Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma.
BACKGROUND
Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity.


OBJECTIVE
To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions.


METHODS
Levels of 3-bromotyrosine and 3,5-dibromotyrosine were measured in sputum supernatants using stable isotope dilution gas chromatography-mass spectrometry in a randomized, placebo-controlled, crossover study of treatment with terbutaline, budesonide, and their combination in patients with persistent asthma. Thirty-four individuals were randomized, and 28 completed the study.


RESULTS
Treatment with budesonide lowered median 3-bromotyrosine levels compared with treatment with placebo, terbutaline, and budesonide-terbutaline (0.24 vs 0.64, 0.62, and 0.43 3-bromotyosine/tyrosine [mmol/mol]; P < .05) and lowered median 3,5-dibromotyrosine levels compared with placebo and terbutaline treatments (0.04 vs 0.11 and 0.07 3,5-dibromotyrosine/ tyrosine [mmol/mol], P < .05). Unlike eosinophil numbers, 3-bromotyrosine and 3,5-dibromotyrosine levels did not increase with terbutaline treatment compared with placebo treatment but were significantly raised when terbutaline was added to budesonide treatment. 3-Bromotyrosine levels correlated significantly with eosinophil cationic protein levels in all groups.


CONCLUSIONS
3-Bromotyrosine and 3,5-dibromotyrosine levels reflect treatment effects in asthma and support previous findings that SABAs impair the anti-inflammatory effects of inhaled corticosteroids. In addition to eosinophil numbers and eosinophil cationic protein levels, these modified tyrosine residues provide useful information about the inflammatory state of the airways.
van Dalen
Christine J
CJ
Centre for Public Health Research, Massey University, Wellington, New Zealand. c.j.vandalen@massey.ac.nz
Aldridge
Ruth E
RE
Chan
Timothy
T
Senthilmohan
Revathy
R
Hancox
Robert J
RJ
Cowan
Jan O
JO
Taylor
D Robin
DR
Town
G Ian
GI
Kettle
Anthony J
AJ
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000378:metabolism*; D013726:Terbutaline / Q000008:administration & dosage*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D055815:Young Adult
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D014443:Tyrosine; D019819:Budesonide; C082610:3,5-dibromotyrosine; C118327:3-bromotyrosine; D013726:Terbutaline