What are the first‑line inhaled corticosteroids for persistent asthma and their recommended dosing regimens?

First-Line Inhaled Corticosteroids for Persistent Asthma

Low-dose inhaled corticosteroids (ICS) are the preferred first-line controller medication for all patients with persistent asthma, with fluticasone propionate 100-250 mcg/day or budesonide 200-400 mcg/day administered twice daily providing optimal control with minimal systemic effects. 1

Recommended First-Line ICS Regimens

Adults and Adolescents ≥12 Years

• Fluticasone propionate 100-250 mcg/day (divided twice daily) is a preferred first-line option, delivering 80-90% of maximum therapeutic benefit at these low doses 1
• Budesonide 200-400 mcg/day (divided twice daily) is an equally effective alternative with a well-established safety profile 1, 2
• Beclomethasone dipropionate 200-500 mcg/day is another acceptable first-line option 2
• For patients with adherence concerns, as-needed low-dose ICS-formoterol used concomitantly with SABA is an acceptable alternative to daily low-dose ICS 3

Children 5-11 Years

• Fluticasone propionate 100 mcg twice daily at age-appropriate dosing is recommended 1
• Budesonide 200-400 mcg/day is an appropriate alternative 2
• Low-dose ICS is the preferred Step 2 treatment for mild persistent asthma 3

Children Under 5 Years

• Daily low-dose ICS is the preferred option for mild persistent asthma (Step 2 care) 3
• Cromolyn and leukotriene receptor antagonists are available alternatives, though less effective than ICS 3
• For moderate persistent asthma (Step 3 care), either add long-acting beta2-agonists to low-dose ICS OR increase ICS to medium-dose range 3

Delivery Technique and Administration

• Use a spacer or valved holding chamber with metered-dose inhalers to increase lung deposition by 10-20% and reduce oropharyngeal side effects like thrush 1, 2
• Instruct patients to rinse mouth and spit after each inhalation to further minimize local adverse effects 1
• Verify proper inhaler technique before considering dose escalation, as poor technique is a common cause of apparent treatment failure 1

When to Step Up Therapy

Indicators for Treatment Intensification

• SABA use >2 days/week for symptom relief (excluding exercise prevention) indicates inadequate control requiring step-up 1, 2
• Nighttime awakenings due to asthma symptoms 2
• Persistent daytime symptoms despite optimal inhaler technique 3

Preferred Step-Up Approach

• Add a long-acting beta2-agonist (LABA) to low-dose ICS rather than increasing ICS dose alone for patients ≥12 years with moderate persistent asthma 3, 4, 1
• This combination provides greater improvement in lung function (weighted mean difference 0.12 L/sec), symptoms, and exacerbation reduction compared to doubling ICS dose 5
• Fluticasone/salmeterol 250/50 mcg twice daily or budesonide/formoterol 200/6 mcg twice daily are preferred combination options 4, 2

Critical Safety Warning

• LABAs must NEVER be used as monotherapy for asthma because this increases risk of severe exacerbations and asthma-related deaths 3, 4, 1, 2
• LABAs must always be combined with ICS in a single inhaler or as separate inhalers 1, 2

Alternative Controller Options (Less Preferred)

• Leukotriene receptor antagonists (montelukast 10 mg once daily for adults; 5 mg for children 6-14 years) are appropriate alternatives for mild persistent asthma, though less effective than ICS 2, 6
• Meta-analysis demonstrates ICS superiority over montelukast with weighted mean difference of 4.6% predicted FEV1 and 5.6% more asthma control days 6
• Theophylline is the least preferred option due to side effect profile and need for serum monitoring (target 5-15 mcg/mL) 3, 4, 1

Monitoring and Follow-Up

• Assess treatment response within 2-6 weeks of initiating therapy 1
• If no clear benefits within 4-6 weeks, stop treatment and consider alternative therapies or diagnoses 3
• Once asthma control is sustained for 2-4 months, step down therapy to the minimum dose required to maintain control 1, 2
• Continue monitoring for at least 3 months of stable control before considering further dose reduction 1

Common Pitfalls to Avoid

• Do NOT increase ICS dose short-term for worsening symptoms in adherent patients ≥4 years with mild-moderate asthma, as this provides no benefit 3
• Do NOT start with high-dose ICS, as this provides no clinically meaningful advantage over low-dose ICS (only 5% improvement in FEV1) 2
• Do NOT use intermittent ICS as equivalent to daily ICS—daily treatment is superior for lung function, airway inflammation, and asthma control 7
• Verify medication adherence and address environmental factors before escalating therapy 1, 2

Evidence Supporting Early ICS Initiation

• Low-dose ICS reduces risk of severe asthma-related events similarly across all symptom frequency subgroups, including patients with symptoms ≤2 days/week (hazard ratio 0.54; 95% CI 0.34-0.86) 8
• ICS are the most effective single long-term controller medication, superior to leukotriene modifiers, theophylline, or cromones 1, 9
• ICS improve lung function, reduce symptoms, prevent exacerbations, and may reduce asthma mortality 9