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Association between Lung Function, Laboratory Animal Research Work, and the CD14/-1619 G Allele

¹ Department of Medicine, Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado

Correspondence and requests for reprints should be addressed to Karin Pacheco, M.D., M.S.P.H., National Jewish Health, 1400 Jackson St., Denver, CO 80206. E-mail: pachecok{at}njhealth.org

Introduction: Workers using laboratory animals (LA) in research have high rates of animal-related symptoms and sensitization. Exposures to endotoxin and animal allergens are causally associated with these adverse health outcomes. CD14 is a cell surface and circulating marker that binds endotoxin and mediates its cellular effects. We hypothesized that LA-exposed researchers with the more endotoxin-responsive CD14 alleles (CD14/-1619 G or CD14/-159 T) would report more symptoms and have lower lung function than unexposed coworkers with the less endotoxin responsive CD14 alleles A and C. Methods: We enrolled 476/522 (91%) researchers who completed a symptom and exposure questionnaire; prick skin testing to LA allergens; spirometry; and gave blood for genotyping to CD14/-1619 and -159 alleles by real-time PCR. Results were analyzed by univariate and then stepwise logistic regression for the 375 (79%) white workers. Results: Subjects included 36 animal handlers (Group A), 184 scientists (Group B), 135 technicians (Group C), and 20 unexposed coordinators. CD14/-1619 and -159 genotypes were in HWE. Distribution of alleles was similar by job title and sex. LA chest symptoms were significantly more common in researchers (Groups B and C) who work with LA in their labs (OR, 3.8 [2.0–7.2]; P < 0.0001), and twice as common in women (P = 0.02). FEV₁ percent predicted was lower in subjects working with LA both in the animal facility and their own labs (P = 0.05) and having a CD14/-1619 G allele (P = 0.006), compared with unexposed workers with a CD14/-1619 A allele. We saw no effect with CD14/-159 alleles. LA sensitization, defined as one or more positive skin tests to LA, did not contribute to these models. Conclusions: Exposure to LA is a strong predictor of chest symptoms, particularly in women researchers, whereas CD14 genotypes are not. Those LA researchers who have the more endotoxin-responsive CD14/-1619 G allele and who work with lab animals in both the animal facility and their own labs have lower FEV₁ percent predicted, suggesting an effect of both exposure and genotype on lung function.

FOOTNOTES

Supported by 1 K23 AI053572 [GenBank] NIAID/NIH, 1 R01 AI 59618 NIAID/NIH, and M01 RR000051 NIH.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form December 19, 2008; accepted in final form January 8, 2009)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pacheco, K. A. Articles by Rose, C. S. Search for Related Content PubMed Articles by Pacheco, K. A. Articles by Rose, C. S.