
Very Severe
≤ 0.7
<30 **
** < 50%predicted plus respiratory failure or clinical signs of right heart failure
Smoking and COPD
Males
Females
Former
smokers
30 ml/year
22 ml/year
Current
smokers
66 ml/year
54 ml/year
Anthonisen NR, et.al. Am J Respir Crit Care Med 166:675-9, 2002.
Disease Progression
Decramer Thorax 2010;65:837-841
Dynamic Hyperinflation
Obstructive Diseases
• Asthma
– Reversible airflow obstruction
– Inflammation prominent
• Emphysema
– Permanent
– Destruction of the respiratory
bronchioles
• Chronic Bronchitis
– Sputum production 3
months/year for 2 years
Patients Have All Combinations
Chronic Bronchitis
Normal Lung
Acinus
Centrilobular
Emphysema
Panlobular
Emphysema
Centrilobular emphysema in
COPD with no bronchial
abnormalities
Centrilobular emphysema in
COPD with widespread
bronchial wall thickening
Centrilobular Emphysema
• Emphysema of smokers and coal workers
• Worst in upper lung fields of each lobe of the
lung
• Inflammatory changes in small airways are
common
Paraseptal emphysema
• Selective expansion of alveoli adjacent to
connective tissue septa and bronchovascular
bundles
• Most notable sub pleural
• More Common in Young (<40) smokers
Paraseptal Emphysema
Don’t mistake this for honeycombing
Panacinar = Panlobar Emphysema
• Alpha1 antitrypsin deficiency and familial
cases
• Generally emphysema of non-smokers
• Can co-exist with centrilobular
• Most widespread and most severe
• More severe at lung bases but distributed
throughout lung
Alpha 1 Antitrypsin
Alpha 1 Antitrypsin
• Lung and liver disease
• Lower lung panacinar emphysema with bronchial wall
thickening
• Frank bronchietasis with PiZZ phenotype
• Bullous formation relative uncommon
• Serum protein that inhibits lysosomal proteases during
inflammation preventing the damaging effects of elastases
released by macrophages and neutrophils
PiMM
Normal 1-levels
PiMZ
Decreased 1-levels to 60%
PiZZ
Decreased 1-levels to 1020%
GOLD
• Collaborative project of NHLBI and WHO
– Increase awareness of COPD
– Decrease morbidity and mortality
Stage
Criteria
Stage 0 (at risk)
Chronic cough and sputum; Normal PFT
Stage I (mild)
FEV1/FVC<70%; FEV1 > 80%; ± Sx
Stage IIA (moderate)
FEV1/FVC<70%; FEV1 50-79%; ± Sx
Stage IIB (moderate)
FEV1/FVC<70%; FEV1 > 30-49%; ± Sx
Stage III (severe)
FEV1/FVC<70%; FEV1 < 30% or presence of respiratory failure
or right heart failure
Modified Stepwise Approach to
Treatment
MILD
MODERATE
SEVERE
VERY SEVERE
FEV1>80%
FEv1 50-79%
FEV1 30-49%
FEV1<30% or failure
Smoking cessation; Reduce risk factors; Vaccination
Pulmonary Rehab based on functional status
O2
Surgery
Short acting bronchodilators PRN if respiratory symptoms
Long acting bronchodilators
ICS, if freq. exac (≥ 2/yr.)
GoldCOPD.org
Available Drugs
SABA
Albuterol
Pirbuterol
Levalbuterol
Beta-2 agonists
LABA
Salmeterol
Formoterol
Arformoterol
Olodaterol
Budesonide
Fluticasone
Mometasone
ICS
???
SAMA
Ipratropium
Antimuscarinics
LAMA
Tiotropium
Aclidinium
Roflumilast
Theophylline
???
