ORIGINAL ARTICLE

TNF polymorphisms modify endotoxin exposure-associated longitudinal lung function decline

Hongxi Zhang¹, Jingqing Hang^1,2, Xiaorong Wang², Wei Zhou², Bixiong Sun¹, Helian Dai¹, Li Su², David C Christiani^2,3

¹ Shanghai Putuo District People’s Hospital, Shanghai, China
² Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
³ Pulmonary and Critical Care Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA

Correspondence to:
Dr D C Christiani
Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA; dchris{at}hsph.harvard.edu

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.

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

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