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Questions and Answers
What is primarily responsible for the immediate phase of an asthma attack?
Which class of antiasthmatic drugs directly reverses bronchospasm?
In aspirin-induced asthma, what is the result of inhibiting cyclooxygenase (COX)?
What factors can trigger an asthma attack once established?
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What characterizes bronchial hyperreactivity in asthma?
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Which of these is a common feature of chronic severe asthma?
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Which parameter is monitored to assess asthma treatment effectiveness?
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What role do β2-adrenoceptor agonists play in asthma management?
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Which characteristic is NOT typical of asthma?
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What is the primary function of Th2 cytokines in asthma?
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What triggers Th2 cell activation in individuals with asthma?
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Which of the following best describes the nature of asthma?
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What impact do IL-5 and GM-CSF have in asthma pathogenesis?
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Which cells are primarily affected by the action of IL-4 and IL-13 in asthma?
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What can lead to the spontaneous remission of asthma in some individuals?
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Which of the following is a common symptom of asthma?
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What is the primary clinical use of muscarinic receptor antagonists (M3) in patients with COPD?
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Which of the following best describes the mechanism of action of glucocorticoids in treating asthma?
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What condition should prompt caution when using muscarinic receptor antagonists?
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Which of the following glucocorticoids is NOT typically administered via inhalation?
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What is a common adverse effect associated with the use of inhaled glucocorticoids?
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Why might glucocorticoids be less effective in some patients with asthma despite high doses?
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What combination of drugs is often used in the triple therapy for COPD?
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When should oral glucocorticoids be primarily reserved in asthma treatment?
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What is the primary mechanism of action for cysteinyl leukotriene receptor antagonists?
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Which of the following is a characteristic of biologic therapy in asthma treatment?
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In the stepwise approach to managing asthma, what is recommended at Step 3?
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For patients experiencing acute asthma exacerbations, which treatment is typically required?
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What is a key benefit of using montelukast in asthma management?
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Which statement about prolonged treatment with oral prednisolone is true?
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Which cytokine does tezepelumab target in asthma therapy?
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What is the primary role of long-acting bronchodilators in asthma management?
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Which treatment is recommended for managing severe acute asthma, known as status asthmaticus?
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What is the primary cause of Chronic Obstructive Pulmonary Disease (COPD)?
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What role does adrenaline play in allergic emergencies?
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In the context of COPD, what is a late complication that may occur?
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What is the intended effect of leukotriene antagonists in asthma management?
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Which statement is correct regarding the pathogenesis of emphysema within COPD?
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What initial symptoms should one expect in a patient suffering from COPD?
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What additional treatment may be considered for chronic asthma if symptoms persist despite maximum inhaled corticosteroid use?
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Study Notes
Asthma
- Chronic disease that narrows and swells the airways in the lungs, making breathing difficult
- Symptoms: shortness of breath, wheezing, chest pain, coughing with or without sputum production or haemoptysis
- Heterogeneous disease, meaning it can have different causes, manifestations, and treatment responses
- Characterized by chronic airway inflammation, bronchial hyperreactivity, and variable and reversible airflow limitation
- Involves both large and small conducting airways
- Most cases follow a variable course involving viral-induced wheezing and allergen sensitization
- Can spontaneously resolve or begin in adulthood
Asthma Pathogenesis
- Involves both genetic and environmental factors
- Activated T cells with a Th2 cytokine production profile are located in the bronchial mucosa of asthmatics
- Th2 cytokines attract inflammatory granulocytes like eosinophils to the mucosal surface
- IL-5 and GM-CSF participate in epithelial damage, a factor in bronchial hyperreactivity
- Promote IgE synthesis and reactivity and stimulate B cells to make IgE
- Enhance eosinophil adhesion to the endothelium
Characteristics of Asthma
- Reversible airway obstruction
- Airway inflammation
- Bronchial hyperreactivity
Asthma Attacks
- Can be triggered by viral infection, exercise, and atmospheric pollutants
- Aspirin-induced asthma (AIA) is more common in adults and can be severe
- NSAIDs, especially aspirin, can precipitate asthma in sensitive individuals by inhibiting cyclooxygenase, which shifts the metabolic pathway towards lipoxygenase, producing leukotrienes, potent inflammatory mediators and bronchoconstrictors.
