COPD in 2007 Israel E. Priel, MD, FCCP Department of Pulmonary Medicine The Edith Wolfson Medical...

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….”

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.



Natural History in SmokersThe Fletcher-Peto Diagram

COPD International Your International Support

Networkhttp://www.copd-international.com/



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.



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



From Sexy to Deadly



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



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 ?





Spirometry









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





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



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



Less than 20% of patients withCOPD have been diagnosed by a doctor

Perception of COPDThe Public at Large

• Unawareness• Low philantropic

activityQuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture.

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



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





COPD prototypes:The Pink Puffer and the Blue Bloater





Many Faces of COPD








are needed to see this picture.QuickTime™ and a




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



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

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



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)







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



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

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 !


are needed to see this p icture.




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)





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 ?



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”






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



COPD in 2007 Israel E. Priel, MD, FCCP Department of Pulmonary Medicine The Edith Wolfson Medical...

Documents

Transcript of COPD in 2007 Israel E. Priel, MD, FCCP Department of Pulmonary Medicine The Edith Wolfson Medical...