Asthma Overview and Pathogenesis

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Questions and Answers

What is primarily responsible for the immediate phase of an asthma attack?

Eosinophils

Increased levels of cysLTs (correct)

Bronchial hyperreactivity

Dendritic cells presenting antigens

Which class of antiasthmatic drugs directly reverses bronchospasm?

Glucocorticoids

β2-adrenoceptor agonists (correct)

Cysteinyl leukotriene receptor antagonists

Muscarinic receptor antagonists

In aspirin-induced asthma, what is the result of inhibiting cyclooxygenase (COX)?

Decreased production of leukotrienes

Suppression of bronchial hyperreactivity

Increased production of prostaglandins

Shifting of metabolic pathways towards lipoxygenase (correct)

What factors can trigger an asthma attack once established?

Viral infection, exercise, and atmospheric pollutants Signup and view all the answers

What characterizes bronchial hyperreactivity in asthma?

Heightened responsiveness to stimuli Signup and view all the answers

Which of these is a common feature of chronic severe asthma?

Increased eosinophil activity Signup and view all the answers

Which parameter is monitored to assess asthma treatment effectiveness?

Forced expiratory volume in 1 second (FEV1) Signup and view all the answers

What role do β2-adrenoceptor agonists play in asthma management?

They promote bronchodilation and inhibit mediator release. Signup and view all the answers

Which characteristic is NOT typical of asthma?

Permanent narrowing of airways Signup and view all the answers

What is the primary function of Th2 cytokines in asthma?

Attracting inflammatory granulocytes Signup and view all the answers

What triggers Th2 cell activation in individuals with asthma?

Environmental allergens Signup and view all the answers

Which of the following best describes the nature of asthma?

A heterogeneous disease with variable presentations Signup and view all the answers

What impact do IL-5 and GM-CSF have in asthma pathogenesis?

Causing damage to the airway epithelium Signup and view all the answers

Which cells are primarily affected by the action of IL-4 and IL-13 in asthma?

B cells for IgE production Signup and view all the answers

What can lead to the spontaneous remission of asthma in some individuals?

Changes in environmental factors Signup and view all the answers

Which of the following is a common symptom of asthma?

Shortness of breath Signup and view all the answers

What is the primary clinical use of muscarinic receptor antagonists (M3) in patients with COPD?

As a regular daily treatment Signup and view all the answers

Which of the following best describes the mechanism of action of glucocorticoids in treating asthma?

They reduce bronchial hyperreactivity and decrease cytokine formation Signup and view all the answers

What condition should prompt caution when using muscarinic receptor antagonists?

Ocular hypertension Signup and view all the answers

Which of the following glucocorticoids is NOT typically administered via inhalation?

Prednisolone Signup and view all the answers

What is a common adverse effect associated with the use of inhaled glucocorticoids?

Oropharyngeal candidiasis Signup and view all the answers

Why might glucocorticoids be less effective in some patients with asthma despite high doses?

Due to incomplete understanding of their mechanism Signup and view all the answers

What combination of drugs is often used in the triple therapy for COPD?

Inhaled corticosteroids, long-acting β2-adrenoceptor agonists, and long-acting muscarinic antagonists Signup and view all the answers

When should oral glucocorticoids be primarily reserved in asthma treatment?

For patients with severe asthma that do not respond to inhalation treatments Signup and view all the answers

What is the primary mechanism of action for cysteinyl leukotriene receptor antagonists?

They block CysLT1 and CysLT2 receptors in the respiratory system. Signup and view all the answers

Which of the following is a characteristic of biologic therapy in asthma treatment?

Dupilumab inhibits IL-4 signaling by blocking its receptor. Signup and view all the answers

In the stepwise approach to managing asthma, what is recommended at Step 3?

Incorporate a long-acting bronchodilator into treatment. Signup and view all the answers

For patients experiencing acute asthma exacerbations, which treatment is typically required?

Intravenous hydrocortisone followed by oral prednisolone. Signup and view all the answers

What is a key benefit of using montelukast in asthma management?

It helps reduce exercise-induced asthma symptoms. Signup and view all the answers

Which statement about prolonged treatment with oral prednisolone is true?

It may be necessary for a few severely affected patients. Signup and view all the answers

Which cytokine does tezepelumab target in asthma therapy?

Thymic stromal lymphoprotein (TSLP) Signup and view all the answers

What is the primary role of long-acting bronchodilators in asthma management?

They minimize reliance on increased doses of inhaled corticosteroids. Signup and view all the answers

Which treatment is recommended for managing severe acute asthma, known as status asthmaticus?

Oxygen and intravenous hydrocortisone Signup and view all the answers

What is the primary cause of Chronic Obstructive Pulmonary Disease (COPD)?

Cigarette smoking Signup and view all the answers

What role does adrenaline play in allergic emergencies?

It activates β2 adrenoreceptors and manages airway obstruction Signup and view all the answers

In the context of COPD, what is a late complication that may occur?

Pulmonary hypertension leading to cor pulmonale Signup and view all the answers

What is the intended effect of leukotriene antagonists in asthma management?

They exert a corticosteroid-sparing effect Signup and view all the answers

Which statement is correct regarding the pathogenesis of emphysema within COPD?

It results in destruction of alveoli and elastin fibres Signup and view all the answers

What initial symptoms should one expect in a patient suffering from COPD?

Intermittent cough with morning symptoms during winter Signup and view all the answers

What additional treatment may be considered for chronic asthma if symptoms persist despite maximum inhaled corticosteroid use?

Oral corticosteroids like prednisolone Signup and view all the answers

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.