1. OBSTRUCTIVE AIRWAY DISEASE
Airways - obstructive disease
Lungs - restrictive disease
Obstructive airway syndrome
 Asthma
 Chronic bronchitis
 Emphysema

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

4. The asthma triad Asthma 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

10. SLIDE 1.3
The photomicrograph on the left shows normal human airway mucosa, with the airspace above, pseudostratified respiratory epithelium, and rather bland sub-epithelial tissue.
On the right, this photomicrograph shows infiltration of numerous eosinophils and other inflammatory cells into the submucosal tissue. Thickening at the basement membrane (BM) is apparent, but most striking is the desquamation of airway epithelium, with numerous eosinophils within the denuded epithelium. This epithelial damage may predispose the patient with asthma to a greater sensitivity to airway triggers (i.e. airway hyperresponsiveness).

11. Severe asthma –alive
Epithelial shedding
Severe asthma –autopsy
Mucus plugging
Normal

13. Ask about triggers Allergens animal dander dust mites pollen fungi
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)
Anyone suspected of suffering from asthma should be asked whether any specific triggers bring on or aggravate their respiratory symptoms
Drug therapy should always be considered as a possible cause of asthma symptoms. The most important drugs to check for are NSAIDs (such as acetylsalicylic acid) and 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 < 75%)
Reversibility to inh. salbutamol (>15%)
Provocation testing  bronchospasm
- exercise
- histamine/allergen inhalation

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
In general practice, annual consultation rates for COPD per 10,000 population, rise from 417 at ages 45–64 to 886 at ages 65–74 and 1032 at ages 75–84; values that are up to four times the equivalent rates for angina.1
COPD places a heavy burden on society, industry and the health services. Although the direct costs of the disease are estimated at £486 million, once the effects on productivity, social security and disability payments are taken into account, the wider impact on the economy is estimated at more than £1.5 billion each year.2
References:
1. Royal College of General Practitioners, Office of Population, Census and Surveys, Department of Health. Mortality statistics from general practice. Fourth National Study, 1991–1992. London: HMSO, 1995.
2. Calverley PMA, Sondhi S. The burden of obstructive lung disease in the UK – COPD and asthma. Thorax 1998; 52 (suppl 4): A83 and poster presented at the BTS meeting, 1998.

18. COPD -A multicomponent disease process
Noxious particles or gases, e.g. smoking
Inflammation
Mucociliary dysfunction
Tissue Damage
Development of obstruction and ongoing disease progression
The disease process in COPD has a number of components which can be summarised under the following headings - muco-ciliary dysfunction, tissue damage and inflammation.1
These components are associated with an ongoing disease process which leads to obstruction of airflow and symptoms of COPD ( e.g.. Breathlessness and worsening quality of life) as well as a decline in exacerbations and lung function. These factors are all linked to the decline in health status seen in COPD
Characteristics of the disease:
Exacerbations
Reduced lung function
Symptoms:
Breathlessness
Worsening quality of life

20. Disease processes in COPD
Cigarette smoke
CD8+
lymphocyte ?
Alveolar macrophage
Neutrophil chemotatic factors,
cytokines (IL-8), mediators (LTB4),
oxygen radicals
Neutrophil
Exposure to inhaled noxious particles and gases causes inflammation of the lungs that can lead to COPD if the normal protective and/or repair mechanisms are overwhelmed or defective
Cigarette smoke and other irritants activate macrophages and airway epithelial cells in the respiratory tract which release neutrophil chemotactic factors, including interleukin 8 (IL-8)and leukotriene B4. Neutrophils and macrophages then release proteases that break down connective tissues in the lung parenchyma and also stimulate mucus hypersecretion. Proteases are normally counteracted by protease inhibitors such as a1-antitrypsin, secretory leukoprotease inhibitor (SLPI) and tissue inhibitors of matrix metalloproteinases.
Cytotoxic T cells (CD8+ lymphocytes) may also be involved in the inflammatory cascade, possibly through involvement in the destruction of alveolar wall epithelial cells.
In COPD there appears to be an imbalance between proteases and antiproteases (either an increase in proteases, or a deficiency of antiproteases) which lead to inflammatory changes in the airways including damage of the respiratory mucosa.
Reference:
1. Barnes PJ. Chronic Obstructive Pulmonary Disease. New Engl J Med 2000; 343(4): -
Protease
inhibitors
Proteases
mucus hypersecretion
(chronic bronchitis)
Alveolar wall destruction
(emphysema)
Progressive airflow limitation

21. Mucociliary function in the healthy state
mucus
Mucociliary transport is the process by which mucus and the particles trapped in the mucus are moved out of the airways to be swallowed.
Co-ordinated beating of the cilia in the healthy state is essential in clearing mucus from the airways
Damage to the cilia can occur due to the activity of enzymes such as neutrophil elastase. Neutrophil elastase is released from neutrophils which are attracted into the airways by e.g. tobacco smoke, bacterial toxins etc. This damage compromises the ability of the cilia to perform the function of mucociliary transport

22. Damage to the respiratory mucosa due to bacterial infection
Healthy
COPD patients have recurrent respiratory tract infections (a common pathogen being H. influenzae)
The bacteria damage the airway tissue (for example, breaking down the epithelial cell walls) leading to loss of ciliated cells
H. influenzae

23. Destruction of the Alveoli
Normal
Emphysema
In the normal state there are large numbers of alveoli which is where gas exchange occurs
In emphysema many of the alveoli have been destroyed leading to increased air spaces - this is due to the action of proteases such as neutrophil elastase and relates to an imbalance between proteases and anti-proteases

24. COPD Chronic Bronchitis Emphysema Chronic neutrophilic inflammation
Mucus hypersecretion
Smooth muscle spasm and hypertrophy
Partially reversible
Alveolar destruction
Impaired gas exchange
Loss of bronchial support
Irreversible

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