Analyze Diet
PloS one2015; 10(9); e0136284; doi: 10.1371/journal.pone.0136284

Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model.

Abstract: Endobronchial ultrasonography (EBUS) revealed differences in the thickness of the layer representing subepithelial tissues (L2) between human asthmatics and controls, but whether this measurement correlates with airway smooth muscle (ASM) remodeling in asthma is unknown. In this study, we sought to determine the ability of EBUS to predict histological ASM remodeling in normal and equine asthmatic airways. We studied 109 isolated bronchi from the lungs of 13 horses. They underwent EBUS examination using a 30 MHz radial probe before being processed for histology. ASM remodeling parameters were evaluated in EBUS images (L2 thickness, L2 area, L2 area/internal perimeter [Pi] and L2 area/Pi2) and histological cuts (ASM area/Pi2), and compared. EBUS was then performed ex vivo on the lungs of 4 horses with heaves, an asthma-like condition of horses, and 7 controls to determine whether central bronchial remodeling could be detected with this technique. An optimized approach was developed based on data variability within airways, subjects, and groups, and then validated in 7 horses (3 controls, 4 with heaves) that underwent EBUS in vivo. L2 area was significantly associated to ASM area in isolated lungs (p<0.0001), in the absence of significant bias related to the airway size. Bronchial size significantly affected EBUS ASM-related parameters, except for L2 area/Pi2. L2 area/Pi2 was increased in the airways of asthmatic horses compared to controls, both ex vivo and in vivo (p<0.05). Bronchial histology confirmed our findings (AASM/Pi2 was increased in asthmatic horses compared to controls, p<0.05). In both horses with heaves and controls, L2 was composed of ASM for the outer 75% of its thickness and by ECM for the remaining inner 25%. In conclusion, EBUS reliably allows assessment of asthma-associated ASM remodeling of central airways in a non-invasive way.
Publication Date: 2015-09-08 PubMed ID: 26348727PubMed Central: PMC4562526DOI: 10.1371/journal.pone.0136284Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses a study that evaluates the effectiveness of Endobronchial Ultrasonography (EBUS) for predicting airway smooth muscle (ASM) remodeling in equine asthmatic airways.

Objective of the Research

  • The main goal of the research was to assess whether EBUS could provide an accurate indication of ASM remodeling. This phenomenon, which involves changes in the structure of the airway smooth muscle, is associated with asthma.

Research Method

  • To achieve this, the researchers examined 109 isolated bronchi from the lungs of 13 horses, using EBUS with a 30 MHz radial probe before proceeding to histology.
  • ASM remodeling parameters were assessed in both EBUS images and histological cuts, then compared.
  • Further testing with EBUS was performed ex vivo on the lungs of four horses with heaves (a condition similar to asthma) and seven control horses.

Findings

  • The study discovered that there was a significant correlation between L2 area and ASM area in the isolated lungs.
  • The study also found that while bronchial size significantly impacted EBUS ASM-related parameters, it did not significantly affect the L2 area/Pi2.
  • Moreover, the L2 area/Pi2 was found to be increased in the airways of asthmatic horses compared to control horses, both ex vivo and in vivo.
  • A histological examination of bronchial tissue confirmed these findings.
  • Finally, in both control horses and those with heaves, ASM made up about 75% of the L2 thickness, while the extracellular matrix (ECM) comprised the remaining 25%.

Conclusion

  • The researchers concluded that EBUS can reliably assess ASM remodeling of central airways in a non-invasive way, which is associated with asthma.

Cite This Article

APA
Bullone M, Beauchamp G, Godbout M, Martin JG, Lavoie JP. (2015). Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model. PLoS One, 10(9), e0136284. https://doi.org/10.1371/journal.pone.0136284

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 9
Pages: e0136284
PII: e0136284

Researcher Affiliations

Bullone, Michela
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, Q, Canada.
Beauchamp, Guy
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, Q, Canada.
Godbout, Mireille
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, Q, Canada.
Martin, James G
  • Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Q, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, Q, Canada.

MeSH Terms

  • Airway Remodeling
  • Animals
  • Asthma / diagnostic imaging
  • Asthma / pathology
  • Bronchi / diagnostic imaging
  • Cell Proliferation / physiology
  • Diagnostic Imaging
  • Disease Models, Animal
  • Horses
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Muscle, Smooth / diagnostic imaging
  • Ultrasonics
  • Ultrasonography

