Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.


METHODS
Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry. Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.


RESULTS
FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.


CONCLUSIONS
Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD.
Rytilä
Paula
P
Division of Allergology, University of Helsinki, Helsinki, Finland. paula.rytila@hus.fi
Rehn
Tiina
T
Ilumets
Helen
H
Rouhos
Annamari
A
Sovijärvi
Anssi
A
Myllärniemi
Marjukka
M
Kinnula
Vuokko L
VL
D000368:Aged; D000447:Aldehydes / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001944:Breath Tests; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000447:Aldehydes; D015415:Biomarkers; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D007781:Lactoferrin; C027576:4-hydroxy-2-nonenal