Evidence map›Paper›PMID 27518660›Full record

ArticleThe New England journal of medicine2016

Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children.

Michelle M Stein, Cara L Hrusch, Justyna Gozdz, Catherine Igartua, Vadim Pivniouk, Sean E Murray, Julie G Ledford, Mauricius Marques Dos Santos, Rebecca L Anderson, Nervana Metwali and 10 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05063149 (Protecting Late-moderate Preterm Infants From Respiratory Tract Infections and Wheeze in Their First Years of Life by Using Bacterial Lysates.), which is not on this map. Cited by 471 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
471citing papers in PubMed, 3 pooled it
137.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05063149 phase3recruitingnot on this mapstarted 2022, after this paper: background citation

Protecting Late-moderate Preterm Infants From Respiratory Tract Infections and Wheeze in Their First Years of Life by Using Bacterial Lysates.

TypeinterventionalSponsorFranciscus GasthuisRan2022 to 2026Enrolled500ConditionsWheezing, LRTI, PrematureArmsBroncho-Vaxom, Placebo
3 · Its place in the literature

Who cites it

471 citing papers in PubMed, 3 syntheses or guidelines pooled it, 924 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Genetic ancestry is associated with asthma, and this could be modified by environmental factors. A systematic review.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2023
    Pooled it
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
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  11. Article
  12. Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026
    Review
  13. Toward Meta-Omics Governance of the Urban Microbiome Commons.Annals of the New York Academy of Sciences · 2026
    Review
  14. Review
  15. Article
  16. The Role of the Indoor Exposome in Food Allergy Development.Current allergy and asthma reports · 2026
    Review
  17. Review
  18. Article
  19. Article
  20. Review

411 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 2 countries.

Michelle M Stein *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Cara L Hrusch *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Justyna Gozdz *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Catherine IgartuaDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Vadim PivnioukDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Sean E MurrayDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Julie G LedfordDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Mauricius Marques Dos SantosDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Rebecca L AndersonDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Nervana MetwaliDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Julia W NeilsonDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Raina M MaierDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Jack A GilbertDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Mark HolbreichDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Peter S ThorneDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Fernando D MartinezDepartment of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Erika von Mutius *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Donata Vercelli *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Carole Ober *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Anne I Sperling *Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
Argonne National Laboratory · USUniversity of Arizona · USUniversity of Iowa · USUniversity of Chicago · US

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI CHIEN-MIN KAO · 1985 to 2026
$122.1M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
RESEARCH TRAINING IN RESPIRATORY BIOLOGYT32HL007605 · NHLBI · UNIVERSITY OF CHICAGO · PI Yun Fang, Gokhan M. Mutlu · 1985 to 2026
$18.1M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
Regulation and expression of HLA-G in asthmatic airwaysU19AI095230 · NIAID · UNIVERSITY OF CHICAGO · PI KRISHNAN, JERRY A. · 2011 to 2016
$10.5M
Sex-Specific Genetic Architecture of Asthma-Associated Quantitative TraitsR01HL085197 · NHLBI · UNIVERSITY OF CHICAGO · PI OBER, CAROLE · 2007 to 2015
$7.6M
Surfactant Protein-A regulation of eosinophil apoptosis in asthmaR01HL125602 · NHLBI · UNIVERSITY OF ARIZONA · PI LEDFORD, JULIE GUNNELLS · 2015 to 2019
$1.9M
The role of SP-A in Mp-induced exacerbations during allergic airway disease.R00HL111151 · NHLBI · UNIVERSITY OF ARIZONA · PI LEDFORD, JULIE GUNNELLS · 2014 to 2016
$716k
NCI NIH HHS P30 CA014599NHLBI NIH HHS R00 HL111151NHLBI NIH HHS R01 HL085197NHLBI NIH HHS R01 HL125602NHLBI NIH HHS T32 HL007605NIAID NIH HHS U19 AI095230NIEHS NIH HHS P30 ES005605NIEHS NIH HHS P30 ES006694NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

backgroundThe Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices. The populations also show striking disparities in the prevalence of asthma, and little is known about the immune responses underlying these disparities.

methodsWe studied environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples. Whole blood was collected to measure serum IgE levels, cytokine responses, and gene expression, and peripheral-blood leukocytes were phenotyped with flow cytometry. The effects of dust extracts obtained from Amish and Hutterite homes on immune and airway responses were assessed in a murine model of experimental allergic asthma.

resultsDespite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish, whereas median endotoxin levels in Amish house dust was 6.8 times as high. Differences in microbial composition were also observed in dust samples from Amish and Hutterite homes. Profound differences in the proportions, phenotypes, and functions of innate immune cells were also found between the two groups of children. In a mouse model of experimental allergic asthma, the intranasal instillation of dust extracts from Amish but not Hutterite homes significantly inhibited airway hyperreactivity and eosinophilia. These protective effects were abrogated in mice that were deficient in MyD88 and Trif, molecules that are critical in innate immune signaling.

conclusionsThe results of our studies in humans and mice indicate that the Amish environment provides protection against asthma by engaging and shaping the innate immune response. (Funded by the National Institutes of Health and others.).

Indexed as

AgricultureEnvironmental ExposureImmunity, InnateAdaptor Proteins, Vesicular TransportAdolescentAnimalsAsthmaChildChristianityCross-Sectional StudiesCytokinesDisease Models, AnimalDustFemaleGene ExpressionHumansAdaptor Proteins, Vesicular TransportCytokinesDustImmunoglobulin EMyd88 protein, mouseMyeloid Differentiation Factor 88Ticam1 protein, mouse

Identifiers

PMID27518660
PMCPMC5137793
OpenAlexW2484915396

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