Statistical methods for the blood beryllium lymphocyte proliferation test.

Abstract

The blood beryllium lymphocyte proliferation test (BeLPT) is a modification of the standard lymphocyte proliferation test that is used to identify persons who may have chronic beryllium disease. A major problem in the interpretation of BeLPT test results is outlying data values among the replicate well counts (approximately 7%). A long-linear regression model is used to describe the expected well counts for each set of Be exposure conditions, and the variance of the well counts is proportional to the square of the expected count. Two outlier-resistant regression methods are used to estimate stimulation indices (SIs) and the coefficient of variation. The first approach uses least absolute values (LAV) on the log of the well counts as a method for estimation; the second approach uses a resistant regression version of maximum quasi-likelihood estimation. A major advantage of these resistant methods is that they make it unnecessary to identify and delete outliers. These two new methods for the statistical analysis of the BeLPT data and the current outlier rejection method are applied to 173 BeLPT assays. We strongly recommend the LAV method for routine analysis of the BeLPT. Outliers are important when trying to identify individuals with beryllium hypersensitivity, since these individuals typically have large positive SI values. A new method for identifying large Sls using combined data from the nonexposed group and the beryllium workers is proposed. The log(SI)s are described with a Gaussian distribution with location and scale parameters estimated using resistant methods. This approach is applied to the test data and results are compared with those obtained from the current method.