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A cleanroom sleeping environment's impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders.

Faber S, Zinn GM, Boggess A, Fahrenholz T, Kern JC, Kingston HM - BMC Complement Altern Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Medicine, The Children's Institute, 1405 Shady Avenue, Pittsburgh, PA, 15217, USA. sfa@the-institute.org.

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.

Trial registration: Clinical Trial Registration Number NCT02195401 (Obtained July 18, 2014).

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Related in: MedlinePlus

Results of the clinical laboratory differences for CD3%, CD4%, WBCs, IgA, and zinc/copper ratio. When applying a cutoff at age 5, separating the younger four children from the older six children, significant decreases were seen for CD3% (p = 0.036) and CD4% (p = 0.028), and a significant increase was seen for WBC (p = 0.031). Trends for increased IgA (p = 0.059) in the younger cohort and elevated zinc/copper ratios (p = 0.061) in the older cohort were present. For CD3% change, two points overlap at +2 in the older cohort. For CD4% change, two points overlap at both – 1 and +1 in the older cohort. In the older cohort for IgA change, two points overlap at – 15.
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Fig5: Results of the clinical laboratory differences for CD3%, CD4%, WBCs, IgA, and zinc/copper ratio. When applying a cutoff at age 5, separating the younger four children from the older six children, significant decreases were seen for CD3% (p = 0.036) and CD4% (p = 0.028), and a significant increase was seen for WBC (p = 0.031). Trends for increased IgA (p = 0.059) in the younger cohort and elevated zinc/copper ratios (p = 0.061) in the older cohort were present. For CD3% change, two points overlap at +2 in the older cohort. For CD4% change, two points overlap at both – 1 and +1 in the older cohort. In the older cohort for IgA change, two points overlap at – 15.

Mentions: Significant clinical results for several markers of immune regulation are summarized in Table 2. When separated into cohorts, the younger children significantly decreased their CD3% (p = 0.036) and CD4% (p = 0.028) compared to the older children. Total white blood cell (WBC) count significantly increased in the younger children and decreased in the older children (p = 0.031). The younger cohort tended to increase their IgA levels, while the older cohort tended to lower their IgA levels (p = 0.059). The clinical laboratory plasma zinc/serum copper ratio exhibited a tendency to increase in the older six children compared to the four younger children (p = 0.061). The results for these markers of immune dysregulation for the two cohorts are shown in Figure 5.Table 2


A cleanroom sleeping environment's impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders.

Faber S, Zinn GM, Boggess A, Fahrenholz T, Kern JC, Kingston HM - BMC Complement Altern Med (2015)

Results of the clinical laboratory differences for CD3%, CD4%, WBCs, IgA, and zinc/copper ratio. When applying a cutoff at age 5, separating the younger four children from the older six children, significant decreases were seen for CD3% (p = 0.036) and CD4% (p = 0.028), and a significant increase was seen for WBC (p = 0.031). Trends for increased IgA (p = 0.059) in the younger cohort and elevated zinc/copper ratios (p = 0.061) in the older cohort were present. For CD3% change, two points overlap at +2 in the older cohort. For CD4% change, two points overlap at both – 1 and +1 in the older cohort. In the older cohort for IgA change, two points overlap at – 15.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374395&req=5

Fig5: Results of the clinical laboratory differences for CD3%, CD4%, WBCs, IgA, and zinc/copper ratio. When applying a cutoff at age 5, separating the younger four children from the older six children, significant decreases were seen for CD3% (p = 0.036) and CD4% (p = 0.028), and a significant increase was seen for WBC (p = 0.031). Trends for increased IgA (p = 0.059) in the younger cohort and elevated zinc/copper ratios (p = 0.061) in the older cohort were present. For CD3% change, two points overlap at +2 in the older cohort. For CD4% change, two points overlap at both – 1 and +1 in the older cohort. In the older cohort for IgA change, two points overlap at – 15.
Mentions: Significant clinical results for several markers of immune regulation are summarized in Table 2. When separated into cohorts, the younger children significantly decreased their CD3% (p = 0.036) and CD4% (p = 0.028) compared to the older children. Total white blood cell (WBC) count significantly increased in the younger children and decreased in the older children (p = 0.031). The younger cohort tended to increase their IgA levels, while the older cohort tended to lower their IgA levels (p = 0.059). The clinical laboratory plasma zinc/serum copper ratio exhibited a tendency to increase in the older six children compared to the four younger children (p = 0.061). The results for these markers of immune dysregulation for the two cohorts are shown in Figure 5.Table 2

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Medicine, The Children's Institute, 1405 Shady Avenue, Pittsburgh, PA, 15217, USA. sfa@the-institute.org.

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.

Trial registration: Clinical Trial Registration Number NCT02195401 (Obtained July 18, 2014).

Show MeSH
Related in: MedlinePlus