Definitions

1. Asthma is a chronic inflammatory condition associated with reversible hyperreactivity of the intra-pulmonary airways. May be extrinsic (allergic) or intrinsic.

Chronicity	Days with symptoms	Nights with symptoms	Peak flow
Mild intermittent or Infrequent episodic	<2x per week or sig.episodes >6wks apart	<2x per month	>80%
Mild persistent or Frequent episodic	3 – 6x per week or sig.episodes <6wks apart	>2x per month	>80%
Moderate persistent	Daily, multiple ED pres	>1x per week	60 – 80%
Severe persistent	Continual	Frequent	<60%

Epidemiology

1. Prevalence in Ausralia: 5–10% Adults, ~15% Children – higher in ages 2–6y (?from including misdiagosed viral-associated wheeze) – recently falling. 9% of US children.
2. M>F children but more F persist into adulthood
3. FamHx, maternal smoking & atopy associations
4. Higher incidence in developed countries, but possibly more severe in less developed ones
5. ? Breast feeding protective

Risk Factors

RF for exacerbation

1. Viruses esp recent upper respiratory infection
2. Allergy – contact with animals with fur and/or feathers, house dust mites (in mattresses, pillows, furniture, carpets) or pollen exposure
3. Airborne chemicals or irritants incl perfumes, exposure to smoke
4. Changes in weather
5. Exercise
6. Strong emotional expression (laughing or crying)
7. Drug exposure (aspirin, beta blockers)
8. Food additives/preservatives, e.g. tartrazine dye

RF for death

1. Labile asthma – sudden severe attacks
2. History in past 12mo of any of:
   1. >3 ED visits, >2 hospitalisations, or ICU adm
   2. Intubation
   3. Recent withdrawal from PO steroids or current use of PO steroids,
   4. Co-morbidities such as cardiac disease, HIV, psychiatric disease
   5. Illicit drug use
   6. Poor patient perception of airflow obstruction and its severity

Pathophysiology

1. Initial spastic bronchoconstriction
2. Release of inflammatory mast cell mediator (e.g. histamine, PGD2, LTC4, LTD4, and LTE4) → mucous hypersecretion, mucosal oedema, increase in bronchial smooth muscle tone
3. Finally inflammatory & immune cell (eosinophils, basophils, neutrophils & T-helper cells) infiltration, exacerbating these changes which narrow the intrathoracic airways

Complications

1. Pneumothorax, pneumomediastinum, pneumopericardium, subcut emphysema
2. Mucous plugging, segmental atelectasis
3. Nosocomial pneumonia
4. Respiratory failure
5. Drug toxicity, electrolyte disturbance (↓K , ↓PO4,↓Mg2 )
6. Anoxic brain injury, death
7. Others: MI, BSL, lactic acidosis,

Clinical Features

History

1. Asthma pattern, triggers, Cx & Mx (inhaler & PO steroids freq, hospital admissions, PEFR)
2. This episode:
   1. Assess possible precipitants & RF for death
   2. Presence of typical symptoms for patient (cough, wheezing, dyspnoea, chest tightness)
   3. Onset and the duration of symptoms
   4. What Rx given so far
   5. FamHx, Allergies, Other PMHx incl atopy, other medications, smoking/rec drugs

Examination

1. Vital signs (HR, BP, RR, T, SaO2)
2. Decide on likely severity:
   1. Mild: Cough, wheeze, no respiratory distress, active, talks in sentences, PEFR/FEV1 >60% pred, SaO2>94%
   2. Moderate: Cough, wheeze, mild respiratory distress, reduced activity, talks in phrases, may have pulsus paradoxus, PEFR/FEV1 40–60% pred, SaO2 90–94%
   3. Severe: Marked respiratory distress, unable to feed/single words, reduced breath sounds, pulsus paradoxus, cyanosis, PEFR/FEV1 <40% pred if capable, , SaO2<90%
   4. Life-threatening: Exhaustion (feeble respiratory effort), decreased LOC, silent chest, bradycardia, hypotension, PEFR/FEV1 unable to perform, SaO2<80%

Investigations

1. Oximetry – doesn’t always correlate with degree of alveolar hypoventilation.
2. PEFR if >5y (~[5 x Height/cm] – 400 l/min in children) – effort/technique dependent, not greatly useful in acute setting, but may be of use to highlight dips or monitor Rx.
3. FEV1 – For older child & adult
4. Arterial blood gas if severe to look for rising PCO2 & exhaustion
5. U&E – if iv salbutamol to be used (checking for hypokalaemia)
6. [CXR – if severe, high Temp, PTX suspected, 1st presentation, focal signs, not improving]

Differential Diagnosis

1. Episodic viral wheeze
2. CF, bronchiolitis or bronchitis, COAD, pneumonia
3. Anaphylaxis
4. Cardiac asthma
5. FB ingestion, croup & upper airway obstruction
6. Neoplasm or carcinoid syndrome
7. Recurrent PE
8. Systemic vasculitis involving the lungs

Management

1. O2 (60–100%) to maintain SaO2>94%. ?Consider high-flow in sev children.
2. Mild: Inh salbutamol. Then if chest not clear or still distressed → Moderate, else d/c.
3. Moderate: Inh salbutamol x 3 q20min prednisolone. If no improvement → Severe
   1. If partial improvement: continue stretching salbutamol q1–4h, r/v before each due dose.
   2. Admit if not progressing sufficiently to d/c.
   3. Otherwise (for Mild & Moderate) when clear/undistressed at 3–4hr post-dose & PEFR>60%: r/v technique, d/c on inh salbutamol q4h for 1–2 days and taper, ± 3 day prednisolone course, formal asthma Mx plan, f/u appt.
4. Severe: Cont. neb salbutamol through high flow O2. Add ipratropium. Get IV access. Take ABG, bloods & consider CXR. IV magnesium ± salbutamol. Give IV steroid. Admit HDU.
5. Life-threatening: As for Severe.
   1. IV salbutamol. Beware SIADH/↓K /↑lactate**.
   2. Consider CPAP or in extremis: IPPV, adrenaline, aminophylline, ketamine/GA. Adm ICU.
6. Antibiotics: Not routinely indicated. Consider only if likely bacterial infection.

Acute Drug Summary

1. Short acting β-agonists – first line. E.g. salbutamol, terbutaline, adrenaline
   1. Inh salbutamol – minimises systemic effects (SE: ↑HR, tremor, headache, ↓K ).

      Pat. gets 10% neb dose. NB. Oral β-agonists not effective in asthma.

      1. (<20kg) 4–6 puffs inhaled via spacer/MDI or 2.5mg neb q20min-q4h-prn
      2. (>20kg) 8–12 puffs inhaled via spacer/MDI or 5mg neb q20min-q4h-prn
      3. Continuous nebs 20ml/hr of 5mg/ml sol
   2. IV salbutamol (5mg/5ml) – no meta-analysis evidence for use in Severe. May → lactic acidosis & Q/V mismatch. Various regimes.
      1. Child: (15mcg/kg over 10min OR 5mcg/kg/min for 1hr) then 1mcg/kg/min
      2. Adult: bolus 5mcg/kg over 1min then infusion at 5–10mcg/kg/hr
   3. Adrenaline – α & β1 effects too. No good evidence better than selective agents.
      1. Moderate: 5ml 1:1000 Neb. Life-threatening: 0.1ml/kg 1:10,000 IM.
2. Corticosteroids – normally for 3–5d (if course<10d then do not need to taper)
   1. PO prednisolone init dose 2mg/kg/day then 1mg/kg/day PO (max 50mg)
   2. IV methylprednisolone 1mg/kg q6h (max 50mg) for 24h then bd for 24h then daily
   3. IV dexamethasone 0.15mg/kg to 8mg or IV hydrocortisone 4mg/kg to 200mg q6h
   4. High-dose inhaled CS may have some acute benefit, but growth SE in children
3. Anticholinergics – augments β-agonists in Severe. Debatable use for Moderate.
   1. Inh ipratropium bromide q20min x3 → q6h
      1. (<20kg) 4 x 20mcg puffs inhaled via spacer/MDI or 250mcg neb
      2. (>20kg) 8 x 20mcg puffs inhaled via spacer/MDI or 500mcg neb
4. If Severe and failure of standard Rx:
   1. IV MgSO4 50% 1.2–2.4g=10–20mmol (child 0.1ml/kg=50mg/kg=0.02mmol/kg) bolus over 20–60min (infusion 0.06ml/hr or nebs controversial). SE: ↓BP, ↓LOC.
   2. IV aminophylline – Narrow therapeutic range. (SE: vomiting, headache, abdo pain, palpitations, and intractable seizures )
      1. Adults: 5mg/kg over 30min (if not reg med) then infusion 0.6mg/kg/hr
      2. Children 5mg/kg over 30min, then 1mg/kg/hr
   3. Heliox: 60 %He:O2 mixture with lower density (& better flow) than air mixtures.
5. If Life-threatening and failure of standard Rx:
   1. IV ketamine 1–2mg/kg then up to 5–40mcg/kg/min infused for sedation/bronchodilation OR inh sevoflurane/isoflurane at 1–2% inspired conc.

