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Asthma & COPD By: Salome Aigbe-JosephDisclaimer • Information from this session is aimed to aid students with their learning, not replace lectures given by the University of Manchester Medical School as UoMCTSS is not affiliated with the university. • Any enquiries: @uomctss on InstagramAsthma • reversible airflow obstruction due to airway hyper-responsiveness • Caused by inflammation and muscle tightening around the airways which makes it harder to breath • usually presents in childhood and associated with other features of atopy (eczema and hay fever) • Chronic Asthma • Irreversible airflow obstruction and inflammation due to airway remodellingAetiology GENETICS AND CLEAN HYPOTHESIS COLD AIR AND EXERCISE ENVIRONMENTAL FACTORSSigns & Symptoms Persistent Coughing Wheezing Shortness of Breath Chest tightnessTypes of Asthma Atopic Non-Atopic Drug-induced OccupationalAtopic Asthma • Also known as extrinsic asthma • Type I IgE-mediated hypersensitivity reaction • Begins in childhood and is triggered by environmental allergens • Positive family history is commonAtopy • Group of disorders that appear to run in families • Atopic March • How allergic diseases develop over childhoodcourse of infancy and childhoodNon-atopic Asthma • Also known as Intrinsic Asthma • no evidence of allergen sensitization • Normally due to respiratory infections due to viruses Drug Induced Asthma • Aspirin • Occurs in individuals with recurrent rhinitis and nasal polyps • Also sensitive to NSAIDs • Experience asthmatic attacks and urticaria • Due to the mechanism of action of aspirin, it inhibits COX pathway tipping the balance towards bronchoconstrictor leukotrienes Occupational Asthma • Stimulated by fumes, organic and chemical dusts, gases and chemicals • Induces an asthma attack after repeated exposurePathogenesis Initial Phase Secondary Sensitisation Reaction Phase ReactionSensitisation Initial sensitization to inhaled allergens stimulate Th2 cells IL-4 -> stimulates production of IgE by B Cells IL-5 -> eosinophil chemotactic agent Th2 cell secrete cytokines IL-13 -> stimulate mucus secretion from bronchial submucosal glands and promote IgE production by B cellsSensitisation • Fc part of IgE binds to FCeR on mast cells/basophils exposing its variable region à 10-15 process • When antigen reappears, they come into contact with sensitized mast cells and stimulate it and a cause an initial phase reaction and secondary reaction https://sphweb.bumc.bu.edu/otlt/MPH-Modules/PH/RespiratoryHealth/RespiratoryHealth6.htmlInitial Phase Reaction Mast cells undergo degranulation secreting preformed products (primary mediators) •histamine •proteases •neutrophil chemotactic factor •eosinophil chemotactic factor Proteases •Further tissue damage causing release of more inflammation mediators •Convert C3 and C5 into C3a and C5a which will bind to the receptors on mast cells-> stimulate mast cells further Histamine •Vasodilation •Increased vascular permeability -> partial oedema in area •Spasms due to to histamine receptors on smooth muscle lining •Increasing glandular secretions causing luminal obstruction •Narrowing of lumen of tract • protein synthesis of cytokinested which leads to • Cytokines (secondary mediators) are released by Secondary mast cells and act as signalling molecules Reaction • IL-3 and IL-5 which are chemotactic agents for eosinophils • IL-3 and IL-5 are produced by Th2 cells • Eotaxin produced by airway epithelial cells recruit eosinophil to site of inflammation • Major Basic Protein (MBP) of eosinophils cause epithelial damage and more airway constriction • Mast cells secrete leukotrienes which attract Secondary neutrophils • Leukotrienes are responsible for bronchoconstriction Reaction • Neutrophils stimulate inflammation and destruction of airway epithelial cells • Eosinophils secrete granular contents • Histaminases à reduces inflammation • Eneutrophils destroy leukotrienes