Correlation between change in pulmonary function and suppression of reactive nitrogen species production following steroid treatment in COPD.
BACKGROUND
Reactive nitrogen species (RNS) have a number of inflammatory actions and the production of these molecules has been reported to be increased in the airways of patients with chronic obstructive pulmonary disease (COPD), which suggests that they may be involved in the inflammatory and obstructive process in COPD.


METHODS
The relationship between the reduction in RNS and the improvement in pulmonary function was studied in 18 patients with COPD following steroid treatment (800 micro g beclomethasone dipropionate inhalation for 4 weeks). Twelve patients were treated with inhaled steroids and the others received placebo treatment. Forced expiratory volume in 1 second (FEV(1)) and airway responsiveness to histamine were measured before and after treatment. Induced sputum cells were stained with anti-nitrotyrosine antibody, a footprint of RNS, and RNS formation was assessed by measuring nitrotyrosine immunoreactivity. The immunoreactivity of inducible nitric oxide synthase (iNOS) in induced sputum and exhaled NO levels were also measured.


RESULTS
Treatment with steroids resulted in a significant reduction in both nitrotyrosine and iNOS immunoreactivity in sputum cells compared with pretreatment levels (both p<0.01). The reduction rates in both parameters were significantly related (p<0.05). The reduction in nitrotyrosine and iNOS immunoreactivity was correlated with the improvement in FEV(1) (p<0.05) and airway responsiveness to histamine (p<0.01). None of the parameters was significantly changed by placebo administration.


CONCLUSIONS
These results suggest that RNS may be involved in the reversible component of inflammation in COPD that is suppressed by steroids. Further studies using specific inhibitors for RNS are needed to clarify their effects on the long term progression of COPD.
Sugiura
H
H
Division of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ichinose
M
M
Yamagata
S
S
Koarai
A
A
Shirato
K
K
Hattori
T
T
D000280:Administration, Inhalation; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001507:Beclomethasone / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013183:Sputum
D000893:Anti-Inflammatory Agents; D026361:Reactive Nitrogen Species; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001507:Beclomethasone