Inhaled triple therapy and airway hyperresponsiveness in persistent asthma

Abstract

Adding a long-acting muscarinic antagonist (LAMA) is recommended in the guidelines for a patient with asthma not controlled on inhaled corticosteroid (ICS)/long-acting β-agonist (LABA). The change in forced expiratory volume in 1 second (FEV1) resulting from the addition of LAMA to ICS/LABA may be relatively small or less than the minimal clinically important difference, and as such, improved airway caliber is not the primary mechanism for a reduction in exacerbations with LAMA therapy. 1 Lipworth B.J. Emerging role of long acting muscarinic antagonists for asthma. Br J Clin Pharmacol. 2014; 77: 55-62 Crossref PubMed Scopus (33) Google Scholar Exacerbations are, in part, determined by the effects on airway hyperresponsiveness (AHR) in which a LAMA might be expected to confer additional airway smooth muscle–stabilizing effects when added to ICS/LABA. 2 Currie G.P. Jackson C.M. Ogston S.A. Lipworth B.J. Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids. Qjm. 2003; 96: 435-440 Crossref PubMed Scopus (23) Google Scholar Aside from effects on airway smooth muscle, there may be neuronal and paracrine actions of LAMAs that may reduce exacerbations. 1 Lipworth B.J. Emerging role of long acting muscarinic antagonists for asthma. Br J Clin Pharmacol. 2014; 77: 55-62 Crossref PubMed Scopus (33) Google Scholar Indirect challenge tests with agents such as mannitol are thought to be more physiological than direct agents such as histamine or methacholine in that they better reflect the underlying inflammation status as opposed to the function of airway smooth muscle alone. 3 Nair P. Martin J.G. Cockcroft D.C. et al. Airway hyperresponsiveness in asthma: measurement and clinical relevance. J Allergy Clin Immunol Pract. 2017; 5: 649-659.e2 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar