COPD AND ASTHMA

Differential Diagnosis
Chronic Bronchitis

Emphysema

COPD

Airflow Obstruction

Asthma
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Asthma Is A Disease Of The Large & COPD The Small Airways

Asthma
trachea

Chronic Bronchitis

Emphysema
bronchi

Chronic Bronchitis

alveoli
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ASTHMA
Sensitizing agent

COPD
Noxious agent

Airway inflammation CD4+ T-lymphocytes Eosinophils

Airway inflammation CD8+ T-lymphocytes Macrophages Neutrophils

Completely reversible

Airflow limitation

Completely irreversible
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OVERLAP BETWEEN COPD AND ASTHMA

COPD
Neutrophils No AHR No steroid response

ASTHMA
Eosinophils

~10%

AHR Steroid response

Wheezy bronchitis
AHR,Airway Hyper Responsiveness 6

ASTHMA v COPD
Inflammation CELLS ASTHMA Mast cells Eosinophils CD4 T cells Macrophages MEDIATORS COPD Neutrophils CD8 T cells Macrophages++

LTD4,histamine IL-4,IL- LTB4 5, IL-8, TNFa, ROS + ROS+++

EFFECTS

All airways Little fibrosis Ep shedding

Periph airways Lung destruction Fibrosis + Sq metaplasia

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Response steroids

+++

COPD

MUCUS HYPERSECRETION IN COPD

Mucus Epithelium

Acetylcholine Tachykinins Proteinases

Sensory nerve

Goblet cell hyperplasia

SP Cholinergic ACh nerve N E Mucus gland hyperplasia Cytokines ROS

Cytokines (TNF-) Oxidants Growth factors MUC genes

MUC5a, MUC8
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neutrophil elastase

INFLAMMATION
Neutrophils

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Emphysema
Destruction of the alveolar wall damages pulmonary capillaries by tearing/sobk, fibrosis, or thrombosis Inelastic/kk u collapsible bronchioles Enlarged air sacs due to destruction of alveolar walls (bullae)

Walls of individual sacs torn (repair not possible)

Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis
Acc/mnyrtai,obvinytagfy
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Bronchiole

Air passage narrowed by plugged/smbat and swollen mucous membrane

Chronic Bronchitis
Presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded

Mucus and pus impede/meng gu action of respiratory cilia

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Wall thickening inflammation - mucus gland hypertrophy

Bronchus

Secretions
Wall thickening inflammation repair -- remodeling

Bronchiole

Loss of alveolar attachments Wall thinning inflammation elastolysis Coalescencegbn ganhgy Elasticity 13

Alveoli

COPD Pathology and Abnormal Breathing Mechanics

Airway resistance Elastic recoil

Expiratory flow limitation Work of
breathing/purse lips Dyspnea, cough and other respiratory Quality of life

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Faktor resiko yg lain

Kebiasaan merokok merupakan satusatunya penyebab kausal yang terpenting Riwayat terpajan polusi udara di lingkungan dan tempat kerja Hipereaktiviti bronkus Riwayat infeksi saluran nafas bawah berualang Defisiensi antitripsin alfa-1 (jarang di Indonesia)

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Patogenesis of COPD
Obstruksi yang terjadi bersifat ireversibel Terjadi karena perubahan struktural pada saluran nafas kecil Terjasi inflamasi, fibrosis, metaplasi sel goblet dan hipertropi otot polos

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Diagnosis banding
Asma SOPT Pneumothoraks Gagal jantung kronik Bronkiektasis Destroyed lung

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COPD - SYMPTOMS
COUGH AND MUCOID SPUTUM DYSPNOEA - SLOWLY PROGRESSIVE WHEEZE OEDEMA (IF COR PULMONALE) WINTER EXACERBATIONS

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COPD - SIGNS
HYPERINFLATION DECREASED EXPANSION CHEST PROLONGED EXPIRATION/WHEEZE SIGNS PULMONARY HYPERTENSION AND/OR RVH ( CARDIAC FAILURE) CYANOSIS HYPERCAPNIA

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The Vicious Cycle of COPD

Shortness of breath

Anxiety

Reduced activities

Reduced activities

Muscle weakness

Depression & social isolation

Malnutrition
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MANAGE STABLE COPD

EDUCATION

PHARMACOLOGIC

NON PHARMACOLOGIC

- stop smoking - disease course - medication - prevention of disease progression - trigger avoidance

REGULAR : Bronchodilator -Anticholinergic -Beta 2 agonist -Xantin -SABA+LABA -LABA+ICS As nedeed: ExpectorantMu colytic Antioxydant

-Rehabilitation -Vaccination -Nutrition -Mechanical vent -surgical Intervention

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GOLD Guidelines for COPD

Stage 0: At Risk

Diagnosis
Chronic cough/sputum PFTs within normal limits No symptoms

Treatment

Avoid risk factors (smoking cessation)

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GOLD Guidelines for COPD

Stage I: Mild

Diagnosis
FEV1 >80% predicted FEV1/FVC <70% With/without symptoms

Treatment
Avoid risk factors Short-acting bronchodilator PRN

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GOLD Guidelines for COPD

Stage II: Moderate

Diagnosis

50% FEV1 <80% predicted FEV1/FVC <70% With/without symptoms

Treatment Avoid risk factors Regular therapy with 1 bronchodilators Inhaled corticosteroids if significant symptoms and lung function response Rehabilitation

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GOLD Guidelines for COPD

Stage III:Severe

Diagnosis
30% FEV1 < 50% predicted FEV1/FVC < 70% With/without symptoms

Treatment Avoid risk factors Regular therapy with 1 bronchodilators Rehabilitation Inhaled corticosteroids if significant symptoms and lung function response or if repeated exacerbations
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GOLD Guidelines for COPD

Stage IV: Very Severe
Diagnosis FEV1 < 30% predicted

Treatment

Avoid risk factors

Regular therapy with 1 bronchodilators

Inhaled corticosteroids if significant symptoms and lung function response or repeated exacerbations Rehabilitation Treatment of complications

FEV1/FVC < 70%

Respiratory failure
Right-side-of-theheart failure

Long-term O2 therapy for hypoxic respiratory failure

Evaluate for surgical treatment
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Acute Exacerbations of COPD (AECOPD)

Common during winter months Symptoms

Breathlessness Wheeze Cough Increased sputum production

Causes

Viral infection (e.g., rhinovirus) Environmental causes (including smoking) Allergy Bacterial infection

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The Downward Spiral

COPD
Mucus hypersecretion Exacerbation Continued smoking Exacerbation Alveolar destruction Hypoxemia

Lung inflammation
Airway obstruction Impaired mucus clearance Submucosal gland hypertrophy Exacerbation

DEATH

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2 Agonist

Bronchodilator Response
Anticholinergic

Asthma Response
Panel A

COPD Response
Panel B
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MANAGING EXACERBATIONS

ANTIBIOTICS CONTROLLED OXYGEN BRONCHODILATOR - BETA AGONIST ANTICHOLINERGIC, THEOPHYLLINE STEROIDS INTUBATION/VENTILATION TREAT HEART FAILURE IF PRESENT

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Treatment of ECOPD(1#)

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Treatment of ECOPD(2#)

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Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Modify natural course Reduce mortality Prevent and treat complications Minimize side effects from treatment

COPD: Management Goals

Reducing airflow obstruction

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Asthma Bronchiale
Asthma is a common disease with significant morbidity, mortality and cost. To be prop early treated asthma must be characterized by lung function, symptoms and medication use. Asthma is a variable disease. Stability translates into fewer exacerbations and lower cost. Stability is best achieved with controller therapy.

Prop.mnopangdtgy

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Asthma
Definition: Airways hyper-responsiveness, reversible airways obstruction Pathophysiology: Inflammation

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Fakta / Problem
Tingkat asma terkontrol sangat rendah
PASIEN Guideline DOKTER

Tidak tahu Tidak mengerti Motivasi rendah Biaya

Kurang tersebar Sulit aplikasi/penerapan

Misdiagnosis Under-treatment Over-treatment t.u.cortsteroid inh

konsep & tujuan terapi asma: terapi asma bukan 39 hanya terapi simtomatik !!!

Physical Examination
Wheeze

Usually heard without a stethoscope

Dyspnoea

Rhonchi heard with a stethoscope Use of accessory muscles

Remember

Absence of symptoms at the time of examination does not exclude the diagnosis of asthma
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Bronchoconstriction

Before

10 Minutes After Allergen Challenge

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Evolusi Terapi Asma

Large use of short-acting 2-agonists 1975 ICS treatment introduced 1972 Adding
LAA to ICS therapy Kips et al, AJRCCM 2000 Pauwels et al, NEJM 1997 Greening et al, Lancet 1992

Fix combination ICS+LABA Fear of short-acting 2-agonists

1980

1985 1990
SYM/016/Dec08-De

2000

1995
Inflammation Remodelling

Bronchospasm

MODERN VIEW OF ASTHMA

Allergen
Macrophage Th2 cell Eosinophil Mucus plug Nerve activation Epithelial shedding Mast cell Neutrophil

Subepithelial fibrosis Plasma leak Oedema Sensory nerve activation

Mucus Vasodilatation hypersecretion New vessels hyperplasia

Cholinergic reflex Bronchoconstriction 43 Hypertrophy/hyperplasia

Virus? Adenosine Exercise Fog

Mast cell

2-Agonists

BRONCHOCONSTRICTION
Airway smooth muscle Eosinophil

Antigen
Macrophage

AIRWAY HYPERRESPONSIVENESS Virus?

