Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol.
BACKGROUND
Budesonide/formoterol maintenance and reliever therapy maintains asthma control and reduces exacerbation frequency compared with higher fixed-dose combination regimens. Its effects on eosinophilic airway inflammation and structure are unknown.


OBJECTIVE
We sought to compare the effects of budesonide/formoterol 200/6 microg twice daily plus as-needed with budesonide/formoterol 800/12 microg twice daily on airway eosinophils and remodeling.


METHODS
This 52-week, parallel-group, randomized, double-blind study of 127 asthma patients who were symptomatic despite therapy compared (1) the change between induced sputum percent eosinophils at baseline and the geometric mean of 4 on-treatment values and (2) the change in endobronchial biopsy eosinophil counts pre- and post-treatment.


RESULTS
Mean daily doses of budesonide/formoterol were 604/18 microg in the maintenance and reliever therapy group and 1,600/24 microg in the high fixed-dose group. In the former, the geometric mean percent sputum eosinophils remained unchanged (1.6% to 1.9%), whereas biopsy specimen subepithelial eosinophils increased (6.2 to 12.3 cells/mm(2)). Sputum and biopsy eosinophil counts decreased with high fixed-dose treatment (2.2% to 1.2% and 7.7 to 4.8 cells/mm(2), respectively), resulting in significant treatment differences of 0.7% (ratio, 1.8; 95% CI, 1.2-2.8; P = .0038) and 7.5 cells/mm(2) (ratio, 2.9; 95% CI, 1.6-5.3; P < .001), respectively. There were no between-treatment differences in reticular basement membrane thickness, exhaled nitric oxide, exacerbation frequency, or FEV(1).


CONCLUSIONS
Compared with fixed-dose combination treatment containing a 4-fold higher maintenance dose of budesonide, budesonide/formoterol maintenance and reliever therapy is associated with higher eosinophil counts, but these remain within the range associated with stable clinical control.
Pavord
Ian D
ID
Department of Respiratory Medicine, Institute for Lung Health, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. ian.pavord@uhl-tr.nhs.uk
Jeffery
Peter K
PK
Qiu
Yusheng
Y
Zhu
Jie
J
Parker
Debbie
D
Carlsheimer
Asa
A
Naya
Ian
I
Barnes
Neil C
NC
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001772:Blood Cell Count; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate