Threshold of biologic responses of the small airway epithelium to low levels of tobacco smoke.
BACKGROUND
Epidemiologic data demonstrate that individuals exposed to low levels of tobacco smoke have decrements in lung function and higher risk for lung disease compared with unexposed individuals. Although this risk is small, low-level tobacco smoke exposure is so widespread, it is a significant public health concern.


OBJECTIVE
To identify biologic correlates of this risk we hypothesized that, compared with unexposed individuals, individuals exposed to low levels of tobacco smoke have biologic changes in the small airway epithelium, the site of the first abnormalities associated with smoking.


METHODS
Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays were used to assess genome-wide gene expression; urine nicotine and cotinine were used to categorize subjects as "nonsmokers," "active smokers," and "low exposure." Gene expression data were used to determine the threshold and induction half maximal level (ID₅₀) of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses.


RESULTS
There was no threshold of urine nicotine without a small airway epithelial response, and only slightly above detectable urine cotinine threshold with a small airway epithelium response. The ID₅₀ for nicotine was 25 ng/ml and for cotinine it was 104 ng/ml.


CONCLUSIONS
The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low-level tobacco smoke exposure to lung health risk, identifies the genes most sensitive to tobacco smoke, and defines thresholds at which the lung epithelium responds to low levels of tobacco smoke.
Strulovici-Barel
Yael
Y
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Omberg
Larsson
L
O'Mahony
Michael
M
Gordon
Cynthia
C
Hollmann
Charleen
C
Tilley
Ann E
AE
Salit
Jacqueline
J
Mezey
Jason
J
Harvey
Ben-Gary
BG
Crystal
Ronald G
RG
D000328:Adult; D003367:Cotinine / Q000652:urine; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009538:Nicotine / Q000652:urine; D012313:RNA / Q000032:analysis; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects* / Q000032:analysis
D014028:Tobacco Smoke Pollution; D012313:RNA; D009538:Nicotine; D003367:Cotinine