Grant Funding

  • R0017988 / Canadian Institutes of Health Research

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 33 references
  1. Hirota N, Martin JG. Mechanisms of airway remodeling.. Chest 2013 Sep;144(3):1026-1032.
    doi: 10.1378/chest.12-3073pubmed: 24008953google scholar: lookup
  2. James AL, Bai TR, Mauad T, Abramson MJ, Dolhnikoff M, McKay KO, Maxwell PS, Elliot JG, Green FH. Airway smooth muscle thickness in asthma is related to severity but not duration of asthma.. Eur Respir J 2009 Nov;34(5):1040-5.
    doi: 10.1183/09031936.00181608pubmed: 19282340google scholar: lookup
  3. Pepe C, Foley S, Shannon J, Lemiere C, Olivenstein R, Ernst P, Ludwig MS, Martin JG, Hamid Q. Differences in airway remodeling between subjects with severe and moderate asthma.. J Allergy Clin Immunol 2005 Sep;116(3):544-9.
    pubmed: 16159622doi: 10.1016/j.jaci.2005.06.011google scholar: lookup
  4. Kaminska M, Foley S, Maghni K, Storness-Bliss C, Coxson H, Ghezzo H, Lemière C, Olivenstein R, Ernst P, Hamid Q, Martin J. Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction.. J Allergy Clin Immunol 2009 Jul;124(1):45-51.e1-4.
    doi: 10.1016/j.jaci.2009.03.049pubmed: 19481790google scholar: lookup
  5. Ebina M, Takahashi T, Chiba T, Motomiya M. Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study.. Am Rev Respir Dis 1993 Sep;148(3):720-6.
    pubmed: 8368645doi: 10.1164/ajrccm/148.3.720google scholar: lookup
  6. James AL, Elliot JG, Jones RL, Carroll ML, Mauad T, Bai TR, Abramson MJ, McKay KO, Green FH. Airway smooth muscle hypertrophy and hyperplasia in asthma.. Am J Respir Crit Care Med 2012 May 15;185(10):1058-64.
    doi: 10.1164/rccm.201110-1849OCpubmed: 22403800google scholar: lookup
  7. Bullone M, Chevigny M, Allano M, Martin JG, Lavoie JP. Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses.. J Appl Physiol (1985) 2014 Oct 1;117(7):806-15.
  8. James AL, Maxwell PS, Pearce-Pinto G, Elliot JG, Carroll NG. The relationship of reticular basement membrane thickness to airway wall remodeling in asthma.. Am J Respir Crit Care Med 2002 Dec 15;166(12 Pt 1):1590-5.
    pubmed: 12471074doi: 10.1164/rccm.2108069google scholar: lookup
  9. Hürter T, Hanrath P. Endobronchial sonography: feasibility and preliminary results.. Thorax 1992 Jul;47(7):565-7.
    pmc: PMC463872pubmed: 1412103doi: 10.1136/thx.47.7.565google scholar: lookup
  10. Baba M, Sekine Y, Suzuki M, Yoshida S, Shibuya K, Iizasa T, Saitoh Y, Onuma EK, Ohwada H, Fujisawa T. Correlation between endobronchial ultrasonography (EBUS) images and histologic findings in normal and tumor-invaded bronchial wall.. Lung Cancer 2002 Jan;35(1):65-71.
    pubmed: 11750715doi: 10.1016/s0169-5002(01)00284-7google scholar: lookup
  11. Kurimoto N, Murayama M, Yoshioka S, Nishisaka T, Inai K, Dohi K. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion.. Chest 1999 Jun;115(6):1500-6.
    pubmed: 10378540doi: 10.1378/chest.115.6.1500google scholar: lookup
  12. Soja J, Grzanka P, Sładek K, Okoń K, Ćmiel A, Mikoś M, Mikrut S, Pulka G, Gross-Sondej I, Niżankowska-Mogilnicka E, Szczeklik A. The use of endobronchial ultrasonography in assessment of bronchial wall remodeling in patients with asthma.. Chest 2009 Sep;136(3):797-804.
    doi: 10.1378/chest.08-2759pubmed: 19429721google scholar: lookup
  13. Kita T, Fujimura M, Kurimoto N, Sone T, Inuzuka K, Hirose T, Oribe Y, Myou S, Nakao S. Airway wall structure assessed by endobronchial ultrasonography and bronchial hyperresponsiveness in patients with asthma.. J Bronchology Interv Pulmonol 2010 Oct;17(4):301-6.
    pubmed: 23168950doi: 10.1097/LBR.0b013e3181f9f09bgoogle scholar: lookup
  14. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
  15. Robinson NE, Olszewski MA, Boehler D, Berney C, Hakala J, Matson C, Derksen FJ. Relationship between clinical signs and lung function in horses with recurrent airway obstruction (heaves) during a bronchodilator trial.. Equine Vet J 2000 Sep;32(5):393-400.
    pubmed: 11037260doi: 10.2746/042516400777591147google scholar: lookup
  16. Koblinger K, Nicol J, McDonald K, Wasko A, Logie N, Weiss M, Léguillette R. Endoscopic assessment of airway inflammation in horses.. J Vet Intern Med 2011 Sep-Oct;25(5):1118-26.
  17. Sumi Y, Foley S, Daigle S, L'Archevêque J, Olivenstein R, Letuvé S, Malo JL, Hamid Q. Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure.. Clin Exp Allergy 2007 Dec;37(12):1781-7.
