TNF polymorphisms modify endotoxin exposure-associated longitudinal lung function decline.

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.

Low normal alpha-1-antitrypsin serum concentrations and MZ-phenotype are associated with byssinosis and familial allergy in cotton mill workers.

Recent studies have shown a close association between byssinosis and airborne endotoxin concentrations. Endotoxin might induce byssinosis through the release of biochemical mediators as the broncheoalveolar surface. Alpha-1-antitrypsin (alpha-1-A) which neutralizes enzymes released by granulocytes is known to be important. This study evaluates the possible importance of alpha-1-A concentration and the heterozygosity (Pi-S and Pi-Z alleles), in the prevalence of byssinosis and familial allergy. 253 cotton workers were interviewed and clinically studied to identify persons with the cotton lung disease, byssinosis, and atopic disease. Serum was available for alpha-1-A concentration determination in 226 individuals, and for Pi phenotyping in 206. The overall prevalence of byssinosis was 30/226 (13%). In the group with alpha-1-A < or = 35 mumol l-1 the prevalence was 5/18 (28%), versus the prevalence 25/208 (12%) in the group with alpha-1-A > 35 mumol l-1 (p < 0.1, Fishers exact test). MZ phenotype was associated with an increased prevalence of byssinosis compared with the MM-group: 3/8 (38%) and 25/187 (13%), p < 0.1, Fishers exact test. An association between MZ-phenotype and familial allergy was found: 4/8 (50%) contra 23/187 (12%), p < 0.05, Fishers exact test. In a logistic regression model controlling for confounding by endotoxin, tobacco exposure, sex, and age, the odds ratio for byssinosis in the MZ-phenotype group was significantly elevated 5.8 (1.1-30.3). Odds ratio for familial allergy was also significantly elevated in the MZ-group 2.8 (1.3-5.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiological investigation of the role of family susceptibility and occupational and family histories in the development of byssinosis among workers exposed to flax dust.

Epidemiological investigation of 475 workers exposed to dust in flax processing has shown that family susceptibility has a decisive role in the development of byssinosis in those workers. Workers whose fathers had occupational history of exposure to flax dust were more resistant to the development of the disease than those whose fathers had no such history. Such tolerance was much higher in workers whose fathers were byssinotic than those with byssinosis-free fathers. Further hereditary and immunological investigations are, however, needed.