A.2 Bronchial Asthma Flashcards
A.2 Bronchial Asthma
define
Asthma is a respiratory disease that is characterized by chronic airway inflammation and manifests with variable respiratory symptoms and expiratory airflow limitation
Acute asthma exacerbation: a reversible worsening of the clinical features of asthma that develops over a short period of time and can progress to life-threatening asthma.
A.2 Bronchial Asthma
Epidemiology
Prevalence
- 5–10% of the US population
Sex: differs depending on age of onset
♂ > ♀ in patients < 18 years
♀ > ♂ in patients > 18 years
Age of onset
- Allergic asthma: typically in childhood
- Nonallergic asthma: typically > 40 years
A.2 Bronchial Asthma
Etiology Allergic asthma
(extrinsic asthma)
Cardinal risk factor: atopy
Environmental allergens: pollen (seasonal), dust mites, domestic animals, mold spores
Allergic occupational asthma from exposure to allergens in the workplace (e.g., flour dust)
A.2 Bronchial Asthma
Etiology Nonallergic asthma
(intrinsic asthma)
- Viral respiratory tract infections (one of the most common stimuli, especially in children)
- Cold air
- Physical exertion (laughter, exercise-induced asthma)
- Gastroesophageal reflux disease (GERD): often exists concurrently with asthma
- Chronic sinusitis or rhinitis
Medication, e.g.:
Aspirin
NSAIDs
Beta blockers
- Stress
- Irritant-induced occupational asthma (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents)
A.2 Bronchial Asthma
General Pathophys
Asthma is an inflammatory disease driven by T-helper type 2 cells (Th2-cell) that manifests in individuals with a genetic predisposition. It consists of the following three pathophysiologic processes:
- Bronchial hyperresponsiveness
- Bronchial inflammation
- Symptoms are primarily caused by inflammation of the terminal bronchioles, which are lined with smooth muscle but lack the cartilage found in larger airways.
- Overexpression of Th2-cells → inhalation of antigen results in production of cytokines (IL-3, IL-4, IL-5, IL-13) → activation of eosinophils and induction of cellular response (B-cell IgE production) → bronchial submucosal edema and smooth muscle contraction → bronchioles collapse - Endobronchial obstruction caused by:
Increased parasympathetic tone
Reversible bronchospasm
Increased mucus production
Mucosal edema and leukocyte infiltration into the mucosa with hyperplasia of goblet cells
Hypertrophy of smooth muscle cells
A.2 Bronchial Asthma
allergic asthma pathophys
IgE-mediated type 1 hypersensitivity to a specific allergen
Characterized by mast cell degranulation and release of histamine after a prior phase of sensitization
A.2 Bronchial Asthma
Aspirin Induced Asthma Pathophys
Aspirin-exacerbated respiratory disease is characterized by the Samter triad:
Inhibition of COX-1 → ↓ PGE2 → ↑ leukotrienes and inflammation → submucosal edema → airway obstruction
Chronic rhinosinusitis with nasal polyposis
Asthma symptom
A.2 Bronchial Asthma
clinical
Persistent, dry cough that worsens at night, with exercise, or on exposure to triggers/irritants (e.g., cold air, allergens, smoke)
End-expiratory wheezes
Dyspnea (shortness of breath)
Chest tightness
Prolonged expiratory phase on auscultation
Hyperresonance to lung percussion
A.2 Bronchial Asthma
DX Spirometry
Spirometry can be paired with specialized tests in obstructive lung diseases, e.g., bronchodilator responsiveness testing, or bronchial challenge tests.
Indication: first-line test
Supportive findings
- Expiratory airway limitation: i.e., ↓ FEV1 and ↓ FEV1/FVC ratio
A.2 Bronchial Asthma
TX
Stepwise asthma treatment
Prescribe asthma relievers and maintenance bronchodilators depending on the severity and previous response to treatment.
Step 1 Low-dose ICS-formoterol as needed Mild/infrequent symptoms
Step 2 Daily low-dose ICS or as-needed ICS-formoterol Symptoms >2x/month
Step 3 Low-dose ICS-LABA daily Troublesome symptoms, ≥1 exacerbation/year
Step 4 Medium-dose ICS-LABA ± LAMA Poor control, frequent symptoms
Step 5 High-dose ICS-LABA + specialist referral ± biologics Severe asthma, uncontrolled on step 4
A.2 Bronchial Asthma
SABA
Short-acting beta-2 agonists
Inhaled: albuterol
Oral: terbutaline
A.2 Bronchial Asthma
ICS
ICS = inhaled corticosteroid
Beclomethasone, budesonide, fluticasone – ↓ inflammation
A.2 Bronchial Asthma
LABA:
Long-acting beta-2 agonists
Salmeterol, formoterol – long-acting bronchodilation
A.2 Bronchial Asthma
LAMA
Tiotropium bromide
A.2 Bronchial Asthma
SAMA
Short-acting muscarinic antagonists (SAMA)
Ipratropium bromid
A.2 Bronchial Asthma
Oral Glucocorticoids
Methylprednisolon
MOA: nhibit transcription factors (e.g., NF-κB) → ↓ expression of proinflammatory genes
A.2 Bronchial Asthma
LTRAs
Leukotriene receptor antagonists (LTRAs)
Montelukast
Zafirlukast
MOA: Prevent leukotrienes from binding to their G protein-coupled receptors (CysLT1) → ↓ bronchoconstriction and inflammation
A.2 Bronchial Asthma
Biological
Anti-IgE (omalizumab)
Anti-IL-5 (mepolizumab, benralizumab)
Anti-IL-4R (dupilumab)
