COPD (CHRONIC OBSTRUCTIVE

PULMONARY DISEASE) EMPHYSEMA PULMONUM
Dr.dr.Tahan P.H., SpP., DTCE., MARS Penyakit Dalam FK-UWKS 26-11-12

Introduction
Chronic 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
Other Asia and islands Middle Eastern Crescent
Latin America and Caribbean Sub-Saharan Africa India Established market economies Former Socialist economies

Male/1000

Female/1000

0

2

4

6

8

10

12

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.

Hypothetical Male Patient With COPD Symptoms
Diagnosed as COPD by 65% of physicians

65% 49% Hypothetical Female Patient With COPD Symptoms
Diagnosed as COPD by 49% of physicians

COPD symptoms in women were most commonly misdiagnosed as asthma
Chapman KR, et al. Chest. 2001;119:1691-1695.

COPD IS AN INCREASINGLY COMMON CAUSE OF DEATH WORLDWIDE
Cause of Death Rank in 2002 Rank in 2030

Ischaemic heart disease Cerebrovascular disease Lower respiratory infections

1 2 3

1 2 5

HIV/AIDS
COPD Perinatal conditions Diarrhoeal diseases Tuberculosis Trachea, bronchus, lung cancers Road traffic accidents

4
5 6 7 8 9 10

3
4 9 16 23 6 8

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

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

COPD HAS PULMONARY AND SYSTEMIC COMPONENTS
Inhaled substances + Genetic susceptibility

Airway inflammation

Mucociliary dysfunction

Structural changes

Systemic inflammation

Airway limitation

Breathlessness Bronchitis: coughing, sputum production Emphysema: hyperinflation, wheezing
NYC/DAXAS/10/012

Weight changes Co-morbidities (e.g. diabetes, cardiovascular disease)

WHAT IS THE ROLE OF INFLAMMATION IN COPD?

Cigarette smoke Epithelial cells

Macrophage/Dendritic cell Monocyte

Neutrophil

Fibroblast
Fibrosis

CD8+ Tc cell

Proteases

Obstructive bronchiolitis

Emphysema

Mucus hypersecretion

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.

CHRONIC INFLAMMATION PLAYS A CENTRAL ROLE IN COPD
Smoke Pollutants Key inflammatory cells Neutrophils CD8+ T-lymphocytes Macrophages

Adapted from Barnes PJ, in Stockley, et al (editors), Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
NYC/DAXAS/10/012

COPD INFLAMMATION IS DIFFERENT FROM ASTHMA INFLAMMATION

COPD
Onset Inflammatory cells

Asthma

Airflow limitation

NYC/DAXAS/10/012

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.

AIRWAY INFLAMMATION OCCURS FROM COPD ONSET AND INCREASES WITH DISEASE SEVERITY
100
GOLD Stage I GOLD Stages II and III

Airways with measurable cells (%)

80

GOLD Stage IV

60

40

20

0

Neutrophils GOLD stage I
Adapted from Hogg JC et al, 2004.
NYC/DAXAS/10/012

Macrophages GOLD stage II dan III

CD8+ cells

GOLD stage IV

HOW IS COPD DIAGNOSED AND MANAGED?

NYC/DAXAS/10/012

COPD IS DIAGNOSED BASED ON SYMPTOMS, RISK FACTORS AND SPIROMETRY

+

NYC/DAXAS/10/012

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.

