1. Pathophysiology of COPD and Asthma
Fern White & tom Sutherland grant

2. Definition of Asthma
A chronic inflammatory disorder of the airways … in susceptible individuals, inflammatory symptoms are usually associated with widespread but variable airflow obstruction and an increase in airway response to a variety of stimuli. Obstruction is often reversible, either spontaneously or with treatment.
Affects 5-8% of the UK population.
Characterised by recurrent episodes of dyspnoea, cough, wheeze, caused by reversible airways obstruction.

3. Definition of COPD
Chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. Traditionally regarded as a combination of smoking-related lung diseases - emphysema; chronic bronchitis.
Common progressive disorder, affecting 10-20% of over 40s.

4. COPD is an umbrella term for…

5. Pathophysiology of Asthma?
Increase mucus production - from goblet hyperplasia, hypertrophy of mucus glands.
Airway thickening - fibrosis of bronchial wall.
Bronchoconstriction - smooth muscle hypertrophy.
Three factors contribute to airway narrowing:
Bronchial muscle contraction, triggered by various stimuli
Mucosal swelling / inflammation, caused by mast cell and basophil degranulation, resulting in release of inflammatory mediators
Increased mucus production
Inflammation - mast cell degranulation, Eosinophil infiltration, inc. permeability, oedema.

6. Asthma triggers?

7. Pathophysiology of COPD
Blue bloaters: Decreased alveolar with a low pO2 and high pCO2. Irresponsive to CO2, therefore cyanosed and at risk of developing cor pulmonale.
Pink puffers: Increased alveolar ventilation, near normal pO2 and normal – low pCO2. Over-responsive to CO2, therefore pink and tachypniac. Tend to be thin and at increased risk of type 1 respiratory failure.

8. How does smoking lead to lung disease?
Loss of cilia
Squamous metaplasia
Mucous hypersecretion (Goblet cell hyperplasia)
Low grade alveolar inflammation
Neutrophils counts in alveoli increased
Proteinases released from inflammatory cells destroys alveolar walls
Leads to emphysema
Fibrosis of small airways leads to small airways disease
Individual factors affect the extent and rate of these changes

9. What cells are involved?
Asthma
COPD
CD4 T-lymphocytes
Mast cell
Eosinophil
B cell
CD8 T-lymphocytes
Macrophages
Neutrophils

10. To summarise…

11. Clinical presentation
Asthma
Signs/symptoms:
Wheeze
Cough
Chest tightness
Dyspnoea
DIB
Things to look for on Hx
Date of onset
Other atopic disease
Family Hx
Smoking/Occupation/Pets
Provocation
Things to ask
Day time control
Amount of relieving meds required
Night time control
COPD
Signs/Symptoms
Sputum
SMOKING
Work Hx
Family Hx (α1-antitrypsin)
How long have they had a cough
Productive cough
Clinical presentation
DDX for a long-standing cough:
- COPD
- Asthma
- V.long standing virus
- Cancer

12. Diagnosing using spirometry and peak flow
Asthma = Diurnal variation of >20% on 3 days a week for 2 weeks.
Spirometry: Diagnose restrictive and obstructive airway diseases, using forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1).
Predicted FEV1 and FVC used against Height, Weight, Age, Gender.
FEV1/FVC ratios:
<0.7 = obstructive lung disease (both asthma and COPD)
>0.7 = restrictive lung disease
To diagnose asthma: an improvement in ratio should be seen following beta agonist trial.
Contraindications: recent surgery, ENT disorders, recent pneumothorax, haemoptysis, communicable disease
Reversibility
Give salbutamol and retest FEV1. If increased after salbutamol it’s more likely to be asthma, not COPD

13. Know this graph! Black = Normal Blue = Obstructive (COPD)
Red = Restrictive
Obstructive
Narrowed airways, reduces the amount of air that can pass through at any time
Reduces FEV1
e.g. COPD and Asthma
Restrictive
Lungs can’t expand as much, so FVC is reduced
e.g. Interstitial lung diseases, sarcoidosis, obesity

14. COPD staging by spirometry: Gold staging.

15. Acute asthma management
O xygen high flow
S albutamol nebuliser
H ydrocortisone IV
I pratropium bromide
T heophylline
If this isn’t working then intubate

16. Long term management of asthma
Step 1: short acting beta 2 agonist (salbutamol)
Step 2: Add low dose inhaled corticosteroid
Step 3: Add long acting beta 2 agonist
Step 4: Increase to high dose inhaled corticosteroids
Step 5: Add on therapies including oral corticosteroids

17. Management of COPD
Smoking cessation advice - only way to prolong life expectancy.
Bronchodilator therapy: short-acting ß2-agoinst (salbutamol); short-acting anticholinergic (ipratropium)
Combination therapy: long-acting ß2-agonist (salmeterol); inhaled steroid (beclomethasone); long-acting anticholinergic (tiotropium)
Oral theophylline: only if short and long-acting bronchodilators ineffective or inappropriate
Long term oxygen therapy (LTOT)
Infection prevention – flu jab
Rescue packs – steroids + antibiotics

18. Oxygen, salbutamol, hydrocortisone, ipratropium, theophilline
QUIZ!
Asthma is a chronic inflammatory disease that causes airway restriction, is variable and non-reversible. TRUE/FALSE
The immune cells involved in asthma are: B-cells, IgE, mast cells, eosinophils, cytokines and leukotrines TRUE/FALSE
Obstructive airway disease will have a FEV1/FVC ratio of > TRUE/FALSE
Acute management of asthma?
6. Chronic stepwise management of asthma?
FALSE
TRUE
FALSE
Oxygen, salbutamol, hydrocortisone, ipratropium, theophilline
Salbutamol, low dose steroids, Salmeterol, high dose steroids, oral prednisolone

19. Quiz!
CD8 T-lymphocytes, Macrophages, Basophils are all involved in COPD. TRUE/FALSE
Reversible component of COPD?
Fibrosis and narrowing of the airways and loss of elastic recoil due to alveolar destruction are the irreversible causes of airflow obstruction in COPD. TRUE/FALSE.
Asthma causes 3 airway pathologies What are they?
FALSE
BRONCHOCONSTRICTION
TRUE
Classic triad of symptoms in asthma? Expiratory wheeze
Cough
SOB (dysnpnoea) especially at night
Smooth muscle dysfunction
Airway inflammation
Airway remodelling

20. A lecherous reprobate, Shef Kirollos, 66, comes into your clinic complaining that his asthma has been getting worse. He was recently diagnosed with heart failure, and has been taking Propranalol for the condition.
1. What type of drug is propranolol? (1)
Beta Blocker
2. What is the basic MoA of the above drug? (3)
Blocks β1 receptors in the heart
Prevents conversion of ATP to cAMP by adenylyl cyclase and activation of PKA, therefore reducing intracellular calcium
Negative inotropic, chronotropic and dromotropic effect on the heart
*Note there are β1 and β2 receptors in both lung and heart, but β1 strongly predominates in heart, and β2 strongly predominates in lungs
3. Why might it be a bad idea to give someone with asthma propranolol?
Propranalol has an antagonist effect on beta receptors in the lungs -> resulting in smooth muscle constriction -> further narrowing of already narrowed airways -> exacerbating the effects of asthma

21. Thank-you! Any questions? F.white@warwick.ac.uk