Wheezing conditions Flashcards
ASTHMA
Define and summarise asthma
Outline the epidemiology (number of chidren affected, trend in prevalence, risks for hospitalisation)
Asthma
Chronic inflammatory disease of the airways characterized by reversible airway obstruction and bronchospasm (non-infectious)
- History of respiratory symptoms- dry cough, SOB, expiratory wheeze, tachypnoea/WOB
- Decreased FEV1 to FVC ratio with bronchodilator reversibility on PFTs
Epidemiology
- Most common chronic disease in children
- In 2017–18, an estimated 10% (around 460,000) of Australian children aged 0–14 had asthma as a long-term condition.
Asthma was more common among boys aged 0–14 years (12%) compared with girls (7.9%) - AIHW
- Increasing prevalence despite improvement in diagnosis, management, therapies, especially in developed/urbanised countries - WHO
- 40,000 hospitalisations 2010-11, higher likelyhood if remote, Indigenous, lower SES, NESB
ASTHMA
Outline the triggers, pathophysiology & natural history of asthma
Triggers
1. Viral infections (rhinovirus most common)- school age
2, Allergen exposure- dust mite, pet dander, pollens, cockroach, mould
3. Irritant exposure- smoke/tobacco, dry/cold air, exercise, emotional stress, laughing
Pathophysiology
Airway obstruction caused by inflammation + bronchoconstriction and airway hyperresponsivity
1. Early phase (reversible)
- Smooth muscle hyperplasia (bronchi/bronchioles)
- Increased vascular permeability & increased mast cells/immune mediators
- Leads to airflow obstruction → increased resistance to airflow → restrictive disease (unable to expel air) → hyperinflation
- Uneven distribution throughout lungs, VQ mismatch
2. Late phase (irreversible)
- Oedema, scarring, fibrosis
- Thick mucus plugs, mucosal oedema, thickened BM
Mediators
- Th2 & Th 17 cells (atopy)- excessive
- Trigger/allergen → antigens presented by dendritic cells → Th2 cell → IL4 & IL5
- IL4: IgE antibodies (type 1 hypersensitivity) → mast cells (histamine, leukotriene, prostaglandin)
(Histamine stimulates bronchospasm, inflammation, oedema, - Leukotriene- bronchoconstriction/mucus thickening)
- IL5: eosinophils → release of leukotriene/cytokines
- Acetylcholine- bronchoconstriction - M3 receptors/increased secretions
Natural history
- Most episodic (30-70% will improve with time), some will have lifelong
- Disease severity in childhood corelates with outcomes in adulthood
ASTHMA
Define the risk factors and possible adverse outcomes of asthma. What risk factors are associated with adverse outcomes?
Causes
- Genetic
- Environment
- Hygiene hypothesis
- Early exposure to viruses/bacteria
Risk factors
- Atopy (allergic rhinitis, atopic dermatitis, food allergy/anaphylaxis)
- Previous ICU, poor compliance, interval symptoms
Adverse outcome associations
- Increased risk of exacerbations: uncontrolled symptoms, poor technique/inadequate dosing/lack of AAP, >1 severe episodes in a year, FEV <60% predicted, sputum/blood eosinophilia, low SES, smoke/air pollution/allergen exposure (+ freq viral illnesses), sudden onset
- Risk of life threatening events: food allergy (anaphylaxis)
- Fixed obstruction: severe asthma/several hospitalisations or PICU, bronchiolitis, smoke/pollution exposure
- Treatment related: Frequent oral/inhaled steroids, poor technique
ASTHMA
Outline common presenting symptoms of asthma. How is it diagnosed, what are some diagnostic tests?
What are some differential diagnoses?
