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COPD in 2007
Israel E. Priel, MD, FCCP
Department of Pulmonary Medicine
The Edith Wolfson Medical Center
M.T.• 56 year old lady, 37 pack -year smoking .Quit one year ago.
Used to work in housekeeping• Childhood Hx. of ‘bronchitis”• Pneumonia : 1986• Increasing SOB - gradually worsening• Diagnosed as having COPD 2 years ago• Two episodes of mechanical ventilation• Awaiting Lung Transplantation• “ I live on the first floor. I rarely leave the house : no
elevator and can’t walk the stairs . The smallest effort is an incredible burden….”
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Natural History in SmokersThe Fletcher-Peto Diagram
COPD International Your International Support
Networkhttp://www.copd-international.com/
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You can learn to control this disease, instead of letting it control you!You can learn to control this disease , instead of letting it control you
Learn more about Chronic Obstructive Pulmonary Disease (COPD)
YOU ARE NOT ALONE !
• It is estimated that there are currently 12 million people in the USA diagnoses with COPD
•It is estimated that an additional 12 million or more are still undiagnosed, as there are in the beginning stages and have few or minimal symptoms and have not sought health care yet
It is predicted that close to 600 million cases could possibly be found worldwide
Chronic obstructive pulmonary disease risk is related to the total burden of
inhaled particles.
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Nutrition
Infections
Socio-economic status
Aging Populations
COPD Risk Factors
• Cigarette smoking• The rest:
Occupational or environmental exposures to:
DustsGassesVapors or fumes
Exposure to biomass smoke Malnutrition Early life infections Genetic predisposition : A1AT
deficiency Increased airway responsiveness Asthma
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From Sexy to Deadly
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A 1933 ad for Chesterfield cigarettes from the ‘Saturday Evening Post’
The components of COPD
AIRFLOW LIMITATION
SMALL AIRWAY DISEASEAirway InflammationAirway remodeling
PARENCHYMAL DESTRUCTIONLoss of alveolar attachments
Decrease of elastic recoil
INFLAMMATION
The relative importance of each component varies from The relative importance of each component varies from patient to patientpatient to patient
Chronic Airflow Limitation
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The Definition of Asthma
Asthma is like LOVE
• Everybody knows what it is - yet it is very difficult to define
The definition of COPD
• Chronic Obstructive Pulmonary Disease is a preventable and treatable disease , responsible for a large human and economic burden around the world
• It is characterized by airflow limitation that is not fully reversible
• The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.
• Although COPD affects the lungs , it also produces significant systemic consequences.
COPD HypothesesThe Dutch Hypothesis:• Asthma and COPD are the
same disease “the same bird with different feathers
The British Hypothesis:• COPD is due to chronic
infection , completely different from asthma
The American Hypothesis:• COPD is due to direct toxic
effect of cigarette smokeCould COPD be an autoimmune
Disease ?
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Spirometry
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John Hutchinson
•Important for diagnosis•Important for follow-up•Important for prognosis
Spirometric Classification of severity of COPD (GOLD 2006)
Stage CharacteristicsBased on post BD spirometry
I Mild COPD FEV1/FVC < 70%FEV1 > 80% predictedWith or without chronic symptoms (cough, sputum)
II Moderate COPD FEV1/FVC < 70%50%< FEV1 < 80% predictedWith or without chronic symptoms (cough, sputum)
III Severe COPD FEV1/FVC < 70%30%< FEV1 < 50% predictedWith or without chronic symptoms (cough, sputum)
IV Very severe COPD
FEV1/FVC < 70%FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure
At Risk Stage
• Formerly known as GOLD stage 0• Patients with chronic respiratory symptoms
(cough, sputum or dyspnea) and normal respiratory function
• No proof that this stage progresses to GOLD stage 1 or higher COPD
• Nevertheless, people with symptoms and normal lung function have lower quality of life and higher risk of hospitalization and mortality in follow-up
COPD prevalence
In the USA : • 23.6 million adults > 18 years
(NHANES III) (13.9%)• Estimated 2.4 million (1.4%
of the population had GOLD stage 3 or 4 with an FEV1 < 50%
• The majority - mild or moderate disease
• About 4 million receive treatment
• Undiagnosed ?• At Risk ?
