Disease-modifying anti-asthmatic drugs

Drugs available for asthma treatment in the first decades of the 20th century (sympathomimetic agents such as oral ephedrine, intravenous adrenaline, or inhaled epinephrine; anticholinergics such as inhaled scopolamine; methylxanthines such as oral caffeine or theophylline 1 von Mutius E Drazen JM A patient with asthma seeks medical advice in 1828, 1928, and 2012. N Engl J Med. 2012; 366: 827-834 Crossref PubMed Scopus (29) Google Scholar ) aimed at relieving acute and life-threatening airway obstruction, but did not target the underlying pathophysiology of asthma (which was unknown at that time) and were not intended to induce any long-term therapeutic benefit. Systemic glucocorticoids and inhaled short-acting beta-2 agonists were introduced in the 1950s with the same concept of symptom relief. 2 Schwartz E Oral cortisone therapy in intractable bronchial asthma. J Am Med Assoc. 1951; 147: 1734-1737 Crossref PubMed Scopus (8) Google Scholar , 3 Burrage WS Irwin JW The role of cortisone in the treatment of severe bronchial asthma. N Engl J Med. 1953; 248: 679-682 Crossref PubMed Scopus (1) Google Scholar , 4 Cander L Comroe Jr, JH A method for the objective evaluation of bronchodilator drugs: effects of dapanone, isuprel, and aminophylline in patients with bronchial asthma. J Allergy. 1955; 26: 210-218 Summary Full Text PDF PubMed Scopus (13) Google Scholar Additionally, systemic glucocorticoids were associated with severe adverse effects and inhaled short-acting beta-2 agonists were associated with increased mortality. 5 Ekström M Nwaru BI Hasvold P Wiklund F Telg G Janson C Oral corticosteroid use, morbidity and mortality in asthma: a nationwide prospective cohort study in Sweden. Allergy. 2019; 74: 2181-2190 Crossref PubMed Scopus (43) Google Scholar , 6 Pearce N Beasley R Crane J Burgess C Jackson R End of the New Zealand asthma mortality epidemic. Lancet. 1995; 345: 41-44 Summary PubMed Scopus (155) Google Scholar , 7 Inman WH Adelstein AM Rise and fall of asthma mortality in England and Wales in relation to use of pressurised aerosols. Lancet. 1969; 2: 279-285 Summary PubMed Google Scholar , 8 Johnston SL Edwards MR Mechanisms of adverse effects of {beta}-agonists in asthma. Thorax. 2009; 64: 739-741 Crossref PubMed Scopus (30) Google Scholar , 9 Spitzer WO Suissa S Ernst P et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med. 1992; 326: 501-506 Crossref PubMed Scopus (1060) Google Scholar , 10 Sears MR Taylor DR Print CG et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 1990; 336: 1391-1396 Summary PubMed Scopus (860) Google Scholar Cromones, available since the 1960s, 11 Howell JB Altounyan RE A double-blind trial of disodium cromoglycate in the treatment of allergic bronchial asthma. Lancet. 1967; 2: 539-542 Summary PubMed Google Scholar had an acceptable safety profile, but inferior efficacy compared with even low doses of inhaled corticosteroids. 12 Guevara JP Ducharme FM Keren R Nihtianova S Zorc J Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database Syst Rev. 2006; 2006Cd003558 Google Scholar Thus, until the 1970s, maintenance treatment of asthma was based on a regular application of reliever therapies, which were either associated with side-effects or had limited clinical efficacy. Furthermore, due to non-specific modes of action and few alternative options, any appreciation that clinical phenotypes of asthma existed was mainly academic: a one-size-fits-all approach was applied for every patient with asthma (figure).