- *Symptoms**
- Cough: persistent, occurs through night & early morning
- Difficulty breathing- SOB, increased WOB, irritability/restlessness, fatigue
- Wheeze
Interval symptoms: night time cough/sleep disturbance, early morning cough/wheeze, exercise induced cough, frequent bronchodilator use
- *Diagnosis**
- Usually clinical: recurrent/persistent wheeze, bronchodilator response, atopy/allergies, absence of alternative Dx, supportive investigations
- *Tests**
- Spirometry (>5yrs): FEV1 <80% predicted, FEV1/FVC <75% (varies with age), MMEF <67% & bronchodilator reversability FEV1 >12%
- PEFV not recommended
- CXR if suspecting other differentials- pneumonia, inhaled FB
- Fractional exhaled nitrous oxide (FeNO): supportive of diagnosis, suggests eosinophilic inflammation, helpful to rule out DDx
- Allergy/SPT: 80% positive SPT to HDM
- *DDx**
- Small airway calibre (benign): <6yrs
- Suppuritive lung disease- CF, bronchiectasis- clubbing
- FB: localised wheeze/decreased air entry, history of choking
- Cardiac failure: murmur, poor feeding, cyanosis, oedema
- Mediastinal mass: tracheal deviation
ASTHMA
How do we assess & manage acute asthma attacks?
Outline principles of treatment for acute asthma
Why can VQ mismatch occur with salbutamol administration?
- *Assessment**
- General appearance/mental state
- WOB
- SpO2, ability to talk
- Chest examination
- Wheeze not a good marker of severity
- *Supportive Mx**
- Oxygen for low SpO2 only (sats may be initially preserved with decreasing ventillation due to gas trapping)
- CPAP
- Intubation/ventillation at low pressures
Medications
- Salbutamol (ventolin/asmol): 6puffs <6yrs, 12 puffs >6yrs 20minly for 1hr (burst therapy), continuous nebulised salbutamol,
→ salbutamol toxicity (tachycardia, tachypnoea, metabolic acidosis, high lactate)
- Ipratropium Bromide (atrovent): 4 puffs <6yrs, 8 puffs >6yrs 20minly 1hr (once only)
- Steroids: (decreased duration of hospital stay)
oral- prednisolone 2mg/kg dose, 1mg/kg 2-3 days if ongoing salbutamol requirement, avoid in preschoolers
methylprednisolone: if severe- 1mg/kg Q6H
- Aminophylline: loading 10mg/kg IV max 500mg
- MgSO4- 50mg/kg over 20mins, ICU admission
- IV salbutamol other states
Nb: Prednisolone & VIW
Foster et al 2018 (Lancet):?Effect of prednisolone on length of hospital stay in 24-72mo with VIW in ED. RCT, double blind, placebo controlled trial- single centre- Perth WA. 624 treatment, 605 intention to treat (300 placebo/305 pred). Mean length 6h pred, 9h control.
- *VQ mismatch in salbutamol use**
- Transient worsening saturations, within first 30mins
- Increased perfusion to poorly ventilated areas of lung/diversion of perfusion from well ventilated lung
- Rx supplemental oxygen, arterial system should correct
ASTHMA
Outline principles of long term treatment of asthma
Goals: decreased frequency of symptoms + minimal side effects
- *Infrequent episodic asthma:** symptom free for up to 6 weeks, without symptoms between flares
- *Frequent episodic asthma:** flare ups >6weekly, no interval symptoms
- *Persistent asthma:**
- Mild: Day Sx 1x weekly, Night Sx 2x monthly
- Moderate: Day Sx daily, Night Sx weekly, sometimes impact activity/sleep
- Severe Day Sx daily, Night Sx daily, frequent impact on activity/sleep
Assessing quality of asthma control
- *- Good:** no limitation on activity, no night time symptoms, day symptom <2x per week, reliever <2x per week with good relief
- *- Partial:** mild limitation on activity/night sx, >2x day symptoms per week & need for reliever with good response
- *- Poor:** day symptoms >2x per week, ongoing sx despite reliver, impact on limitation/night sx
Principles
- Regular assessment, monitoring, education, management of contributing factors (environmental, comorbidities)
- Preventative Rx: interval symptoms, poor control, VIW over winter months
→ can use ICS, monteleukast, cromone, ICS & LABA, biologics
