What are the recommended inhaled corticosteroids (ICS) and laboratory tests for moderate to severe asthma?

Recommended Inhaled Corticosteroids and Laboratory Tests for Moderate to Severe Asthma

Inhaled Corticosteroid Selection

For moderate to severe asthma, the preferred treatment is low-to-medium-dose inhaled corticosteroids (ICS) combined with a long-acting beta2-agonist (LABA), not ICS monotherapy. 1, 2

First-Line ICS/LABA Combinations

• Fluticasone propionate/salmeterol (Advair) is the most extensively studied combination, with doses of 100-250 mcg/day fluticasone for moderate asthma 3, 4
• Budesonide/formoterol (Symbicort) can be used as both maintenance and reliever therapy (SMART protocol) for patients ≥12 years old, providing rapid symptom relief while maintaining anti-inflammatory control 1, 2
• Formoterol-containing combinations are preferred when using the SMART protocol due to rapid onset of action, unlike salmeterol which has delayed onset 2

Specific Dosing Recommendations

For moderate persistent asthma:

• Fluticasone propionate: 100-250 mcg/day combined with LABA 3
• Budesonide: 180-600 mcg/day combined with LABA 3
• Beclomethasone dipropionate: Alternative option if first-line agents not tolerated 2, 3

For severe persistent asthma requiring step-up:

• Medium-to-high-dose ICS/LABA combinations (fluticasone 250-500 mcg/day or budesonide 600-1200 mcg/day) 1, 2
• Consider adding oral corticosteroids if inadequate control persists 1

Critical Safety Warning

Never prescribe LABA as monotherapy for asthma—this is associated with increased risk of asthma-related death. 5, 2, 6 LABAs must always be combined with ICS to mitigate this risk 2, 6. The FDA label explicitly contraindicates LABA monotherapy based on the SMART trial, which showed a 4.37-fold increased relative risk of asthma-related deaths 6.

Alternative Treatment Options (Less Preferred)

If ICS/LABA combination is not suitable:

• Medium-dose ICS monotherapy is less effective than adding LABA but remains an option 1
• Low-to-medium-dose ICS plus leukotriene modifier (montelukast) is an alternative, though inferior to ICS/LABA for patients ≥12 years 5, 1
• Low-to-medium-dose ICS plus theophylline is least preferred due to side effect profile and need for serum monitoring 5, 1

Laboratory Tests for Moderate to Severe Asthma

Baseline Assessment

No routine laboratory tests are specifically required for initiating ICS therapy in moderate to severe asthma. However, certain tests should be obtained based on clinical context:

• Serum IgE level and allergen-specific IgE (RAST) or skin testing if considering biologic therapy (omalizumab) for patients ≥12 years with inadequate control on medium-to-high-dose ICS/LABA 2
• Complete blood count with differential to assess eosinophil count if considering eosinophilic phenotype or biologic therapies 2

Monitoring for ICS-Related Adverse Effects

For patients on high-dose ICS (>1 year duration) or frequent oral corticosteroid courses:

• Bone densitometry (DEXA scan) to assess for osteoporosis risk, particularly in perimenopausal women 5
• Slit-lamp eye examination to screen for posterior subcapsular cataracts 5
• Morning plasma cortisol or 24-hour urinary cortisol if clinical concern for hypothalamic-pituitary-adrenal (HPA) axis suppression, though this is rare with inhaled therapy 5

Monitoring for Theophylline (If Used)

• Serum theophylline concentration must be monitored if theophylline is added to ICS therapy, maintaining levels between 5-15 mcg/mL 5, 1

Treatment Algorithm

1. Confirm diagnosis and severity: Assess impairment (symptoms, rescue inhaler use >2 days/week, nighttime awakenings) and risk (exacerbation history) 5

2. Initiate low-to-medium-dose ICS/LABA combination as first-line therapy 1, 2

3. Assess response at 4-6 weeks: If no clear benefit, discontinue and consider alternative diagnoses or adjust therapy 5, 3

4. Step up if inadequate control: Increase to medium-to-high-dose ICS/LABA 1, 2

5. Consider add-on therapy for severe asthma: Add leukotriene modifier, or evaluate for biologic therapy (omalizumab, mepolizumab, benralizumab) based on phenotype 2

6. Step down once control achieved for 2-4 months: Reduce to lowest effective dose to minimize adverse effects 5

Common Pitfalls to Avoid

• Do not start with high-dose ICS monotherapy—combination therapy with LABA at lower ICS doses provides superior control with less systemic exposure 1, 7
• Do not prescribe salmeterol for as-needed use—it has delayed onset and is unsuitable for acute symptom relief 2
• Do not forget spacer/valved holding chamber with MDIs—reduces oropharyngeal deposition and local side effects like thrush 5, 2
• Instruct patients to rinse mouth after ICS use—minimizes oral candidiasis and dysphonia 5, 3
• Reassess if SABA use exceeds 2 days/week—indicates inadequate control requiring treatment intensification 5, 3