A meta-analysis of the dose-response relationship of inhaled corticosteroids in adolescents and adults with mild to moderate persistent asthma.
BACKGROUND
Although inhaled corticosteroids (ICS) are commonly used in the treatment of persistent asthma, the relationship between dose and clinical response remains unclear.


OBJECTIVE
This study investigated whether ICS exhibit a dose-response relationship in the treatment of mild to moderate persistent asthma.


METHODS
This was a meta-analysis of published randomized clinical trials concerning the relationship between ICS dose and response in asthma. Relevant studies were identified through a search of PubMed and MEDLINE for articles on asthma and ICS published between January 1996 and January 2001. The search was limited to publications classified as clinical trials that included the text words asthma and corticosteroids, glucocorticoids, beclomethasone, budesonide, fluticasone, flunisolide, mometasone, or triamcinolone acetonide. Five clinical measures were considered: morning peak expiratory flow rate (AM PEFR), evening PEFR (PM PEFR), forced expiratory volume in 1 second (FEV(1)), beta-agonist use, and asthma symptom score (severity of symptoms on a given day, as evaluated by patients).


RESULTS
Forty-three studies were identified, of which 16 met the criteria for inclusion in the meta-analysis. These studies involved 4 agents: fluticasone propionate, triamcinolone acetonide, budesonide, and mometasone furoate. A statistically significant dose response in AM PEFR was observed with fluticasone propionate, triamcinolone acetonide, and budesonide (respective 95% CIs, 4.9 to 11.5, 4.7 to 18.0, and 5.8 to 24.9). A statistically significant dose response to fluticasone propionate and triamcinolone acetonide was also observed in PM PEFR (95% CIs, 2.0 to 8.7 and 2.4 to 13.7) and asthma symptom score (95% CI, -0.069 to -0.002 and -0.60 to -0.10). In terms of FEV(1), the dose response was statistically significant only with budesonide (95% CI, 0.025 to 0.17). Dose-response relationships were not disproportionately driven by the highest doses, and the greatest effects on response were seen at doses below or at the low end of the recommended range, suggesting that use of high doses of ICS may contribute only marginally to efficacy.


CONCLUSIONS
Dose-response relationships were not uniformly observed with all drugs or for all measures of response. Use of higher doses of ICS in patients with mild to moderate persistent asthma does not appear to increase the efficacy of these drugs.
Bousquet
Jean
J
Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire Montpellier, France. jean.bousquet@wanadoo.fr
Ben-Joseph
Rami
R
Messonnier
Mark
M
Alemao
Evo
E
Gould
A Lawrence
AL
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use*; D000328:Adult; D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents