EHR519 2024 Week 13a Patho, Meds, Considerations Asthma and CF PDF

Warning This material has been produced and communicated to you by or on behalf of Charles Sturt University in accordance with section 113P of the copyright act (Act). The material in this communication may by subject to copyright under the act. Any further reproduction or c...

Warning This material has been produced and communicated to you by or on behalf of Charles Sturt University in accordance with section 113P of the copyright act (Act). The material in this communication may by subject to copyright under the act. Any further reproduction or communication of this material by you may be the subject of copyright protection under this act. Do not remove this notice  Pathophysiology, considerations and medications for asthma and cystic fibrosis EHR519 Week 13a Learning Outcomes be able to explain the pathophysiology of Asthma and Cystic Fibrosis as it relates to exercise physiology; be able to outline the risk factors, complications and co-morbidities that must be accounted for when applying exercise interventions to individuals with Asthma and Cystic Fibrosis; be able to describe the effects of commonly prescribed medications on acute and chronic exercise responses that must be accounted for when applying exercise interventions to individuals with Asthma and Cystic Fibrosis; be able to explain the diagnostic techniques and treatment procedures used in the treatment of Asthma and Cystic Fibrosis; 4  Asthma “Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness and cough, that vary over time and in intensity, together with variable expiratory airflow limitation” (GINA, 2023) Hyperresponsiveness of the airway to direct and indirect stimuli and can involve chronic inflammation Symptoms typically resolve (transient) with experiences of flare ups. Pathology may be present even when symptoms are not present Around 2.7 million Australians had asthma in 2017-18 Prevalence of asthma increased from 9.9% in 2007-08 to 11% in 2020-21 (ABS) Similar for boys and girls aged 0–14 (9.3%; 7.7%) higher for females over the age of 15 for all age groups except for those aged 25–34 likely from complex interaction between changing airway size and hormonal changes during adolescence + differences in environmental exposures First Nations people were 1.6 times (18%) as likely to report having asthma as non-Indigenous Australians (11%) 5  Asthma phenotypes Allergic asthma: easily recognised: often commences in childhood, associated with a past and/or family history of allergic disease, sputum examination shows airway inflammation Patients usually respond well to inhaled corticosteroid (ICS) treatment. Non-allergic asthma: the cellular profile of the sputum of these patients may be neutrophilic, eosinophilic or contain only a few inflammatory cells. Demonstrate a lesser short-term response to ICS. Adult-onset (late-onset) asthma: particularly women, present for the first time in adulthood. Mostly non-allergic, often require higher doses of ICS or relatively refractory to corticosteroid treatment. Rule out occupational asthma Asthma with persistent airflow limitation: some with long-standing asthma develop airflow limitation that is persistent or incompletely reversible (from airway wall remodelling). Asthma with obesity: some obese patients with asthma have prominent respiratory symptoms and little eosinophilic airway inflammation. Little evidence about the natural history of asthma after diagnosis: one longitudinal study showed that approximately 16% of adults with recently diagnosed asthma may experience clinical remission (no symptoms or asthma medication for at least 1 year) within 5 years 6  Environmental Factors Pathophysiology Allergens Indoor (mites, mould) 3 components to asthma Outdoors (pollens, fungi) 1. Airway inflammation – primary contributing factor Infections (viral) 2. Intermittent airflow obstruction Smoking (active and passive) 3. Bronchial hyperresponsiveness Diet Medications (aspirin, nonsteroidal agents) Host Factors Genetics Obesity Gender 7  Airway inflammation Can be episodic & variable, but airway inflammation is persistent Inflammation, and thus obstruction, is primarily in the medium sized bronchi CD4 lymphocyte – promotes inflammation through immunoglobulin E, eosinophils, basophils and mast cells Allergic inflammation may be due to excessive expression of Th2 cytokines Influences from cytokines, histamine, NO and prostaglandins Inflammation promotes Oedema Structural changes (remodelling of airways) hypertrophy & hyperplasia of airway wall angiogenesis and increased submucosal gland size 8 Inflammation and Asthma 9 Pathogenesis of allergic asthmatic inflammation. Allergens are presented to naïve T cells. Environmental & inflammatory factors activate the respiratory epithelium to release (TSLP) and other inflammatory mediators that recruit leukocytes and skew dendritic cell function toward an allergic response. Dendritic cells induce the differentiation of T cells into T-helper 2 (Th2)-specific helper cells and Th17 cells. Th2 cells induce (IgE) antibody production from B cells via IL-4 & IL-13 stimulation. IgE binds to mast cell & basophils receptors and in the presence of allergen, release mediators that induce bronchoconstriction and enhance the inflammatory response. Production of IL-5 from Th2 cells increases eosinophil levels. CCL,chemokine ligand;GM-CSF,granulocytemacrophage colony-stimulating factor;PGD2,prostaglandinD2;SCF,stem cell Inflammatory mediators from eosinophils, T cells, macrophages factor;TNF-a, tumor necrosis factor-alpha & neutrophils = damaged airway, bronchoconstriction, inflammation and remodelling. 