Respiratory JC017: Cough And Wheezing: Asthma, Allergic Lung Diseases Flashcards
Conditions with cough and wheezing
Asthma: a disease presents with **Cough + **Airflow obstruction
Diseases with cough
- Rhinitis, Sinusitis, Otitis
- **Bronchitis (chronic / postviral)
- **Asthma
- **Bronchiectasis
- Cystic fibrosis
- **Pneumonia
- ***Diffuse pulmonary fibrosis
Diseases with airflow obstruction
- **COPD
- **Asthma
- ***Bronchiolitis obliterans
- Cystic fibrosis
- Laryngeal narrowing (Organic / Functional)
- Tracheal / Major bronchial obstruction
Asthma
- Heterogeneous disease
- ***Chronic airway inflammation
Defined by:
1. History of respiratory symptoms
- **Wheezing (airway obstruction)
- **SOB
- Chest tightness
- ***Cough
- Vary over ***Time + Intensity
- **Variable **expiratory airflow limitation
Classification of Asthma
- Atopic asthma
- individuals with a tendency to atopy / predisposition to synthesise **IgE to common allergens
—> ↑ IgE **Z-score —> ↑ Asthma prevalence
- usually in children / young adults with history of infantile **eczema, **allergic rhinitis - Nonatopic asthma
- no evidence of atopy
- adults
Epidemiology of Asthma
- ↓ prevalence in North America, Western Europe
- ↑ prevalence in Africa, Latin America, Part of Asia
- 8.6% in HK
***Asthma risk factors
Host predisposition
1. Genetics: those involved in immunological pathways
2. ***Atopy
3. Gender (younger: male; adult: female)
4. Obesity
Environmental risk factors
- **Causes vs **Triggers
Causes:
1. ***Indoor aeroallergens
- house dust mites
- pets
- cockroaches
- ***Outdoor aeroallergens
- alternaria
- tobacco smoke
- air pollution - ***Occupational agents
- 5-15% of adult onset asthma
Triggers (記: Trigger得exercise + cold air):
1. **Exercise
2. **Cold air (e.g. winter)
Obesity and Asthma
- ↑ Co-morbidities, ↓ Lung function
- Exact mechanisms unknown
—> Effect on lung mechanics
—> ***Pro-inflammatory state (cytokines from adipocytes)
Common allergens in HK
-
**D. Pteronyssinus (i.e. house dust mite)
- **Der p1 + ***Der f1 allergens
- feed on human dander
- thrive on warm temperature and high humidity
- allergen in fecal pellets - Cockroach
- Cat dander
- Dog hair
- Penicillium
- Royal jelly
- Grass pollen
Air pollution and Asthma
***Dose-response relationship
↑ in health care utilisation
- hospital admission
- A/E visits
- unscheduled visits to doctors
Infection and Asthma
**Viral infection may trigger an **acute attack in pre-existing asthma
However:
- Exposure to some microbes in early infancy may protect against asthma development (Hygiene hypothesis)
Hygiene hypothesis:
- postulated by Strachan
- Allergic diseases are prevented by infections in early childhood, transmitted by contact with older children
—> Large family size
—> Having older siblings
—> Day care
—> Animal contact
—> Stable exposure
—> Drinking unpasteurised farm milk
—> Pet keeping
***Immunopathogenesis of Asthma
T-helper lymphocytes
Th0
—> **Extracellular pathogens (allergens)
—> **↑↑ Th2 (allergy-related)
—> activate ***B cells, Eosinophils, Mast cells
—> Histamine, Leukotrienes, Chemokines, TNF-α
—> Allergic inflammation and tissue damage
—> Asthma
If early exposed to microbes (Endotoxins, Mycobacteria, Virus):
Th0
—> ↑↑ Th1 (infection-related) (↓ Th2!!! —> possible ↓ allergy)
—> IFN-γ
—> Cell-mediated immunity
—> Killing of microbes, Complement activation, Killing of infected cells
***Mechanisms of airflow obstruction in asthma
- ***Airway inflammation
- eosinophils
- lymphocytes - Mucous hypersecretion
- ***goblet cells hyperplasia - Smooth muscle constriction + hyperplasia
- ***bronchospasm
Clinical features of Asthma
***Episodes of dyspnea + cough + wheeze
Episodes:
- transient / prolonged
- ***worse at night / early morning
- may present as persistent cough only (i.e. Cough-variant asthma)
***DDx of Wheeze
Generalised wheeze
- **COPD
- **Bronchiectasis
- ***Bronchiolitis obliterans
- Viral bronchiolitis (children)
Localised wheeze
- Tumour
- Foreign body
***Diagnosis of Asthma
- Compatible history
- **symptomatology
- **environmental triggers -
Variable airflow obstruction
- demonstrate presence of airflow obstruction
- improve in FEV1 (>200ml / ***>=12% from baseline) / PEF after bronchodilator
- diurnal variation in PEF / variation in PEF over a period of time -
Non-specific airway hyperresponsiveness
- bronchial challenge test (NOT essential for Dx)
Assessment of Asthma
- Severity
- assessed **retrospectively from **level of treatment required to control symptoms / exacerbations
- assessed after patient has been on controller treatment for **several months
- severity is **NOT static, may change over time / as different treatments become available - Identify triggering factors
***Categories of Asthma severity
記: PRN controller —> Low dose ICS —> LABA —> Moderate/High dose ICS + LABA + Add-on agents
Mild:
- well-controlled with Steps 1 / 2