PDEI
Short Acting b-agonists
• All equal efficacy
• Studies show HFA and CFC have equal efficacy
• Tachycardia decreased with spacer use and
rinsing mouth after use
Importance of Spacer
Barnes et.al 1998 Asthma Basic Mechanisms and Clinical Management
Short Acting Anti-muscarinics
• Decreases secretions
• Longer acting than albuterol
• Blocks bronchoconstriction from inhaled
irritants
• Spiriva
– 4x/day = once a day Spiriva
– Competitive inhibitor
Cardiac Risk, Ipratroprium, Tiotropium
• Better tolerated than beta-agonists
• Meta-analysis - increased CV deaths in
patients on anti-muscarinics
• UPLIFT - 4 yr trial - decreased fatal
cardiovascular event risk with Tiotropium
• Clinical trial safety database
Tiotropium – no increased risk
Celli. Am J Respir Crit Care Med. 2009;180(10):948
Celli. Chest. 2010;137(1)20
Tiotropium
Delays Next
Exacerbation/
Hospitalization
Niewoehner, D. E. et. al. Ann Intern Med 2005;143:317-326
GOLD ICS Therapy
• Candidates
– Symptomatic patients with spirometric response
– Patient with daily sputum production
– Patients with variability in symptoms
– FEV1 < 50% with frequent exacerbations needing
steroids or Abx
• Trial 6 weeks – 3 months
Oral Steroid Therapy
• 10-20% will have significant response to oral
steroids
– 2 week trial of steroids improves PFTs then
continue ICS
• Effective for acute exacerbation
• Antibiotics decrease relapse rate
Oral Steroid Therapy
• Conflicting results in stable COPD patients
– Significant side effects
• Exacerbations (10-14 day courses)
– Decreased treatment failure
– Rapid improvement in PFTs and symptom scores
– Decreased in hospital stay
– Maximum benefit in the first 2 weeks
Thompson WH et al. Am J Respir Crit Care Med. 1996;154:407-412.
Davies L et al. Lancet. 1999;354:456-460.
Niewoehner D et al. N Engl J Med. 1999;340:1941-1947.
Antibiotic Use
• Chronic Macrolides
– Decreases exacerbations
– Increased resistance
• Macrolides/Doxycycline at home for early
exacerbation treatment
Theophilline
• Positive effects for COPD
– Stimulate respiratory center
– Improves muscle function
– Anti-inflammatory
• Negative effects for COPD
– Increases GERD
– Narrow therapeutic window
– Significant drug-drug interactions
– Significant food interaction (fatty foods)
Roflumilast
• Unknown exact mechanism
– Selectively inhibits phosphodiesterase Type 4
leading to increased intracellular cAMP
• Decreases exacerbations
• Use with caution in liver disease, depression
(suicide)
Is There a Drug To Cure COPD?
• No existing medications will change the
inherent decline in lung function related to
age/smoking
• Goal of Tx:
– Decreased symptoms
– Decreased complications
Other Modalities
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•
•
•
•
Nutrition
Post-nasal drip treatment
Flu vaccine reduces serious illness
Pneumovax: >65 or <65 with FEV1 <40%
Statins?!?
– Slower decline in PFTs, decrease exacerbation
rate, decreased death rate
Frost. Chest 2007;131:1006-12
Keddissi. Chest 2007; 132:1764-71
Aspiration and GERD - Risks
• Medical risk factors
– CVA, Parkinsons, Dementia, medications
• Medication risk factors
– Calcium channel blockers, bisphosphonates, iron
supplements, NSAIDS, potassium, anticholinergics,
narcotics, nitrates, progesterone, benzodiazepines
Aspiration and GERD
• PPI – before meals
• Lifestyle changes
– Elevation of head of bed 4-6 inches
– Minimizing caffeine/mint
– Avoiding eating/drinking 2-3 hours before bed
Oxygen therapy
100
• PaO2 < 55 or
• PaO2 = 56-59
with evidence of
pulmonary
hypertension,
polycythemia or
cor pulmonale
90
80
COT
70
Cumulative
Survival
(%)
60
50
MRC
O2
NOT
40
MRC
controls
30
20
10
0
0
10
20
30
40
50
60
70
Months
Flenley DC. Chest. 1985;87:99-103
Pulmonary Rehabilitation
• Benefit from exercise training programs
• Improved health status
–
–
–
–
↑ exercise tolerance & QOL
Return to function
↓ dyspnea & fatigue
↓ hospitalization & LOS
• ↓ exacerbations
• Improves survival
Lung Surgery
• Bullectomy
• Lung Reduction Study - NETT trial
– Increased mortality in patients with DLCO<25%
predicted
– Benefit in patients with asymmetric lung disease
by HRCT
– 7.9% 90 day mortality vs 1.9% control
– 28% had improved exercise capacity at 6
months/15% at 2 years
NETT. NEJM 2003: 348:2059-73.
