Validity of measurement of two specific biomarkers for the assessment of small airways inflammation in asthma.
BACKGROUND
Small airways inflammation in asthma has been supposed to contribute to instability of the disease and therapy resistance. This study was designed to determine the validity of measurement of N(epsilon)-(carboxymethyl)lysine (CML) levels in induced sputum and alveolar concentrations of nitric oxide (NO) for the assessment of small airways inflammation in asthma.


METHODS
The authors measured CML levels in induced sputum and the bronchial flux (Jno) and alveolar concentration (C(alv)) of NO in 37 asthmatic patients and 15 normal controls. After initial analysis, all asthmatics were randomly assigned to receive inhaled fluticasone propionate (FP; 400 microg/day, n = 21) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP; 400 microg/day, n = 16) for 12 weeks. And then the determination of exhaled NO level and sputum induction was performed after the treatment period.


RESULTS
CML levels in induced sputum were significantly higher in asthmatics than in normal controls (median [interquartile range], asthmatics: 53.0 [44.8-64.3] microg/ml, normal controls: 22.0 [14.8-28.3] microg/ml; p < .01). Similarly, Jno and C(alv) were also higher in asthmatics. Moreover, CML level was closely correlated with C(alv) but not with Jno in asthmatics (r = .47, p = .005). Jno was significantly correlated with forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), and CML level and C(alv) were correlated with forced expiratory flow between 25% and 75% of FVC (FEF(25-75)), an index of small airways obstruction. After FP treatment, the decrease in CML level and Calv were very small. In contrast, these levels were markedly decreased after HFA-BDP treatment. Moreover, even after FP or HFA-BDP treatment, CML level was significantly correlated with C(alv).


CONCLUSIONS
This novel, noninvasive technique of measurement of CML levels in induced sputum and C(alv) may prove to be important not only in the evaluation of small airways inflammation but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.
Kanazawa
Hiroshi
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kanazawa-h@med.osaka-cu.ac.jp
Kyoh
Shigenori
S
Asai
Kazuhisa
K
Hirata
Kazuto
K
D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy; D001507:Beclomethasone / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000737:chemistry; D005260:Female; D000068298:Fluticasone; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D011650:Pulmonary Alveoli / Q000737:chemistry; D015203:Reproducibility of Results; D013183:Sputum / Q000737:chemistry
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D009569:Nitric Oxide; C048496:N(6)-carboxymethyllysine; D000068298:Fluticasone; D008239:Lysine; D001507:Beclomethasone