- ***PRN controller / Low dose ICS
Moderate:
- well-controlled with Step 3
- ***Low dose ICS / LABA
Severe:
- require Step 4 / 5
- ***Moderate / High dose ICS/LABA +/- Add-on (e.g. LAMA)
- or remain uncontrolled despite treatment
Treatment goals of Asthma
Complete control
- No attacks, A/E visits, hospitalisation
- No symptoms / fewest possible
- No limitation of activity
- **Normal / Near normal lung function
- **Least aerosol bronchodilator use
- Least SE from medication
Management of Asthma
- Pharmacotherapy
- ***Relievers: Bronchodilators
—> SABA
—> LABA
—> Anticholinergics (SAMA, LAMA)
—> Theophylline
-
**Preventors: Anti-inflammatory drugs
—> **Inhaled / Oral steroids
—> Nedocromil sodium
—> Sodium cromoglycate
—> **Leukotriene receptor antagonist (LTRA) (Montelukast)
—> **Anti-IgE (Omalizumab)
—> Other biologics (e.g. Anti-IL5)
- Prevention
- Patient education
***Bronchodilators
- Short-acting β2 agonists (SABA)
- Salbutamol (Ventolin)
- Terbutaline (Bricanyl) - Long-acting β2 agonists (LABA)
- Salmeterol (Serevent)
- Formoterol (Oxis) - Anticholinergic (Tiotropium (LAMA), Ipratropium (SABA))
- Xanthines (Theophylline)
- Short-acting β2 agonists (SABA)
- Use when necessary (PRN)
- Inhaled vs Oral
- Salbutamol (Ventolin)
- Terbutaline (Bricanyl)
SE:
- tremor, headache, tachycardia, arrhythmia (∵ ***sympathomimetic action)
- ↑ mortality with frequent use alone
- Long-acting β2 agonists (LABA)
- ***Regular use
- Prolonged bronchodilation: ***12 hours
- Salmeterol (Serevent)
- Formoterol (Oxis)
—> In combination with ***Low dose ICS (<800 ug/day) as an alternative to High dose ICS
***Anti-inflammatory preventors
- ***Inhaled / Oral steroids
- Beclomethasone (Becotide, Becloforte)
- Budesonide (Pulmicort)
- Fluticasone (Flixotide) - Nedocromil sodium
- Sodium cromoglycate (used in paediatrics)
- ***Leukotriene receptor antagonist (LTRA) (Montelukast)
- ***Anti-IgE (Omalizumab)
- Other biologics (e.g. Anti-IL5)
- Inhaled / Oral / IV steroids
Oral / IV steroids:
- used in Acute episodes (avoid long term use ∵ SE)
Inhaled steroids:
1. Beclomethasone (Becotide, Becloforte)
2. Budesonide (Pulmicort)
3. Fluticasone (Flixotide)
Benefits:
- Improve symptom control
- **↓ exacerbation
- **↓ mortality
- ***↓ lung function decline
Disadvantage:
- NOT an immediate bronchodilator
- take ***~1 week to work
(SE (UpToDate):
- Hoarseness
- Oral thrush
- Allergic contact dermatitis
- Systemic SE of steroids)
- Leukotriene receptor antagonist
Montelukast
- **Oral
- OD
- Mild to Moderate asthma
- Effective in **exercise-induced bronchospasm
- Effective in preventing aspirin-induced asthma, angioedema etc.
- **Steroid-sparing effect
- **Unmask previously undiagnosed ***Churg-Strauss syndrome (disorder marked by blood vessel inflammation) (∵ steroids mask Churg-Strauss syndrome)
- Anti-IgE Ab
Omalizumab
- Indicated in **Moderate - Severe asthma with suboptimal control despite **maximal ICS/LABA +/- LTRA / theophylline / steroid-dependent asthma
- ONLY for ***atopic asthma (i.e. elevated IgE + positive skin prick test)
SE:
- ***Anaphylaxis
***Guidelines for Asthma treatment
***GINA (Global Initiative for Asthma)
Controller:
Step 1: PRN Low dose ICS-Formoterol
Step 2: Daily Low dose ICS / PRN Low dose ICS-formoterol
Step 3: **Low dose ICS-LABA
Step 4: **Medium dose ICS-LABA
Step 5: ***High dose ICS-LABA (+/- add-on therapy e.g. Tiotropium, Anti-IgE, Anti-IL5/5R, Anti-IL4R)
Reliever:
- PRN Low dose ICS-Formoterol (ICS-LABA) / PRN SABA
GINA assessment of asthma control
Questionnaire
1. Symptom control
- **Daytime / Nighttime symptoms
- **Frequency of use of reliever
- ***Activity limitation
- Risk factors for poor asthma outcomes
Prevention of Asthma
- House dust mite avoidance (e.g. Atopic asthma)
- encasement of mattresses, pillows, duvets with vinyl covers
- hot water wash of all bedding regularly < 2 weeks
- remove carpets
- no stuffed toys
- cleaning of environments - Cat allergens
- remove cat
- hard surface floor
- remove upholstered furniture
- HEPA filter
- wash cat weekly
Patient education
- What is asthma
- What are triggers and how to avoid
- How drugs work
- How to use inhaler properly
- Necessary to use preventors regularly
- What to do during acute attack
- When to contact doctor / go to A/E
Monitoring of PEF (SpC FM)
Short-term monitoring:
- Following an exacerbation, to monitor recovery
- Following a change in treatment, to help in assessing whether the patient has responded
- If symptoms appear excessive (for objective evidence of degree of lung function impairment)
- To assist in identification of occupational or domestic triggers for worsening asthma control
Long-term monitoring:
- For earlier detection of exacerbations, mainly in patients with poor perception of airflow limitation
- For patients with a history of sudden severe exacerbations
- For patients who have difficult-to-control or severe asthma
