Asthma

• Asthma is a heterogenous disorder characterized by airway inflammation, airway hyperresponsiveness, and paroxysmal symptoms like dyspnea, chest tightness, wheezing, sputum production, and coughing
• It is a chronic condition
• Symptoms may be intermittent

Pathophysiology

• Chronic airway inflammation involves "allergic asthma" (80% of patients) due to environmental allergens and T helper 2 lymphocyte infiltration
• "Non-allergic asthma" results from inflammatory responses to irritants or neutrophilic infiltration
• Airway hyperresponsiveness is exaggerated bronchoconstriction in response to stimuli, with poorly understood pathophysiology involving genetics, airway muscle physiology, inflammation, and structural changes

Epidemiology

• Lifetime prevalence is about 10% in Canada, with ~20% in children/adolescents.
• Global prevalence is between 1-18%, with increasing rates in resource-rich countries.
• Increasing prevalence is linked to "hygiene hypothesis", sedentary lifestyles, and increased indoor time

Clinical Diagnosis

• Diagnosis includes respiratory symptoms such as dyspnea, chest tightness, wheezing, sputum production, and/or coughing
• Symptoms can be worse at night
• Symptoms vary over time
• There are common triggers including allergens, extreme weather, exercise, viral infections and irritants
• Concomitant atopy is present 80% of the time
• There must be objective evidence of reversible airway obstruction
• Documented improvement with SABA (+/- corticosteroids) in children 1-5 years
• Spirometry

Spirometry

• A gold standard pulmonary function test (PFT) used
• Measures forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC)
• Measures reversibility of airflow limitation with post-bronchodilator FEV₁
• Not usually performed on children < 6 years without proper instruction
• Ideally done prior to controller therapy
• A decrease of 10-15% post-exercise shows Asthma

Medications

Relievers

• Short-acting inhaled beta agonists (SABA) like salbutamol and terbutaline
• Induce airway smooth muscle relaxation (B2 activation); onset in 5-8 minutes, duration of 3-6 hours
• Used PRN to RELIEVE symptoms
• Adverse effects: nausea, tremor, anxiety, tachycardia, hypokalemia

Controllers

• Inhaled corticosteroids (ICS) such as fluticasone, ciclesonide, and mometasone
• Reduce airway inflammation; taken on a daily bases
• Adverse effects: oral candidiasis, dysphonia, decreased growth velocity, adrenal suppression
• Other controllers are long-acting beta agonists (LABA), long-acting muscarinic antagonists (LAMA), and leukotriene receptor antagonists (LRTA)

Other Medications Used

• Ipratropium is a short-acting muscarinic antagonist (SAMA) that is used in the context of an exacerbation in combination with salbutamol
• There is no evidence for extended use beyond ED
• Adverse effects is dry mouth and blurry vision
• Magnesium sulfate is administered intravenously in severe exacerbations to induce bronchodilation and reduce ED admissions
• The NNT is 5

Systemic Corticosteroids

• Used in the initial treatment of moderate to severe exacerbations
• Decrease inflammatory mediators; should be administered as soon as possible in at triage
• Delayed onset of action; short-term adverse effects is insomnia, mood changes, GERD, increased appetite, hyperglycemia, and increased WBCs
• Long-term adverse effet is adrenal suppression

Systemic Dosing

• Dexamethasone dose is 0.3-0.6 mg/kg/dose PO daily for 1-2 days, up to 12-16 mg
• Prednisone dose is 1 mg/kg/dose PO daily for 5 days, up to 50 mg

Well-Controlled Asthma

• Daytime symptoms ≤ 2 days/week, nighttime symptoms < 1 night/week and mild, normal physical activity, mild/infrequent exacerbations, and no absence from work/school
• ≤ 2 doses per week of reliever, FEV1 or PEF ≥ 90% of personal best, PEF diurnal variation < 10-15%, sputum eosinophils < 2-3%
• If 1+ criteria is not met, consider poorly controlled

Assessment of Severity

• Defined by medication intensity required to maintain control
• Not defined by initial diagnosis
• Table outlines asthma severity classifications of Very mild, Mild, Moderate and Severe

