JC17 (Medicine) - Asthma and Allergic Lung Diseases Flashcards
Define Asthma
Asthma: defined a chronic inflammatory disorder of airways
□ Leading to widespread but variable airflow obstruction
□ R_eversible_ either spontaneously or with treatment
□ Inflammation is a/w bronchial hyper-responsiveness to a variety of stimuli
4 types of asthma
□ Atopic asthma: individuals with tendency to atopy
→ Predisposition to synthesize IgE to common allergens
→ Hx of infantile eczema and allergic rhinitis
□ Non-atopic asthma: individuals with no evidence of atopy
→ Usually in adults
→ Often triggered by respiratory infections and inhaled air pollutants
□ Drug-induced asthma: asthma provoked by drugs (eg. aspirin)
□ Occupational asthma: provoked by occupational pollutants (eg. fumes, organic dusts)
4 host risk factors to asthma
□ Genetics: certain genes with ↑risk of asthma (eg. IL-3, IL-4, TNF-α…)
□ Atopy: ↑asthma prevalence with ↑serum IgE level
□ Gender: M>F in children/young adults, F>M in adults
□ Obesity: asthma more common and difficult to control if BMI >30kg/m2
→ Obese subjects usually have poorer lung function and more co-morbidities
Environmental triggers of Asthma
□ Allergens:
→ Indoor: fecal pellets of house dust mites, pets, cockroaches
→ Outdoor: alternaria (a genus of Ascomycete fungi), air pollution, tobacco smoke/ second hand smoke
→ Occupational (5-15% of adult onset asthma)
□ Infection
□ Other triggers: exercise, cold air
Describe the T-helper cell response to Intracellular vs Extracellular pathogens
Naïve CD4+ T cells (Th0) activated by interaction with Ag presented by MHC-II
Further differentiation based on predominant cytokine profile
- Th1 differentiation facilitated by IFN-γ, IL-12 → promotes cell-mediated immunity → ↑macrophage, neutrophil, CD8+ T cells activity → elimination of intracellular bacteria and viruses
- Th2 differentiation facilitated by IL-4, IL-5 → promotes humoral immunity → ↑IgE production, mast cell and eosinophil recruitment, growth and differentiation → elimination of extracellular pathogens (eg. parasites)
- Reciprocal inhibition
Compare Th1 vs Th2 mediated immune response
Naïve CD4+ T cells (Th0) activated by interaction with Ag presented by MHC-II
Th1 differentiation facilitated by IFN-γ, IL-12 → promotes cell-mediated immunity → ↑macrophage, neutrophil, CD8+ T cells activity → elimination of intracellular bacteria and viruses
Th2 differentiation facilitated by IL-4, IL-5 → promotes humoral immunity→ ↑IgE production, mast cell and eosinophil recruitment, growth and differentiation → elimination of extracellular pathogens (eg. parasites)
Explain the Hygiene Hypothesis and propensity of atopy
Hygiene hypothesis: proposed mechanism behind atopic tendency in some individuals
□ Childhood microbial exposure associated with ↓allergy and asthma
→ Lifestyle: ↑family size, older siblings, day care
→ Farming: animal contact, stable exposure, drinking unpasteurized farm milk
→ Animal exposure: pet keeping
□ Reason: ↓childhood Th1 activation → poor Th1 development → hyperactive Th2 system → overreaction to allergens (Type I hypersensitivity)
Explain the effects of hypersensitivity reaction on airway
→ Bronchoconstriction due to abnormal smooth muscle response to inflammation
→ Airway inflammation due to vasogenic oedema and inflammatory infiltrate
→ Mucous hypersecretion
Describe Type I hypersensitivity reaction against allergens
Atopic asthma: type I HS reaction towards allergens
Allergen exposure → Th2 response activated → IL-4 → ↑IgE production
→ binds to and sensitizes mast cells
→ further exposure to same allergen results in release of mast cell mediators (immediate phase) → IL-5
→ eosinophil activation and recruitment (delayed phase)
Explain mechanism of aspirin-induced asthma
Aspirin-induced asthma: inhibition of cyclooxygenase → arachidonic acid shunted towards lipoxygenase pathway → ↑leukotrienes (potent bronchoconstrictors)
Explain exercise-induced asthma
Exercise-induced asthma: hyperventilation → water + heat loss from mucosa → lining irritated → inflammatory mediator release
Describe the sequalae of chronic airway inflammation
1) Airway hyper-reactivity
2) Airway remodeling
□ Chronic inflammation results in irreversible structural changes predisposing to airflow obstruction
□ Includes:
→ Smooth muscle hyperplasia → ↑bronchoconstriction
→ Goblet cell hyperplasia → ↑mucus secretion
→ Fibrosis → airway wall thickening
Define the clinical features of asthma
- S/S
- Temporal pattern
- Associated symptoms
Recurrent episodic attacks of wheezing, chest tightness, breathlessness, cough
Characteristically occurs following exposure (5-15min) and resolve with trigger avoidance or asthma medications
Classically with diurnal variation → worse at night or early morning
± signs of atopy: allergic rhinitis, eczema
Ddx of generalized wheeze and localized wheeze
D/dx of generalized wheeze:
- COPD
- Bronchiectasis
- Bronchiolitis obliterans
- Viral bronchiolitis (in children)
D/dx of localized wheeze:
- Tumour
- Foreign body
Outline Diagnosis for Asthma
- Clinical features
- Lung Function test metrics
1) Predominantly clinical based on compatible Hx ± P/E
□ Hx: variable symptoms of wheezes, cough, chest tightness, SOB
□ P/E: characteristic widespread, polyphonic wheezes during attacks
2) Lung Function Test: Spirometry or Peak flow meter
≥1 instance of ↓FEV1/FVC, i.e. ≤75% in adult, ≤85% in children
≥12% and 200mL ↑FEV1 after bronchodilator or ICS
>10% diurnal variability in twice daily PEF over 1-2w
Specific test for airway hypersensitivity
Airway hyper-reactivity: by bronchoprovocation test
≥20% ↓FEV1 post-methacholine/histamine at standard dose
≥15% ↓FEV1 post-hyperventilation, hypertonic saline or mannitol challenge
Second line investigations for Asthma
□ Allergic status: skin prick test, total/allergen-specific IgE, serum eosinophil count
□ CXR: normal or hyperinflated ± lobar collapse (2o to mucus obstruction) → mainly to exclude alternative d/dx
□ Flow-volume loop: ‘scooped out’ concave appearance signifying diffuse intrathoracic airflow obstruction
□ Airway inflammation tests:
→ Sputum eosinophil count >2%
→ Exhaled breath NO concentration (FENO)
Characteristic spirometry graph shape for asthma
“Scooped out appearance”
Major Ddx of Asthma
COPD
asthma-COPD overlap syndrome (ACOS)
Bronchiectasis
Central airway obstruction
Tests to rule out major Ddx of Asthma
1) COPD: Diagnosed by abnormal post-bronchodilator spirometry
2) Bronchiectasis: Diagnosed by CXR/HRCT demonstrating airway dilatation (‘tram-line’ appearance)
3) Central airway obstruction: Spirometry also shows obstructive pattern but flow volume loop is characteristic for upper airway obstruction (expiratory plateau)
