Transcript No Slide Title

OBSTRUCTIVE AIRWAY DISEASE
• Airways - obstructive disease
Lungs - restrictive disease
• Obstructive airway syndrome
 Asthma
 Chronic bronchitis
 Emphysema
OBSTRUCTIVE AIRWAY DISEASE
Terminology
• Early onset / late onset
• Atopic / non-atopic
• Extrinsic / Intrinsic
The asthma triad
Reversible
Airflow
Obstruction
Asthma
Airway
Hyperresponsiveness
Airway
Inflammation
Dynamic evolution of asthma
Bronchoconstriction
Brief
symptoms
Chronic
airway
inflammation
exacerbations
BHR
Airway
remodeling
fixed
airway
obstruction
Hallmarks of Remodeling in asthma
Basement Membrane
Thickening
Submucosa
Smooth Muscle
Collagen Deposition
Hypertrophy
THE INFLAMMATORY CASCADE
Genetic predisposition + Trigger factor
(e.g. viral, allergen, chemicals)
Airway inflammation
Mediators
(e.g. histamine, leukotriene)
Twitchy smooth muscle
(Hyper-reactivity)
• Avoidance
• Anti-inflammatory
- corticosteroid
• Anti-leukotriene
Antihistamine
• Bronchodilators
- 2-agonists
The “Tip” of the Iceberg
TITANIC
TITANIC
Symptoms/
Exacerbations
Airflow
obstruction
Bronchial
hyperresponsiveness
Airway
inflammation
Severe asthma –alive
Epithelial shedding
Severe asthma –autopsy
Mucus plugging
Normal
Ask about triggers
Symptoms can occur or worsen in the presence of:
Allergens
 animal dander
 dust mites
 pollen
 fungi
Others
 exercise
 viral infection
 smoke
 changes in temperature
 chemicals
 drugs (NSAIDs, ß-blockers)
ASTHMA - THE CLINICAL SYNDROME
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Episodic symptoms and signs
Diurinal variability – nocturnal/early morning
Non-productive cough, wheeze
Triggers
Associated atopy ( rhinitis , conjunctivitis, eczema)
Family history of asthma
Wheezing due to turbulent airflow
DIAGNOSIS OF ASTHMA
• History and examination
• Diurinal variation of peak flow rate
• Reduced forced expiratory ratio
(FEV1/FVC < 75%)
• Reversibility to inh. salbutamol (>15%)
• Provocation testing  bronchospasm
- exercise
- histamine/allergen inhalation
High socioeconomic impact of COPD
• 1.5 million GP consultations in the UK per year
• 24 million lost working days in the UK
per year
Economic impact per year
• Direct NHS costs – £486 million2
• Additional indirect costs – £1.5 billion (1995)2
COPD -A multicomponent disease process
Noxious particles or gases, e.g. smoking
Inflammation
Mucociliary
dysfunction
Tissue Damage
Development of
obstruction and
ongoing disease
progression
Characteristics of the disease:
• Exacerbations
• Reduced lung function
Symptoms:
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Breathlessness
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Worsening quality of life
Disease processes in COPD
Cigarette smoke
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CD8+
lymphocyte
Alveolar macrophage
Neutrophil chemotatic factors,
cytokines (IL-8), mediators (LTB4),
oxygen radicals
Neutrophil
Protease
inhibitors
Proteases
Alveolar wall destruction
(emphysema)
mucus hypersecretion
(chronic bronchitis)
Progressive airflow limitation
Mucociliary function in the healthy state
mucus
Damage to the respiratory mucosa due to
bacterial infection
Healthy
H. influenzae
Destruction of the Alveoli
Normal
Emphysema
COPD
Emphysema
Chronic Bronchitis
• Chronic neutrophilic
inflammation
• Mucus hypersecretion
• Smooth muscle spasm
and hypertrophy
• Partially reversible
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Alveolar destruction
Impaired gas exchange
Loss of bronchial support
Irreversible
PROTEASE IMBALANCE IN EMPHYSEMA
Smoking
Genetic
Protease
Antiprotease
Alveolar
Destruction
Emphysema
COPD -THE CLINICAL SYNDROME
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Chronic symptoms - not episodic
Smoking
Non-atopic
Daily productive cough
Progressive breathlessness
Frequent infective exacerbations
Chronic bronchitis- wheezing
Emphysema- reduced breath sounds
CHRONIC CASCADE IN COPD
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Progressive fixed airflow obstruction
Impaired alveolar gas exchange
Respiratory failure: PaO2 PaCO2
Pulmonary hypertension
Right ventricular hypertrophy/failure
(i.e. cor pulmonale)
• Death
Stopping smoking arrests further decline in lung volume
Asthma vs COPD
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Non smokers
Allergic
Early or late onset
Intermittent symptoms
Non productive cough
Non progressive
Eosinophilic inflammation
Diurnal variability
Good corticosteroid response
Good bronchodilator response
Preserved FVC and TLCO
Normal gas exchange
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Smokers
Non allergic
Late onset
Chronic symptoms
Productive cough
Progressive decline
Neutrophilic inflammation
No diurnal variability
Poor corticosteroid response
Poor bronchodilator response
Reduced FVC and TLCO
Impaired gas exchange