10  Bronchial hyperresponsiveness Exaggerated bronchoconstriction from one or more stimuli (endogenous or exogenous) Hallmark/ defining feature and the most characteristic clinical feature of asthma Correlation with degree of acute inflammation Stimulation of the smooth muscle 11  Asthma diagnosis Diagnosis of asthma is based on identifying both a characteristic pattern of respiratory symptoms such as wheezing, shortness of breath (dyspnoea), chest tightness or cough, and variable expiratory airflow limitation. Pattern of symptoms important, as symptoms may be due to acute or chronic conditions other than asthma (e.g. COPD, bronchiectasis, cystic fibrosis and chronic upper airway cough syndrome). Diagnosis should be done when the patient first presents, as features may improve spontaneously or with treatment Difficult to confirm a diagnosis once on ICS treatment (reduces variability of symptoms and lung function) 12  Asthma features Features typical of asthma: Respiratory symptoms of wheeze, shortness of breath, cough and/or chest tightness: Patients (especially adults) experience more than one of these types of symptoms. – worse at night or in the early morning, – vary over time and in intensity – triggered by viral infections (colds), exercise, allergen exposure, changes in weather, laughter, or irritants (exhaust fumes, smoke). Features that decrease the probability that symptoms are due to asthma: Isolated cough with no other respiratory symptoms Chronic production of sputum SOB associated with dizziness, paresthesia (light-headedness or peripheral tingling) Chest pain Exercise-induced dyspnoea with noisy inspiration 13  Diagnosis continued History and family history symptoms in childhood, history of allergic rhinitis or eczema, or a family history of asthma or allergy, increases the probability that the respiratory symptoms are due to asthma (not all phenotypes) Physical examination (often normal) most frequent abnormality is expiratory wheezing, (may be absent or only on forced expiration) and may be absent during severe asthma exacerbations from severely reduced airflow (‘silent chest’), but other physical signs of respiratory failure are usually present. Lung function testing to document variable expiratory airflow limitation Those with asthma have variable expiratory airflow limitation (varies over time & magnitude), from normal to severely obstructed in the same patient. Poorly controlled = greater variability in lung function. Testing by well-trained staff, calibrated equipment (inline filter) – FEV1 more reliable than PEF – Reduced FEV1 common in other lung diseases (or poor spirometric technique), but a reduced FEV1/FVC ratio, compared with the lower limit of normal, indicates expiratory airflow limitation – Spirometers now include multi-ethnic age-specific predicted values. 14  Diagnosis continued Bronchial provocation tests Inhaled methacholine, histamine, Moderately sensitive for a diagnosis of asthma but have limited specificity. Allergy tests Atopy increases the probability of allergic asthma but is not specific for asthma or present in all phenotypes. Can be identified by skin prick testing or levels of specific immunoglobulin E (sIgE) in serum. Positive skin test or positive sIgE does not mean that the allergen is causing symptoms – relevance of allergen exposure and its relation to symptoms must be confirmed by the patient’s history 15  Diagnostic criteria for asthma in adults, adolescents, and children 6–11 years (GINA report 2023) 1. HISTORY OF TYPICAL VARIABLE RESPIRATORY SYMPTOMS Feature Symptoms or features that support the diagnosis of asthma Wheeze, shortness of breath, More than one type of respiratory symptom (in adults, isolated cough is seldom chest tightness and cough due to asthma) (Descriptors may vary between Symptoms occur variably over time and vary in intensity cultures and by age) Symptoms are often worse at night or on waking Symptoms are often triggered by exercise, laughter, allergens, cold air Symptoms often appear or worsen with viral infections 2. CONFIRMED VARIABLE EXPIRATORY AIRFLOW LIMITATION Feature Considerations, definitions, criteria 1. Documented* excessive The greater the variations, or the more occasions excess variation is seen, the more confident the diagnosis. If initially negative, tests can be repeated variability in lung function*(one during symptoms or in the early morning. or more of the following) Positive bronchodilator (BD) Adults: increase in FEV1 of >12% and >200 mL (greater confidence if increase is >15% and >400 mL). Children: increase in FEV1 from baseline of >12% responsiveness (reversibility) predicted. Measure change 10–15 minutes after 200–400 mcg salbutamol (albuterol) or equivalent, compared with pre-BD readings. Positive test more test likely if BD withheld before test: SABA ≥4 hours, twice-daily LABA 24 hours, once-daily LABA 36 hours Excessive variability in twice- Adults: average daily diurnal PEF variability >10%* daily PEF over 2 weeks Children: average daily diurnal PEF variability >13%* Increase in lung function after 4 Adults: increase in FEV1 by >12% and >200 mL (or PEF † by >20%) from baseline after 4 