  18. Jones RL, Elliot JG, James AL. Estimating airway smooth muscle cell volume and number in airway sections. Sources of variability.. Am J Respir Cell Mol Biol 2014 Feb;50(2):246-52.
    doi: 10.1165/rcmb.2013-0029OCpubmed: 24007332google scholar: lookup
  19. Shaw TJ, Wakely SL, Peebles CR, Mehta RL, Turner JM, Wilson SJ, Howarth PH. Endobronchial ultrasound to assess airway wall thickening: validation in vitro and in vivo.. Eur Respir J 2004 Jun;23(6):813-7.
    pubmed: 15218991doi: 10.1183/09031936.04.00119904google scholar: lookup
  20. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP. Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma.. Am J Respir Cell Mol Biol 2011 Jul;45(1):181-7.
    doi: 10.1165/rcmb.2010-0300OCpubmed: 20935189google scholar: lookup
  21. Setlakwe EL, Lemos KR, Lavoie-Lamoureux A, Duguay JD, Lavoie JP. Airway collagen and elastic fiber content correlates with lung function in equine heaves.. Am J Physiol Lung Cell Mol Physiol 2014 Aug 1;307(3):L252-60.
    doi: 10.1152/ajplung.00019.2014pubmed: 24879055google scholar: lookup
  22. Lambert RK, Wiggs BR, Kuwano K, Hogg JC, Paré PD. Functional significance of increased airway smooth muscle in asthma and COPD.. J Appl Physiol (1985) 1993 Jun;74(6):2771-81.
    pubmed: 8365980doi: 10.1152/jappl.1993.74.6.2771google scholar: lookup
  23. Oliver MN, Fabry B, Marinkovic A, Mijailovich SM, Butler JP, Fredberg JJ. Airway hyperresponsiveness, remodeling, and smooth muscle mass: right answer, wrong reason?. Am J Respir Cell Mol Biol 2007 Sep;37(3):264-72.
    pmc: PMC1994228pubmed: 17463392doi: 10.1165/rcmb.2006-0418OCgoogle scholar: lookup
  24. Ebina M, Yaegashi H, Chiba R, Takahashi T, Motomiya M, Tanemura M. Hyperreactive site in the airway tree of asthmatic patients revealed by thickening of bronchial muscles. A morphometric study.. Am Rev Respir Dis 1990 May;141(5 Pt 1):1327-32.
    pubmed: 2187387doi: 10.1164/ajrccm/141.5_Pt_1.1327google scholar: lookup
  25. Ebina M, Yaegashi H, Takahashi T, Motomiya M, Tanemura M. Distribution of smooth muscles along the bronchial tree. A morphometric study of ordinary autopsy lungs.. Am Rev Respir Dis 1990 May;141(5 Pt 1):1322-6.
    pubmed: 2187386doi: 10.1164/ajrccm/141.5_Pt_1.1322google scholar: lookup
  26. Herszberg B, Ramos-Barbón D, Tamaoka M, Martin JG, Lavoie JP. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.. J Allergy Clin Immunol 2006 Aug;118(2):382-8.
    pubmed: 16890762doi: 10.1016/j.jaci.2006.03.044google scholar: lookup
  27. James AL, Hogg JC, Dunn LA, Paré PD. The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening.. Am Rev Respir Dis 1988 Jul;138(1):136-9.
    pubmed: 3202392doi: 10.1164/ajrccm/138.1.136google scholar: lookup
  28. Araujo BB, Dolhnikoff M, Silva LF, Elliot J, Lindeman JH, Ferreira DS, Mulder A, Gomes HA, Fernezlian SM, James A, Mauad T. Extracellular matrix components and regulators in the airway smooth muscle in asthma.. Eur Respir J 2008 Jul;32(1):61-9.
    doi: 10.1183/09031936.00147807pubmed: 18321931google scholar: lookup
  29. James A, Carroll N. Airway smooth muscle in health and disease; methods of measurement and relation to function.. Eur Respir J 2000 Apr;15(4):782-9.
  30. Bolliger CT, Mathur PN, Beamis JF, Becker HD, Cavaliere S, Colt H, Diaz-Jimenez JP, Dumon JF, Edell E, Kovitz KL, Macha HN, Mehta AC, Marel M, Noppen M, Strausz J, Sutedja TG. ERS/ATS statement on interventional pulmonology. European Respiratory Society/American Thoracic Society.. Eur Respir J 2002 Feb;19(2):356-73.
    pubmed: 11866017doi: 10.1183/09031936.02.00204602google scholar: lookup
  31. Ernst A, Silvestri GA, Johnstone D. Interventional pulmonary procedures: Guidelines from the American College of Chest Physicians.. Chest 2003 May;123(5):1693-717.
    pubmed: 12740291doi: 10.1378/chest.123.5.1693google scholar: lookup
  32. Elliot JG, Jones RL, Abramson MJ, Green FH, Mauad T, McKay KO, Bai TR, James AL. Distribution of airway smooth muscle remodelling in asthma: relation to airway inflammation.. Respirology 2015 Jan;20(1):66-72.
    doi: 10.1111/resp.12384pubmed: 25257809google scholar: lookup
  33. Falcone F, Fois F, Grosso D. Endobronchial ultrasound.. Respiration 2003 Mar-Apr;70(2):179-94.
    pubmed: 12740516doi: 10.1159/000070066google scholar: lookup

