U13W1 - asthma and COPD Flashcards
How prevalent is COPD?
Develops in 35 to 40% of smokers
Most common in over 40yrs
Present in 2% of the population.
What are the risk factors associated with COPD?
Modifiable: Smoking - up to 50% of smokers develop COPD, occupational pollution, environmental pollution.
Nom-modifiable: Alpha 1 antitrypsin deficiency, variant of nicotinic ACh receptor altes addictiveness of smoking, history or childhood respiratory infections or asthma.
What are the two main components of the pathophysiology of COPD?
Emphysema - irreversible enlargement of dairspaces distal to the terminal bronchiole often accompanied with alveolar wall destruction
Bronchitis - persistant cough with sputum form 3month consecutivly for 2years or more in absence of other identifiable disease. Inflammation of the bronchi and upper airway
What is the pathogenesis of emphysema?
Smoking/pollutant -> ROS
Pollutant/damage -> inflammation leads to increased inflammatory mediators and ROS, recruitement of neutrophils alongside macrophages, T cells and B cells.
Proteases are released from immune cells and eithelial cells such as neutrophil elastase.
In patients with alpha 1 antitrypsen deficient cannot defend against protease activity
Leads to protease-antiprotease imbalance.
Damage to respiratory epithelium and parenchymal lung damage.
Damage to alveoli -> loss of elastic recoild and radial tension-> enlarged alveoli and air trapping, collapsed airway = functional obstruction.
Reducation in respirayory capillaries - reduced gas exchange.
What are the histological changes seen in a patient with emphysema?
Increased airspaces - hyperinflation
Loss of regular acinar structure - decreased SA or alveolar sacs and ducts due to destruction of alveolar walls.
Increased neutrophil infiltrate.
What is the clinical determinant of chronic bronchitis?
Productive cough for 3 months in at least 2 consecutive years.
What are some general changes in the airway of a person with chronic bronchitis?
Lumen - obstruction, increased mucus production, abnormaly dehydrated mucus in appearance, pulmonary edema.
Epithelium - inc goblet cells in small airways, neutrophils infiltrate, may become sqaoumous metaplasia or dysplasia due to mutagenic effects of cigarette smoke, fibrosis
Underlying glands - hypertrophy and hyperplasia of underlying gland, increased thickness and number - contributes to mucus plugging.
Smooth muscle - higher level fo proliferation, hypersensitive.
What signs and symptoms do we see in patients with chronic bronchitis?
Prooductive cough
Central Cyanosis - blue bloater presentation
Cor pulmonale
Wheeze on exhalation
Obsese
Peripheral odema
How can smoking trigger asthma?
Substances settlint in the lining of the airways
Damages the cilia and causes the elungs to make more mucous than normal
What are some signs that asthma is getting worse?
Require high doses or medication or more frequent inhaler use to continue with daily activities.
Decrease in exercise tolerance.
More nighttime wakening
Increase in hospitalisations
Fixed airflow obstruction indicates airway remodeling (BM thickening has occurred)
What clinical assessments are done for a suspected asthma case?
Sputum analysis - white blood cell composition
Blood analysis - allergy testing, total IgE, specific IgE test in response to specific allergens,
Spiromtery - FEV1, FVC, FEF25-75, FEF50, FEF75, Peak flow test
Reversibility test - spirometer and bronchodilator
Exhaled nitric oxide test - high in conditions with inflammatory airways
What are the main treatment barriers in asthma?
Difficult to avoid triggers/allergens
Poor adherence with controller medication
Inappropriate inhlaer technique
Inadequate patient education
What are some common asthma triggers?
Infections - cold, viral respiratory, sinusitis, bronchitis
Inhaled allergens - pollen, feathers, dust mites, animal danders, feathers
Irritant inhalants - cold air, air pollution, smoke, chemical resins
Drugs - aspirin, beta blockers
Flood - sulfites in shrimp for example
Exercise
What differential diagnosis are important to consider in asthma?
COPD - progressive and chronic
Acute bronchitis - productive cough and wheezing
Pneumonia - also norm fever and severe and sudden
heart failure - left sided cause pulmonary odema
GERD - chronic cough and wheeze if airway irritated
Anaphylaxis - also hives, itching and swelling
Foreign body aspiration - children, consider history
Pulmonary embolism - chest pain, history and risk factors
What are the main drug recommendations for each class?
SABA - salbutamol
LABA - salmeterol
Inhaled corticosteroid - beclometasone or budesonide
Oral Corticosteroid - prednisolone
Biologics - moalizumab
What is the mechanism of salmeterol in the treatment of asthma?
Class - LABA
Chem - adrenaline analogue
Pharmacology - agonist at beta 2 adrenergic receptors in bronchial smooth muscle this is GPCR, activated G protein subunit
Activates adenylate cyclase - increase cAMP production etc etc …. smooth muscle relaxation, dilating the airways.
Clinical: long term management and control of symptoms, night time symptoms, mainly due to longer set in time.
Compare and contrast salbutamol and salmeterol
Salbutamol = SABA, rapid onset, lasts for 4-6hrs, immediate relief normally as needed
Salmeterol = LABA, sustained effect lasts for 12 hours, maintenance (twice daily), slower onset of action
What are some of the unintended effects of prednisolone in asthmatic?
Increased hepatic gluconeogenesis, lipolysis and catabolism
Decrease hepatic glucose uptake
Increase renal GFR, Ca2+ excretion and urate excretion.
What are some of the physiological effects of prednisolone?
Inhibits the activation of various immune cells, T-lymphocytes, B-lymphocytes, macrophages and mast cells - hence less inflammatory medaitors and impaired immune response to antigens and allergens
Decreases vasodilation, capillary permeability, reduced oedema and inflammation in affected tissues.
Compare and contrast the use of prednisolone and budesonide in asthmatics.
Prednisolone - starts as pro-drug prednisone, metabolised in liver to active prednisolone, high systemic effects due to high oral bioavailability, longer duration of action 1/2x a day, used for wide range of systemic inflammatory and autoimmune condition
Budesonide - high topical effects, low systemic bioavailability as strong first pass effect in liver, so normally inhaled and reduced whole body side effects, shorter duration of action, normally used for loacalised inflammatory conditions such as asthma, COPD or allergic rhinitis.
What is another term used to describe spirometry?
Pulmonary Function Testing
What are the different lung capacities?
Inspiratory capacity - tidal volume + inspiratory reserve
Vital capacity - Inspiratory capcity + expiratory reserve volume
Functional residual capacity - Expiratory reserve and residual volume
Total lung capacity - vital capacity plus residual lung volume
What are the different volumes that make up the lungs?
Inspiratory reserve volume
Tidal volume
Expiratory reserve volume
Residual volume