ArticleNature communications2015
The polymeric mucin Muc5ac is required for allergic airway hyperreactivity.
2 registry-linked trialsOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 168 papers.
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168citing papers in PubMed
15.8field-weighted citation impact, top 1% of its field
What it found
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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.
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.
NCT03513458 phase1 / phase2withdrawnnot on this mapstarted 2020, after this paper: background citation
Late Phase Administration Anakinra as a Rescue Treatment for Inhaled Allergen Challenge-Induced Airway Inflammation
NCT03513471 phase1 / phase2withdrawnnot on this mapstarted 2019, after this paper: background citation
Early Phase Administration of Anakinra as a Rescue Treatment for Inhaled Allergen Challenge-Induced Airway Inflammation
Who cites it
168 citing papers in PubMed, 282 citations in OpenAlex.
- Natural Products Targeting Airway Inflammation and Mucus Hypersecretion: Molecular Mechanisms and Therapeutic Potential for Respiratory Health.Nutrients · 2026Review
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- Beyond Eosinophil Depletion: IL-5 as a Context-Dependent Regulator of Airway Immune Networks.International journal of molecular sciences · 2026Review
- Lung maneuvers of large amplitudes for probing physiological alterations in mouse models of asthma.Animal models and experimental medicine · 2026Article
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Comprehensive Review of Natural Products Against Allergic Rhinitis and Asthma: From Sensitization to Chronic Remodeling.International journal of molecular sciences · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Butyrate SilencesAllergy, asthma & immunology research · 2026Article
- In Vitro Evaluation of the Inhibitory Effects of Linarin on Histamine-Induced Expression of Proinflammatory Cytokines, Mucin 5AC, and Aquaporin 5 in Human Nasal and Bronchial Epithelial Cells.The Kaohsiung journal of medical sciences · 2026Article
- Proteomic profiling of equine airway mucus reveals compositional changes in asthmatic phenotypes.Scientific reports · 2026Article
- The FOXA transcription factors in allergic airway disease and asthma.Frontiers in allergy · 2026Review
- Single Cell Transcriptomic Atlas Reveals Cellular Heterogeneity and Molecular Mechanisms in Pediatric Airway Hyperresponsiveness Epithelium.International journal of genomics · 2026Article
- Airway epithelial dysfunction in asthma pathogenesis: epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities.Frontiers in allergy · 2026Review
- Methacholine hyperresponsiveness in mice with house dust mite-induced lung inflammation is not associated with excessive airway constriction ex vivo.Experimental physiology · 2025Article
- Inhibitory effects of Raphanus sativus root extracts on MUC5AC gene expression in human airway epithelial cells.NPJ science of food · 2025Article
- Combustion products of burn pit constituents induce more changes in asthmatic than non-asthmatic murine lungs.Particle and fibre toxicology · 2025Article
- Risk factors analysis of airway mucus plugs in community-acquired refractory mycoplasma pneumoniae pneumonia: a case-control study.Italian journal of pediatrics · 2025Article
- Hederasaponin C ameliorates chronic obstructive pulmonary disease pathogenesis by targeting TLR4 to inhibit NF-κB/MAPK signaling pathways.Chinese medicine · 2025Article
- Enhanced allergic Eustachian tube response in surfactant protein D knockout mice induced by ovalbumin.The World Allergy Organization journal · 2025Article
- Parasympathetic Airway Hyperreactivity Is Enhanced in Acute but Not Chronic Eosinophilic Asthma Mouse Models.American journal of respiratory cell and molecular biology · 2025Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Christopher M EvansDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Dorota S RaclawskaDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Fani TtofaliDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Deborah R LiptzinDepartment of Pediatrics, University of Colorado School of Medicine, 13123 East 16th Avenue, B-395, Aurora, Colorado 80045, USA.
Ashley A FletcherDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Daniel N HarperDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Maggie A McGingDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Melissa M McElweeDepartment of Pulmonary Medicine, University of Texas, MD Anderson Cancer Center, PO Box 301402, Houston, Texas 77030, USA.
Olatunji W WilliamsPediatrics, Peyton Manning Children's Hospital, 8402 Harcourt Road, Suite 731, Indianapolis, Indiana 46260, USA.
Elizabeth SanchezDepartment of Pulmonary Medicine, University of Texas, MD Anderson Cancer Center, PO Box 301402, Houston, Texas 77030, USA.
Michelle G RoyDepartment of Pulmonary Medicine, University of Texas, MD Anderson Cancer Center, PO Box 301402, Houston, Texas 77030, USA.
Kristen N KindrachukImmunopathogenesis Section, Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4071, MSC 6606, Bethesda, Maryland 20892-6606, USA.
