title: Lung inflammation biomarkers and lung function in children chronically exposed to arsenic.
abstract: Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases.
authors.affiliation: Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico; School of Medicine, University Juarez of Durango, Gomez Palacio, Durango, Mexico. Electronic address: edgar_olivascalderon@hotmail.com.
authors.forename: Edgar
authors.initials: E
authors.lastname: Olivas-Calderón
authors.affiliation: Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico. Electronic address: rrecio@yahoo.com.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Recio-Vega
authors.affiliation: Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ, USA; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA. Electronic address: gandolfi@pharmacy.arizona.edu.
authors.forename: A Jay
authors.initials: AJ
authors.lastname: Gandolfi
authors.affiliation: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA. Electronic address: lantz@email.arizona.edu.
authors.forename: R Clark
authors.initials: RC
authors.lastname: Lantz
authors.affiliation: Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico. Electronic address: taniagc2201@hotmail.com.
authors.forename: Tania
authors.initials: T
authors.lastname: González-Cortes
authors.affiliation: Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico. Electronic address: cesargonzalezalba@hotmail.com.
authors.forename: Cesar
authors.initials: C
authors.lastname: Gonzalez-De Alba
authors.affiliation: Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: jfroines@ucla.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Froines
authors.affiliation: School of Medicine, University Juarez of Durango, Gomez Palacio, Durango, Mexico. Electronic address: dr.jorge.espinosa@gmail.com.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Espinosa-Fematt
mesh_terms: D001151:Arsenic / Q000009:adverse effects* / Q000652:urine*; D001152:Arsenicals / Q000378:metabolism; D015415:Biomarkers; D002101:Cacodylic Acid / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D060766:Drinking Water / Q000032:analysis*; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D011014:Pneumonia / Q000139:chemically induced* / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D012424:Rural Population; D013147:Spirometry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014873:Water Pollutants / Q000009:adverse effects* / Q000652:urine*
chemical_list: D001152:Arsenicals; D015415:Biomarkers; D060766:Drinking Water; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019715:Tissue Inhibitor of Metalloproteinase-1; D014873:Water Pollutants; D002101:Cacodylic Acid; D020780:Matrix Metalloproteinase 9; C020300:monomethylarsonic acid; D001151:Arsenic
keywords: Arsenic; Lung inflammation; Metalloproteinase-9 (MMP-9); Soluble receptor for advanced glycation end products (sRAGE); Sputum; Tissue inhibitor of metalloproteinase (TIMP-1)