Acute inhalation of cigarette smoke increases lower respiratorytract nitric oxide concentrations

摘要

BACKGROUND—Cigarette smoking is associated with a number of common pulmonary diseases including chronic airflow limitation and bronchial carcinoma. Lower respiratory tract (LRT) nitric oxide (NO) concentrations are reduced in habitual cigarette smokers between cigarettes, and although this finding has been implicated in the pathogenesis of smoking related disease, the underlying mechanisms are unclear. A study was undertaken to determine the nature and time course for changes in LRT NO concentrations following acute inhalation of cigarette smoke.
METHODS—Twenty four healthy habitual smokers were studied. The concentration of LRT NO in exhaled breath before, one and ten minutes after smoking a single cigarette was measured using chemiluminescence.
RESULTS—LRT NO concentrations increased in all subjects from a mean (SE) of 2.6 (0.27) to 4.8 (0.26) ppb (p<0.0001) at one minute, and at 10 minutes remained significantly raised above the baseline level at 3.2 (0.25) ppb (p = 0.003). The mean (95% CI) increases in NO concentrations were 2.2 (1.7 to 2.7) and 0.6 (0.2 to 1.0) ppb, respectively.
CONCLUSIONS—These findings were unexpected in both their direction and time course. They suggest a novel mechanism for the handling of NO in the human lung. Wehypothesise that NO is trapped in the epithelial lining fluid (ELF) ofthe normal human respiratory tract in bioequivalent forms such asS-nitrosothiols or peroxynitrite and that this trapping mechanism issensitive to the redox state of the ELF. LRT NO concentrations willthus increase with oxidant exposure and decline as pulmonaryantioxidant defence mechanisms take effect. These findings may haveimplications for the pathogenesis and diagnosis of oxidant mediatedpulmonary disease.