title: A cleanroom sleeping environment's impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders.
abstract: BACKGROUND
  An emerging paradigm suggests children with autism display a unique pattern of environmental, genetic, and epigenetic triggers that make them susceptible to developing dysfunctional heavy metal and chemical detoxification systems. These abnormalities could be caused by alterations in the methylation, sulfation, and metalloprotein pathways. This study sought to evaluate the physiological and behavioral effects of children with autism sleeping in an International Organization for Standardization Class 5 cleanroom.
  
  
  METHODS
  Ten children with autism, ages 3-12, slept in a cleanroom for two weeks to evaluate changes in toxin levels, oxidative stress, immune dysregulation, and behavior. Before and after the children slept in the cleanroom, samples of blood and hair and rating scale scores were obtained to assess these changes.
  
  
  RESULTS
  Five children significantly lowered their concentration of oxidized glutathione, a biomarker of oxidative stress. The younger cohort, age 5 and under, showed significantly greater mean decreases in two markers of immune dysregulation, CD3% and CD4%, than the older cohort. Changes in serum magnesium, influencing neuronal regulation, correlated negatively while changes in serum iron, affecting oxygenation of tissues, correlated positively with age. Changes in serum benzene and PCB 28 concentrations showed significant negative correlations with age. The younger children demonstrated significant improvements on behavioral rating scales compared to the older children. In a younger pair of identical twins, one twin showed significantly greater improvements in 4 out of 5 markers of oxidative stress, which corresponded with better overall behavioral rating scale scores than the other twin.
  
  
  CONCLUSIONS
  Younger children who slept in the cleanroom altered elemental levels, decreased immune dysregulation, and improved behavioral rating scales, suggesting that their detoxification metabolism was briefly enhanced. The older children displayed a worsening in behavioral rating scale performance, which may have been caused by the mobilization of toxins from their tissues. The interpretation of this exploratory study is limited by lack of a control group and small sample size. The changes in physiology and behavior noted suggest that performance of larger, prospective controlled studies of exposure to nighttime or 24 hour cleanroom conditions for longer time periods may be useful for understanding detoxification in children with autism.
  
  
  BACKGROUND
  Clinical Trial Registration Number NCT02195401 (Obtained July 18, 2014).
authors.affiliation: Medicine, The Children's Institute, 1405 Shady Avenue, Pittsburgh, PA, 15217, USA. sfa@the-institute.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Faber
authors.affiliation: Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA. zinng@duq.edu.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Zinn
authors.affiliation: Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA. boggessa@duq.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Boggess
authors.affiliation: Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA. fahrenholzt@yahoo.com.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fahrenholz
authors.affiliation: Mathematics and Computer Science, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA. kernj@duq.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Kern
authors.affiliation: Chemistry and Biochemistry, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA. kingston@duq.edu.
authors.forename: H M Skip
authors.initials: HM
authors.lastname: Kingston
mesh_terms: D001321:Autistic Disorder / Q000097:blood / Q000150:complications / Q000276:immunology / Q000628:therapy*; D001554:Benzene / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex; D015704:CD4 Antigens; D002648:Child; D002652:Child Behavior; D002653:Child Behavior Disorders / Q000209:etiology / Q000517:prevention & control*; D002659:Child Development Disorders, Pervasive / Q000097:blood / Q000150:complications / Q000276:immunology / Q000628:therapy*; D002675:Child, Preschool; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood; D006798:Housing; D006801:Humans; D008658:Inactivation, Metabolic; D007501:Iron / Q000097:blood; D008274:Magnesium / Q000097:blood; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000097:blood; D011446:Prospective Studies; D012890:Sleep; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014427:Twins
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D015704:CD4 Antigens; D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; D007501:Iron; D008274:Magnesium; D001554:Benzene