title: Optimal asthma control, starting with high doses of inhaled budesonide.
abstract: The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1-16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200- and 1,600-microg x day(-1) starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with 3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16 (p=0.03) [corrected]. During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2 occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.
authors.affiliation: Institute of Respiratory Medicine, Royal Prince Alfred Hospital and University of Sydney, Camperdown, NSW, Australia.
authors.forename: H K
authors.initials: HK
authors.lastname: Reddel
authors.forename: C R
authors.initials: CR
authors.lastname: Jenkins
authors.forename: G B
authors.initials: GB
authors.lastname: Marks
authors.forename: S I
authors.initials: SI
authors.lastname: Ware
authors.forename: W
authors.initials: W
authors.lastname: Xuan
authors.forename: C M
authors.initials: CM
authors.lastname: Salome
authors.forename: C A
authors.initials: CA
authors.lastname: Badcock
authors.forename: A J
authors.initials: AJ
authors.lastname: Woolcock
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide; D006632:Histamine