weeks of ICS-containing treatment, outside respiratory weeks of treatment infections Positive exercise challenge test Adults: fall in FEV1 of >10% and >200 mL from baseline Children: fall in FEV 1 of >12% predicted, or PEF >15% from baseline Positive bronchial challenge test Fall in FEV1 from baseline of ≥20% with standard doses of methacholine, or ≥15% with standardised hyperventilation, hypertonic saline or mannitol (usually only for adults) challenge Excessive variation in lung Adults: variation in FEV1 of >12% and >200 mL between visits, outside of respiratory function between visits (good infections. Children: variation in FEV1 of >12% in FEV 1 or >15% in PEF † between specificity but poor sensitivity) visits (may include respiratory infections) AND 2 Documented* expiratory At a time when FEV1 is reduced (e.g. during testing above), confirm that FEV1/FVC is also reduced compared with the lower limit of normal 16 (it is usually airflow limitation >0.75–0.80 in adults, >0.90 in children 21  Diagnosis continued In clinical practice Once a defect has been confirmed, variation is generally assessed from variation in FEV1 or PEF Variability may occur over the course of one day (diurnal variability), from day to day, visit to visit, seasonally, or from a reversibility test. – ‘Reversibility’ (now called ‘responsiveness’) = rapid improvements in FEV1 (or PEF), within minutes following rapid-acting bronchodilator e.g. 200–400 mcg salbutamol, or more sustained improvement over days or weeks after the introduction of ICS – An increase or decrease in FEV 1 of >12% and >200 mL from baseline, or (if spirometry is not available) a change in PEF of at least 20%, is accepted as being consistent with asthma (adults) – normal range FEV1 reduces the probability that the symptoms are due to asthma 17 https://www.asthmaaustralia.org.au/national/about- asthma/manage-your-asthma/your-asthma-medicine 18 Medications for the Treatment of Asthma cont. Cystic fibrosis 21  Cystic Fibrosis (CF) Genetic disorder that effects respiratory, metabolic and reproductive systems Chromosome 7 mutation Results in altered production and function of cystic fibrosis transmembrane regulator (CRTR) – protein that is a chloride channel regulator and reabsorption of sodium and water on respiratory epithelium Causes excessive viscid mucus which causes obstruction of passageways Pancreatic and bile ducts Intestines Bronchi Increased sodium and chloride concentrations in sweat Respiratory failure accounts for 95% of morbidity and mortality associated with CF Early and aggressive intervention – life expectancy of Aust. CF = 38 years Diagnosis usually in infancy (adult variant CF increasing) 22 In relation to the respiratory system... Abnormal CRTR alters water, sodium and chlorine movement across the cell membrane Production of a thick and dry mucus, obstructing bronchial airway, causing bacterial infections and inflammation Lung tissue is progressively destroyed → eventually leading to respiratory failure 23  Effects on the Respiratory System The constant mucus production creates an environment prone to bacteria, inflammation and infection In children, diagnosis is associated with presence of chronic infection, cough, sputum production, crackles, wheezing, fever, failure to thrive Often misdiagnosed with asthma, allergies or bronchitis. Chest radiographs important – identify changes such as bronchiectasis (irregular and dilated airways) Spirometry assessments included reduced FEV1 and forced expiratory flow, and hyperinflation Lower the FEV1, the more severe the disease. Mild 70-89%, moderate 40-69% severe < 40% Technology for infants 24 Effects on the Gastrointestinal Systems Exocrine pancreatic insufficiency is present in approximately 85% of CF patients Malabsorption of nutrients (fat, protein and vitamins) Frequent, fatty stools and abdominal pain Increased need for higher caloric intake and poor utilisation Malnutrition and inability to maintain body weight Correlation between ideal body mass and effects on respiratory system Gastrointestinal tube may be required for advanced nutritional issues Other common conditions included liver disease, endocrine pancreatic insufficiency (CF-related diabetes) and gallbladder disease. 25 Effects on the Metabolic Systems With age, an increase in development of cystic-fibrosis-related diabetes 30% adults (18-34 years) and 40% (>35 years) Due to scarring of the pancreas Responsible for insulin secretion Key to why exercise is important! Blood glucose monitoring important and recognise signs of hypo or hyperglycaemia. 26  Effects on the Skeletal System Evidence of bone disease, with increased risk in >10 years old 20 % prevalence aged between 18-34 years 40% at 35 years Early intervention (diet and exercise) to minimise the risk of osteoporosis Effects on the Mental Health >25% adults with CF experience symptoms of depression and anxiety Becomes more prominent later in life After 12 years old, recommendation for yearly screenings during routine clinical visits 27 Effects on Sinuses Development of pansinusitis and nasal polyposis is common Results in difficulty breathing through the nose Can create bacterial colonisation, contributing to lung disease Antibiotics, nasal irrigations and endoscopic surgeries Effects on Sweat Glands Chloride transport abnormality in all epithelial cells Use sweat test for CF diagnosis Greater than 60 mEq.dL-1 = CF diagnosis 28