NIPPV/Mechanical Ventilation

1. BIPAP: CPAP ↓work of breathing and PS may improve gas exchange. May ↓need for ETT.
2. Intubation indications (last resort as high risk of barotrauma with PPV). Use cuffed ETT.
   1. Apnoea/cardiac arrest or decreased LOC
   2. Exhaustion or rising PCO2 despite maximal therapy
   3. Severe hypoxia or acidosis
3. RSI: Use ketamine if possible. Propofol or midazolam/fentanyl are alternatives.
4. Aim: Oxygenation without barotrauma from hyperinflation & auto-PEEP (both common)
5. Use
   1. Volume cycle ventilator or hand bag, not time-cycled
   2. Low RR (6–8bpm or half of normal for age)
   3. Low tidal volumes (5–6ml/kg)
   4. Long I:E ratio (1:3–6)
   5. Inspiratory flow rate 60–100L/min
   6. Minimal PEEP ≤ 5cmH2O (so no ↑hyperinflation)
   7. PAP<40cmH2O
   8. Permissive hypercarbia (up to pH 7.15 & PCO2 80mmHg) & aim SaO2>91%
   9. Sedate (fentanyl plus propofol or midazolam. Avoid morph→histamine) ± paralyse to prevent ↑PAP by patient agitation,
   10. If ↓BP hyperinflated , interrupt IPPV ?PTX ± apply external chest decompression

Non-acute therapies

1. Inhaled long acting β-agonists – salmeterol, eformoterol. Last about 12hrs.
2. Inhaled corticosteroids – Beclomethasone, budesonide, fluticasone. Can cont if on PO steroid.
3. Leukotriene receptor antagonists – PO montelukast 5–10mg OD. For chronic sev, exercise and aspirin-related asthma. ?Role in episodic viral wheeze. May spare steroid/ β-agonist use. Research continues for IV efficacy in acute exacerbations.
4. Cl- channel blockers – Sodium cromoglycate. Dry powder or MDI. Inhib. mast cell degranulation. Useful as prophylaxis in allergic or exercise-induced asthma.

Methylxanthines

1. Theophylline – small therapeutic window. SE incl N/V, arrhythmias, fits.
2. Chronic poor control or inability to tolerate steroids may req additional immunosuppression, e.g. cyclosporin or methotrexate. Alternatives include continuous SC terbutaline, anti-IgE monoclonal antibody omalizumab q2–4weekly or four weekly SC
3. New therapies: vaccine against IL–13, omalizumab (anti-IgE monoclonal Ab), Chinese herbs

Prognosis

1. Overall mortality <2% of presentations, increases to >10% if req. mechanical ventilation.
2. Reduced childhood growth, usually as a result of poor control.
3. Inhaled steroids >400mcg (beclometasone) or >200mcg (fluticasone)/day may slow growth velocity but not affect attainment of normal height.
4. Doses >800mcg/day (beclometasone) or >400mcg (fluticasone)/day may risk adrenal suppression.
5. Absence from school and educational disadvantage

Prevention

1. Address RF for exacerbations & avoidance of precipitants.
2. Asthma education
3. Stress compliance with Rx, preventers and asthma Mx plan.