Predictors of QOL and mortality
• Spirometry• Fat free Body mass• Functional status• Exercise capacity• Respiratory symptoms other than cough or
sputum• Presence of co-morbid diseases i.e.
depression or heart failure
COPD is a Cinderella Condition
• Limited recognition from patients
• Limited recognition from physicians
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COPD is • Underperceived• Underdiagnosed• Undertreated
The burden of COPD
• In the year 2000 - USA• 8 million physician visits• 1.5 million ED visits• 726000 hospital admissions• 119000 deaths• -------------------• COPD is associated with significant co-morbid
disease such as cardiovascular disease and cancer
Patients diagnosed as having COPD had higher rate of admissions with
• Pneumonia• Hypertension• Heart failure• IHD• Pulmonary Vascular Disease• Thoracic Malignancies• Ventilatory Failure-------------------------------------------------------------THAN age adjusted patients with no Dg of COPD
Patients with COPD had higher age-adjusted in- hospital mortality for:
• Pneumonia• Hypertension• Heart failure• Ventilatory Failure• Thoracic Malignancies
---------------------------------------------------------------
THAN patients who were discharged with the above Dg but without COPD
Perception of COPDThe Patient
• Many patients - never heard of COPD
• Poor patient education• Shame/Stigma/ Guilt• Underestimation of severity
of disease• Feeling worthless, low
self - estimation, sleep disturbance, poor appetite , poor concentration, agitation
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COPD and Depression
• Depression : A common and often profound co-morbid condition
• Anxiety in 37% of depressed patients with COPD• Depression may diminish functional ability and
lower perceived Quality of Life• Depressed patients are less likely to follow
treatment plans and are more likely to be hospitalized
• Overlap between symptoms of COPD and depression
Perception of COPDThe Physician
• 88% of internists and 85% of Family Physicians - familiar with the term
• 69% of internists and 73% of GP-s unaware of professional guidelines for the diagnosis and management of COPD
• Nihilistic approach• Underdiagnosis
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Less than 20% of patients withCOPD have been diagnosed by a doctor
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Perception of COPDThe Public at Large
• Unawareness• Low philantropic
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James Kiley PhD, from the NIH
COPD is high on mortality, low on public recognition
DiagnosisThink of the diagnosis of COPD for patients who are:
• Over 35 years old• Smokers or ex- smokers• Have any of the following
symptoms:– Exertional breathlessness
• easier to perform activities that allow the patients to brace the arms and to use accessory muscles of respiration
– Chronic Cough– Regular sputum production– Frequent “winter bronchitis”– WheezeAnd NO CLINICAL FEATURES
OF ASTHMA
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COPD?
Doctor Thinking
COPD or ASTHMA ?
Clinical features COPD Asthma
Smoker or ex-smoker Nearly all Possible
Symptoms under age 35 Rare Often
Chronic productive cough Common Uncommon
Breathlessness Persistent and progressive
Variable
Night time waking with breathlessness and or wheeze
Uncommon Common
Significant diurnal or day to day variation of symptoms
Uncommon Common
COPD Imaging
CXR• Hyperinflation• Flat Diaphragms• Retrosternal EmphysemaChest CT• Poorly defined , low
attenuation lesions• Absence of definable
walls
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COPD prototypes:The Pink Puffer and the Blue Bloater
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Many Faces of COPD
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Physical Examination in COPD
• Rarely diagnostic in COPD• Low sensitivity and specificity• Physical signs of airflow
limitation– Rarely present until significant
impairment in lung function occurs
• Barrel chest• Accessory muscles• Low, flat diaphragm• Diminished Breath Sounds
SYMPTOMScoughcough
sputumsputumshortness of breathshortness of breath
EXPOSURE TO RISKFACTORS
tobaccotobaccooccupationoccupation
indoor/outdoor pollutionindoor/outdoor pollution
SPIROMETRYSPIROMETRY
Diagnosis of COPDDiagnosis of COPD
Lung Function in COPD
Loss of elastic recoil
EmphysemaBronchospasmChronic InflammationMucus retention
Airway narrowing
Pulmonary Hyperinflation in COPD patients
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Sutherland ERN Engl J Med2004;350: 2689-2697
Spirometry
SPIROMETRY
• The measurement of lung function is the best way to diagnose COPD
• The routine use of spirometry in the periodic assessment of the adult patient is controversial
• ? Does earlier detection of COPD change the course of the disease or increase the rate of smoking cessation
• The knowledge of COPD might increase the smoking cessation
• Interventions other than smoking cessation may alter the natural history of the disease
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Assessment Tools for COPD
• The change in FEV1 has been the traditional metric to follow the progression of COPD in affected patients
• Various treatments have targeted the accelerated decline in FEV1 , in an attempt to modify or alter the disease process.
