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Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.

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Title: Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.
Authors: Li D; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China., Yue Z; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China., Zhen G; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Source: Inhalation toxicology [Inhal Toxicol] 2026 Oct; Vol. 38 (9), pp. 513-523. Date of Electronic Publication: 2026 Jun 19.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Informa Healthcare Country of Publication: England NLM ID: 8910739 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-7691 (Electronic) Linking ISSN: 08958378 NLM ISO Abbreviation: Inhal Toxicol Subsets: MEDLINE
Imprint Name(s): Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : Hemisphere Pub. Corp., c1989-
MeSH Terms: Sepsis*/epidemiology , Sepsis*/blood , Metals, Heavy*/toxicity , Metals, Heavy*/blood , Environmental Exposure*/adverse effects , Environmental Pollutants*/blood , Environmental Pollutants*/toxicity, Lymphopenia/epidemiology ; Lymphopenia/chemically induced ; Biomarkers/blood ; United States/epidemiology ; Cadmium/blood ; Lead/blood ; Humans ; Female ; Male ; Nutrition Surveys ; Adult ; Middle Aged ; Neutrophils ; Disease Susceptibility ; Lymphocytes
Abstract: Background: Sepsis is a life-threatening syndrome of immune dysregulation; preexisting lymphopenia and an elevated neutrophil-to-lymphocyte ratio (NLR) heighten host susceptibility. Chronic low-dose exposure to lead (Pb), cadmium (Cd), and mercury (Hg) is immunotoxic, but its association with these pre-sepsis markers in the general population remains unclear.
Methods: We analyzed 12,580 adults from NHANES 2011-2018. Outcomes were lymphopenia (absolute lymphocyte count <1.0 × 109/L) and high NLR (top quartile). Survey-weighted logistic and Weighted Quantile Sum (WQS) regressions evaluated individual and joint mixture effects. Restricted cubic splines modeled dose-response relationships. Continuous exposure models were also constructed to minimize information loss.
Results: Fully adjusted models showed higher quartiles of Pb, Cd, and Hg were each associated with greater odds of lymphopenia and high NLR. Comparing highest to lowest quartiles, ORs for lymphopenia were 1.85 (95% CI 1.42-2.41) for Pb, 1.66 (95% CI 1.28-2.15) for Cd, and 1.52 (95% CI 1.15-2.01) for Hg. Continuous models confirmed that each log2-fold increase in blood metals was associated with significantly reduced absolute lymphocyte counts and elevated NLR (all p < 0.05). The WQS index was positively associated with lymphopenia (OR 1.63) and high NLR (OR 1.48).
Conclusion: In a nationally representative sample, chronic low-level exposure to Pb, Cd, and Hg was independently associated with an immune profile linked to sepsis susceptibility, suggesting environmental metal reduction as a potential population-level strategy to reduce sepsis risk.
Contributed Indexing: Keywords: Heavy metals; NHANES; environmental epidemiology; immune dysregulation; lymphopenia; neutrophil-to-lymphocyte ratio; sepsis
Substance Nomenclature: 0 (Metals, Heavy)
0 (Environmental Pollutants)
0 (Biomarkers)
00BH33GNGH (Cadmium)
2P299V784P (Lead)
Entry Date(s): Date Created: 20260619 Date Completed: 20260929 Latest Revision: 20260929
Update Code: 20260929
DOI: 10.1080/08958378.2026.2687782
PMID: 42319987
Database: MEDLINE
FullText Text:
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DbLabel: MEDLINE
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PubType: Academic Journal
PubTypeId: academicJournal
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  Label: Title
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  Data: Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+D%22&quot;&gt;Li D&lt;/searchLink&gt;; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yue+Z%22&quot;&gt;Yue Z&lt;/searchLink&gt;; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhen+G%22&quot;&gt;Zhen G&lt;/searchLink&gt;; Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%228910739%22&quot;&gt;Inhalation toxicology&lt;/searchLink&gt; [Inhal Toxicol] 2026 Oct; Vol. 38 (9), pp. 513-523. &lt;i&gt;Date of Electronic Publication: &lt;/i&gt;2026 Jun 19.
