2.ASTHMA PPT MKU Year 4 Internal Medicine Notes OmpathStudy

2.ASTHMA PPT MKU Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.1 / NGUGI -- Slide 1 ASTHMA DR. ROSSLYN NGUGI Slide 2 INTRODUCTION: A common chronic inflammatory condition whose symptoms include\nWheeze,\nChest tightness,\nCough\nShortness of breath\n•The symptom often worsens at night.\n•Starts in childhood - 3 and 5 years and may either worsen or improve during adolescence Slide 3 INTRODUCTION: Classically it has three characteristics:\n•Airflow limitation: usually reversible spontaneously or with treatment\n•Airway hyperresponsiveness: wide range of stimuli\n•Bronchial inflammation with \n–T lymphocytes, \n–Mast cells, \n–Eosinophils with associated plasma exudation \n–Oedema \n–Smooth muscle hypertrophy \n–Matrix deposition \n–Mucus plugging \n–Epithelial damage Slide 4 EPIDEMIOLOGY: More common in more developed countries.\n May become more frequent as individuals adopt a more ‘westernized’ lifestyle.\n Worldwide, approximately 300 million people have asthma.\n This is expected to rise to 400 million by 2025. Slide 5 CLASSIFICATION: Classified into extrinsic and intrinsic asthma but there is considerable overlap.\n •Extrinsic asthma\n–most frequently in atopic - 90% of children and 70% of adult. –Childhood asthma is often accompanied by eczema (atopic dermatitis).\n •Intrinsic asthma\n–Often starts in middle age.\n–Non-atopic individuals may develop asthma in middle age from extrinsic causes such as sensitization to occupational agents. Slide 6 AETIOLOGY AND PATHOGENESIS: Atopy and allergy.\nGenetic.\nEnvironmental factors.\nIncreased responsiveness of the airways of the lung (airway hyperresponsiveness). Slide 7 ATOPY AND ALLERGY: The term ‘atopy’ describe a group of disorders, including asthma and hayfever, which: \n•run in families.\n•have characteristic wealing skin reactions to common allergens in the environment.\nhave circulating allergen-specific antibodies (later shown to be IgE).\nDirect link of presence of Allergen-specific IgE and the prevalence of asthma.\n•Genetic and environmental factors affect serum IgE levels. Your text here Slide 8 GENETIC: No single gene for asthma.\nBut several genes, in combination with environmental factors, appear to influence the development of asthma.\nGenes controlling the production of the cytokines IL-3, IL-4, IL-5, IL-9, IL-13 and GM-CSF – which in turn affect:\n–mast and eosinophil cell development\n–longevity as well as IgE production\n•Present in a cluster on chromosome 5q31-33 (the IL-4 gene cluster) Slide 9 ENVIRONMENTAL FACTORS: Early childhood exposure to allergens and maternal smoking has a major influence on IgE production.\nRole of intestinal bacteria and childhood infections in shaping the immune system in early life.\nGrowing up in a relatively ‘clean’ environment may predispose towards an IgE response to allergens ‘hygiene hypothesis’\nComponents of bacteria (e.g. lipopolysaccharide endotoxin, immunostimulatory CpG DNA sequences, flagellin), viruses (e.g. SS- and DS-RNA) and ungi (e.g. chiton, a cell wall component) Slide 10 Increased responsiveness of the airways of the lung (airway hyperresponsiveness) Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma\ncan be demonstrated by asking patients to inhale gradually increasing concentrations of histamine or methacholine (bronchial provocation tests).\nThis induces transient airflow limitation in susceptible individuals (approximately 20% of the population);\nthe severity of BHR can be graded according to the provocation dose (PD) or concentration (PC)\nPatients with clinical symptoms of asthma respond to very low doses of methacholine,\nBHR can also be assessed by exercise testing or inhalation of cold dry air, mannitol or hypertonic saline.\nThese are indirect tests that release endogenous mediators such as histamine, prostaglandins and leukotrienes which then cause bronchoconstriction.\nIndirect measures of BHR correlate more closely with symptoms Slide 11 Cont. Some patients also react to methacholine but at higher doses, e.g. those with:\n–attacks of asthma only on extreme exertion, e.g. winter sports enthusiasts.\n–wheezing or prolonged periods of coughing following a viral infection.\n–seasonal wheeze during the pollen season.\n–allergic rhinitis, but not complaining of lower respiratory symptoms until specifically questioned.\n–and some subjects with no respiratory symptoms.\nAlthough the degree of BHR can be influenced by allergic mechanisms, its pathogenesis and mode of inheritance involve a combination of airway inflammation and tissue remodelling. Slide 12 PRECIPITATING FACTORS: Occupational sensitizers.\nNon-Specific\n–Cold air and exercise\n–Atmospheric pollution and irritant dusts, vapours and fumes\n–Diet\n–Emotion\n–Drugs: Non-steroid anti-inflammatory drugs (NSAIDs) and Beta-blockers\n–Allergen-induced asthma Slide 13 OCCUPATIONAL SENSITIZERS: Occupational asthma - 15% of all asthma cases.\n •Asthma can be due to\n–Low molecular w