• Are we measuring the right thing ?– Smoking cessation is the only intervention that slows
the accelerated decline in lung function
LUNG FUNCTION is poorly related to clinical
outcomes: • Dyspnea
• Exercise performance
• Exacerbations
-----------------------------
• These patient - centered metrics are more important to individual patients than FEV1
Alternative metrics to assess disease modification in COPD
• Inspiratory Capacity
• Exercise Capacity– The 6 minute walk distance
• Dyspnea measures
• Health Status
• Multidimentional indices (BODE)
• Acute exacerbations
BODE = Body mass index, airflow Obstruction, Dyspnea, Exercise performance
MRC Dyspnea Scale
Grade Degree of breathlessness related to activities
1 Not troubled by breathlessness except on strenuous exercise.
2 Short of breath when hurrying or walking up a slight hill.
3 Walks slower than contemporaries on level because of breathlessness or has to stop for breath when walking at own pace
4 Stops for breath after walking about 100 m or after a few minutes on the level
5 Too breathless to leave the house or breathless when dressing or undressing
The BODE scoreFour factors predict increased risk of death:
• BODY MASS INDEX• The degree of airflow obstruction (FEV1)• Dyspnea• Exercise tolerance (6 MW distance)-------------------------------------------------------• Patients with higher BODE score - are at higher risk of death• BODE index has a stronger ability to discriminate the
probability of survival among patients than FEV1• The BODE score predicts hospitalization better than FEV1
Computation of the BODE score
Variable Points on BODE Index
0 1 2 3
FEV1
% predicted
> 65 50-64 36-49 <35
6MW distance m
>350 250-349
150-249 < 149
MRC dyspnea scale
0-1 2 3 4
BMI > 21 < 21
Pathophysiological/Clinical features of COPD
Airflowlimitation
Mucociliarydysfunction
Airflow limitation
Declining lung functionSymptoms
ExacerbationsDeteriorating health status
Decreasing Exercise tolerance
Systemic component
Structuralchanges
Airwayinflammation
COPD and Comorbidities
Extrapulmonary Effects• Weight Loss• Nutritional
abnormalities• Skeletal muscle
dysfunction
Increased Risk for:• MI/ Angina Pectoris• Osteoporosis• Bone Fractures• Respiratory Infection• Diabetes• Depression• Sleep Disorders• Anemia• Glaucoma• Lung Cancer
COPD often develops in long-time smokers in middle age
Patients often have a variety of other diseases, related to either smoking or aging
The impact of COPD
The impact of COPD on an individual patient depends on
• the severity of symptoms (especially breathlessness and decreased exercise capacity)
• the Systemic Effects• The Comorbidities• Not just the degree of airflow limitation
Consequences of disease progression in COPD
Airflow Limitation, Lung HyperinflationGas Trapping
Increased Dyspnea
Deconditioning Reduced Exercise Tolerance
Exacerbations
Decline inLung Function
Inactivity
Deterioration inHealth Status
Poor Health related Quality of life
Disability Disease Progression Death
COPD is: a multi- component disease
with systemic involvement & inflammation
Respiratory system
Systemic inflammation
Target organs
•Anxiety and Depression, Insomnia, Neuro-cognitive Impairment•Metabolic Disturbances•Nutritional Disturbances, Hypermetabolism•Treatment - related adverse effects
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Systemic effects ofCOPD
Bronchitis &Bronchiolitis Emphysema
Airway Inflammation
Systemic Inflammation
AirflowLimitation
SymptomsExercise tolerance
HRQLAECOPDPrognosis
Systemic effects of COPD
Weight Loss (cachexia)Skeletal muscle dysfunctionCardiovascular diseaseOthers
OsteoporosisDepressionFatigueCancer
Systemic Inflammation in COPDFACTS & UNKNOWNS
Facts• Low Grade systemic
inflammation occurs in COPD patients
• It persists after quitting smoking• It increases during acute
exacerbations• Steroids decrease systemic
inflammatory markers in stable COPD
• The origin of the systemic inflammation in COPD is likely to be multifactorial
Unknowns• Why systemic and pulmonary
inflammation persists after quitting smoking ?
