Systemic Corticosteroids in Respiratory Disease

Systemic corticosteroids treat acute exacerbations of asthma and COPD and several other respiratory conditions. They act by genomic anti-inflammatory effects, with onset in 4 to 6 hours and peak effect at 12 to 24 hours, and have no immediate bronchodilator effect.

Mechanism. The drug binds the glucocorticoid receptor, reduces inflammatory gene expression and raises anti-inflammatory gene expression. It restores beta 2 receptor responsiveness and reduces eosinophilic inflammation, mucus and oedema.

Pharmacokinetics. Prednisolone is the active form of prednisone, which requires hepatic activation, so prednisolone is preferred in liver disease. Oral absorption is near complete.

Differences. Oral dosing is as effective as intravenous dosing. Intravenous route is for vomiting, inability to swallow or impending respiratory failure. Dexamethasone has the longest action and is used for short courses in children and croup.

Representative regimens.

• Acute asthma in adults: prednisolone 40 to 50 mg orally once daily for 5 to 7 days, given within 1 hour of presentation in severe attacks. If oral dosing is impossible, hydrocortisone 100 mg intravenously every 6 hours.
• Acute asthma in children: prednisolone 1 to 2 mg/kg once daily to a maximum of 40 mg for 3 to 5 days. Dexamethasone 0.6 mg/kg (maximum 16 mg) as one or two doses is an alternative.
• COPD exacerbation: prednisolone 30 to 40 mg orally once daily for 5 days. Longer courses add harm without benefit.
• Croup: dexamethasone 0.15 mg/kg orally as a single dose, with up to 0.6 mg/kg in severe croup.
• Pneumocystis pneumonia with hypoxaemia (arterial oxygen under 9.3 kPa or 70 mmHg on air): prednisolone 40 mg twice daily on days 1 to 5, 40 mg once daily on days 6 to 10, and 20 mg once daily on days 11 to 21, started within 72 hours of antimicrobial treatment.
• COVID-19 needing oxygen: dexamethasone 6 mg once daily orally or intravenously for up to 10 days. It is not advised without hypoxaemia.
• Chronic conditions (sarcoidosis, organising pneumonia, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, interstitial lung disease flares) use specialist-directed prednisolone, starting at 0.5 to 1 mg/kg daily and tapering over months.

Tapering. Courses of 3 weeks or less need no taper. Longer courses are tapered, with adrenal suppression assumed.

Timing. Give oral doses in the morning.

Adverse effects. Hyperglycaemia, hypokalaemia, fluid retention, hypertension, insomnia, mood disturbance and psychosis, dyspepsia, myopathy and immunosuppression. Long courses cause osteoporosis, cataract, skin thinning and adrenal suppression.

Infection risks.

• Tuberculosis can reactivate, so check for latent infection before prolonged courses.
• Strongyloides hyperinfection is fatal and occurs in endemic tropical regions, including East Africa. Consider presumptive ivermectin 200 mcg/kg once daily for 2 days before prolonged courses in at-risk patients, especially with eosinophilia.
• Hepatitis B can reactivate.
• Kaposi sarcoma can flare in HIV infection.

Interactions. Rifampicin, phenytoin and carbamazepine induce metabolism and lower prednisolone effect, so higher doses may be needed. Ritonavir, cobicistat, itraconazole and clarithromycin raise methylprednisolone and dexamethasone exposure. NSAIDs add ulcer risk, diuretics add hypokalaemia, and warfarin control may change. Live vaccines are avoided at 20 mg daily or more of prednisolone for more than 14 days.

Monitoring. Glucose (raise insulin in diabetes), blood pressure, potassium, mood and sleep. For courses over 3 months at 7.5 mg daily or more, give calcium and vitamin D and consider bisphosphonate and gastric protection.

Special groups. Pregnancy: prednisolone is acceptable, as the placenta inactivates most of it, and dexamethasone crosses to the foetus. Watch for gestational diabetes. Breastfeeding: acceptable, and feeding 4 hours after doses over 40 mg reduces infant exposure. Children: short courses are safe, and repeated courses affect growth. Older adults: hyperglycaemia, delirium and fracture risk. Hepatic impairment: use prednisolone, not prednisone. Renal impairment: no adjustment.

Referral and escalation. Two or more oral corticosteroid courses in a year for asthma needs review of control, adherence and step-up, and specialist assessment for severe asthma and biologic treatment. After more than 3 weeks of treatment, give a steroid card, advise sick day rules, and treat adrenal crisis with hydrocortisone 100 mg intravenously.