à reduce attraction of 1. Hypertrophy and hyperplasia of bronchial smooth muscle 2. Epithelial injury Airway 3. Increased airway vascularity 4. Increased subepithelial mucus gland Remodelling hypertrophy/hyperplasia 5. Overall thickening of airway wall 6. Basement membrane is thickenedhttps://calgaryguide.ucalgary.ca/asthma-pathogenesis/Diagnosis • Dependent on NICE or SIGN158 • Presentation of Symptoms • Clinic History • Spirometry • Exhaled Nitric Oxide (FeNO) • Peak Flow Test • Bronchodilator Reversibility • Methacholine Challenge Testing • Skin Prick Test https://www.nice.org.uk/guidance/ng80/resources/algorithm-b-objective-tests-for-asthma-in-children-and-young-people-aged-5-to-16-pdf-4656176750 • test dynamic lung volume → measure how much air you can breathe out in one forced breath • forced expiratory volume (FEV1) : forced exhaled air at 1 second • forced vital capacity (FVC) : amount of air that can be forcibly exhaled from lungs after taking Spirometry the deepest breath possible (normal last 6 seconds) • carried out with device à spirometer • measurements depend on age, height, gender • normal : FEV1/FVC = 80% • Anything less is diagnoses of asthma • measures inflammation of the airway • measures fractional exhaled nitric oxide → steady expiration • Breath out through a filtered mouthpiece into small portable device for ~10secs Exhaled FeNo • nitric oxide is a biomarker for asthma • chronic asthmaed in ongoing monitoring ofPeak Flow Chart • how quickly you can blow air out of your lungs • device used : peak flow meter • normal range : 400-700 L/min • depends on height, age, and gender • Monitoring and diary • keep a diary to make a chart • peak flow chart shows a period of untreated asthma and after preventer inhaler starts • monitoring am and pm • should be low in the morning • should be high in pmOther •Bronchodilator Reversibility • medication used : short acting B2-adrenergic agonist • responsiveness testing to see if your lung function gets better with medication and if so, how much •Methacholine Challenge Testing • also known as Bronchoprovocation testing • how reactive or responsive your lungs are • inhale doses of methacholine (drug that narrows airways) • breathing test will be repeated after each dose to measure the degree of narrowing or constriction of airways •Skin Prick Test • measure specific IgE to allergens • used for allergen asthmaT reatment • Bronchodilators • Inhaled Corticosteroids • Combined Inhalers • Theophylline • Muscarinic Receptor Antagonists • Leukotriene Receptor Antagonists • BiologicsBronchodilators • Three Types • Long-Acting Beta Agonist (LABA) (preventer) • β2 –adrenergic receptor • Short Acting Beta Agonist agonists (SABA) (reliver) • Given by inhalation • Duration of action is 8-12 hours • Dilates smooth muscle • Given by inhalation • Maximum effect within • given twice daily • Inhibits mediator release 30 minutes • Used as adjunctive therapy from mast cells • Ex. Salmetrol, Formoterol • Duration of action à • Increase muscle clearance 3-5 hours • Used as needed to • Ultra-long acting (ultra-LABA) → vilanterol, indacaterol • Side Effects control symptoms • duration of action around 24 hours • Tremor • Ex. Salbutamol, • given 1x daily • Tachycardia terbutaline • used in same way as LABAs • Cardiac dysrhythmia • Ex. Vilanterol, indacterol • glucocorticoids are main anti-inflammatory drugs used to treat asthma • mimic the actions of cortisol à produced in adrenal cortex and released at elevated levels in response to stress and low blood glucose concentration Inhaled • reduces the production of : Corticosteroids • cleukocyte chemotaxins(leukotriene C4 and D4), • binflammatory cellscruitment and activation ofOther T reatment • Theophylline • Phosphodiesterase inhibitor and adenosine receptor antagonist • competes with adenosine for binding to its receptors thereby promoting bronchodilation and reducing the release of inflammatory mediators • Muscarinic