• Likely that systemic inflammation contributes to the pathophysiology of many systemic effects of COPD ( skeletal muscle dysfunction, osteoporosis, cardiovascular disease
• The impact on clinical outcomes (mortality , health status ) of pharmacologically induced reduction of systemic inflammation is unproven
Acute Exacerbations of COPDDefinition
• Sustained worsening of the patient’s symptoms from the normal state (beyond day to day variations), with acute onset
• At least two of the following clinical criteria:– A recent increase in :
• Breatlessness• Sputum volume• Sputum purulence
– Often accompanied by hypoxemia and worsened hypercapnia
• Cough• Accompanied by fever or signs of upper airway
congestion
Exacerbations
• Exacerbations are a major cause of morbidity, mortality and the need for urgent care or hospital admission .
• Significant contributor to the cost of care• Significant contributor to lost work productivity• Exacerbation profiles vary among patients• Patients underreport exacerbations by 50%
COPD Exacerbations Descriptive Features
• Number of exacerbations• Type of exacerbations (outpatient versus inpatient versus ER
visit)• Time to first exacerbation• Severity of exacerbation ( Admission to ICU/ IM floor• Use of Mechanical Ventilation or noninvasive ventilatory support• The Duration of exacerbation------------------------------------------• Exacerbations are difficult to use as an endpoint for a variety
of reasons ( no uniform definition, no accepted biomarker etc)
COPD ExacerbationsGrading
Level Therapy
Level 1 At home
Level 2 In the hospital
Level 3 Respiratory failure
COPD ExacerbationTherapy
• Anticholinergic Aerosols• Beta - agonists• Theophylline - adjust dosage• Antibiotics ( if there is change in sputum color or
consistency)• Mucokinetics• Respiratory Stimulants ? ?• Anxiolytics
COPD ExacerbationPharmacologic Therapy
• Inhaled Bronchodilators– both nebulizers and
hand held inhalers with spacer can be used
– in hypercapnic or acidotic patients - the nebulizer should be driven by compressed air ( not oxygen)
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Hand - held inhaler with Spacer
Nebulizers
COPD ExacerbationPharmacologic Therapy
Systemic CorticosteroidsIf no significant contraindication :
• Recommended in all patients admitted to hospital with COPD Exacerbation
• Recommended in patients managed in the community with COPD exacerbation- if significant increase of breathlessness exists
• Lower rate of relapse ( 27 vs. 43%)
• Greater increase in FEV1 from baseline (34±42% vs. 15±31
Problems:• Hyperglycemia• Myopathy• Secondary infections• Mood changes• Adrenal Suppression• More common in the elderly
CONSIDER OSTEOPOROSISProphylaxis
COPD Exacerbation Non- Pharmacologic Therapy
• TLC
• Chest Physical Therapy ± PEP masks
• Oxygen– the aim of supplemental oxygen Rx. in COPD exacerbation is to
maintain adequate levels of oxygenation (SaO2 > 90%) without precipitating respiratory acidosis or worsening hypercapnia
• Non Invasive ventilatory Support (BiPAP)– The treatment of choice for persistent hypercapnic ventilatory failure
during exacerbations, despite optimal medical therapy
• Mechanical Ventilation ( if all fails)
Optimism
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Goals of Effective COPD Management
• Prevent Disease Progression
• Relieve Symptoms
• Improve Exercise Tolerance
• Improve Health Status
• Prevent and Treat Complications
• Prevent and Treat Exacerbations
• Reduce Mortality
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Pharmacologic Treatment of COPD
• Bronchodilators– Beta 2 agonists
• SABA (short acting)• LABA (long acting)• Relax the smooth muscles in
the airways by stimulation of beta adrenergic receptors in muscles - leading to bronchodilation
– Anticholinergics• Short acting (Ipratropium)• Long acting (Tiotropium)
– Methylxanthines
• Relax airway smooth muscle/ reverse the increased bronchomotor tone
• Improve lung emptying during tidal breathing/ reduce hyperinflation
• Relatively small changes in FEV1• Larger changes in Lung Volume• Reduction of RV/ air trapping• Delayed onset of dynamic
hyperinflation during exercise• Reduced perception of
breathlessness
BRONCHODILATORS:Short acting bronchodilators:
• Recommended for rescue of symptoms in patients with mild disease
Long acting bronchodilators:
• Improve symptoms• Improve Exercise tolerance• Improve Health Status• Reduce exacerbations• ? Effect on long term
decline in lung function• ?? Effect on mortality• Consider combination of
different classes or with ICS
Airflow obstruction in COPD is to some extent reversible ! Bronchodilators may have several beneficial non-bronchodilator activities !
