COPD Chronic Obstructive Pulmonary

Disease

Dr.dr.Tahan P.H., SpP., DTCE., MARSPenyakit Dalam FK-UWKS

15-06-12

IntroductionChronic Obstructive Pulmonary Disease (COPD) is one of the top five causes of global mortality

COPD affects 210 million people worldwide and causes 3 million deaths annually (5% of all deaths worldwide)1

It is predicted to become the third leading cause of global mortality by 20302

The economic burden of COPD is high, with costs increasing as the disease progresses

- Costs associated with severe COPD are up to 17 times higher than those associated with mild COPD3

- High costs are associated with treatment of exacerbations, such as hospitalisation3

- Indirect costs include loss of productivity in the workplace owing to symptoms3

Worldwide Prevalence of COPD

Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2005.

Male/1000

Female/1000

0 2 4 6 8 10 12

Former Socialist economies

Established market economies

India

Sub-Saharan Africa

Latin America and Caribbean

Middle Eastern Crescent

Other Asia and islands

Chapman KR, et al. Chest. 2001;119:1691-1695.

Hypothetical Male Patient With COPD Symptoms

Hypothetical Female Patient With COPD Symptoms

Diagnosed as COPD by 65% of physicians

Diagnosed as COPD by 49% of physicians

65%

49%

COPD symptoms in women were most commonly misdiagnosed as asthma

COPD Misdiagnosis Is Common in Women

Mathers CD, et al. PLoS Med. 2006;3:2011-2030.

COPD Is an Increasingly Common Cause of Death Worldwide

Cause of Death Rank in 2002 Rank in 2030

Ischaemic heart disease 1 1

Cerebrovascular disease 2 2

Lower respiratory infections 3 5

HIV/AIDS 4 3

COPD 5 4

Perinatal conditions 6 9

Diarrhoeal diseases 7 16

Tuberculosis 8 23

Trachea, bronchus, lung cancers 9 6

Road traffic accidents 10 8

What is COPD?Global Initiative for Chronic Obstructive Lung

Disease (GOLD) defines COPD as (2009):“a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gases”

Key points:- COPD is preventable and treatable- Airway limitation is not fully reversible and is usually

progressive- Extrapulmonary (systemic) effects play a significant

role- Associated with chronic inflammation in response to

inhaled noxious irritants

COPD IS CAUSED BY INHALATION OF NOXIOUS SUBSTANCES

Mucociliary Apparatus

Airway limitation

COPD has pulmonary and systemic components

Airwayinflammation

Structuralchanges

Mucociliarydysfunction

Systemicinflammation

BreathlessnessBronchitis: coughing, sputum production

Emphysema: hyperinflation, wheezing

Weight changesCo-morbidities

(e.g. diabetes, cardiovascular disease)

Inhaled substances +Genetic susceptibility

NYC/DAXAS/10/012

WHAT IS THE ROLE OF INFLAMMATION IN COPD?

COPD Is a Disease Characterised by Inflammation

Cigarette smoke

Epithelial cells

CD8+ Tc cell

Emphysema

Proteases

Mucus hypersecretion

Macrophage/Dendritic cell

NeutrophilMonocyte

Fibroblast

Obstructive bronchiolitis

Fibrosis

Chronic Inflammation plays a central role in COPD

Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.

Smoke Pollutants

Inflammation

Chronic inflammationStructural changes

Neutrophils

CD8+ T-lymphocytes

Macrophages

Key inflammatory cells

Systemic inflammation

Airflow limitation

Bronchoconstriction, oedema, mucus,

emphysema

Acute exacerbation

NYC/DAXAS/10/012

COPD inflammation is different from asthma inflammation

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.

AsthmaAsthma

EosinophilsCD4+ T-

lymphocytesMast cells

Reversible

Sensitising agent

Inflammatory cells

COPDCOPD

NeutrophilsCD8+ T-

lymphocytesMacrophages

Noxious agent

Not fully reversible Airflow limitation

Onset

NYC/DAXAS/10/012

Airway Inflammation occurs from COPD onset and increases with disease severity

0

20

40

60

80

100GOLD Stage I

GOLD Stages II and III

GOLD Stage IV

Adapted from Hogg JC et al, 2004.

Airw

ays

with

mea

sura

ble

cells

(%)

Neutrophils Macrophages CD8+ cells

NYC/DAXAS/10/012

GOLD stage I GOLD stage IVGOLD stage II dan III

How is COPD diagnosed and managed?

NYC/DAXAS/10/012

SYMPTOMSCough

Sputum productionShortness of breath

RISK FACTORSTobacco

Occupational hazardsIndoor/outdoor pollution

+

Spirometry

COPD is diagnosed based on symptoms, risk factors and spirometry

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.NYC/DAXAS/10/012

Classification of cough

• Cough is classified into acute and chronic and• Clinically subdivided into productive and

dry cough.

