Repurposing drugs as inhaled therapies in asthma.

For the first 40 years of the 20th century treatment for asthma occurred in response to an asthma attack. The treatments were given by injection or orally and included the adrenergic agonists adrenalin/epinephrine and ephedrine and a phosphodiesterase inhibitor theophylline. Epinephrine became available as an aerosol in 1930. After 1945, isoprenaline, a non-selective beta agonist, became available for oral use but it was most widely used by inhalation. Isoprenaline was short-acting with unwanted cardiac effects. More selective beta agonists, with a longer duration of action and fewer side-effects became available, including orciprenaline in 1967, salbutamol in 1969 and terbutaline in 1970. The inhaled steroid beclomethasone was available by 1972 and budesonide by 1982. Spirometry alone and in response to exercise was used to assess efficacy and duration of action of these drugs for the acute benefits of beta2 agonists and the chronic benefits of corticosteroids. Early studies comparing oral and aerosol beta2 agonists found equivalence in bronchodilator effect but the aerosol treatment was superior in preventing exercise-induced bronchoconstriction. Inhaled drugs are now widely used including the long-acting beta2 agonists, salmeterol and formoterol, and the corticosteroids, fluticasone, ciclesonide, mometasone and triamcinolone, that act locally and have low systemic bio-availability. Repurposing drugs as inhaled therapies permitted direct delivery of low doses of drug to the site of action reducing the incidence of unwanted side-effects and permitting the prophylactic treatment of asthma.