What is the recommended treatment regimen for a patient with severe persistent asthma?

Treatment of Severe Persistent Asthma

For severe persistent asthma, initiate high-dose inhaled corticosteroids combined with long-acting beta2-agonists as the foundation of therapy, and add oral systemic corticosteroids (1-2 mg/kg/day, generally not exceeding 60 mg/day) if control cannot be achieved or maintained with this combination alone. 1

Foundation Therapy

• High-dose inhaled corticosteroids provide the most effective anti-inflammatory action and form the cornerstone of severe persistent asthma treatment. 1
• Long-acting beta2-agonists must be added to high-dose inhaled corticosteroids as standard combination therapy—never use LABAs as monotherapy, as this is contraindicated and increases risk of severe exacerbations and death. 1, 2
• The combination of fluticasone propionate/salmeterol (available in strengths of 100/50,250/50, and 500/50 mcg) delivers both anti-inflammatory and bronchodilator effects in a single device, which may improve adherence. 3

When Initial Combination Therapy Fails

If patients cannot achieve or maintain control with high-dose ICS/LABA, add oral systemic corticosteroids at 1-2 mg/kg/day (maximum 60 mg/day). 1 This represents Step 5 therapy and should be implemented before considering other add-on agents.

Alternative Add-On Options (Before Oral Corticosteroids)

• Leukotriene receptor antagonists (e.g., montelukast) can be added to ICS/LABA, though this combination is less effective than ICS/LABA alone compared to ICS plus leukotriene modifiers. 4, 5
• Tiotropium (long-acting anticholinergic) has demonstrated effectiveness in several asthma subgroups when added to ICS/LABA. 6
• Theophylline is a less preferred option due to its side effect profile and need for monitoring. 5

Acute Exacerbation Management

For severe persistent asthma patients experiencing acute exacerbations (defined by inability to complete sentences, respiratory rate ≥25/min, heart rate ≥110/min, PEF <50% predicted):

• Administer nebulized salbutamol 5 mg or terbutaline 10 mg with oxygen as the driving gas (40-60%). 7
• Give prednisolone 30-60 mg orally or hydrocortisone 200 mg IV immediately. 7
• Add ipratropium bromide 250-500 mcg nebulized if life-threatening features present or inadequate response after 15-30 minutes. 7
• Consider aminophylline 250 mg IV over 20 minutes for life-threatening exacerbations (caution if patient already on theophyllines). 7

Rescue Medication

• All patients with severe persistent asthma require short-acting beta2-agonists available for symptom relief as needed. 1
• If no nebulizer available during acute exacerbation, administer 2 puffs of beta-agonist via large volume spacer and repeat 10-20 times. 7

Monitoring Requirements

• Regular monitoring for symptom control and medication side effects is essential. 1
• Patients should have their own peak flow meter with self-management plan. 7
• Consultation with an asthma specialist is strongly recommended for all patients with severe persistent asthma. 1
• Before prescribing long-term nebulized bronchodilator therapy for chronic persistent asthma, demonstrate clinically useful bronchodilation with a home trial monitoring peak flow—require ≥15% increase from baseline before recommending treatment. 7

Critical Pitfalls to Avoid

• Never use long-acting beta2-agonists without inhaled corticosteroids—this is contraindicated and increases mortality risk. 1, 2
• Do not underestimate severity based on absence of wheezing—a "silent chest" with feeble respiratory effort indicates life-threatening asthma. 7
• Avoid delaying systemic corticosteroids in acute exacerbations—underuse of corticosteroids is a major factor in preventable asthma deaths. 7
• Before escalating therapy, verify proper inhaler technique, medication adherence, and address comorbidities that may worsen asthma control. 6

Hospital Admission Criteria

Admit patients with any of the following:

• Life-threatening features (PEF <33% predicted, silent chest, cyanosis, bradycardia, confusion, exhaustion, or coma). 7
• Features of acute severe asthma persisting after initial treatment, especially PEF <33%. 7
• Recent hospital admission, previous severe attacks, or afternoon/evening presentation. 7

Discharge Planning

Before hospital discharge, ensure:

• Patient has been on discharge medication for 24 hours with verified inhaler technique. 7
• PEF >75% of predicted or best with diurnal variability <25%. 7
• Treatment includes oral steroid tablets and inhaled steroids plus bronchodilators. 7
• GP follow-up arranged within 1 week and specialist follow-up within 4 weeks. 7