Productive coughis present at an expectoration

rate of 30 ml/24 hours,

Classification of cough

• Acute cough is defined as one lasting less than three weeks

• Chronic cough is defined as one lasting

greater than eight weeks

Acute Cough ... < 3 weeks

• URTI : Sinusitis viral / bacterial• URTI triggering exacerbations of Chronic

Lung Disease eg Asthma; COPD• Pneumonia • Left Ventricular Heart Failure• Foreign Body Aspiration

Differential Diagnosis

INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN ADULTS

SYMPTOMSMILD MODERATE

SEVERE AND LIFE-THREATENING

Physical Exhaustion No No Yes, may have paradoxical chest wall movement

Pulse rate < 100 / min 100 – 120 / min > 120 / min

Central cyanosis absent May be present Likely to be present

Wheeze intensity variable Moderate Often quiet

Peak expiratory flow(% predicted)

. 75% 50 – 75% < 50 %

Arterial Blood Gas Test not necessary If initial response is poor

Yes

–Relieve symptoms–Improve exercise tolerance–Improve health status

–Prevent and treat exacerbations–Prevent disease progression–Prevent and treat complications–Reduce mortality

Adapted from the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.

GOALS OF COPD MANAGEMENT

Improve current control

Reduce future risks

NYC/DAXAS/10/012

Continued smoking leads to rapid decline of FEV1

Adapted from Fletcher C and Peto R , 1977.

100

Smoked regularly and susceptible to

its effects

Never smoked or not

susceptible to smoke

Stopped at 45

Stopped at 65

Disability

Death

FEV 1 (%

of v

alue

at a

ge 2

5)

25

50

75

0

Age (years)25 50 75

Disability

NYC/DAXAS/10/012

What are exacerbations ?

NYC/DAXAS/10/012

“an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication”1

– May be mild, moderate or severe in nature. More severe exacerbations can require hospitalisation and are associated with a prolonged recovery period2

– Commonly caused by bacterial/viral infections of the lungs and airways1

– Associated with increases in markers of inflammation3,4

– Distressing for patients and their loved ones

What are exacerbations?

Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation as:

frequent exacerbations drive disease progression

Patients with frequent exacerbations

Increased risk of recurrent exacerbations

Increased inflammation

Lower quality of life Increased mortality rate

Increased likelihood of hospitalisation

Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.

Faster disease progression

NYC/DAXAS/10/012

Cough and sputum production indicate an increased risk of exacerbations

– Number of exacerbations

Adapted from Burgel PR et al, 2009.

Frequent exacerbations

Chronic cough and sputum

Chronic inflammation

Num

ber o

f exa

c er b

ation

s pe

r p a

tien t

per

ye a

r

0

1

2

3

Patients WITH chronic cough and

sputum

Patients WITHOUT chronic cough and

sputum

p<0.0001

NYC/DAXAS/10/012

Definitions of Exacerbations

COPD exacerbations were classified in clinical studies as follows:

– ‘Severe’ COPD exacerbation

–Requiring hospitalisation and/or leading to death

– ‘Moderate’ COPD exacerbation

–Initiation of oral or parenteral glucocorticosteroid therapy is required

Calverley PMA et al, 2009. Fabbri L,et al, 2009.NYC/DAXAS/10/012

Pulmonary and Systemic Inflammation in Exacerbations

Systemicinflammation

Bronchoconstrictionoedema, mucus

Expiratory flowlimitation

Cardiovascularcomorbidity

Exacerbationsymptoms

Dynamichyperinflation

InflamedCOPD airways

Greater airwayinflammation

Viruses

BacteriaPollutants

EFFECTS

TRIGGERS

28Reprinted from The Lancet, 370, Wedzicha JA, Seemungal TA, COPD exacerbations: defining their cause and prevention, 786-796, Copyright 2007, with permission from Elsevier.

FACTORS PRECIPITATING ACUTE FAILURE

•Sputum retention•Bronchospasm•Infection•Pneumothorax•Large bullae•Uncontrolled O2 - administration•Pulmonary embolism•Left-ventricular failure•End-stage disease

PATHO- PHYSIOLOGY….

FACTORS AFFECTING AIR-FLOW

• Mucosal edema• Hypertrophy of mucosa• Increased secretions• Increased bronchospasm • incr. Airway tortuosity• More airway turbulance• Loss of lung recoil

PATHO-PHYSIOLOGY….contd

AIR-FLOW OBSTRUCTION

PROLONGED EXPIRATION

PULMONARY HYPERINFLATIONDUE TO AIR-TRAPPING

INCREASED WORK OF BREATHING

DYSPNOEA

PATH-PHYSIO…..CONTD

ALVEOLAR DISTORTIONAND DESTRUCTION

LOSS OF HYPOXIA CAUSING

CAPILLARY BED PULMONARY

VASOCONSTRICTION

PULMONARY HYPERTENSION

SECONDARY VASCULAR CHANGES

COR-PULMONALE

Pharmacological treatments should be added stepwise as copd progresses

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2009. Available from: http://www.goldcopd.org.

