title: Effects of add-on montelukast on airway hyperresponsiveness in patients with well-controlled asthma - a pilot study.
abstract: OBJECTIVE
  Control of airway inflammation is the cornerstone of asthma management. The aim of the present pilot study was to assess the effects of a leukotriene receptor antagonist (LTRA) added to a basic treatment of inhaled corticosteroids (ICS) and long-acting beta-agonist (LABA) on airway hyperresponsiveness, inflammation, and quality of life in well-controlled patients with asthma.
  
  
  METHODS
  Seventeen patients (age 18-65, 11 women) with well-controlled asthma presenting airway hyperresponsiveness to mannitol and methacholine challenge were given add-on montelukast on a stable ICS + LABA for 4 weeks. Quality of life and selected parameters of airway inflammation were measured at baseline and at study end. (ClinicalTrials.gov (NCT01725360)).
  
  
  RESULTS
  Adding montelukast to ICS + LABA resulted in an increase in mean FEV1 (+4.5%, p = 0.057), cumulated higher dose of mannitol (+32.5%, p = 0.023) and methacholine (+17.2%, 0.237) in the provocation test, lower airway reactivity with mannitol and methacholine (response dose ratio (RDR) -50.0%, p = 0.024 and -44.3%, p = 0.006, respectively), and improved airway sensitivity to mannitol and methacholine (+12.1%, p = 0.590 and +48.0%, p = 0.129 for PD15 and PD20 FEV1, respectively). Changes in inflammation parameters (blood eosinophil count, serum eosinophil cationic protein, and exhaled nitric oxide) were consistent with these findings. Asthma-related quality of life improved significantly in all domains and overall (from 5.3 at baseline to 6.1 at the final visit, p < 0.001). The main limitation was the absence of a control group.
  
  
  CONCLUSIONS
  The consistency of the changes in airway hyperresponsiveness and inflammation as well as in quality of life observed with an add-on therapy with montelukast in well-controlled asthma patients during 4 weeks suggests that residual inflammation may represent an area for further improvement of asthma control to be explored in adequately powered randomized controlled trials.
authors.affiliation: Clinic of Internal Medicine, University Hospital BaselSwitzerland.
authors.forename: Nina
authors.initials: N
authors.lastname: Kononowa
authors.affiliation: Clinic of Allergology, University Hospital Basel, Switzerland; University Clinic of Rheumatology, Clinical Immunology and Allergology, University Hospital BernSwitzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Michel
authors.affiliation: Medical Faculty, University of Basel and Clinic of Internal Medicine, Canton Hospital Baselland, LiestalSwitzerland.
authors.forename: David
authors.initials: D
authors.lastname: Miedinger
authors.affiliation: University Clinic of Rheumatology, Clinical Immunology and Allergology, University Hospital BernSwitzerland.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Pichler
authors.affiliation: Medical Faculty, University of Basel and Clinic of Internal Medicine, Canton Hospital Baselland, LiestalSwitzerland.
authors.forename: Prashant N
authors.initials: PN
authors.lastname: Chhajed
authors.affiliation: University Clinic of Rheumatology, Clinical Immunology and Allergology, University Hospital BernSwitzerland.
authors.forename: Arthur
authors.initials: A
authors.lastname: Helbling
authors.affiliation: Medical Faculty, University of Basel and Clinic of Internal Medicine, Canton Hospital Baselland, LiestalSwitzerland.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Leuppi
keywords: AHR, Airway hyperresponsiveness; AQLQ, Asthma Quality of Life Questionnaire; BHR, Bronchial hyperreactivity; BPT, Bronchial provocation test; ECP, Eosinophil cationic protein; FeNO, Fraction of exhaled nitric oxide; FEV1, Forced expiratory volume in one s; Airway hyperresponsiveness; Airway inflammation; Asthma; Asthma control; Leukotriene receptor antagonists; Mannitol provocation test; Methacholine provocation test