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 cough is defined as one lasting greater than eight weeks

 Chronic

ACUTE COUGH ... < 3 WEEKS
Differential Diagnosis
 

 

URTI : Sinusitis viral / bacterial URTI triggering exacerbations of Chronic Lung Disease eg Asthma; COPD Pneumonia Left Ventricular Heart Failure Foreign Body Aspiration

INDIKATOR KUNCI UTK MENDIAGNOSIS COPD Gejala Sesak Keterangan Progresif (sesak bertambah berat seiring berjalannya waktu) Bertambah berat dengan aktivitas Persisten (menetap sepanjang hari) Pasien mengeluh berupa “perlu usaha untuk bernafas” Berat, sukar bernafas, terengah-engah Hilang timbul dan mungkin tidak berdahak Setiap batuk kronik berdahak dapat mengindikasi COPD Asap rokok Debu Bahan kimia ditempat kerja Asap dapur Usia > 40 thn TES FAAL PARU DX PASTI

Batuk Kronik Batuk kronik Berdahak Riwayat terpajan faktor resiko

Salah satu indikator (+)

Diagnosis Anamnesis
Riwayat merokok Riwayat terpajan zat iritan Riwayat penyakit emfisema pada keluarga Terdapat faktor predisposis: BBLR; ISPA berulang; lingkungan asap rokok dan polusi udara Batuk berulang ± dahak Sesak ± mengi

Pemeriksaan Fisik
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
Palpasi: fremitus melemah, sela iga melebar

Faal Paru
VEP 1 % merupakan parameter yang paling umum dipakai untuk menilai beratnya COPD dan mamantau perjalanan penyakit OBSTRUKSI: %VEP1 (VEP1/VEP1 pred) < 80%

Perkusi: Hipersonor, batas jantung mengecil, diafragma rendah
Auskultasi: Suara nafas vesikuler normal, atau melemah Terdapat ronki dan atau mengi

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

Diagnosis Banding Diagnosis COPD Gejala Onset pada usis pertengahan, GX progresif lambat, lamanya riwayat merokok, sesak saat aktivitas, sebagian besar hambatan aliran udara, ireversible 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 Ronki halus di bagian bawah; foto toraks: jantung membesar, edema paru, Uji Paal Paru: restriksi bukan obstruksi

Asma

Gagal Jantung Kongestif

Bronkiektasis

Sputum produktif dan purulen; umumnya terkait dgn infeksi bakteri; auskultasi ronki kasar; Foto toraks: pelebaran dan penebalan bronkus
Onset segala usia; foto toraks: infiltrat; Sputum BTA Onset pada usia muda;bukan perokok; mungkin punya riwayat rheumatoid arthritis atau pajanan asap Lebih banyak pada laki-laki bukan perokok; hampir semua menderita sinusitis kronik;

TB Bronkiolitis obliterans Panbronkiolitis difus

KLASIFIKASI Derajat Derajat 0 At Risk Derajat I: ringan Klinis Batuk kronik + sputum Batuk kronik + sputum (tidak sering) Sering tidak menyadari bahwa faal paru mulai menurun Faal Paru Still normal VEP1/KVP < 70% VEP1 ≥ 80% prediksi

Derajat II: Sedang

GX sesak mulai dirasakan saat aktivitas dan kadang ditemui GX batuk dan produksi sputum
GX sesak lebih berat, penurunan aktivitas, rasa lelah dan serangan eksaserbasi semakin sering dan berdampak pada kualitas hidup Gx derajat III + tanda-tanda gagal nafas atau gagal jantung kanan. Kualitas hidup memburuk dan dapat mengancam jiwa

VEP1/KVP < 70% 50% < VEP1 < 80% prediksi
VEP1/KVP < 70% 30% < VEP1 < 50% prediksi VEP1/KVP < 70% VEP1 < 30% prediksi @ < 50% + gagal nafas

Derajat III: Berat

Derajat IV: Sangat berat

INITIAL ASSESSMENT OF SEVERITY OF ACUTE ASTHMA IN ADULTS

SYMPTOMS Physical Exhaustion Pulse rate Central cyanosis

MILD No < 100 / min absent

MODERATE No 100 – 120 / min May be present

SEVERE AND LIFETHREATENING Yes, may have paradoxical chest wall movement > 120 / min Likely to be present

Wheeze intensity
Peak expiratory flow (% predicted)

variable
. 75%

Moderate
50 – 75%

Often quiet
< 50 %

Arterial Blood Gas

Test not necessary

If initial response is poor

Yes

GOALS OF COPD MANAGEMENT
Relieve symptoms  Improve exercise tolerance  Improve health status

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

NYC/DAXAS/10/012

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.

CONTINUED SMOKING LEADS TO RAPID DECLINE OF FEV1
100
Smoked regularly and susceptible to its effects Never smoked or not susceptible to smoke

FEV1 (% of value at age 25)

75

50

Disabilit y
Stopped at 45

Disabilit y 25 Death 0 25 50 Age (years) 75

Stopped at 65

NYC/DAXAS/10/012

Adapted from Fletcher C and Peto R , 1977.

WHAT ARE EXACERBATIONS ?

NYC/DAXAS/10/012

WHAT ARE EXACERBATIONS?
Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation as: “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

  

NYC/DAXAS/10/012

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.

FREQUENT EXACERBATIONS DRIVE DISEASE PROGRESSION

Patients with frequent exacerbations

Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.
NYC/DAXAS/10/012

COUGH AND SPUTUM PRODUCTION INDICATE AN INCREASED RISK OF EXACERBATIONS

Number of exacerbations

3

2

p<0.0001

1

0
Patients WITH chronic cough and sputum Patients WITHOUT chronic cough and sputum

NYC/DAXAS/10/012

Adapted from Burgel PR et al, 2009.

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
TRIGGE RS
Viruses Bacteria Pollutants

EFFECTS

Inflamed COPD airways Greater airway inflammation

Systemic inflammation

Bronchoconstricti on oedema, mucus Expiratory flow

limitation Cardiovascular comorbidity

Exacerbation symptoms

Dynamic hyperinflation
32

Reprinted 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

PATH-PHYSIO…..CONTD
ALVEOLAR DISTORTION AND DESTRUCTION

LOSS OF CAUSING

HYPOXIA

CAPILLARY BED
VASOCONSTRICTION

PULMONARY

PULMONARY HYPERTENSION SECONDARY VASCULAR CHANGES

PHARMACOLOGICAL TREATMENTS SHOULD BE ADDED STEPWISE AS COPD PROGRESSES
Stage IV: Very Severe
FEV1/FVC<0.70 FEV1 <30% predicted or FEV1 <50% predicted plus chronic respiratory failure

Stage I: Mild
FEV1/FVC<0.70 FEV1 ≥80% predicted

Stage II: Moderate
FEV1/FVC<0.70 50% FEV1 <80% predicted

Stage III: Severe
FEV1/FVC<0.70 30% FEV1 <50% predicted

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

Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long-term oxygen if chronic respiratory failure Consider surgical procedures

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

MANAGEMENT Non Invasive

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 * GENERAL HYDRATION * DIURETICS / LOW DIGOXIN IF LVF * HEPARIN S /C FOR D V T / PULM EMBOLISM * NUTRITION * RESPIRATORY STIMULANTS COUGH

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

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

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.

Jenis emfisema berdasarkan lokasi kerusakan:
• 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.

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 Volume Reduction for Emphysema

The Concept of lung Volume Reduction • Lung volume Reduction 1. – 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 improvement 2. – 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
encompasses damage to the airways, and chronic pulmonary and systemic inflammation

 The

major risk factor for developing COPD is tobacco smoking

 COPD

 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

inflammation is characterised by increased neutrophils, CD8+ T-lymphocytes and macrophages, as well as cytokines and other inflammatory mediators
 Inflammatory

 COPD-specific

processes activated in asthma are different from COPD-specific inflammation

inflammation is present from the onset of COPD and increases with disease progression. Airway inflammation increases during exacerbations
 Effective

 Chronic

COPD management should include agents that target the chronic inflammation underlying the disease

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 Mucous hypersecretion Exacerbation Continued smoking Exacerbation Alveolar destruction Hypoxaemia Airway obstruction Impaired mucous clearance Submucousal gland hypertrophy Exacerbation Lung inflammation

DEATH
From 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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