Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Threshold of Biologic Response of the Small Airway Epithelium to Low Levels of Tobacco Smoke


ABSTRACT: Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.” The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 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, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke. Affymetrix arrays were used to assess the gene expression data of smoking-responsive genes in the in small airway epithelium obtained by fiberoptic bronchoscopy of 48 healthy non-smokers (non-smoker or Nsaets), 65 healthy smokers (smoker), 7 symptomatic smokers (SYMs) and a healthy occasional smoker (OcSs). YSB and LO contributed equally to the study.

ORGANISM(S): Homo sapiens

SUBMITTER: Yael Strulovici-Barel 

PROVIDER: E-GEOD-19667 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Threshold of biologic responses of the small airway epithelium to low levels of tobacco smoke.

Strulovici-Barel Yael Y   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  

American journal of respiratory and critical care medicine 20100806 12


<h4>Rationale</h4>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.<h4>Objectives</h4>To identify biologic correlates of this risk we hypothesized that, compared with unexposed individuals, individuals exposed to low levels of tobacco sm  ...[more]

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