Citations

This article has been cited 13 times.
  1. Soja J, Górka K, Gross-Sondej I, Jakieła B, Mikrut S, Okoń K, Ćmiel A, Sadowski P, Szczeklik W, Andrychiewicz A, Stachura T, Bochenek G, Bazan-Socha S, Sładek K. Endobronchial Ultrasound is Useful in the Assessment of Bronchial Wall Changes Related to Bronchial Thermoplasty.. J Asthma Allergy 2023;16:585-595.
    doi: 10.2147/JAA.S404254pubmed: 37284335google scholar: lookup
  2. Ekpruke CD, Silveyra P. Airway remodeling in asthma.. Ann Transl Med 2022 Nov;10(22):1189.
    doi: 10.21037/atm-22-5059pubmed: 36544664google scholar: lookup
  3. Mainguy-Seers S, Boivin R, Pourali Dogaheh S, Beaudry F, Hélie P, Bonilla AG, Martin JG, Lavoie JP. Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses.. Sci Rep 2022 Jan 10;12(1):446.
    doi: 10.1038/s41598-021-03955-9pubmed: 35013387google scholar: lookup
  4. Abe Y, Suga Y, Fukushima K, Ohata H, Niitsu T, Nabeshima H, Nagahama Y, Kida H, Kumanogoh A. Advances and Challenges of Antibody Therapeutics for Severe Bronchial Asthma.. Int J Mol Sci 2021 Dec 22;23(1).
    doi: 10.3390/ijms23010083pubmed: 35008504google scholar: lookup
  5. Bessonnat A, Hélie P, Grimes C, Lavoie JP. Airway remodeling in horses with mild and moderate asthma.. J Vet Intern Med 2022 Jan;36(1):285-291.
    doi: 10.1111/jvim.16333pubmed: 34877706google scholar: lookup
  6. Lo Feudo CM, Stucchi L, Alberti E, Stancari G, Conturba B, Zucca E, Ferrucci F. The Role of Thoracic Ultrasonography and Airway Endoscopy in the Diagnosis of Equine Asthma and Exercise-Induced Pulmonary Hemorrhage.. Vet Sci 2021 Nov 15;8(11).
    doi: 10.3390/vetsci8110276pubmed: 34822649google scholar: lookup
  7. Millares-Ramirez EM, Lavoie JP. Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids.. J Vet Intern Med 2021 Jul;35(4):2026-2034.
    doi: 10.1111/jvim.16159pubmed: 34048095google scholar: lookup
  8. Cheng SL. Immunologic Pathophysiology and Airway Remodeling Mechanism in Severe Asthma: Focused on IgE-Mediated Pathways.. Diagnostics (Basel) 2021 Jan 6;11(1).
    doi: 10.3390/diagnostics11010083pubmed: 33419185google scholar: lookup
  9. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
    doi: 10.3389/fvets.2020.00450pubmed: 32903600google scholar: lookup
  10. Rosenberg HF, Druey KM. Modeling asthma: Pitfalls, promises, and the road ahead.. J Leukoc Biol 2018 Jul;104(1):41-48.
    doi: 10.1002/JLB.3MR1117-436Rpubmed: 29451705google scholar: lookup
  11. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017 Aug 18;7(1):8843.
    doi: 10.1038/s41598-017-09414-8pubmed: 28821845google scholar: lookup
  12. Trivedi A, Hall C, Hoffman EA, Woods JC, Gierada DS, Castro M. Using imaging as a biomarker for asthma.. J Allergy Clin Immunol 2017 Jan;139(1):1-10.
    doi: 10.1016/j.jaci.2016.11.009pubmed: 28065276google scholar: lookup
  13. Bullone M, Hélie P, Joubert P, Lavoie JP. Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.. J Vet Intern Med 2016 Sep;30(5):1739-1746.
    doi: 10.1111/jvim.14556pubmed: 27527123google scholar: lookup