Add long-termoxygen if chronicrespiratory failureConsider surgicalprocedures

Add regular treatment with one or more long-actingbronchodilators (when needed); Add rehabilitation

Active reduction of risk factor(s); influenza vaccinationAdd short-acting bronchodilator (when needed)

Stage III:Severe

Stage IV:Very Severe

Stage II:ModerateStage I:

Mild

FEV1/FVC<0.70

FEV1 ≥80%predicted

FEV1/FVC<0.70

50% FEV1 <80%predicted

FEV1/FVC<0.70

30% FEV1 <50%predicted

FEV1/FVC<0.70

FEV1 <30%predicted orFEV1 <50%predicted pluschronic respiratoryfailure

Add inhaled glucocorticosteroids ifrepeated exacerbations

NYC/DAXAS/10/012

MANAGEMENT – NONINVASIVE

# BRONCHODILATORS

• ROUTINELY GIVEN

• HELP RESIDUAL BRONCHODILATION

AND MUCO-CILIARY CLEARANCE

[ I.V.AMINOPHYLLINE / B2-AGONIST / IPRATROPIUM ]

…CONTD

CONSERVATIVE MANAGEMENT ….contd

# ANTIBIOTICS

# STEROIDS … AVOID IN ARF DUE TO INFECTION

# OTHER

* STEAM / PHYSIOTHERAPY / ENCOURAGE COUGH

* GENERAL HYDRATION

* DIURETICS / LOW DIGOXIN IF LVF

* HEPARIN S /C FOR D V T / PULM EMBOLISM

* NUTRITION

* RESPIRATORY STIMULANTS

MANAGEMENT - NON CONSERVATIVE….

1. INVASIVE TECHNIQUES FOR SPUTUM CLEARANCE

• OROPHARYNGEAL / NASOPHARYNGEAL SUCTION

• NASO-PHARYNGEAL AIR-WAY

• THERAPEUTIC AND DIAGNOSTIC F O B

• MINI TRACHEOSTOMY/ CRICOTHYROTOMY FOR SUCTION

• ENDOTRACHEAL INTUBATION

* FOR BETTER ACCESS

* FOR VENTILATORY SUPPORT

• TRACHEOSTOMY

* IF VERY THICK SECRETIONS

* INTUBATION > SEVEN DAYS

Emphysema• The fourth leading cause of death in the US• 3‐4 million people in the US suffer from emphysema• Current treatment is limited in efficacy

Bronchoscopic Lung VolumeReduction for Emphysema

The Concept of lung Volume Reduction• Lung volume Reduction1. – Removal of the most destroyed hyperinflated poorly perfused areas of the lung can enhance

the function of the remaining “normal” lung and leads to func(onal and symptoma(c improvement2. – Applicable in heterogeneous emphysema (upper lobe predominant)• Multiple retrospective and prospective studies reported success with surgical lung volume reduction

SUMMARY

COPD is a debilitating disease that presents a huge healthcare and economic burden around

the world The major risk factor for developing COPD is tobacco smoking COPD encompasses damage to the airways,

and chronic pulmonary and systemic inflammation

The symptoms of COPD include breathlessness, chronic cough and sputum production

Chronic inflammation in the airways and systemic circulation contributes to the pathology

of COPD COPD-specific inflammation is characterised by increased neutrophils, CD8+ T-lymphocytes and

macrophages, as well as cytokines and other inflammatory mediators

Inflammatory processes activated in asthma are different from COPD-specific inflammation

Chronic inflammation is present from the onset of COPD and increases with disease progression.

Airway inflammation increases during exacerbations

Effective COPD management should include agents that target the chronic inflammation

underlying the disease

Exacerbations are attacks in which symptoms increase beyond daily variations

Patients with frequent exacerbations have a poor prognosis and increased risk of

mortality

Inflammation is increased during exacerbations

The symptoms of chronic cough and sputum production are associated with an increased

risk of exacerbations

Preventing exacerbations is a major goal of COPD management

COPD is diagnosed based on medical history, exposure to risk factors and assessment of lung

function by spirometry

GOLD guidelines recommend seven goals for COPD management, including reducing the

frequency of exacerbations

Non-pharmacological management of COPD includes smoking cessation

GOLD guidelines recommend stepwise addition of pharmacological treatments based on the

severity of COPD

The Downward Spiral in COPDCOPD

Airwayobstruction

Exacerbation

Mucoushypersecretion

Continuedsmoking

Lunginflammation

Alveolardestruction

Impairedmucous clearance

Submucousal glandhypertrophy

Exacerbation

Exacerbation

Hypoxaemia

DEATHFrom the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008. Available from: http://www.goldcopd.org.

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