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.
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
Ian D
ID
Pavord
Peter K
PK
Jeffery
Yusheng
Y
Qiu
Jie
J
Zhu
Debbie
D
Parker
Asa
A
Carlsheimer
Ian
I
Naya
Neil C
NC
Barnes
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