CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Faizal Drissa Hasibuan

Bagian Penyakit Dalam Fak.Kedokteran Universitas YARSI

JAKARTA

GOLD (2002) Global Initiative for Chronic Obstructive Lung Disease

WHO & NHLBI

A disease state 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 of gasses.
The major cause is smoking

Chronic Obstructive Pulmonary Disease (COPD)

Spectrum of chronic respiratory diseases characterized by cough, sputum production, dyspnea, airflow limitation and impaired gas exchange.

MORBIDITY
Dyspnea on exertion HRQoL

MORTALITY
Chronic Obstructive Bronchitis
Emphysema

Progressive
Incidence worldwide

Exacerbations (acute & subacute symptoms)

More frequent & severe

PATHOGENESIS OF COPD
NOXIOUS
HOST FACTORS ANTI OXIDANTS [ environmental ]

PARTICLE GASES

LUNG INFLAMMATION
ANTI OXIDANTS ANTI PROTEINASES [ genetic ]

OXIDATIVE STRESS
REPAIR MECHANISM

PROTEINASE IMBALANCE
REPAIR MECHANISM

COPD

ANTI PROTEASE ENZYME 1-Antitrypsin

CELLS & INFLAMMATORY MEDIATORS IN COPD PATHOGENESIS MEDIATORS

CELLS
Macrophages Neutrophils CD8+ Lymphocytes Eosinophils Epithelial cells Fibroblasts

IL-8, GRO-1 MCP-1, MIP-1 GM-CSF Endothelin Substance P

EFFECTS

MUCUS HYPERSECRETION FIBROSIS

PROTEINASES
Neutrophil elastase Cathepsin Proteinase-3 MMPs

ALVEOLAR WALL DESTRUCTION

REACTIVE OXYGEN SPECIES IN COPD ANTIOXIDANTS Glutathione Analogs Vitamins C, E N-acetylsisteine Nitrones [spin-trap] IL-8 O2, H2O2 OH, ONOO
Neutrophil recruitment

Antiproteinases SLPI 1-AT Proteolysis

NF-KB TNF

ISOPROSTANES Mucus secretion Plasma leak

Bronchoconstriction

ADRENERGIC & CHOLINERGIC ( MUSCARINIC ) RECEPTORS

ADRENERGIC RECEPTORS

CHOLINERGIC RECEPTORS

DIAGNOSIS OF COPD
1
SYMPTOMS COUGH SPUTUM DYSPNEA

2
EXPOSURE TO RISK FACTORS Tobacco Smoke Occupation Indoor / outdoor pollution

SPIROMETRY

Table 1. Elements necessary for the diagnosis of COPD.

Chronic airways obstruction

FEV1 < 84% and FEV1/VC < 88 or 89% of predicted values. Reversibility < 12% of predicted FEV1 by 2sympathomimetic or anticholinergic drug. Continuous presence and verified on at least three occasions during the year.

Additional elements

Patients is usually over 50 years of age. Usually a smoker and/or other environmental factors present. Often signs of emphysema (abnormal diffusion and radiology)

Differential diagnosis

Asthma
Cystic fibrosis Byssinosis Bronchiectasis Bronchiolitis obliterans

Table 2. Clinical distinction between COPD and asthma

(Modified according to Vermiere 1993).

Pattern
Clinical
Onset at a young age Relatively sudden onset

COPD
-

Asthma
++ ++

Smoker (now or previously)

Atopy Eosinophilia/raised total IgE Recurrent dyspnoea and wheezing

+++
+ + +

+
++ ++ ++

Nasal symptoms

++ -

++
+++ ++

Basic abnormalities
Bronchial hyperresponsiveness Reversibility rapid and/or complete

Parenchymal destruction

++

- = (almost) never; + = sometimes; ++ = frequently; +++ = (almost) always

Complications
NUTRITIONAL DISORDER

COPD

CARDIO VASCULAR DISORDER

SYSTEMIC INFLAMMATORY RESPONS

SYSTEMIC EFFECT OF COPD

RESPIRATORY MUSCLE DISFUNCTION

PSYCHOLOGICAL FACTOR
ANXIETY DEPRESSION

HANDICAP / DISABILITY

GOALS OF COPD TREATMENT

1 SMOKING CESSATION GLOBAL GOALS 3 LONG TERM GOALS

2
SHORT TERM GOALS
IMMEDIATE BENEFITS RELIEF OF SYMPTOMS [ BREATHLESSNESS ]

PREVENT DISEASE PROGRESSIVE REDUCE EXACERBATIONS IMPROVE QUALITY OF LIFE IMPROVE EXERCISE TOLERANCE REDUCE MORTALITY

COPD MANAGEMENT
1
ESTABLISH DIAGNOSIS ASSESS SYMPTOMS STOP SMOKING HEALTHY LIFESTYLE IMMUNISATION

2
TREAT OBSTRUCTION BRONCHODILATORS

3
ASSESS FOR HYPOXIA LONG TERM OXYGEN THERAPY

4 PULMONARY REHABILITATION PROGRAMME

1 STOP SMOKING
TRIAL OF BUPROPION NICOTINE REPLACEMENT

LONG TERM OXYGEN THERAPY [ SELECTED PATIENT ]