Receptor Antagonists • bind to muscarinic receptors on bronchiole smooth muscle and prevent the binding of acetylcholine (neurotransmitter) released from parasympathetic nerves innervating bronchioles • Ex. Ipratropium • Leukotriene Receptor Antagonists • lwell as on mast cells and other inflammatory cells where they cause the release of inflammatory mediatorsconstriction as • leukotriene antagonists counteract these effects • Ex. Montelucast • Biologics • more precise medications depending on asthma severity • Anti IgE, Anti IL-5 • Ex. omalizumab Asthma Attacks What happens? What are the treatments? • Signs • Nebuliser with bronchodilator • wheezing, coughing and chest tightness • Use of oxygen, compressed air or ultrasonic becoming severe and constant power to break up solutions and suspensions • being too breathless to eat, speak or sleep into small aerosol droplets that are inhaled • breathing faster from the mouthpiece of the device • compressor than turns liquid medication into • fast heartbeat fine mist allowing a large dose of medicine to • drowsiness, confusion, exhaustion or dizziness be inhaled through mouthpiece of face mask • blue lip or fingers • Prednisolone • fainting • normally due to a virus that triggers it • stops inflammation in airways getting worse • reduce your asthma symptoms • lower your risk of having life-threatening asthma attack • Chronic Obstructive Pulmonary Disease • Umbrella term for multiple lung disease à emphysema, chronic bronchitis • Not fully reversible airflow obstruction COPD • Progressive airflow limitation and tissue destruction • Abnormal inflammatory response of the lungs to noxious particles of gasesAetiology • Cigarette smoking • Environmental and Occupational Exposures • Alpha-1 Antitrypsin DeficiencySigns and Symptoms Sputum Productive production Cough à white or clear Dyspnoea WheezePathophysiology • Oxidative stress and protease-antiprotease imbalance • Emphysema is one of the structural changes in COPD • Destruction of the alveolar air sacs • Chronic Bronchitis • Productive cough and airway inflammation • Iand macrophage recruitmenty response à neutrophils • These release inflammatory mediators • Cytokines TNF-α, IL-1, IL-6 and IL-8 • Pof elasticity à airway collapse during exhalation àss hyperinflation of lungs • This causes CO2 elevations à Type 2 Respiratory Failure • Also, due to reduction of ventilation à CO2 retentionEmphysema • Centriacinar • Respiratory bronchioles are affected • Associated with chronic bronchitis • Panacinar • bronchioles to terminal alveoli • Distal/Paraseptal • Distal alveoli is affected • IrregularDiagnosis • Signs and Symptoms • Spirometry • airflow obstruction = post-bronchodilator FEV1/FVC ration that is less than 70% • History of Cor Pulmonale • Right-sided heart failure secondary to lung disease • Caused by pulmonary hypertension due to hypoxia • Hypoxia → pulmonary arterial vasoconstriction → increased pulmonary artery pressure → right ventricular hypertrophy → right ventricular failure T reatment • Smoking Cessation • Bronchodilators • Inhaled Corticosteroids • Oral Theophylline • Antibiotics à sputum production • Pulmonary Rehabilitation • First Line treatment: Dual Bronchodilation • Mild COPD: Mono Bronchodilation • Severe (Recurrent Exacerbations) : Triple Therapy (2 bronchodilator and ICS) Pulmonary Rehabilitation • 6 weeks of activities including educational learning of COPD and physical exercise • multidisciplinary programme of care for people with chronic respiratory impairment • individually tailored • recommended by NICE • All with COPD including people who have had recent hospitalisation for acute exacerbation • programme : physical training, disease education; nutritional, psychological and behavioural intervention • Proven to : • improve functional exercise capacity • improve health status • reduce dyspnoea • some health economic advantagesAny Questions • Email: salome.aigbe-joseph@student.manchester.ac.uk