COPD

COPD (CHRONIC OBSTRUCTIVE PULMONARY DISEASE)

EMPHYSEMA PULMONUM

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

26-11-12

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

Reproduced from The Lancet, Vol 364, Barnes PJ & Hansel TT, "Prospects for new drugs for chronic obstructive pulmonary disease", pp985-96. Copyright © 2004, with permission from Elsevier.

Cigarette smoke

Epithelial cells

CD8+ Tc cell

Emphysema

Proteases

Mucus hypersecretion

Macrophage/Dendritic cell Neutrophil

Monocyte

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

AsthmaAsthma

EosinophilsCD4+ T-

lymphocytesMast cells

Reversible

Sensitising agent

Inflammatory cells

COPDCOPD

NeutrophilsCD8+ T-

lymphocytesMacrophages

Noxious agent

Not fully reversible

Airflow limitation

Onset

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

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 IV

GOLD stage II dan III

HOW IS COPD DIAGNOSED AND MANAGED?

NYC/DAXAS/10/012

SYMPTOMSCough

Sputum productionShortness of breath

RISK FACTORSTobacco

Occupational hazards

Indoor/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 cough

is 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

INDIKATOR KUNCI UTK MENDIAGNOSIS COPD

Gejala Keterangan

Sesak Progresif (sesak bertambah berat seiring berjalannya waktu)Bertambah berat dengan aktivitasPersisten (menetap sepanjang hari)Pasien mengeluh berupa “perlu usaha untuk bernafas”Berat, sukar bernafas, terengah-engah

Batuk Kronik Hilang timbul dan mungkin tidak berdahak

Batuk kronik Berdahak

Setiap batuk kronik berdahak dapat mengindikasi COPD

Riwayat terpajan faktor resiko

Asap rokokDebuBahan kimia ditempat kerjaAsap dapur

Salah satu indikator

(+)

Usia > 40 thn

TES FAAL PARU

DX PASTI

Diagnosis

Anamnesis Pemeriksaan Fisik Faal Paru

Riwayat merokokRiwayat terpajan zat iritanRiwayat penyakit emfisema pada keluargaTerdapat faktor predisposis: BBLR; ISPA berulang; lingkungan asap rokok dan polusi udaraBatuk berulang ± dahakSesak ± mengi

Inspeksi: -pursed-lips breathing (mulut setengah terkatup/ mencucu)-Barrel chest-penggunaan otot bantu nafas-hipertrofi otot bantu nafas-pelebaran sela iga-bila telah terjadi gagal jantung kanan, terlihat denyut vena jugularis di leher dan edema tungkai-penampilan Pink puffer atau Blue bloater

VEP 1 % merupakan parameter yang paling umum dipakai untuk menilai beratnya COPD dan mamantau perjalanan penyakit

OBSTRUKSI:%VEP1 (VEP1/VEP1 pred)< 80%

Palpasi: fremitus melemah, sela iga melebar

Perkusi:Hipersonor, batas jantung mengecil, diafragma rendah

Auskultasi:Suara nafas vesikuler normal, atau melemahTerdapat ronki dan atau mengi

Pink Puffer: gambaran khas pd emfisema, pasien kurus, kulit kemerahan dan pernafasan Pursed-lips breathingBlue bloater: gambaran khas pd bronkitis kronis, pasien gemuk sianosis, edema tungkkai, dan ronki basah basal

Diagnosis Banding

Diagnosis Gejala

COPD Onset pada usis pertengahan, GX progresif lambat, lamanya riwayat merokok, sesak saat aktivitas, sebagian besar hambatan aliran udara, ireversible

Asma Onset awal sering pada anak; GX bervariasi dari hari ke hari; GX malam hari/menjelang pagi; Disertai atopi, rinitis atau eksem; riwayat keluarga dengan asma; sebagian besar keterbatasan aliran udara reversible

Gagal Jantung Kongestif

Ronki halus di bagian bawah; foto toraks: jantung membesar, edema paru, Uji Paal Paru: restriksi bukan obstruksi

Bronkiektasis Sputum produktif dan purulen; umumnya terkait dgn infeksi bakteri; auskultasi ronki kasar; Foto toraks: pelebaran dan penebalan bronkus

TB Onset segala usia; foto toraks: infiltrat; Sputum BTA

Bronkiolitis obliterans

Onset pada usia muda;bukan perokok; mungkin punya riwayat rheumatoid arthritis atau pajanan asap

Panbronkiolitis difus

Lebih banyak pada laki-laki bukan perokok; hampir semua menderita sinusitis kronik;

KLASIFIKASI

Derajat Klinis Faal Paru

Derajat 0At Risk

Batuk kronik + sputum Still normal

Derajat I:ringan

Batuk kronik + sputum (tidak sering)Sering tidak menyadari bahwa faal paru mulai menurun

VEP1/KVP < 70%VEP1 ≥ 80% prediksi

Derajat II:Sedang

GX sesak mulai dirasakan saat aktivitas dan kadang ditemui GX batuk dan produksi sputum

