title: Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?
abstract: Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of 'cholinergic tone'. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.
authors.affiliation: 1] Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK [2] Research in Real Life Ltd, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.affiliation: Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Fromer
authors.affiliation: Family Physician Airways Group of Canada, Richmond Hill, ON, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Kaplan
authors.affiliation: Department of General Practice, University of Groningen, University Medical Center, Groningen, The Netherlands.
authors.forename: Thys
authors.initials: T
authors.lastname: van der Molen
authors.affiliation: Son Pisa Primary Health Care Centre, Balearic Health Service, Palma de Mallorca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Román-Rodríguez
mesh_terms: D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D006801:Humans
chemical_list: D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D003692:Delayed-Action Preparations