copd. objectives how important is copd? what is copd? how to treat copd? what is the prognosis?
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COPD
Objectives
• 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 % of Smokers Demographic
19.3% US Adults
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 Age
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 povertyCDC, 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
CDC, NHIS 2009, 2011
• 50% of COPD patients have limited ability to work
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
Oxidative Stress
Cigarette smoke- derived
free radicals and oxidants
Antioxidantgenes
‘Susceptibility’ genes
Inactivation of antiproteases
Lipidperoxidation
Depletion of antioxidant
defenses
Neutrophilsequestration
Transcription of proinflammatory
cytokines
Epithelial permeability
Inflammation
INJURY
MacNee W. Chest. 2000;117:303S-317S.
Role of Bacterial/Viral Infections
Vicious Circle Hypothesis
Sethi S. Chest. 2000;117:286S-291S.
Initiating factors (eg, smoking, childhood respiratory disease)
Impairedmucociliary clearance
Airway epithelial injury
Progression of COPD
Altered elastaseantielastase balance
Bacterial products
Increased elastolytic activity
Inflammatory response
Bacterial colonization
Viral pathogens Associated with COPD Exacerbations
Influ
enza
Parain
fluenza
Rhinoviru
s
Coronaviru
s
Adenovirus
RSV0
10
20
30
40
% E
xace
rbati
ons
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 FEV1 % predicted
Mild ≤ 0.7 > 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.
Decramer Thorax 2010;65:837-841
Disease Progression
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 a1-levelsPiMZ Decreased a1-levels to 60%
PiZZ Decreased a1-levels to 10-20%
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
MILDFEV1>80%
MODERATEFEv1 50-79%
SEVEREFEV1 30-49%
VERY SEVEREFEV1<30% or failure
Long acting bronchodilators
ICS, if freq. exac (≥ 2/yr.)
Short acting bronchodilators PRN if respiratory symptoms
Smoking cessation; Reduce risk factors; Vaccination
Pulmonary Rehab based on functional status
O2
GoldCOPD.org
Surgery
Available Drugs
LAMA
PDEI
ICSLABA
SAMA
SABA
Beta-2 agonists
Anti-muscarinics
BudesonideFluticasone
Mometasone
SalmeterolFormoterol
ArformoterolOlodaterol
Ipratropium
TiotropiumAclidinium
AlbuterolPirbuterol
Levalbuterol
RoflumilastTheophylline
???
???
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):948Celli. 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
• 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;131:1006-12Keddissi. 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
• PaO2 < 55 or
• PaO2 = 56-59 with evidence of pulmonary hypertension, polycythemia or cor pulmonale
0 10 20 30 40 50 60 70
0
10
20
30
40
50
60
70
80
90
100
COT
MRCO2
NOT
MRCcontrols
CumulativeSurvival
(%)
Flenley DC. Chest. 1985;87:99-103
Months
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
• <=65• Maximal medical therapy• Body weight 80-120% of ideal• Favorable social factors• $
Lung Transplant Contraindications
• 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
• Level 3: ICU/Specialized Care
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
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 REALreason
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