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Asthma.pptx
- 1. PHARMACOTHERAPY OF ASTHMA BY:G/Michael T. Gmail: gebremichael.tesfay@ju.edu.et 2/20/2023 1
- 2. Definition and Epidemiologyof 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. • It is a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyper responsiveness and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment. 2/20/2023 2
- 3. Con’t… • Asthma isa globally significant non-communicable disease with major public health consequences for both children and adults, including high morbidity, and mortality in severe cases. • While asthma incidence and prevalence are higher in children, morbidityand mortality are higher in adults. • Childhood asthma is more common in boys while adult asthma is more common in women. • Asthma is affecting 1–18% of the population in different countries. 2/20/2023 3
- 4. Con’t… • Globally, asthmais ranked 16th among the leading causes of years lived with disability and 28th among the leading causes of burden of disease, as measured by disability-adjusted life years. • Around 300 million people have asthma worldwide, and it is likely that by 2025 a further 100 million may be affected. • There is a large geographical variation in asthma prevalence, severity, and mortality. While asthma prevalence is higher in high income countries, most asthma-related mortality occurs in low-middle income countries. 2/20/2023 4
- 5. ETIOLOGY AND PATHOPHYSIOLOGY •The current evidence suggests that asthma is a complex multifactorial disorder and its etiology is increasingly attributed to interactions between genetic susceptibility, host factors, and environmental exposures. Environmental factors : air pollution, pollens, mold and other aeroallergens, drugs and weather Host factors : obesity, nutritional factors, infections, allergic sensitization Genetic factors : asthma susceptibility loci on genes • Although underlying mechanisms of asthma are not yet fully understood, they may include airway inflammation, control of airway tone and reactivity. • It is also now recognized that asthma may not be a single disease but a group of heterogeneous phenotypes with different etiologies and prognoses. 2/20/2023 5
- 6. Con’t… • Most patientsdo experience 2 clear phases of the asthmatic response when exposed to a particular trigger, the ‘‘early’’ phase and the ‘‘late’’ phase. • The ‘‘early’’ phase of the asthma response usually occurs 10-30 minutes following exposure to an asthma trigger and involves the release of inflammatory mediators from IgE-coated mast cells throughout the respiratory passages. • These inflammatory mediators include histamine, prostaglandins, leukotrienes, and interleukins. • These mediators Induce bronchospasm Increase permeability of the airways to antigen Increase vascular permeability and mucus secretion • Activation of vagal nerves in the airway constricts bronchial smooth muscle and increases secretions from mucous-producing cells 2/20/2023 6
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- 8. Con’t… The late-phaseinflammatory reaction occurs 6 to 9 hours after allergen provocation where airway inflammation becomes more prominent. Neutrophils, attracted by chemo-taxis to the area of inflamed airway, leave the more permeable blood vessel and enter the respiratory tissues. Neutrophils are joined by other inflammatory immune cells such as basophils, and eosinophils that escalate the inflammatory response by releasing their own inflammatory mediators. T-lymphocytes may also play an important role in the asthmatic response since a particular subset of T- lymphocytes (TH2) responds to environmental allergens by releasing cytokines that may be a key mechanism of the late-phase response. 2/20/2023 8
- 9. Clinical Presentation andDiagnosis • The following features are typical of asthma and, if present, increase the probability that the patient has 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. Symptoms are often worse at night or in the early morning. Symptoms vary over time and in intensity. Symptoms are triggered by viral infections (colds), exercise, allergen exposure, changes in weather, laughter, or irritants such as car exhaust fumes, smoke or strong smells • The symptoms of asthma can be nonspecific and varied, making the diagnosis difficult. Therefore, a thorough history and physical examination along with spirometry are important for the diagnosis of asthma. 2/20/2023 9
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- 11. Con’t… • Airflow obstructionwith a FEV1/forced vital capacity ratio <0.7 or less than the lower limit of normal (LLN) AND airflow reversibility after inhalation of a short-acting beta-2 agonist (SABA) defined as FEV1 improvement by at least 12% AND/OR 200 Ml indicates a diagnosis of asthma. However, given the variable nature of airflow obstruction asthma patients can present with normal spirometry results. In such patients, bronchoprovocation with methacholine or mannitol can be useful in the asthma diagnosis. A >20% drop in FEV1 provocation concentration (PC20 <16 mg/mL), and now recently a provocation dose (PD20) <400 µg, are currently used and recommended for diagnosis. 2/20/2023 11
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- 19. Management General principlesof asthma management • The long-term goals of asthma management from a clinical perspective are: To achieve good control of symptoms and maintain normal activity levels To minimize the risk of asthma-related death, exacerbations, persistent airflow limitation and side-effects. • The patient’s own goals regarding their asthma and its treatment should also be identified. 2/20/2023 19
