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Faruque Parvez,¹ Yu Chen,² Paul W. Brandt-Rauf,¹ Alfred Bernard,³ Xavier Dumont,³ Vesna Slavkovich,¹ Maria Argos,⁴ Jeanine D’Armiento,⁵ Robert Foronjy,⁵ M. Rashidul Hasan,⁶ HEM Mahbubul Eunus,⁷ Joseph H. Graziano,¹ and Habibul Ahsan⁸

¹Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, USA; ²Department of Environmental Medicine, New York University School of Medicine, New York, USA; ³ Department of Public Health, Catholic University of Louvain, Brussels, Belgium; ⁴Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA; ⁵Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA; ⁶Chest Institute, Dhaka, Bangladesh; ⁷Columbia University Arsenic Research Project in Bangladesh, Dhaka, Bangladesh; ⁸Department of Health Studies and Cancer Research Center, University of Chicago, Chicago, USA

Abstract
Background: Arsenic from drinking water has been associated with malignant and nonmalignant respiratory illnesses. The association with nonmalignant respiratory illnesses has not been well established because the assessments of respiratory symptoms may be influenced by recall bias or interviewer bias because participants had visible skin lesions.

Objectives: We examined the relationship of the serum level of Clara cell protein CC16—a novel biomarker for respiratory illnesses—with well As, total urinary As, and urinary As methylation indices.

Methods: We conducted a cross-sectional study in nonsmoking individuals (n = 241) selected from a large cohort with a wide range of As exposure (0.1–761 µg/L) from drinking water in Bangladesh. Total urinary As, urinary As metabolites, and serum CC16 were measured in urine and serum samples collected at baseline of the parent cohort study.

Results: We observed an inverse association between urinary As and serum CC16 among persons with skin lesions (β = –0.13, p = 0.01) . We also observed a positive association between secondary methylation index in urinary As and CC16 levels (β = 0.12, p = 0.05) in the overall study population ; the association was stronger among people without skin lesions (β = 0.18, p = 0.04) , indicating that increased methylation capability may be protective against As-induced respiratory damage. In a subsample of study participants undergoing spirometric measures (n = 31) , we observed inverse associations between urinary As and predictive FEV₁ (forced expiratory volume measured in 1 sec) (r = –0.37 ; FEV₁/forced vital capacity ratio and primary methylation index (r = –0.42, p = 0.01) .

Conclusions: The findings suggest that serum CC16 may be a useful biomarker of epithelial lung damage in individuals with arsenical skin lesions. Also, we observed the deleterious respiratory effects of As exposure at concentrations lower than reported in earlier studies.

Key words: arsenic, Bangladesh, CC16, Clara cell 16, drinking water, epithelial lung damage, respiratory illnesses. Environ Health Perspect 116:190–195 (2008) . doi:10.1289/ehp.9507 available via http://dx.doi.org/ [Online 6 November 2007]

Address correspondence to H. Ahsan, Department of Health Studies, The University of Chicago, 5841 South Maryland Ave., Suite N102, Chicago, IL 60637 USA. Telephone: (773) 834-9956. Fax: (773) 834-0139. E-mail: habib@uchicago.edu

We thank our staff, field workers, and study participants in Bangladesh without whom this work would have been impossible.

This research was supported by grants P42ES10349, P30ES09089, and ES000260 from the National Institute of Environmental Health Sciences ; and grants R01CA107431, R01CA102484, and CA016087 from the National Cancer Institute.

The authors declare they have no competing financial interests.

Received 12 July 2006 ; accepted 2 November 2007.