Study for Promotion of Health in Recycling Lead – Rationale and design

Abstract

Background. The level at which low-level lead exposure produces subclinical adverse health effects in adults remains to be established. Methods. The Study for Promotion of Health in Recycling Lead (SPHERL) will enroll 500 newly hired workers, whose blood lead during 2 years of follow-up is expected to increase from levels less than 2 μg/dl, as currently observed in the US population, to 20–30 μg/dl. The main outcome variables to be studied are (i) blood pressure (BP) analyzed as a continuous or categorical variable, both cross-sectionally and longitudinally, and using conventional and ambulatory BP measurement; (ii) indexes of glomerular and tubular renal function, (iii) heart rate variability analyzed in the frequency domain as measure of autonomous sympathetic modulation, (iv) peripheral nerve conductivity velocity, (v) neurocognitive performance, and (vi) quality of life. Expected outcomes. Assuming a 10-fold increase in blood lead, SPHERL will have sufficient statistical power to detect over 2 years a steepening of the age-related rise in systolic BP from 1 to 5 mmHg and a doubling of the age-related decline in the estimated glomerular filtration rate from 3.5 to 7.0 ml/min/1.73 m². The longitudinal design of our study complies with the temporality principle of the Bradford–Hill criteria for assessing possible causality between outcomes and exposure. SPHERL will attempt to resolve the apparent contradiction between general population studies showing associations between adverse health effects and low lead exposure with blood lead levels below 5 μg/dl and studies conducted in occupational cohorts indicating that adverse effects of lead exposure occur at much higher blood lead levels.

Trial registration: ClinicalTrials.gov identifier: NCT02243904.

Key Words::

• Autonomic nervous function
• blood pressure
• cardiovascular regulation
• lead
• occupational exposure
• renal function

Acknowledgment

The authors gratefully acknowledge the contribution of the staff at the Studies Coordination Centre in Leuven: Linda Custers, Annick De Soete, Marie-Jeanne Jehoul, Yvette Piccart, Daisy Thijs, and Hanne Truyens.

Role of the funding source

ILZRO supports SPHERL by an unrestricted research grant. In addition, the European Union (grants IC15-CT98-0329-EPOGH, LSHM-CT-2006-037093 InGenious Hyper-Care, HEALTH-F4-2007-201550 HyperGenes, HEALTH-F7-2011- 278249 EU-MASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council Advanced Research Grant 294713 EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.0880.13) gave support to the Studies Coordinating Centre (Leuven, Belgium).

Conflict of interest: None of the authors declares a conflict of interest with regard to the information presented in this manuscript.