Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids.
BACKGROUND
For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.


METHODS
We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.


RESULTS
A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).


CONCLUSIONS
Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)
Lemanske
Robert F
RF
University of Wisconsin School of Medicine and Public Health, Madison, USA. rfl@medicine.wisc.edu
Mauger
David T
DT
Sorkness
Christine A
CA
Jackson
Daniel J
DJ
Boehmer
Susan J
SJ
Martinez
Fernando D
FD
Strunk
Robert C
RC
Szefler
Stanley J
SJ
Zeiger
Robert S
RS
Bacharier
Leonard B
LB
Covar
Ronina A
RA
Guilbert
Theresa W
TW
Larsen
Gary
G
Morgan
Wayne J
WJ
Moss
Mark H
MH
Spahn
Joseph D
JD
Taussig
Lynn M
LM
D000085:Acetates / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004485:Eczema / Q000150:complications; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D016015:Logistic Models; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage*; D000068299:Salmeterol Xinafoate; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol; D011241:Prednisone