Published ahead of print on September 15, 2005, doi:10.1164/rccm.200503-490OC Am. J. Respir. Crit. Care Med., Volume 172, Number 12, December 2005, 1563-1568 A more recent version of this article appeared on December 15, 2005
Submitted on March 29, 2005 TNF-308 Modifies the Effect of Second-Hand Smoke on Respiratory Illness-Related School AbsencesMade Wenten1,1 Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA, 2 Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA, 3 Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA * To whom correspondence should be addressed. E-mail: gillilan{at}usc.edu.
Rationale: Exposure to second-hand smoke (SHS) has been associated with increased risk of respiratory illness in children including respiratory illness-related school absences. The role of genetic susceptibility in risk for adverse effects from SHS has not been extensively investigated in children. Objective: To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness-related school absences associated with SHS exposure. Methods: Incident school absences were collected using an active surveillance system, between January and June 1996, as part of the Air Pollution and Absence Study (APAS), a prospective cohort study nested in the Children's Health Study (CHS). Buccal cells and absence reports were collected on 1351 students from 27 elementary schools in California. Measurements and Main Results: Illness-related school absences were classified as non-respiratory and respiratory illness-related, which were further categorized into upper or lower respiratory illness-related absences based on symptoms. The effect of SHS exposure on respiratory illness-related absences differed by TNF genotype (p-interaction: 0.02). In children possessing at least one copy of the TNF -308 A variant, exposure to two or more household smokers was associated with a two-fold risk of a school absence due to respiratory illness (RR: 2.13, 95% CI: 1.34, 3.40)and a four-fold risk of lower-respiratory illness-related school absence (RR: 4.15, 95% CI: 2.57, 6.71) compared with unexposed children homozygous for the common TNF -308 G allele. Conclusions: These results indicate that a sub-group of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS. Key words: second-hand smoke, TNF, school absence, epidemiology
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