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AnticholinergicsReduce airway tone and improve expiratory flow limitation, hyperinflation and
exercise capacity in COPD
• Short acting : Ipratropium Bromide
• Requires dosing q6h
• Long acting : • Tiotropium• Prolonged BD effect• Prolonged
bronchoprotective effect
• ? Prevention of decline of lung function (UPLIFT Study)
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Methylxantines
• Weak bronchodilator• Respiratory stimulant• Improved diaphragmatic contractility ?• Anti-inflammatory properties• Potential ability to activate the histone decaetylase
system - may enhance the effects of inhaled Corticosteroids
• Beware : Narrow therapeutic - toxic ratio / potential adverse effects
Pharmacologic TreatmentGlucocorticosteroids
• Glucocorticosteroids• Act on multiple locations within the
inflammatory cascade• The effect in COPD is more modest than in
Asthma• Small improvements in FEV1 and small
reduction in bronchial reactivity in stable COPD
• In advanced COPD (FEV1 < 50%) reduction in frequency of exacerbation/ health deterioration
• No evidence of reduction of the rate of FEV1 decline
• Impact on mortality ?
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Outcomes No Oxygen
Control
Nocturnal Nocturnal Continuous
Mortality 29%/year 12%/year 20.2%/year 11.2%/year
MRC Trial
87 COPD patients
Lancet 1981
NOTT
203 COPD patients
Ann Intern Med 1980
Pulmonary Rehabilitation Program
• “I have never taken any exercise , except sleeping and resting”
• “As an example to others, and not that I care for moderation myself, it has always been my rule never to smoke when asleep and never to refrain when awake”
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COPD Rx. according to Stage (GOLD)
Mild
FEV1/VC < 70%FEV1 = 80% predicted
Moderate
FEV1/VC < 70%50% > FEV1 >80% predicted
Severe
FEV1/VC < 70%30% > FEV1 > 50% predicted
Very Severe
FEV1/VC < 70%FEV1 < 30% predictedOr FEV1 < 50% predicted+ Chronic RespiratoryFailure
Active Reduction of Risk Factors, Influenza vaccination------------------------------------------------------------------------------------------------------------------------------------->
Add Short Acting Bronchodilators - when needed------------------------------------------------------------------------------------------------------------------------------------>
Add regular Rx with one or more Long Acting bronchodilators----------------------------------------------------------------------------------------------------->
Add Pulmonary Rehabilitation----------------------------------------------------------------------------------------------------->
Add inhaled GCS------------------------------------------------------>
Add LTOT ifChr Resp Failure----------------------->
Consider Sg.---------------------->
Surgical Options for COPD
• Bullectomy– In carefully selected patients ( reduce dyspnea/ improve
Lung Function
• Lung Volume Reduction Surgery• Lung Transplantation
– Improves QOL and functional capacity in selected patients
– Criteria for referral: FEV1<35% predicted PaO2<55-60mm Hg, PaCO2>50 mm Hg, and secondary pulmonary hypertension
Non- Surgical Lung Volume Reduction
• Endobronchial Valves
• Biologically mediated scar formation
• Pharmacological “lung deflation”
Thank you for your attention
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