OBSTRUCTIVE AIRWAY DISEASE

1

• OBSTRUCTIVE AIRWAY DISEASE
• Airways - obstructive disease
• Lungs - restrictive disease
• Obstructive airway syndrome
• ? Asthma
• ? Chronic bronchitis
• ? Emphysema

2
(No Transcript)
3

• OBSTRUCTIVE AIRWAY DISEASE
• Terminology
• Early onset / late onset
• Atopic / non-atopic
• Extrinsic / Intrinsic

4
The asthma triad
Reversible Airflow Obstruction
Airway Inflammation
Asthma
Airway Hyperresponsiveness
5
Dynamic evolution of asthma
Chronic airway inflammation
Broncho- constriction
Airway remodeling
fixed airway obstruction
Brief symptoms
exacerbations BHR
6
Hallmarks of Remodeling in asthma
Basement Membrane Submucosa Smooth
Muscle
Thickening
Collagen Deposition
Hypertrophy
7
THE INFLAMMATORY CASCADE Genetic predisposition
Trigger factor Avoidance (e.g. viral,
allergen, chemicals) Airway
inflammation Anti-inflammatory -
corticosteroid Mediators
Anti-leukotriene (e.g. histamine,
leukotriene) Antihistamine Twitchy
smooth muscle Bronchodilators
(Hyper-reactivity) - ?2-agonists
8
The Tip of the Iceberg
Symptoms/ Exacerbations
TITANIC
TITANIC
Airflow
obstruction
Bronchial
hyperresponsiveness
Airway
inflammation
9
(No Transcript)
10
(No Transcript)
11
Severe asthma alive Epithelial shedding
Severe asthma autopsy Mucus plugging
Normal
12
(No Transcript)
13
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)

14

• ASTHMA - THE CLINICAL SYNDROME
• 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

15

• DIAGNOSIS OF ASTHMA
• History and examination
• Diurinal variation of peak flow rate
• Reduced forced expiratory ratio
• (FEV1/FVC lt 75)
• Reversibility to inh. salbutamol (gt15)
• Provocation testing ? bronchospasm
• - exercise
• - histamine/allergen inhalation

16
(No Transcript)
17
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

18
COPD -A multicomponent disease process
Noxious particles or gases, e.g. smoking

• Characteristics of the disease
• Exacerbations
• Reduced lung function

• Symptoms
• Breathlessness
• Worsening quality of life

19
(No Transcript)
20
Disease processes in COPD
Cigarette smoke
?
CD8 lymphocyte
Alveolar macrophage
Neutrophil chemotatic factors, cytokines (IL-8),
mediators (LTB4), oxygen radicals
Neutrophil
Proteases
mucus hypersecretion (chronic bronchitis)
Alveolar wall destruction (emphysema)

Progressive airflow limitation
21
Mucociliary function in the healthy state
mucus
22
Damage to the respiratory mucosa due to bacterial
infection
Healthy
H. influenzae
23
Destruction of the Alveoli
Normal
Emphysema
24
COPD
Emphysema
Chronic Bronchitis

• Chronic neutrophilic inflammation
• Mucus hypersecretion
• Smooth muscle spasm and hypertrophy
• Partially reversible

• Alveolar destruction
• Impaired gas exchange
• Loss of bronchial support
• Irreversible

25
(No Transcript)
26
PROTEASE IMBALANCE IN EMPHYSEMA
Smoking Genetic Protease
Antiprotease Alveolar
Destruction Emphysema
27

• COPD -THE CLINICAL SYNDROME
• Chronic symptoms - not episodic
• Smoking
• Non-atopic
• Daily productive cough
• Progressive breathlessness
• Frequent infective exacerbations
• Chronic bronchitis- wheezing
• Emphysema- reduced breath sounds

28

• CHRONIC CASCADE IN COPD
• 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

29
Asthma vs COPD

• 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

• 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