- Increased CysLT receptors contribute to bronchial hyperreactivity
Antiasthmatic Drugs
- Bronchodilators reverse bronchospasm in the immediate phase
- Anti-inflammatory agents inhibit or prevent inflammation in both phases
- Treatment is monitored by measuring forced expiratory volume in 1 second (FEV1), peak expiratory flow rate, oxygen saturation, and arterial blood gases
Bronchodilators
- β2-Adrenoceptor Agonists: Bronchodilate through direct action on β2 adrenoceptors of smooth muscle; inhibit mediator release from mast cells and TNF-α from monocytes, and increase mucus clearance by cilia action
- Theophylline
- Muscarinic Receptor Antagonists (M3): Used for acute exacerbations as an adjunct to other agents, also for COPD
- TIOTROPIUM is used for regular daily use in COPD
- Cautious use in glaucoma, hypertension, urinary retention, and cardiovascular pathologies
Anti-inflammatory Agents
- Glucocorticoids
- Prevent chronic asthma progression and are effective in acute severe asthma
- Given by inhalation or orally
- Effect on bronchial hyperresponsiveness is reached after weeks or months of therapy
- Combined inhaler formulations with long-acting β2-adrenoceptor agonists (LABA) and/or long-acting muscarinic antagonists (triple therapy in COPD)
- Cysteinyl Leukotriene Receptor Antagonists (MONTELUKAST, ZAFIRLUKAST): act on CysLT1 and CysLT2 receptors in respiratory mucosa and infiltrating inflammatory cells
- Decrease acute reactions to aspirin, inhibit exercise-induced asthma, well-tolerated
Biologic Therapy
- Anti-IgE: OMALIZUMAB binds human IgE
- IL-5 antagonists: MEPOLIZUMAB and Reslizumab inhibit IL-5 signaling, reducing eosinophil production and survival, mediating the allergic inflammatory process in asthma.
- IL-4/IL-13 antagonist: DUPILUMAB binds to the alpha subunit of the IL-4 receptor, suppressing type 2 inflammation biomarkers
- Thymic stromal lymphoprotein (TSLP) antagonist: TEZEPELUMAB, TSLP acts as a mediator between the immune system and structural cells of the airway
Asthma Treatment Steps
- Step 1: Short-acting bronchodilator alone (SABA or SAMA)
- Step 2: Add a regular inhaled corticosteroid (ICS)
- Step 3: Add a long-acting bronchodilator (LABA or LAMA)
- Step 4: Add theophylline or leukotriene antagonists
- Step 5: Add a regular oral corticosteroid or consider biologic treatment
Severe Acute Asthma (Status Asthmaticus)
- Medical emergency requiring hospitalization
- Treatment includes:
- Oxygen
- Nebulized Salbutamol
- IV Hydrocortisone
- Oral Prednisolone, in addition to:
- Nebulized Ipratropium
- IV Salbutamol
- Aminophylline, and antibiotics (if infection is present)
- Monitoring through PEFR or FEV1, arterial blood gases, and oxygen saturation
Allergic Emergencies
- Anaphylaxis and angioedema are emergencies with acute airway obstruction
- ADRENALINE is life-saving, given IM or occasionally IV
- Patients at risk may self-administer IM adrenaline using a spring-loaded syringe
- OXYGEN, antihistamine treatment (CHLORPHENAMINE), and glucocorticoids are also indicated.
Chronic Obstructive Pulmonary Disease (COPD)
- Third leading cause of death worldwide (3.23 million deaths in 2019)
- Cigarette smoking is the main cause, while air pollution may contribute
- Clinical features include morning cough, intermittent exacerbations, progressive breathlessness, and late complication of pulmonary hypertension, leading to heart failure (cor pulmonale)
- Exacerbations can cause respiratory failure requiring hospitalization and intensive care
COPD Pathogenesis
- Fibrosis of small airways, leading to obstruction, and/or destruction of alveoli and elastin fibers in the lung parenchyma
- Emphysema causes respiratory failure by destroying alveoli, impairing gas transfer
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Description
This quiz delves into the chronic respiratory condition of asthma, exploring its symptoms, causes, and the underlying mechanisms that contribute to its development. It highlights the role of genetic and environmental factors in asthma pathogenesis and the involvement of specific immune responses. Test your knowledge on this heterogeneous disease and its complexities.