Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults.
BACKGROUND
Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults.


OBJECTIVE
To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles.


METHODS
A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects.


RESULTS
From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV(1)) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg (three of 11, 73%) compared to 2000 microg or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%).


CONCLUSIONS
Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.
Rice-McDonald
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G
Respiratory Medicine Mater Adult Hospital, South Brisbane, Australia. g.ricemcdonald@uq.net.au
Bowler
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Staines
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Mitchell
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C
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012646:Self Administration; D017211:Treatment Failure
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D003907:Dexamethasone; D011239:Prednisolone; D000068298:Fluticasone