Inhaled Corticosteroids

Inhaled corticosteroids are the most effective anti-inflammatory controller treatment in asthma and are used in selected patients with COPD. They reduce airway inflammation, hyperresponsiveness and exacerbations, but they do not relieve acute bronchospasm.

Mechanism. The drug binds the cytoplasmic glucocorticoid receptor, which moves to the nucleus. It switches off inflammatory genes (cytokines, chemokines) by inhibiting NF-kB and AP-1 and switches on anti-inflammatory genes. It also increases beta 2 receptor expression.

Pharmacodynamics. Eosinophils, mast cells and T helper 2 cell infiltration fall, and mucosal oedema, vascular leak and mucus fall. Symptoms improve over days, and airway hyperresponsiveness improves over weeks to months. The dose response curve is flat, so most benefit comes at low to medium dose.

Pharmacokinetics. Lung deposition is 10 to 30 percent. The swallowed fraction undergoes first pass metabolism, and oral bioavailability is under 1 percent for fluticasone and mometasone, and about 10 percent for budesonide. Beclometasone dipropionate and ciclesonide are prodrugs activated in the lung. Fluticasone has the longest tissue retention and accumulates with high dose.

Approximate total daily doses in mcg for adults and adolescents.

Dosing frequency. Beclometasone, budesonide and fluticasone propionate are usually given twice daily. Ciclesonide, mometasone furoate and fluticasone furoate are given once daily.

Differences. Fluticasone and mometasone have the highest systemic potency at high doses. Budesonide and ciclesonide have lower systemic effect. Beclometasone is least affected by CYP3A4 inhibitors.

Asthma. Regular low dose is the first controller. Adding a long acting beta 2 agonist is preferred to raising an inhaled corticosteroid over a medium dose. High dose is specialist use, given as a time limited course. In mild asthma, low dose budesonide with formoterol taken as needed is an alternative to daily treatment.

COPD. Not used alone. Add to a long acting beta 2 agonist with a long acting antimuscarinic when exacerbations continue and the blood eosinophil count is 300 cells/microlitre or more. A count under 100 cells/microlitre argues against it, because pneumonia risk rises.

Technique. Use a spacer with pressurised inhalers and rinse the mouth and spit after each dose to reduce candidiasis and dysphonia.

Adherence. Daily use is needed, and benefit is lost within weeks of stopping.

Adverse effects. Oral candidiasis, dysphonia and cough are common. High dose causes adrenal suppression, bruising, cataract, glaucoma and lower bone density. In children, growth is slowed by about 1 cm in the first year, with about 1 cm lower adult height in long term follow-up. Pneumonia risk rises in COPD.

Adrenal suppression. Present at high doses. During severe illness or injury in such patients, give hydrocortisone 100 mg intravenously for suspected adrenal crisis.

Interactions. Ritonavir and cobicistat strongly inhibit CYP3A4 and markedly raise systemic fluticasone, budesonide and mometasone exposure, causing iatrogenic Cushing syndrome and adrenal suppression. In patients on boosted protease inhibitor regimens, prefer beclometasone. Itraconazole, ketoconazole and clarithromycin act similarly.

Special groups. Pregnancy: continue, as uncontrolled asthma harms the foetus. Budesonide has the most safety data. Breastfeeding: compatible. Children: lowest effective dose, spacer with face mask, and yearly height. Older adults: bruising, cataract and osteoporosis risk. Hepatic impairment: higher exposure with severe disease for budesonide and fluticasone.

Monitoring. Symptoms, exacerbations, adherence and technique each visit. Oral inspection for candidiasis. Yearly height in children. Eye and bone assessment with long term high dose.

Referral and escalation. Uncontrolled disease on medium to high dose combination therapy needs review of adherence, technique and diagnosis, then specialist assessment for severe asthma. Suspected adrenal crisis needs emergency treatment.