Evidence map›Paper›PMID 29384700›Full record

ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2018

Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice.

Laura E Crotty Alexander, Christopher A Drummond, Mark Hepokoski, Denzil Mathew, Alex Moshensky, Andrew Willeford, Soumita Das, Prabhleen Singh, Zach Yong, Jasmine H Lee and 7 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 142 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed, 4 pooled it
13.9field-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.

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

142 citing papers in PubMed, 4 syntheses or guidelines pooled it, 219 citations in OpenAlex.

  1. Pooled it
  2. Exposure to Heated Tobacco Products and Adverse Health Effects, a Systematic Review.International journal of environmental research and public health · 2021
    Pooled it
  3. Lung Damage Caused by Heated Tobacco Products and Electronic Nicotine Delivery Systems: A Systematic Review.International journal of environmental research and public health · 2021
    Pooled it
  4. Pooled it
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Longitudinal Electronic Cigarette Exposures Impair Respiratory Function and Structure in the Female Apoe-/- Mouse.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Cigarette smoking induces NLRP3 inflammasome activation in patients with atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  19. Article
  20. The respiratory epithelium in the era of vaping: insights fromEuropean respiratory review : an official journal of the European Respiratory Society · 2025
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Laura E Crotty AlexanderPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.ORCID 0000-0002-5091-2660
Christopher A DrummondMPI Research, Inc., Surgery and Efficacy Department, Mattawan, Michigan.ORCID 0000-0002-0378-9882
Mark HepokoskiPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Denzil MathewPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Alex MoshenskyPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Andrew WillefordDepartment of Pharmacology, University of California , San Diego, California.
Soumita DasDepartment of Pathology, University of California , San Diego, California.
Prabhleen SinghDivision of Nephrology and Hypertension, Department of Medicine, University of California , San Diego, California.
Zach YongPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Jasmine H LeeDivision of Physiology, Department of Medicine, University of California , San Diego, California.
Kevin VegaDepartment of Pathology, University of California , San Diego, California.
Ashley DuPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
John ShinPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Christian JavierPulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California.
Jiang TianDivision of Cardiovascular Medicine and Center for Hypertension and Personalized Medicine, University of Toledo , Toledo, Ohio.
Joan Heller BrownDepartment of Pharmacology, University of California , San Diego, California.
Ellen C BreenDivision of Physiology, Department of Medicine, University of California , San Diego, California.
University of California San Diego · USUniversity of California System · USMPI Research (United States) · USUniversity of Toledo · USVA San Diego Healthcare System · US

Funding

Program AdministrationP01HL080101 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BERS, DONALD M · 2006 to 2015
$23.4M
UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AGARWAL, ANUPAM · 2008 to 2022
$18.3M
RhoA mediated survival signals in cardiomyocytesR37HL028143 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2010 to 2019
$4.0M
Electronic Cigarette Vapor Inhalation Adversely Affects Lung Cellular and Physiologic Function and Alters Systemic Inflammatory PathwaysR01HL137052 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CROTTY ALEXANDER, LAURA ELISE · 2017 to 2021
$2.3M
Na/K-ATPase Reduction in Renal Disease-Related Cardiac DysfunctionR01HL105649 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI TIAN, JIANG · 2012 to 2016
$1.8M
Renal Oxygenation and Mitochondrial Function in AKIR01DK107852 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SINGH, PRABHLEEN · 2016 to 2020
$1.7M
Cardiomyocyte CaM kinase II as a driver of cardiac inflammation and remodelingR01HL145459 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, MIYAMOTO, SHIGEKI · 2019 to 2022
$1.6M
Evaluating the role of Exogenous administration of micro RNA 29b in preventing Chronic Kidney Disease induced cardiac FibrosisF32DK104615 · NIDDK · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI DRUMMOND, CHRISTOPHER ANSON · 2014 to 2016
$134k
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthmaIK2BX001313 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI CROTTY ALEXANDER, LAURA ELISE · 2011 to 2015
–
Renal Oxygenation in the Pathophysiology of Kidney DiseaseI01BX002175 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI SINGH, PRABHLEEN · 2015 to 2025
–
BLRD VA I01 BX002175BLRD VA IK2 BX001313NHLBI NIH HHS P01 HL080101NHLBI NIH HHS R01 HL105649NHLBI NIH HHS R01 HL137052NHLBI NIH HHS R01 HL145459NHLBI NIH HHS R37 HL028143NIDDK NIH HHS F32 DK104615NIDDK NIH HHS P30 DK079337NIDDK NIH HHS R01 DK107852
6 · The paper itself

Abstract

Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3-6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3-5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson's trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.

Indexed as

Electronic Nicotine Delivery SystemsAnimalsBlood-Air BarrierCytokinesFemaleFibrosisGene ExpressionHumansInflammationMiceMice, Inbred C57BLMice, Inbred ICRNicotineNicotinic AgonistsPrimary Cell CultureRespiratory MucosaCytokinesNicotineNicotinic Agonistscardiorenal dysfunctione-cigaretteelectronic cigarettefibrosisnicotinesystemic inflammation

Identifiers

PMID29384700
PMCPMC6032308
OpenAlexW2786847823

What OpenQuestion holds

Textmetadata
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.