Initial Pharmacotherapy in Children

• Reliever: Salbutamol 100 mcg/puff 1-2 puffs q4-6h PRN administered via spacer with face mask (for < 5 years)
• Controller: Decision based on the level of control and risk of exacerbation
• Start early for lung function
• Prefer low does of ICS

Choice of Inhaled Corticosteroid – Pediatrics

• Ciclesonide: Not labeled for children < 6 years
• Multiple strengths available for Fluticasone dosages

Asthma Exacerbations (Flare-Ups)

• Defined as acute or subacute deterioration of symptom control
• Can occur at the first presentation
• Mild: Increased asthma symptoms not requiring systemic corticosteroids, ED visit, or hospitalization
• Moderate to severe: Increased asthma symptoms requiring the above
• Risk factors: Previous severe exacerbation, poorly controlled asthma, use of >2 SABA inhalers, or current smoker
• Red flags: Reliever lasts <3 hours, unable to speak/walk normally, nasal flaring, continuous wheeze/cough, drowsiness, agitation, or confusion

Goals of Therapy for Exacerbations

• Resolve patient-specific symptoms, prevent admission/mortality, minimize adverse effects, and prevent relapse
• Treat on an individualized basis with a written asthma action plan

Management of Exacerbations - Mild

• Increase reliever or controller
• Increase SABA to q4-6h x 1-2 days before contacting MD
• Systemic corticosteroids if symptoms worsen or do not respond to increased dose

Management of Exacerbations - Moderate to Severe in Pediatrics

• Based on severity as indicated by PRAM score
• Ranges between Supportive Care to Nebulized Medication, Corticosteroids, Magnesium Sulfate and 0.9% Sodium Chloride

Systemic Corticosteroids: Dosing

• Dexamethasone: Dose 0.3-0.6 mg/kg/dose PO daily, Duration 1-2 days
• Prednisone: Dose 1 mg/kg/dose PO daily, Duration 5 days

Choice of Systemic Corticosteroid – Dexamethasone?

• Clinical practice: I day for ED, and 2 days for inpatients.

Nebules vs. MDI (+ Spacer)?

• All doses of MDI should be delivered via spacer/VHC
• Metered dose inhaler (MDI)
• ↓ admission to hospital
• ↓LOS
• ↓ adverse effects
• ↓ cost
• ↑ patient & family satisfaction

Initial Maintenance Pharmacotherapy In Children

• Reliever (PRN)
  • Salbutamol 100 mcg/puff 1-2 puffs q4-6h PRN
  • All MDIs should be administered via spacer device
  • Availability of Terbutaline for Turbuhaler

Discharge Criteria from ED/Hospital

• Key to focus of this is preventing relapse, readmission and future exacerbations
• Continue salbutamol for 24 hours, provide asthma action plan, and do patient education

Interventions to decrease re-admissions

• Provide comprehensive asthma education
• Based on 7-item NIH checklist

Pneumococcal Polysaccharide Vaccine (PPV-23)

• Recommended for patients at high-risk of invasive pneumococcal disease (IPD; bacteremia, meningitis)
• NACI recommends PPV-23 for patients with asthma requiring medical care within the previous 12 months

Medications for Pharmacologic Therapy

• Beta2–Agonists relax airway smooth muscle, while LABA single entity has discouraged/rarely used
• Inhaled Corticosteroids (ICS)
  • Asthma symptoms, Lung function, Quality of life, and related hospitalizations and death are effective
  • Common ADR: Oropharyngeal candidiasis and dysphonia
• Leukotriene Receptor Antagonists
  • The MOA acts by targeting one part of the inflammatory pathway in asthma
  • Only one option in Canada with Montelukast is available
  • The Boxed Warning is: Neuropsychiatric (NP) effects

Pregnancy & Breastfeeding

• Maintaining good control of asthma symptoms is VERY important for pregnant patients.
• Risks of (poorly controlled) Asthma in Pregnancy: ↑ perinatal mortality,↓ birth weight, preterm delivery, fetal hypoxia.
• Medication Choices: It must be emphasized that the risk of poor outcomes due to uncontrolled asthma is vastly higher than the risk posed by asthma medications
• Salbutamol preferred SABA in pregnancy and ICS is reasonable