Does using lower limit of normal values enhance the ability of a single bone mineral density measure to predict fractures?

UNLABELLED: Using a single bone mineral density (BMD) measure, we demonstrated that the lower limit of normal (LLN) method is more consistent in predicting osteoporosis fractures than the T-score in white menopausal women from the Study of Osteoporosis Fracture (SOF). INTRODUCTION: In order to circumvent the inconsistencies and limitations with using the T-score when defining osteoporosis, we propose using 95% LLN values derived from centered polynomial models using the NHANES III BMD measures. The main aim of this study was to compare the two methods in prediction of fracture and agreement in osteoporosis classification using cohort data. METHODS: We compared the fracture prediction ability of the two methods using a single BMD measurement in 4,948 white women aged 67-74 years in the SOF employing kappa statistics, sensitivity, and specificity. RESULTS: The T-score provided inconsistent osteoporosis classification (46.6%) across the five hip regions of interest (ROIs) and this was significantly (p<0.0001) reduced when using the LLN method (36.5%). Kappa statistics of incident fracture during 12 years of follow-up related to the prevalence of osteoporosis at baseline was significantly improved using the LLN method compared to using T-score. Sensitivity and specificity for fracture based on a single BMD measurement of different hip ROIs were more consistent using the LLN method. CONCLUSION: The LLN method provides a more consistent and efficient method for osteoporosis fracture prediction than the T-score in 67- to 74-year-old white women.

Relationship of asthma to irritant gas exposures in pulp and paper mills.

The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS.

Adjusting FVC for the effect of obstruction.

OBJECTIVE: To derive a method of taking into account the effects of obstruction on the FVC, allowing more accurate assessment of other negative ("restrictive") influences. DESIGN: In 656 subjects with airways obstruction, defined as FEV1/FVC of 0.70 or less, regression of FVC was expressed as percentage of predicted value (FVC %PRED) on potential explanatory variables, including FEV1/FVC. The resulting equation was used to adjust FVC %PRED in 530 other obstructed men, to test whether the adjustment resulted in a different relationship of FVC %PRED to body weight. SETTING: A large occupational respiratory surveillance program utilizing rigorously quality-assured and standardized spirometry. SUBJECTS: The study included 5,188 men aged 45 to 65 years who denied fibrogenic dust exposures, including 656 with airways obstruction. RESULTS: There was a significant (p < 0.0001) linear relationship between more severe obstruction (lower FEV1/FVC) and lower FVC %PRED. Depending on which of several predictive equations is used, obstruction explains 15 to 17% of variability in FVC %PRED over the entire range of severity of obstruction. Adjusting for obstruction in the separate group of 530 subjects showed a significantly larger effect of body weight on FVC %PRED. CONCLUSION: A simple equation can be used to discount the negative effects of obstruction on FVC. This allows more accurate clinical interpretation and can be useful in the analysis of epidemiologic data.

Blue-collar normative spirometric values for Caucasian and African-American men and women aged 18 to 65.

Normative spirometric values were derived from 5,042 white (of mainly European ancestry) and black (of mainly African ancestry) men and women paper plant workers who are never-smokers, with no respiratory symptoms or diagnoses and no history of occupational exposure to fibrogenic dusts or irritant chemicals. This cohort was selected from a much larger population under long-term respiratory surveillance (n > 50,000 at 50 plants). Standardized equipment, procedures, and data reduction methods complied with ATS recommendations. Data were collected by the medical departments of the participating companies as part of their routine health surveillance, and the graphic and numeric test results were transmitted to the Tulane University Section of Environmental Medicine for centralized quality assurance, interpretation, and archiving. The large numbers allow derivation of gender- and race-specific reference values. Lower limits of normal were derived and depend upon residual variation and any changes in variation with age. The results indicate that polynomial regression equations provide a significantly better fit than linear regressions with breakpoints. In addition to being more biologically plausible, the polynomial model more closely matches observed longitudinal changes in lung function with age. The age range of the cohort, 18 to 65, provides a regression that more closely matches the observed values in this range, because it does not include "supernormal" elderly survivors, which can lessen the slope of the regression and artifactually increase the predicted values of 50 to 65 yr olds. The regression equations derived for black men and women do not support the use of a single race adjustment (0.85 or 0.88) for all age, sex, height, and spirometric test parameter combinations. These race- and gender-specific regression equations, with their respective lower limits of normal, should improve the detection and quantification of adverse health effects in working individuals and populations.

Cotton dust and across-shift change in FEV1 as predictors of annual change in FEV1.

In this report of a 5-yr longitudinal study of workers employed at six cotton textile mills, exposure and across-shift FEV1 change were evaluated as possible predictors of the annual change in FEV1 for yarn manufacturing workers. A total of 611 workers had three repeatable spirometric tests, over at least 3 yr, and at least one (average of three) across-shift test, while always working the same shift. The "same shift" criterion controlled for the effect of diurnal variation. Average exposure was determined from measures of lint-free elutriated cotton dust in combination with job histories. This study found a significant association between the acute and chronic effects of cotton dust exposure. Both exposure and across-shift change proved to be significant predictors of annual change, and excess annual declines in FEV1 were predicted even for exposures of 200 micrograms/m3 and across-shift drops in FEV1 of 200 ml. These results suggest that, to prevent dust-related chronic decline in lung function, current smokers should be excluded from yarn manufacturing work and exposures should be reduced below 200 micrograms/m3, to approximately 100 micrograms/m3.

Exposure-related declines in the lung function of cotton textile workers. Relationship to current workplace standards.

To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS)

The power to detect differences in average rates of change in longitudinal studies.

With considerable current interest in longitudinal epidemiologic studies, little is available regarding sample size requirements. This paper considers a method for analysis of longitudinal data, where one compares the mean rates of change for two or more groups, and proposes a statistic for use in determining sample size requirements. One calculates individual rates of change with least squares estimates of slopes of individuals' responses regressed over time. The assumption of linear change over time, while clearly not applicable for some data, applies to many biological measurements, either as recorded or with some transformation. The variances of these estimated slopes have two components: within-individual variability based on measurement error and length and frequency of follow-up, and true between-individual slope variability. It is assumed that measurement error is the same for all subjects, so that the total variances differ due to differences in follow-up. The question addressed is: when can one use the usual ANOVA F statistic to compare group means of estimated slopes? Expected mean squares demonstrate that this F is appropriate when either group has the same number of subjects, or when each subject has the same length and frequency of follow-up. A procedure for computing power and sample size is presented, where one can specify the maximum detectable difference in any two average slopes. Moment estimation and maximum likelihood estimation of variance components from prior data are discussed.

Allergic etiology of benign fibrocystic changes of the breast.

We postulate that fibrocystic changes in the female breast are the end result of a series of biochemical events initiated by the mast cell degranulation products histamine and heparin. Two mechanisms are proposed which could lead to mast cell degranulation in breast tissue. First, low progesterone levels lead to decreased intracellular cAMP levels in mast cells which enhance mast cell degranulation. Second, low progesterone levels lead to increased solubilization of breast collagen during tissue turnover. Susceptible individuals may undergo an allergic reaction to soluble collagen resulting in further mast cell degranulation. The degranulation products histamine and heparin may stimulate increased stromal proliferation and vascularization respectively. We provide evidence for the occurrence of histamine release by demonstrating an increased incidence of allergic symptoms in white women with fibrocystic breast changes.