Lung Transplant
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•
•
•
•
<=65
Maximal medical therapy
Body weight 80-120% of ideal
Favorable social factors
$
Lung Transplant Contraindications
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•
•
•
•
•
Untreatable pulmonary infection
Malignancy within last 2 years
Significant dysfunction of other organs (heart)
Significant chest wall/spine deformity
Active smoking/drug and alcohol dependency
Unresolved psychosocial problems
(noncompliance)
• HIV, Hep B, Hep C
• Absence of social support
Acute Exacerbation Classification
• Level 1: Treatment at home
• Level 2: Hospitalization
Clinical Factors Favoring Hospitalization
HR, RR, change in BP
Hypoxia/ hypercapnea
Significant comorbidities
Elderly
Poor home support
Inadequate outpatient
response
ER Visit in last 2 weeks
• Level 3: ICU/Specialized Care
COPD Exacerbation Survival
• 6 month mortality = 24%
• 12 month mortality = 33%
• Survival associated with albumin, BMI, PaO2,
disease duration
Gunen H, Eur Resp J. 2005; 26:234-241.
Acute Exacerbation Treatment
• Oxygen for low saturations
• Bronchodilators
– MDI vs nebulizer
• Steroids 14 day max
– IV vs Oral
– Improves spirometry, decreases relapse rate
– No study on taper
• Education
• Antibiotics
Antibiotics and Survival
• Retrospective cohort
of 50K COPD pts in
Netherlands
• Median time to next
exacerbation delayed
• More benefit in
worse exacerbations
• Fewer treatment
failures with newer
Abx
Roede et al. Thorax 2008: 63:968
NIPPV in Acute Exacerbations
• If pH<7.35, if tolerated
• Decreases symptoms/
morbidity/ mortality
• Avoid in:
–
–
–
–
CV instability,
Uncooperative patient,
ΔMS,
Copious secretions, high
aspiration risk,
– Facial abnormalities
Relapse Rate 20-40%
• If ER visit : 33% recur within 14 days, 17% eventually
need hospitalization
• Risk of Relapse
– Low FEV1
– Increasing medication use (BDs or steroids)
– Prior exacerbations (3 within last 2 years)
– Comorbid conditions
Miravitlles M. Respiration 67:495, 2000.
Heart Rate and COPD
Prognosis
Jensen. Eur Respir J, 2013; 42: 341-349.
From Rabe, KF. NEJM 356:851-854.
Prognosis
• Patients hospitalized
6 mth mortality 24%;
33% 1 year; 39% 2
year; 49% 3 year
FEV1 (L)
Prognosis (years)
1.4
10
1.0
4
0.5
2
Gunen H, Eur Resp J. 2005; 26:234-241.
Summary
• Prevention is key
– Smoking cessation
– Prevent exacerbations and infections
• Symptom management
– Inhaled drugs may help symptoms
• Combination therapy is better than monotherapy
• Pneumonia risk increased with ICS
• Oxygen improves longevity
The
REAL
reason
dinosaurs
became
extinct...