Asthma Overview and Pathogenesis

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

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.