Thomas A WynnImmunopathogenesis Section, Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4071, MSC 6606, Bethesda, Maryland 20892-6606, USA.
Holger K EltzschigDepartment of Anesthesiology, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop B112, Research Complex 2, Room 7124, Aurora, Colorado 80045, USA.
Michael R BlackburnDepartment of Biochemistry and Molecular Biology, The University of Texas-Houston Medical School, 6431 Fannin, Houston, Texas 77030, USA.
Michael J TuvimDepartment of Pulmonary Medicine, University of Texas, MD Anderson Cancer Center, PO Box 301402, Houston, Texas 77030, USA.
William J Janssen1] Department of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA [2] Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
David A SchwartzDepartment of Medicine, University of Colorado School of Medicine, 12700 E 19th Avenue, Mailstop 8611, Research Complex 2, Room 3121, Aurora, Colorado 80045, USA.
Burton F DickeyDepartment of Pulmonary Medicine, University of Texas, MD Anderson Cancer Center, PO Box 301402, Houston, Texas 77030, USA.
University of Colorado Denver · USThe University of Texas MD Anderson Cancer Center · USNational Institute of Allergy and Infectious Diseases · USPeyton Manning Children’s Hospital at St.Vincent · USThe University of Texas Health Science Center at Houston · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUniversity of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MRole of Genetics in Idiopathic Pulmonary Fibrosis (IPF)R01HL097163 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI FINGERLIN, TASHA E., SCHWARTZ, DAVID ALBERT · 2009 to 2018
$16.4MTrangenic Mouse Breeding CoreP01HL114457 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BLACKBURN, MICHAEL R · 2013 to 2017
$10.0MRole of Mucin in Lung Homeostasis and PathophysiologyR01HL080396 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Christopher M Evans · 2009 to 2026
$8.6MMechanisms of Fibrosis in Asthma and Other Fibroproliferative DiseasesZIAAI001019 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WYNN, THOMAS · 2009 to 2018
$7.1MAdenosine Signaling and Lung FibrosisR01HL070952 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BLACKBURN, MICHAEL R · 2002 to 2019
$5.7MControlling the core airway mucin secretion machinery to prevent pathophysiologyR01HL129795 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DICKEY, BURTON F · 2015 to 2023
$3.8MMacrophage Apoptosis in Resolution of Acute Lung InjuryR01HL109517 · NHLBI · NATIONAL JEWISH HEALTH · PI JANSSEN, WILLIAM · 2012 to 2017
$3.1MMUC5B, a novel therapeutic target for Idiopathic Pulmonary Fibrosis (IPF)UH2HL123442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2014 to 2015
$3.0MExtracellular Adenosine During Ventilator Induced Lung InjuryR01HL092188 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ELTZSCHIG, HOLGER K. · 2009 to 2013
$2.1MMolecular Pathways Regulating Airway Goblet Cell Mucin SecretionR01HL097000 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVIS, C. WILLIAM, DICKEY, BURTON F · 2010 to 2013
$2.0MNCI NIH HHS P30 CA016672NCI NIH HHS P30CA016672NCI NIH HHS P30 CA046934NCI NIH HHS P30CA046934NHLBI NIH HHS P01 HL114457NHLBI NIH HHS P01HL114457NHLBI NIH HHS R01 HL070952NHLBI NIH HHS R01HL070952NHLBI NIH HHS R01 HL080396NHLBI NIH HHS R01HL080396NHLBI NIH HHS R01 HL092188NHLBI NIH HHS R01HL092188NHLBI NIH HHS R01 HL097000NHLBI NIH HHS R01HL097000NHLBI NIH HHS R01 HL097163NHLBI NIH HHS R01 HL098294NHLBI NIH HHS R01HL098294NHLBI NIH HHS R01 HL109517NHLBI NIH HHS R01HL109517NHLBI NIH HHS R01 HL119837NHLBI NIH HHS R01HL119837NHLBI NIH HHS R01 HL129795NHLBI NIH HHS R21 HL120770NHLBI NIH HHS R21HL120770NHLBI NIH HHS R33 HL120770NHLBI NIH HHS UH2 HL123442NHLBI NIH HHS UH2HL123442NIDDK NIH HHS R01 DK097075NIDDK NIH HHS R01DK097075NIEHS NIH HHS R21 ES023384NIEHS NIH HHS R21ES023384
Abstract
In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.
Indexed as
AllergensAnimalsAspergillus oryzaeAsthmaBronchial HyperreactivityFemaleImmunohistochemistryInflammationLungMaleMethacholine ChlorideMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMucin 5ACAllergensMethacholine ChlorideMuc5ac protein, mouseMucin 5ACOvalbumin
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Registered trials
NCT03513458ClinicalTrials.gov
NCT03513471ClinicalTrials.gov
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.