VEP1/KVP < 70%50% < VEP1 < 80% prediksi

Derajat III:Berat

GX sesak lebih berat, penurunan aktivitas, rasa lelah dan serangan eksaserbasi semakin sering dan berdampak pada kualitas hidup

VEP1/KVP < 70%30% < VEP1 < 50% prediksi

Derajat IV:Sangat berat

Gx derajat III + tanda-tanda gagal nafas atau gagal jantung kanan. Kualitas hidup memburuk dan dapat mengancam jiwa

VEP1/KVP < 70%VEP1 < 30% prediksi @ < 50% + gagal nafas

INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN ADULTS

SYMPTOMS MILD MODERATE

SEVERE AND LIFE-THREATENING

Physical Exhaustion

No No Yes, may have paradoxical chest wall

movementPulse 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

GOALS OF COPD MANAGEMENT

Improve current control

Reduce future risks

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.NYC/DAXAS/10/012

CONTINUED SMOKING LEADS TO RAPID DECLINE OF FEV1

Adapted from Fletcher C and Peto R , 1977.

100

Smoked regularly

and susceptibl

e to its effects

Never smoked or not susceptible to

smoke

Stopped at 45

Stopped at 65

Disability

Death

FEV

1 (

% o

f valu

e a

t ag

e

25

)

25

50

75

0

Age (years)

25 50 75

Disability

NYC/DAXAS/10/012

WHAT ARE EXACERBATIONS ?

NYC/DAXAS/10/012

WHAT ARE EXACERBATIONS?

“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

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

1. 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. 2. Seemungal TA et al, 2000. 3. Perera et al, 2007. 4. Papi et al, 2006.NYC/DAXAS/10/012

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

Adapted from Burgel PR et al, 2009.

Frequent exacerbations

Chronic cough and sputum

Chronic inflammation

Num

ber o

f ex a

cerb

ation

s pe

r p a

ti en t

per

ye a

r

0

1

2

3

Patients WITH chronic cough and

sputum

Patients WITHOUT chronic cough and

sputum

p<0.0001

Number of exacerbations

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

Bronchoconstriction

oedema, mucus

Expiratory flowlimitation

Cardiovascular

comorbidity

Exacerbationsymptoms

Dynamichyperinflation

InflamedCOPD

airways

Greater airwayinflammation

Viruses

BacteriaPollutants

EFFECTS

TRIGGERS

32Reprinted 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….Acut Failure

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

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

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 inhaled glucocorticosteroids ifrepeated exacerbations

NYC/DAXAS/10/012

MANAGEMENT

Invasive

Non Invasive

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

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

What is EMPHYSEMA PULMONUM ?Emfisema paru-paru adalah keadaan di mana paru mengalami distensi yang abnormal yang disebabkan rupturnya dinding alveoli dengan atau tanpa disertai lolosnya udara ke jaringan interstisial sehingga menyebabkan berkurangnya ruang udara dan sulit bernapas (Blood, 1963).-Pelebaran alveoli-kerusakan pada dinding alveoli bronkioli kehilangan struktur penyangganya pada saat udara dikeluarkan, bronkioli akan mengkerut; -Struktur saluran udara menyempit dan sifatnya menetap -pembesaran paru-paru yang disebabkan oleh menggembungnya alveoli secara berlebihan +/- robeknya dinding alveoli-Udara pernafasan akan terdapat di dalam rongga jaringan interstitial atau tetap berada di dalam rongga alveoli saja

Emfisema Paru-paru merupakan penyakit paru obstruktif kronik dgn gejala utamanya adalah penyempitan (obstruksi) saluran napas, karena kantung udara di paru menggelembung secara berlebihan dan mengalami kerusakan yang luas.

• Centriacinar emfisema ditandai dengan pembesaran rongga udara di bagian proksimal acinus, terutama pada tingkat bronchiolus repiratorius. Seringkali terjadi gangguan rasio perfusi-ventilasi, yang menimbulkan hipoksia, hiperkapnia (peningkatan CO2 dalam darah arteri), polisitemia, dan episode gagal jantung kanan. Adanya sianosis, edema perifer, dan gagal napas.

• Distal acinar emfisema terbatas pada ujung distal alveolus di sepanjang septum interlobularis dan di bawah pleura membentuk bula.

Jenis emfisema berdasarkan lokasi kerusakan:

Panacinar emfisema pembesaran rongga udara yang relatif seragam di seluruh acinus. Merupakan bentuk yang jarang, gambaran khas nya adalah tersebar merata di seluruh paru-paru, meskipun bagian-bagian basal cenderung terserang lebih parah. Tipe ini sering timbul pada hewan dengan defisiensi alfa-1 anti tripsin Ciri khasnya yaitu memiliki dada yang hiperinflasi dan ditandai oleh dispnea saat aktivitas, dan penurunan berat badan.

• Irregular emfisema kerusakan pada parenkim paru tanpa menimbulkan kerusakan pada asinus.

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 functional and symptomatic 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 COPD

COPD

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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