- Reliever (SABA)
- Reliever (SABA) + preventer - low dose (ICS/monteleukast/cromone)
- Reliever (SABA) + preventer- high dose (ICS/monteleukast/cromone) + LABA
SMART therapy:
Journal review SYGMA1/SYGMA2
3,360 pts, 12-65yrs, international, 1yr, severe asthma
- Compared budesonide/formoterol (symbicort) PRN w/ budesonide daily maintainence vs placebo (preventer only)
- Symbicort maintainence superior to PRN in weeks well controlled asthma
- Both had ~60% reduction in severe exacerbations compared to placebo
- PRN- reduced total steroid dose
77% lower in symbicory vs placebo, rate of exac similar in PRN vs maint
ASTHMA
Summarise common medications, dosages in asthma treatment - short term & long term use
(preventers/relievers) and their MOA
Mild/infrequent episodic
- *Salbutamol:** short acting beta agonist (SABA)
- B2 receptor stimulation → bronchodilation, (increased adenylate cyclase/cAMP leading to decreased Ca2+ at muscle, decreased contraction)
- Higher doses, less selective, B1 agonist (heart), tachycardia
- Side effects = tremor, palpitations, tachycardia, hyperactivity, hyperglycemia (high doses)
- Salbutamol toxicity (tachycardia, tachypnoea, metabolic acidosis, high lactate
- *Ipratropium Bromide:** anticholinergic (derivative of atropine)
- Blocks muscarinic acetylcholine receptors (decreased cGMP → decreased Ca2+ → decreased SMsc contraction)
- Non-specific
- Side effects= headache, nausea, taste changes, blurred vision, dizziness, urinary retention, constipation, palpitations
Preventers- frequent episodic, persistent
Inhaled corticosteroids
(fluticasone propionate, beclomethasone, budesonide, ciclesonide)
Decrease airway inflammation/hyperreactivity, activation of eosinophils, IgE/mast cell response, cytokine production and generation of prostaglandins/leukotrienes
- First line preventative treatment
- Needs review after 2-3mo after commencing
- Fluticasone 50-100mcg low dose, 100-250mcg high dose, 80-90%
- Local side effects = dysphonia, thrush (advise mouth washing)
- Systemic side effects (long term use) = adrenal suppression (N&V, dizziness, hypotension), cataracts, decreased bone density/poor growth, skin thinning, hyperactivity/insomnia
- *Monteleukast:** Leukotriene receptor inhibitor (LTb 3/ 4)
- Decreased smooth muscle contraction, inflammation
- Children >2yrs
- Alternative to ICS if frequent episodic/persistent, if unable to tolerate ICS, significant allergic rhinitis, strong concerns about ICS SFx
- Headache, abdominal pain, hallucinations/mood & behaviour changes, increased aggression
- *Cromone** (sodium cromoglycate): Mast cell inhibitor- inhibit IgE activity/histamine release
- Decreased inflammation/airways reactivity, no smooth muscle effects
- Inhaled
- Alternative to ICS/monteleukast, more complex regimen
- Cough, throat irritation, bitter taste, bronchospasm
Formoterol/salmeterol (LABA)
- B agonist
- Children >5, symptomatic despite ICS
- Only initiate if stable
- Possible concerns with increased mortality (phosphorylation and internalization of B2 receptor)
More severe:
- *Magnesium sulfate:** bronchial smooth muscle relaxation
- ?hypermagnesemia competitively blocks calcium channels on smooth muscle
- *Aminophylline:** theophylline derivative
- Decreased cA/GMP at smooth muscle → relaxation, decreased CD4+ T cell response/cytokines, increase diaphragm contractility
- N&V, diarrhoea, headache, insomnia, tremors, seizures, tachycardia/arrythmias
- *Omalizumab:** monoclonal antibody
- Targeted against IgE, reduced IgE mediated response to allergens (type 1 hypersensitivity)
- Moderate-severe allergic asthma
- SC 2-4 weekly
- Injection site reactions, anaphylaxis/urticaria, Churgg-Strauss- vasculitis, thrombocytopenia, MSK pain
Mepolizumab: monoclonal antibody
- Anti IL-5, decreased eosinophil production
- Maintainence therapy for severe asthma with eosinophilic phenotype >12yrs
- SC therapy 4 weekly
