Is a low serum concentration of alpha 1-antitrypsin associated with an increased susceptibility for byssinosis in cotton mill workers? Considerations regarding analytical quality requirements and economical consequences.
We have previously demonstrated an association between development of the cotton lung disease byssinosis and endotoxin concentrations in the work environment. Endotoxin has been shown to exert its effects through granulocyte activation and hence release of elastase and other proteases at the bronchoalveolar surface. alpha 1-Antitrypsin is a protease inhibitor, and hence, alpha 1-Antitrypsin concentrations in the blood and then on the alveolar surface might be important for the protection against endotoxin effects. Airborne endotoxin concentrations in the work place and S-alpha 1-Antitrypsin (a1A) was measured in 226 workers in cotton mills in Vejle and of these 206 were further phenotyped. The following models were considered: Model 1. The S-a1A concentration is determining the risk for development of byssinosis. The lower the concentration, the higher the risk. Model 2. The degree of exposure to endotoxin is determining. The higher the airborne concentration and the longer time working in that, the higher is the risk. Model 3. The phenotype of a1-A is determining. Only MS and/or MZ phenotypes represent a risk disposition. The goals for analytical quality for a1-A measurements were estimated in the two relevant models. The specifications are: Regarding model 1: analytical coefficient of variation CVA < 3% and analytical bias--1 mumol/L < BA < +1 mumol/L. Model 2: a1-A is not of significant importance and specifications cannot be evaluated. Regarding model 3: There is a direct relationship between cut-off point and analytical performance, e.g. an imprecision of SA 3 mumol/L and cut-off of 38 mumol/L will allow for a BA of -1 mumol/L.
Department of Clinical Chemistry, Vejle County Hospital, Denmark.
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Brandslund
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Lund
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Sigsgaard
D002095:Byssinosis / Q000453:epidemiology / Q000209:etiology*; D002624:Chemistry, Clinical / Q000191:economics* / Q000592:standards*; D003365:Costs and Cost Analysis; D004198:Disease Susceptibility; D006801:Humans; D008962:Models, Theoretical; D009784:Occupational Diseases / Q000453:epidemiology / Q000209:etiology*; D009994:Osmolar Concentration; D010641:Phenotype; D011785:Quality Assurance, Health Care; D012307:Risk Factors; D000515:alpha 1-Antitrypsin / Q000032:analysis* / Q000235:genetics
D000515:alpha 1-Antitrypsin