title: Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.
abstract: There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.
authors.affiliation: Institute for Lung Health, Dept of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9PQ, UK ruth.green@uhl-tr.nhs.uk
authors.forename: R H
authors.initials: RH
authors.lastname: Green
authors.forename: C E
authors.initials: CE
authors.lastname: Brightling
authors.forename: S
authors.initials: S
authors.lastname: McKenna
authors.forename: B
authors.initials: B
authors.lastname: Hargadon
authors.forename: N
authors.initials: N
authors.lastname: Neale
authors.forename: D
authors.initials: D
authors.lastname: Parker
authors.forename: C
authors.initials: C
authors.lastname: Ruse
authors.forename: I P
authors.initials: IP
authors.lastname: Hall
authors.forename: I D
authors.initials: ID
authors.lastname: Pavord
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007958:Leukocyte Count; D008176:Lung Volume Measurements; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects; D013183:Sputum / Q000276:immunology; D013440:Sulfides
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D004983:Ethanolamines; D005938:Glucocorticoids; D011804:Quinolines; D013440:Sulfides; D016210:Methacholine Chloride; D019819:Budesonide; C093875:montelukast; D000068759:Formoterol Fumarate