-lymphocyte

Reduction in Asthma Attack Improvement in the control of Asthma symptoms

Barnes PJ

Corticosteroids
Complementary actions of long-acting b2-agonist(LABA) and corticosteroids on the pathophysiology of asthma.
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Bronchodilators

Inhaled therapy is preferred.

Regular treatment with long-acting

bronchodilators is more effective and convenient than treatment with shortacting bronchodilators .(Evidence A)
GOLD. update. 2007
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Inhaled Corticosteroids (ICS): The Most Effective Long-Term Controller Medications for Asthma

The daily use of ICS results in the following: Asthma symptoms will diminish and improvement continues
gradually

Occurrence of severe exacerbations is greatly reduced Use of quick-relief medication decreases Lung function improves significantly, as measured by PEF,
FEV1, and airway hyperresponsiveness

Problems due to asthma may return if patients stop

taking ICS
Guidelines for the Diagnosis and Management of Asthma. 1997. NIH Publication No. 97-4051.
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Bagaimana Kortikosteroid bekerja mempengaruhi On & Off inflamasi

Inflamasi ON :
Sel inflamasi
Enzym- Phospholipase A2

Inflamasi OFF:
Steroid berikatan dengan reseptor Kortikosteroid
Lipocortin menghambat enzim

Masuk ke inti sel

Arachidonic Acid Cascade

Pelepasan mediator

Produksi Lipocortin

Inflamasi saluran napas

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What are the Therapeutic Targets?

Smooth muscle dysfunction

Airway inflammation

Bronchoconstriction Bronchial hyperreactivity Hyperplasia/Hypertrophy Inflammatory mediator release

Inflammatory cell infiltration/activation Mucosal edema Cellular proliferation Epithelial damage Basement membrane thickening

Symptoms/Exacerbations

Adapted from Bousquet et al. Am J Respir Crit Care Med. 2000;161:1720-1745.

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Terapi Masa Depan

Asma Intermit en Persisten
Tidak terkontrol

Tujuan penatalaksanaan asma : TOTAL KONTROL

Terkontrol
Maintain

Quality of live

LABACS Tidak terkontrol

Terkontrol

Tingkatkan dosis
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Boushey H. Is Asthma Control Achieveable ?, European Respiratory Journal , Dec 2004

PRINSIP TERAPI ASMA

Traditonal view : ABC Modern view :CBA

A:Aminofilin B:Beta 2 Agonist/Bronkodilator C:Cortikosteroid

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Beberapa jenis bronkodilator yang sering digunakan Reliever(Pelega)

Nama umum Simpatomimetik Salbutamol Terbutalin Rimiterol Fenoteral Reproterol Aminofilin Teofilin Kolin teofilinat

Nama dagang Ventolin Bricanyl Pulmadil Berotec Bronchodil Phyllocontin Nuelin Choledyl

Mirip kafein

Anti-vagus

Ipratropium bromida Atrovent Suntikan atropin

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 Pencegah/Controller(Pengontrol)
Kortikosteroid inhalasi dan sistemik Sodium kromoglikat Nedokromil sodium Metilsantin Agonis beta-2 kerja lama inhalasi dan oral Leukotriens modifier Antagonis H-1

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Bagan Terapi Asma Saat Ini

Pengontrol Maintenance Pelega (Reliever)
Tingkat 4: PERSISTEN BERAT Terapi harian multi obat
Steroid inhalasi (ICS) Long Acting 2 -agonist (LABA) Oral steroid

Turunkan dosis ketika terkontrol

Inhalasi 2-agonis prn

Menghindari faktor pencetus Tingkat 3: PERSISTEN SEDANG Terapi harian

Steroid inhalasi (ICS) Long Acting 2 -agonist (LABA)

Inhalasi 2-agonis prn

Menghindari faktor pencetus Tingkat 2: PERSISTEN RINGAN Terapi harian

Steroid inhalasi (ICS)

Penyesuaian dosis setelah 3 bulan terkontrol harus tetap dimonitor/evaluasi

Inhalasi 2-agonis prn

Menghindari faktor pencetus Tingkat 1: INTERMITEN Tidak perlu

Inhalasi 2-agonis prn

Menghindari faktor pencetus

Naikkan dosis jika tidak terkontrol

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Thanks for your attention!!

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