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  Data: &lt;i&gt;Publisher: &lt;/i&gt;&lt;searchLink fieldCode=&quot;PB&quot; term=&quot;%22Informa+Healthcare%22&quot;&gt;Informa Healthcare &lt;/searchLink&gt;&lt;i&gt;Country of Publication: &lt;/i&gt;England &lt;i&gt;NLM ID: &lt;/i&gt;8910739 &lt;i&gt;Publication Model: &lt;/i&gt;Print-Electronic &lt;i&gt;Cited Medium: &lt;/i&gt;Internet &lt;i&gt;ISSN: &lt;/i&gt;1091-7691 (Electronic) &lt;i&gt;Linking ISSN: &lt;/i&gt;&lt;searchLink fieldCode=&quot;IS&quot; term=&quot;%2208958378%22&quot;&gt;08958378 &lt;/searchLink&gt;&lt;i&gt;NLM ISO Abbreviation: &lt;/i&gt;Inhal Toxicol &lt;i&gt;Subsets: &lt;/i&gt;MEDLINE
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  Data: &lt;i&gt;Publication&lt;/i&gt;: London : Informa Healthcare&lt;br /&gt;&lt;i&gt;Original Publication&lt;/i&gt;: New York, N.Y. : Hemisphere Pub. Corp., c1989-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Sepsis%22&quot;&gt;Sepsis*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Sepsis+epidemiology%22&quot;&gt;epidemiology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Sepsis%22&quot;&gt;Sepsis*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Sepsis+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy%22&quot;&gt;Metals, Heavy*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy+toxicity%22&quot;&gt;toxicity&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy%22&quot;&gt;Metals, Heavy*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Exposure%22&quot;&gt;Environmental Exposure*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Exposure+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants%22&quot;&gt;Environmental Pollutants*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants%22&quot;&gt;Environmental Pollutants*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants+toxicity%22&quot;&gt;toxicity&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lymphopenia%22&quot;&gt;Lymphopenia&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lymphopenia+epidemiology%22&quot;&gt;epidemiology&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lymphopenia%22&quot;&gt;Lymphopenia&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lymphopenia+chemically+induced%22&quot;&gt;chemically induced&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Biomarkers%22&quot;&gt;Biomarkers&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Biomarkers+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22United+States%22&quot;&gt;United States&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22United+States+epidemiology%22&quot;&gt;epidemiology&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Cadmium%22&quot;&gt;Cadmium&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Cadmium+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lead%22&quot;&gt;Lead&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lead+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Humans%22&quot;&gt;Humans&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Nutrition+Surveys%22&quot;&gt;Nutrition Surveys&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Adult%22&quot;&gt;Adult&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Middle+Aged%22&quot;&gt;Middle Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Neutrophils%22&quot;&gt;Neutrophils&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Disease+Susceptibility%22&quot;&gt;Disease Susceptibility&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Lymphocytes%22&quot;&gt;Lymphocytes&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Sepsis is a life-threatening syndrome of immune dysregulation; preexisting lymphopenia and an elevated neutrophil-to-lymphocyte ratio (NLR) heighten host susceptibility. Chronic low-dose exposure to lead (Pb), cadmium (Cd), and mercury (Hg) is immunotoxic, but its association with these pre-sepsis markers in the general population remains unclear.&lt;br /&gt;Methods: We analyzed 12,580 adults from NHANES 2011-2018. Outcomes were lymphopenia (absolute lymphocyte count &amp;lt;1.0 &#215; 10&lt;superscript&gt;9&lt;/superscript&gt;/L) and high NLR (top quartile). Survey-weighted logistic and Weighted Quantile Sum (WQS) regressions evaluated individual and joint mixture effects. Restricted cubic splines modeled dose-response relationships. Continuous exposure models were also constructed to minimize information loss.&lt;br /&gt;Results: Fully adjusted models showed higher quartiles of Pb, Cd, and Hg were each associated with greater odds of lymphopenia and high NLR. Comparing highest to lowest quartiles, ORs for lymphopenia were 1.85 (95% CI 1.42-2.41) for Pb, 1.66 (95% CI 1.28-2.15) for Cd, and 1.52 (95% CI 1.15-2.01) for Hg. Continuous models confirmed that each log2-fold increase in blood metals was associated with significantly reduced absolute lymphocyte counts and elevated NLR (all p &amp;lt; 0.05). The WQS index was positively associated with lymphopenia (OR 1.63) and high NLR (OR 1.48).&lt;br /&gt;Conclusion: In a nationally representative sample, chronic low-level exposure to Pb, Cd, and Hg was independently associated with an immune profile linked to sepsis susceptibility, suggesting environmental metal reduction as a potential population-level strategy to reduce sepsis risk.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: &lt;i&gt;Keywords: &lt;/i&gt;Heavy metals; NHANES; environmental epidemiology; immune dysregulation; lymphopenia; neutrophil-to-lymphocyte ratio; sepsis
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Metals, Heavy)&lt;br /&gt;0 (Environmental Pollutants)&lt;br /&gt;0 (Biomarkers)&lt;br /&gt;00BH33GNGH (Cadmium)&lt;br /&gt;2P299V784P (Lead)
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  Label: Entry Date(s)
  Group: Date
  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260619 &lt;i&gt;Date Completed: &lt;/i&gt;20260929 &lt;i&gt;Latest Revision: &lt;/i&gt;20260929
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  Data: 20260929
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  Data: 10.1080/08958378.2026.2687782
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  Data: 42319987
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42319987
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        Value: 10.1080/08958378.2026.2687782
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 513
    Subjects:
      – SubjectFull: Lymphopenia epidemiology
        Type: general
      – SubjectFull: Lymphopenia chemically induced
        Type: general
      – SubjectFull: Biomarkers blood
        Type: general
      – SubjectFull: United States epidemiology
        Type: general
      – SubjectFull: Cadmium blood
        Type: general
      – SubjectFull: Lead blood
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      – SubjectFull: Humans
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      – SubjectFull: Female
        Type: general
      – SubjectFull: Male
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      – SubjectFull: Nutrition Surveys
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      – SubjectFull: Adult
        Type: general
      – SubjectFull: Middle Aged
        Type: general
      – SubjectFull: Neutrophils
        Type: general
      – SubjectFull: Disease Susceptibility
        Type: general
      – SubjectFull: Lymphocytes
        Type: general
      – SubjectFull: Sepsis epidemiology
        Type: general
      – SubjectFull: Sepsis blood
        Type: general
      – SubjectFull: Metals, Heavy toxicity
        Type: general
      – SubjectFull: Metals, Heavy blood
        Type: general
      – SubjectFull: Environmental Exposure adverse effects
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      – SubjectFull: Environmental Pollutants blood
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      – SubjectFull: Environmental Pollutants toxicity
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    Titles:
      – TitleFull: Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.
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            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
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