Management of Asthma

Abstract 100 years ago, the main treatments for asthma were the sympathomimetic ephedrine derived from the Chinese herb Ephedra sinica, theophylline tablets derived from tea leaves and cocoa beans, inhaled anticholinergics stramonium and atropine derived from Datura and Belladonna species in the form of “asthma cigarettes,” together with adrenaline injections for acute exacerbations. These treatments were all bronchodilators derived from natural products and evolved into the treatments we use today. Desiccated adrenal gland extract was found to be beneficial in asthma in 1900, and epinephrine (adrenaline) was isolated in 1901. Epinephrine injections led to nebulised adrenaline, which evolved into inhaled β2-agonists as the most effective bronchodilators in asthma. Short-acting inhaled β2-agonists (SABA), such as salbutamol and terbutaline, were developed in the early 1970s and remain the most widely used asthma treatments worldwide. In the 1990s, the long-acting inhaled β2-agonists (LABA) that last over 12 h, salmeterol (slow onset) and formoterol (rapid onset), were developed. In the 2000s, ultra-LABAs, such as indacaterol and vilanterol, that are given once daily became available. But overuse of inhaled β2-agonists was linked to worse asthma control and increased mortality because they do not treat the underlying airway inflammation. The efficacy of orally administered desiccated adrenal glands in the treatment of asthma is most likely explained by steroids derived from the adrenal cortex, since epinephrine from the adrenal medulla is not absorbed after oral ingestion. Corticosteroids are by far the most effective treatment for asthma and target the underlying eosinophilic airway inflammation. Because severe side effects with oral corticosteroids are a major problem, this led to the development of the topically active inhaled corticosteroid beclomethasone propionate in 1970, and subsequently to the safer fluticasone propionate and budesonide. Inhaled corticosteroids have revolutionized the management of asthma as they improve symptoms, prevent exacerbation, and markedly reduce mortality. Combination inhalers containing an inhaled corticosteroid and long-acting inhaled β2-agonist are now the mainstay of asthma therapy. Recently, short-acting β2-agonists as relievers are being replaced by relievers containing an inhaled corticosteroid, together with the rapid onset long-acting inhaled β2-agonists formoterol (anti-inflammatory reliever). This addresses the major issue of poor adherence with inhaled corticosteroids and overuse of β2-agonists. Poor inhaler technique is also a major cause of poor asthma control in the real world and is being addressed with the development of smart inhalers that monitor effective inhaler use and timing. In patients with severe eosinophilic asthma who are not controlled by maximal inhaled therapy, antibodies (given by subcutaneous injection) that block cytokines involved in eosinophilic inflammation (anti-IL-5, anti-IL-4Rα, anti-TSLP) have been very effective and markedly reduce the need for oral corticosteroids. In the future, longer-acting antibodies will simplify the treatment of these patients. Theophylline and inhaled anticholinergics have turned out to be less useful treatments in asthma as they are less effective bronchodilators than β2-agonists, although low-dose theophylline has anti-inflammatory effects. New drugs are also in development for severe non-eosinophilic asthma, which is predominantly neutrophilic. There have been remarkable advances in asthma therapy over the last century, although our current treatments have their origins in the therapies used in 1925.