DEFINITION

COPD
AIRFLOW LIMITATION IN SMALL AIRWAYS PROGRESSIVE

CHRONIC INFLAMMATIO N

PARTIAL REVERSIBLE

IRREVERSIBLE

ALVEOLER STRUCTURE DAMAGED

DECREASED ELASTIC RECOIL

CHRONIC BRONCHITIS MIXED

2 EMPHYSEMATOUS LUNG

GOLD [ NHLBI WHO ] GUIDELINES MANAGEMENT STRATEGY OF COPD WHO 2020 MORTALITY 3 million/year

MORBIDITY & MORTALITY IV in USA

HOSPITAL MORTALITY 10 %

INCREASING PROBLEMS OF COPD

WORSEN HEALTH STATUS

INCREASE OF 51 % ACUTE EXACERBATION IN HOSPITAL ADMISSION BETWEEN 1991 - 2000 PREMATURE DEATH

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

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

EFFECTS

Macrophages Neutrophils CD8+ Lymphocytes Eosinophils Epithelial cells Fibroblasts

MUCUS HYPERSECRETION FIBROSIS ALVEOLAR WALL DESTRUCTION

PROTEINASES
Neutrophil elastase Cathepsin Proteinase-3 MMPs

1 Inflammatory marker

IL-8

Neutrophil chemoatractant

LTB4

TNF-
Neutrophil chemoatractant

4 Acute exacerbation 6

GM-CSF

INFLAMMATORY MEDIATOR IN COPD

7

TGF-
Airway remodelling

Alveolar macrophage recruitment

MCP-1

Substance P
Mukus hypersecretion

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

DIAGNOSIS OF COPD
1
SYMPTOMS COUGH SPUTUM DYSPNEA

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

SPIROMETRY

Complications
NUTRITIONA L DISORDER CARDIO VASCULAR DISORDER

COPD

SYSTEMIC INFLAMMATOR Y RESPONS

SYSTEMIC EFFECT OF COPD

RESPIRATORY MUSCLE DISFUNCTION

PSYCHOLOGICAL FACTOR
ANXIETY DEPRESSION

HANDICAP / DISABILITY

GOALS OF COPD TREATMENT

1 SMOKING CESSATION GLOBAL GOLD 3 LONG TERM GOALS

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 SOON AVAILABLE ] LABA THEOPHYLLINE [ ANTI INFLAMMATORY EFFECT ]

CARBOCYSTINE BROMHEXOL AMBROXOL

MUCOLYTIC S 1

ANTIOXIDANTS 2
N-ACETYLCYSTEINE

OTHER TREATMENT IN COPD

ANTI LEUCOTRIENT S PROPHYLACTI C ANTIBIOTICS
NO EVIDENCE

ANTI INFLAMMATORY DUGS INHALED CORTICOSTEROID ?

1
AVOIDANCE OF POLLUTANT

SURGERY 7
OBESITY & NUTRITIONAL INTERVENTION

2 EXERCISE

NON PHARMACOLOGICAL MANAGEMENT

6 4 5

EDUCATION

PHYSIOTHERAP Y

VACCINATION

PULMONARY REHABILITATION

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 INFLAMMATOR Y MEDIATOR RELEASE ?

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

CONTROL OF THE AIRWAYS

PARASYMPATHETIC NERVE SYSTEM

ANTICHOLINERGIC

CHOLINERGIC RECEPTOR

GUANILCYCLASE

Cyclic GMP
BRONCHOCONSTRICTION

GTP

5GMP

ATP

BRONCHODILATATION ADENYLCYCLASE

5AMP
FOSFODIESTERASE

Cyclic AMP

BETA ADRENERGIC RECEPTOR

METHYLXANTIN BETA 2 AGONIST

SYMPATHETIC NERVE SYSTEM

INCREASED FEV1, FVC,PEF [ < 10 % ]

BRONCHODILATORS EFFECT IN COPD

2 DECREASED HYPERINFLATIO N DECREASED DYSPNOEA IMPROVED EXERCISE TOLERANCE 3

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

BRONCHODILATATION

DECREASED PLASMA EXUDATION

DECREASED CHOLINERGIC NEURO TRANSMISSION

ACTION OF BETA2-AGONISTS IN COPD

INCREASED MUCOCILIAR Y CLEARANCE DECREASED NEUTROPHIL FUNCTION DECREASED BACTERIAL ADHERENCE

DECREASED PLASMA EXUDATION

BRONCHODILATATION
Incl. Small airways

INCREASED RESPIRATOR Y MUSCLE STRENGTH

DECREASED T CELL FUNCTION

ACTION OF METHYLXANTHINE IN COPD

DECREASED NEUTROPHIL FUNCTION

THEOPHYLLINE

INCREASED MUCOCILIAR Y CLEARANCE

DECREASED MACROPHAGE FUNCTION

ANTICHOLINERGICS IN COPD
NORMAL
Vagus nerve

COPD ACh

ACh

VAGAL TONE
The main reversible Component in COPD

Resistance 1/r

ANTICHOLINERGICS

BRONCHO DILATATIO N

ANTICHOLINERGICS BLOCKS MUSCARINIC RECEPTORS THEREBY REDUCTION VAGAL TONE

CLEARANCE OF EXCESS MUCUS

MUSCARINIC RECEPTOR SUBTYPES IN AIRWAYS

PREGANGLIONIC NERVE

M1 + M2 + M3 +
MUSCARINIC RECEPTOR

PARASYMPATHETIC GANGLION

N+ M1 +

NICOTINIC RECEPTOR

ANTICHOLINERGIC
POSTGANGLIONIC NERVE

M2 +
CHOLINERGIC EFFECT

ACh M3 +

AIRWAY SMOOTH MUSCLE

CONTROL OF THE AIRWAYS

ADRENERGIC & CHOLINERGIC ( MUSCARINIC ) RECEPTORS

ADRENERGIC RECEPTORS

CHOLINERGIC RECEPTORS

ADRENERGIC RECEPTORS
RECEPTORS ADRENERGIC

NEURO TRANSMITTER SUB-TYPES OF RECEPTOR

NOR ADRENALINE ALPHA [a1&a2] BETA [b1&b2] Airways dilated & Reduced airflow Obstruction [bronchodilatation]

RESULT OF STIMULATION IN THE LUNGS

CHOLINERGIC RECEPTORS
RECEPTORS CHOLINERGIC

NEURO TRANSMITTER SUB-TYPES OF RECEPTOR

ACETYL CHOLINE MUSCARINIC M1-M2-M3 Airways constricted & increased airflow Obstruction [broncho constriction]

RESULT OF STIMULATION IN THE LUNGS

CHOLINERGIC RECEPTORS
M1-RECEPTORS ENHANCE THE CHOLINERGIC REFLEX

M2-RECEPTORS INHIBIT ACETYLCHOLINE RELEASE

M3-RECEPTORS MEDIATE BRONCHOCONSTRICTION AND MUCUS SECRETION

M4 & M5-RECEPTORS NOT DETECTED IN THE LUNG

NEW BRONCHODILATORS
2 MEDIATOR ANTAGONISTS 3 PROTEASE INHIBITORS

TRIOTROPIUM

NEW DRUG FOR COPD

4 NEW ANTI INFLAMMATOR Y DRUGS 5 ALVEOLAR REPAIR DRUGS

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

Thank You