Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath

The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal mode...

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Bibliographic Details
Published in:Thorax 2004-09, Vol.59 (9), p.757-760
Main Authors: LANE, C, KNIGHT, D, BURGESS, S, FRANKLIN, P, HORAK, F, LEGG, J, MOELLER, A, STICK, S
Format: Article
Language:English
Subjects:
Adolescent
Asthma
Asthma - enzymology
Asthma - pathology
Biological and medical sciences
Breath Tests
Bronchi - enzymology
Child
Epithelial Cells
Female
Humans
Male
Medical sciences
Nitric Oxide - metabolism
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Pneumology
RNA - metabolism
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Summary:The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal models suggest that non-inducible NOS systems have important roles in determining airway reactivity, regulating inflammation, and might contribute significantly to NO measured in exhaled breath. Bronchial epithelial cells were obtained from healthy, atopic, and asthmatic children by non-bronchoscopic brushing. Exhaled NO (FeNO) was measured directly using a fast response chemiluminescence NO analyser. RNA was extracted from the epithelial cells and real time polymerase chain reaction was used to determine the expression of NOS isoenzymes. NOS2 was examined in macrophages and epithelial cells by immunohistochemistry. NOS1 mRNA was not detectable. NOS3 mRNA was detected in 36 of 43 samples at lower levels than NOS2 mRNA which was detectable in all samples. The median FeNO was 15.5 ppb (95% CI 10 to 18.1). There was a significant correlation between FeNO and NOS2 expression (R = 0.672, p
ISSN:0040-6376
1468-3296
DOI:10.1136/thx.2003.014894