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- 21. Con’t… Categories ofasthma medications • The pharmacological options for long-term treatment of asthma fall into the following three main categories: I. Controller medications • These medications contain ICS and are used to reduce airway inflammation, control symptoms, and reduce future risks such as exacerbations and related decline in lung function. People with more severe asthma use controller medication on a regular basis, not only when they have symptoms. 2/20/2023 21
- 22. Con’t… II. Reliever medications •These are provided to all patients for as-needed relief of breakthrough symptoms, including during worsening asthma or exacerbations. Track 1: The reliever is as-needed low dose ICS-formoterol (preferred) Track 2: The reliever is as-needed SABA • They are also recommended for short-term prevention of exercise-induced bronchoconstriction. 2/20/2023 22
- 23. Con’t… Initial controllertreatment • For the best outcomes, ICS-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made, as the evidence suggests that: Early initiation of low dose ICS in patients with asthma leads to a greater improvement in lung function than if symptoms have been present for more than 2–4 years. One study showed that after this time, higher ICS doses were required, and lower lung function was achieved. Patients not taking ICS who experience a severe exacerbation have a greater long-term decline in lung function than those who are taking ICS. For patients with occupational asthma, early removal from exposure to the sensitizing agent and early controller treatment increase the probability of resolution of symptoms, and improvement of lung function and airway hyperresponsiveness. Starting treatment with SABA alone encourages patients to regard it as their main asthma treatment, and increases the risk of poor adherence when daily ICS is subsequently prescribed. 2/20/2023 23
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- 30. Box 6-6. Lowdaily doses of inhaled corticosteroids for children 5 years and younger Con’t… 2/20/2023 30
- 31. Management of WorseningAsthma and Exacerbations • Exacerbations represent an acute worsening in symptoms and lung function from the patient’s usual status, or in some cases, a patient may present for the first time during an exacerbation. • Common exacerbation triggers include: Viral respiratory infections Allergen exposure e.g. grass pollen, fungal spores Food allergy Outdoor air pollution Seasonal changes and/or returning to school in fall (autumn) Poor adherence with ICS • However, a subset of patients present more acutely and without exposure to known risk factors Severe exacerbations can occur in patients with mild or well-controlled asthma symptoms 2/20/2023 31
- 32. Con’t… • The decreasein expiratory airflow can be quantified by lung function measurements such as peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1), compared with the patient’s previous lung function or predicted values. In the acute setting, these measurements are more reliable indicators of the severity of the exacerbation than symptoms. A minority of patients perceive airflow limitation poorly and can experience a significant decline in lung function without a change in symptoms. • The frequency of symptoms may, however, be a more sensitive measure of the onset of an exacerbation than PEF. • Severe exacerbations are potentially life threatening and their treatment requires careful assessment and close monitoring. 2/20/2023 32
- 33. Con’t… Treating exacerbationsin primary care (adults, adolescents, children 6–11years) • The main initial therapies include Repetitive administration of short-acting inhaled bronchodilators Early introduction of systemic corticosteroids, and Controlled flow oxygen supplementation. • The aim is to rapidly relieve airflow obstruction and hypoxemia, address the underlying inflammatory pathophysiology, and prevent relapse. • Infection control procedures should be followed. 2/20/2023 33
- 34. Con’t… Inhaled short-actingbeta2 –agonists • Currently, inhaled salbutamol (albuterol) is the usual bronchodilator in acute asthma management. • For mild to moderate exacerbations, repeated administration of inhaled SABA (up to 4–10 puffs every 20 minutes for the first hour) is an effective and efficient way to achieve rapid reversal of airflow limitation. After the first hour, the dose of SABA required varies from 4–10 puffs every 3–4 hours up to 6–10 puffs every 1–2 hours, or more often. 2/20/2023 34
- 35. Con’t… Controlled oxygentherapy • Oxygen therapy should be titrated against pulse oximetry (if available) to maintain oxygen saturation at 93–95% (94–98% for children 6–11 years). In hospitalized asthma patients, controlled or titrated oxygen therapy is associated with lower mortality and better outcomes than high concentration (100%) oxygen therapy. If supplemental oxygen is administered, oxygen saturation should be maintained no higher than 96% in adults 2/20/2023 35
- 36. Con’t… Systemic corticosteroids •OCS should be given promptly, especially if the patient is deteriorating, or had already increased their reliever and controller medications before presenting. • The recommended dose of prednisolone for adults is 1 mg/kg/day or equivalent up to a maximum of 50 mg/day, and 1–2 mg/kg/day for children 6–11 years up to a maximum of 40 mg/day). • OCS should usually be continued for 5–7 days in adults and 3-5 days in children. 2/20/2023 36
- 37. Con’t… Controller medication •Patients already prescribed controller medication should be provided with advice about increasing the dose for the next 2–4 weeks. • Patients not currently taking controller medication should be commenced on regular ICS-containing therapy, as SABA-only treatment of asthma is no longer recommended. Antibiotics (not recommended) • Evidence does not support routine use of antibiotics in the treatment of acute asthma exacerbations unless there is strong evidence of lung infection. 2/20/2023 37
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