Evidence map›Paper›PMID 33493557›Full record

Observational studyThe Journal of allergy and clinical immunology2021

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

Alisha M Smith, Nathan Harper, Justin A Meunier, Anne P Branum, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Charles S Dela Cruz, Marcos I Restrepo, Diego J Maselli and 17 more

Open access · greenAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Development of a peripheral blood transcriptomic gene signature to predict bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023
    Trial
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 10 institutions in 2 countries.

Alisha M SmithVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex; Department of Microbiology, Immunology & Molecular Genetics, UT Health San Antonio, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Nathan HarperVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex.
Justin A MeunierVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex.
Anne P BranumVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex.
Fabio JimenezVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex.
Lavanya PandrankiVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Andrew CarrilloVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Charles S Dela CruzSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.
Marcos I RestrepoVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Diego J MaselliVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Cynthia G RatherBiogenics Research Chamber, San Antonio, Tex.
Anna H HeisserVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex.
Daniel A RamirezBiogenics Research Chamber, San Antonio, Tex.
Weijing HeVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex.
Robert A ClarkVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Microbiology, Immunology & Molecular Genetics, UT Health San Antonio, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Charles P AndrewsBiogenics Research Chamber, San Antonio, Tex.
Scott E EvansDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Tex.
Jacqueline A PughVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex.
Nu ZhangDepartment of Microbiology, Immunology & Molecular Genetics, UT Health San Antonio, San Antonio, Tex.
Grace C LeeVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; College of Pharmacy, The University of Texas at Austin, Austin, Tex; Pharmacotherapy Education and Research Center, School of Medicine, UT Health San Antonio, San Antonio, Tex.
Alvaro G MoreiraVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Division of Neonatology, Department of Pediatrics, UT Health San Antonio, San Antonio, Tex.
Leopoldo N SegalDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY.
Robert M RamirezBiogenics Research Chamber, San Antonio, Tex.
Robert L JacobsBiogenics Research Chamber, San Antonio, Tex.
Muthu Saravanan ManoharanVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex.
Jason F OkuliczInfectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Tex.
Sunil K AhujaVeterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, Tex; Department of Microbiology, Immunology & Molecular Genetics, UT Health San Antonio, San Antonio, Tex; Department of Medicine, UT Health San Antonio, San Antonio, Tex; Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, Tex. Electronic address: ahujas@uthscsa.edu.
South Texas Veterans Health Care System · USThe University of Texas Health Science Center at San Antonio · USMacroGenics (United States) · USThe University of Texas Health Science Center at Houston · USFoundation for Advancing Veterans Health Research · USBiogen (Switzerland) · CHNew York University · USSan Antonio Military Medical Center · USThe University of Texas MD Anderson Cancer Center · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUM1TR004538 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ROBERT A CLARK, Kenneth M Hargreaves · 2023 to 2026
$22.3M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR002645 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A, HARGREAVES, KENNETH M · 2018 to 2022
$20.4M
Institutional Research Training GrantT32DE014318 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Kenneth M Hargreaves · 2002 to 2026
$12.1M
Host Genetic Determinants of HIV PathogenesisR37AI046326 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AHUJA, SUNIL K · 2005 to 2014
$7.8M
Inducible epithelial resistance: a program investigating mechanisms to protect against acute and chronic complications of pneumoniaR35HL144805 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EVANS, SCOTT E. · 2019 to 2025
$6.2M
Microbial triggers and molecular mechanisms of Th17 mediated airway inflammation-Resubmission-1R01HL125816 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KORALOV, SERGEI BORISOVICH · 2015 to 2019
$3.3M
Inducible epithelial antiviral resistance to prevent asthmaDP2HL123229 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EVANS, SCOTT E. · 2013 to 2013
$2.4M
Lung Microbiome and Inflammation in Early COPDK23AI102970 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SEGAL, LEOPOLDO NICOLAS · 2014 to 2017
$754k
Metformin to improve immunological health and vaccine responsesK23AG066933 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI LEE, GRACE CHOI · 2020 to 2023
$637k
Center for Personalized Medicine: Systems of Biology of Inflammation and ImmunityIP1CX000875 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI AHUJA, SEEMA SINGH, AHUJA, SUNIL K · 2014 to 2017
–
BLRD VA I01 BX004661CSRD VA IP1 CX000875NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR002645NCATS NIH HHS UM1 TR004538NHLBI NIH HHS DP2 HL123229NHLBI NIH HHS R01 HL125816NHLBI NIH HHS R35 HL144805NIAID NIH HHS K23 AI102970NIAID NIH HHS R37 AI046326NIA NIH HHS K23 AG066933NIDCR NIH HHS T32 DE014318
6 · The paper itself

Abstract

backgroundSignifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation.

objectiveWe sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers.

methodsAdults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified.

resultsHDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8

conclusionsRepetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Indexed as

AllergensAsthmaEosinophilsLymphocytesPyroglyphidaeRespiratory MucosaAdultAnimalsFemaleHumansInflammationMaleAllergensAeroallergen challenge chamberallergic rhinoconjunctivitisevoked phenotypeshouse dust mitesmaladaptation

Identifiers

PMID33493557
PMCPMC8298629
OpenAlexW3124019274

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.