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TNF polymorphisms modify endotoxin exposure-associated longitudinal lung function decline
  1. Hongxi Zhang1,
  2. Jingqing Hang1,2,
  3. Xiaorong Wang2,
  4. Wei Zhou2,
  5. Bixiong Sun1,
  6. Helian Dai1,
  7. Li Su2,
  8. David C Christiani2,3
  1. 1Shanghai Putuo District People’s Hospital, Shanghai, China
  2. 2Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3Pulmonary and Critical Care Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to:
 Dr D C Christiani
 Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA; dchris{at}


Objectives: Endotoxin exposure induces airway inflammation, hyper-responsiveness and higher expression of tumour necrosis factor (TNF). This study was conducted to investigate whether TNF polymorphisms modify the effect of endotoxin exposure on chronic declines in lung function.

Methods: Associations between TNF and LTA polymorphisms, endotoxin exposure and lung function were analysed in 263 cotton workers and 230 silk workers as a reference group, who were prospectively followed for 20 years. Multiple linear regression models were used to assess the association, with adjustment for smoking and other covariates.

Results: Endotoxin exposure was associated with faster lung function decline among genotypes associated with higher TNF expression levels, with estimates of annual FEV1 change in relation to endotoxin exposure of –2.9 ml and –6.8 ml in the G/G and G/A+AA genotypes, respectively, for the TNF polymorphism; and –2.0 ml, –4.0 ml and –3.6 ml in A/A, A/G and G/G genotypes, respectively, for the LTA polymorphism. When joint effects of endotoxin exposure and smoking were considered, the effect modification of TNF and LTA polymorphisms was prominent in never smokers.

Conclusions:TNF and LTA polymorphisms may modify the association between occupational endotoxin exposure and longitudinal lung function decline, which was more clearly observed in never smokers.

  • COPD, chronic obstructive pulmonary disease
  • PL-EM, Partition Ligation-Expectation Maximization
  • TNF, tumour necrosis factor

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  • Published Online First 1 March 2007

  • The Study was supported by NIOSH Grant R01OH02421, NIH Fogarty International Institute grant TW00828, and Flight Attendants Medical Research Institute Young Clinical Scientist Award.