Pathophysiology of COPD and Asthma Fern White & tom Sutherland grant

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.

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.

COPD is an umbrella term for…

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.

Asthma triggers?

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.

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

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

To summarise…

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

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

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

COPD staging by spirometry: Gold staging.

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

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

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

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 >0.70 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

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

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

Thank-you! Any questions? F.white@warwick.ac.uk T.s.grant@warwick.ac.uk