α1-Antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts.

BACKGROUND: Severe α1-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1-antitrypsin, but whether they have an increased risk of COPD is uncertain. METHODS: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. RESULTS: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. CONCLUSIONS: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.

Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study.

INTRODUCTION: Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration. METHODS: 163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up. RESULTS: During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively. CONCLUSIONS: Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.

Renal function of chloralkali workers after the cessation of exposure to mercury vapor.

OBJECTIVES: The aims of the study were to assess renal function in chloralkali workers previously exposed to mercury vapor and to assess the impact of selenium status on the biomarkers of kidney function. METHODS: Forty-nine chloralkali workers previously exposed to mercury vapor were compared with 49 age-matched referents in a cross-sectional study. Selected biomarkers of kidney function and biomarkers of selenium status were measured. The index group had been exposed for 13.1 (range 2.8-34.5) years on the average at a mean urinary mercury excretion of 9.3 (range 4.0-25.4) nmol/mmol creatinine a year. The exposure had ceased on an average of 4.8 (range 4.2-10.0) years prior to the examinations. RESULTS: No statistically significant differences were found between the groups for the measured biomarkers of kidney function. The serum selenium concentration and serum glutathione peroxidase activity were associated with the activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG). The results indicate that having higher glutathione peroxidase activity or a higher serum selenium concentration results in a lower excretion of U-NAG. This effect was the most pronounced in the oldest third of the participants. Apparently the well-known association between U-NAG and age could only be found for the participants with a lower selenium status. CONCLUSIONS: Increased activities of U-NAG during ongoing exposure to mercury vapor appear to be reversible upon cessation of exposure. Selenium status has a substantial impact on U-NAG activity and should be considered in studies of U-NAG excretion.

Endocrine and immunologic markers in manganese alloy production workers.

OBJECTIVES: The aim of this study was to investigate selected hormones and immunologic markers in manganese alloy production workers with current and long-term manganese exposure. METHODS: One hundred randomly selected male workers exposed to manganese were compared with 100 male referents (matched for age) from similar process industries in a cross-sectional design. RESULTS: The geometric mean of the exposed workers' urinary manganese concentration was 0.9 (range 0.1-126.3) nmol/mmol creatinine (Cr) versus 0.4 (range 0.1-13.1) nmol/mmol Cr for the referents. The mean duration of exposure to manganese was 20.0 (range 2.1-41.0) years. The geometric mean of the prolactin serum concentration was higher for the exposed subjects than for the referents (229 versus 197 mIE/l, P=0.06). Serum prolactin was associated with current exposure to "soluble inhalable manganese", duration of exposure, and smoking habits. The subjects with the longest duration of exposure to manganese or the highest current exposure to "soluble inhalable manganese" had a statistically significantly higher serum prolactin concentration than the referents. The smokers had a lower serum prolactin concentration than the nonsmokers. The concentrations of the measured immunologic markers were similar in the groups. CONCLUSIONS: The study indicates that manganese exposure can increase the serum prolactin concentration. Both duration and current level of exposure are related to the slight increase, which also appears to be modified by current smoking habits. The serum prolactin concentrations were generally within the reference limits of the laboratory and thus not suitable as an exposure marker at these exposure levels.