COPD PHARMACOTHERAPY
2 4
INHALED CORTICOSTEROIDS ONLY FOR CONCOMITANT ASTHMA

NEW ANTI INFLAMMATORY TREATMENT NEEDED

BRONCHODILATORS

ANTICHOLINERGICS [ TIOTROPIUM = AVAILABLE ] LABA THEOPHYLLINE [ ANTI INFLAMMATORY EFFECT ]

MUCOLYTICS
CARBOCYSTINE BROMHEXOL AMBROXOL

ANTIOXIDANTS 2
N-ACETYLCYSTEINE

OTHER TREATMENT IN COPD

ANTI LEUCOTRIENTS PROPHYLACTIC

ANTIBIOTICS
NO EVIDENCE

ANTI INFLAMMATORY DRUGS INHALED CORTICOSTEROID ?

1
AVOIDANCE OF POLLUTANT

SURGERY 7
OBESITY & NUTRITIONAL INTERVENTION

2 EXERCISE

NON PHARMACOLOGICAL MANAGEMENT

6 4 5

EDUCATION

PHYSIOTHERAPY

VACCINATION

PULMONARY REHABILITATION

Advances in Drug Therapy

Anti smoking measures Nonpharmacologic treatment New treatment Mediator antagonists
New anti inflammatory drugs (Phosphodiesterase 4)

New bronchodilator
Antibiotics Oxygen Corticosteroids

Non-invasive ventilation
Pulmonary rehabilitation Lung-volume reduction surgery

Drug delivery

Future development Molecular genetic

1 INHALED ANTICHOLINERGIC S
IPRATROPIUM BROMIDE OXITROPIUM BROMIDE TIOTROPIUM BROMIDE

BRONCHODILATORS FOR COPD

3

2
BETA 2 AGONIST COMBINATION INHALER
IPRATOPRIUM BROMIDE & SHORT ACTING INHALED BETA 2 AGONIST

SHORT ACTING INHALED BETA 2 AGONIST

4 THEOPHYLLIN E

DECREASED PLASMA EXUDATION ?

1 RELAX AIRWAY SMOOTH MUSCLE

3
DECREASED INFLAMMATORY MEDIATOR RELEASE ?

BRONCHODILATORS IN COPD
5 IMPROVE RESPIRATORY MUSCLE FATIGUE ? 4
DECREASED NEUROTRANSMITTER RELEASE ?

INCREASED FEV1, FVC,PEF [ < 10 % ]

BRONCHODILATORS EFFECT IN COPD

2
DECREASED HYPERINFLATION DECREASED DYSPNOEA

3 IMPROVED EXERCISE TOLERANCE

IMPROVED RESPIRATORY MUSCLE STRENGTH ?

CLINICALLY IRRELEVANT EFFECT ON EXACERBATIONS

NO EFFECT ON PROGRESSION OF DISEASE

INHALED CORTICOSTEROIDS IN COPD

HIGH RISK OF ADVERSE SYSTEMIC EFFECTS

NO SIGNIFICANT EFFECT ON INFLAMMATION

EXPENSIVE SHOULD NOT BE RECOMMENDED

TREAT ASSOCIATED ASTHMA

LONG ACTING ANTICHOLINERGIC

TIOTROPIUM BROMIDE

SIGNIFICANT IMPROVEMENT IN LUNG FUNCTION SUSTAINED OVER 12 MONTHS

SIGNIFICANT REDUCTION IN EXACERBATIONS

STATISTICALLY SIGNIFICANT IMPROVEMENT IN BREATHLESSNESS SCORE

STATISTICALLY SIGNIFICANT IMPROVEMENT IN HEALTH-RELATED QUALITY OR LIFE SCORE

LONG ACTING ANTICHOLINERGIC

TIOTROPIUM BROMIDE

SIGNIFICANTLY REDUCES THE USE OF SHORT ACTING BETA AGONISTS

PROLONGED BLOCKADE OF M3 RECEPTOR SUBTYPE

NO OTHER ANTICHOLINERGIC EFFENTS GREATER THAN IPRATOPRIUM

SAFETY
SAFE & WELL TOLERATED IN CLINICAL STUDY ONLY SIGNIFICANT ADVERSE EVENT IS DRY MOUTH

Antibiotics COPD
Antibiotics Amoxycillin

Exacerbations
Bacterial infections ?
Antibiotic therapy has been linked to accelerated recovery Most common organisms: Streptococcus pneumoniae Haemophillus influenzae Branhamella catarrhalis Virus
Leong TK(2002) Tanjung A(2000)

Cotrimoxazole Amoxycillin Clavulanic acid

Alternative Newer cephalosporin Macrolides (Azithromycin) Quinolone (Levofloxacin)

Azithromycin (Zithromax) = Levofloxacin (Cravit ) (Tanjung A, 2000)

Long Term Oxygen Therapy

The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival.

Pulmonary Rehabilitation Program All COPD-patients benefit from

exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.