The Journal of Allergy and Clinical Immunology
Volume 124, Issue 1 , Pages 45-51.e4 , July 2009

Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction

  • Marta Kaminska, MD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • Susan Foley, MD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • Karim Maghni, DSc, PhD

      Affiliations

    • Centre de Recherche de l'Hopital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
    • ,
  • Claudine Storness-Bliss, BSc

      Affiliations

    • Department of Radiology and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver General Hospital, Vancouver, British Columbia, Canada
    • ,
  • Harvey Coxson, PhD

      Affiliations

    • Department of Radiology and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver General Hospital, Vancouver, British Columbia, Canada
    • ,
  • Heberto Ghezzo, PhD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • Catherine Lemière, MD, MSc

      Affiliations

    • Centre de Recherche de l'Hopital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
    • ,
  • Ronald Olivenstein, MD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • Pierre Ernst, MD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • Qutayba Hamid, MD, PhD

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • ,
  • James Martin, MD, DSc

      Affiliations

    • Meakins-Christie Laboratories, Montreal, Quebec, Canada
    • Corresponding Author InformationReprint requests: James Martin, MD, DSc, Meakins Christie Laboratories, 3626 St Urbain, Montreal, Quebec, Canada, H2X 2P2.

Received 31 July 2008 ,Revised 4 March 2009 ,Accepted 16 March 2009.

References 

  1. Antonicelli L, Bucca C, Neri M, De Benedetto F, Sabbatani P, Bonifazi F, et al. Asthma severity and medical resource utilization. Eur Respir J. 2004;23:723–729
  2. Noonan M, Chervinsky P, Busse W, Weisberg S, Pinnas J, de Boisblanc B, et al. Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life. Am J Respir Crit Care Med. 1995;152:1467–1473
  3. Nakagawa T, Hoshino M. Airway remodeling in asthma: an introduction. Clin Rev Allergy Immunol. 2004;27:1–2
  4. Pepe C, Foley S, Shannon J, Lemiere C, Olivenstein R, Ernst P, et al. Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol. 2005;116:544–549
  5. Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis. 1993;147:405–410
  6. Benayoun L, Druilhe A, Dombret M-C, Aubier M, Pretolani M. Airway structural alterations selectively associated with severe asthma. Am J Respir Crit Care Med. 2003;167:1360–1368
  7. Kelly M, Keatings V, Leigh R, Peterson C, Shute J, Venge P, et al. Analysis of fluid-phase mediators. Eur Respir J. 2002;20(suppl):24S–39S
  8. Proceedings of the ATS Workshop on Refractory Asthma. Current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med. 2000;162:2341–2351
  9. Lemiere C, Ernst P, Olivenstein R, Yamauchi Y, Govindaraju K, Ludwig MS, et al. Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol. 2006;118:1033–1039
  10. Pizzichini E, Pizzichini M, Efthimiadis A, Evans S, Morris M, Squillace D, et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996;154:308–317
  11. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171:912–930
  12. Shannon J, Ernst P, Yamauchi Y, Olivenstein R, Lemiere C, Foley S, et al. Differences in airway cytokine profile in severe asthma compared to moderate asthma. Chest. 2008;133:420–426
  13. Sullivan P, Stephens D, Ansari T, Costello J, Jeffery P. Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies. Eur Respir J. 1998;12:811–815
  14. Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, et al. Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol. 1997;17:326–333
  15. Maghni K, Lemiere C, Ghezzo H, Yuquan W, Malo JL. Airway inflammation after cessation of exposure to agents causing occupational asthma. Am J Respir Crit Care Med. 2004;169:367–372
  16. R Development Core Team (2008). R: a language and environment for statistical computing. R Foundation for Statistical Computing. 2008;
  17. Miller MK, Johnson C, Miller D, Deniz Y, Bleecker E, Wenzel S, et al. Severity assessment in asthma: an evolving concept. J Allergy Clin Immunol. 2005;116:990–995
  18. Bai TR, Cooper J, Koelmeyer T, Pare PD, Weir TD. The effect of age and duration of disease on airway structure in fatal asthma. Am J Respir Crit Care Med. 2000;162:663–669
  19. Moffatt MF, Kabesch M, Liang L, Dixon A, Strachan D, Heath S, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448:470–473
  20. Tavendale R, Macgregor D, Mukhopadhyay S, Palmer C. A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J Allergy Clin Immunol. 2008;121:860–863
  21. Tillie-Leblond I. Airway remodeling is correlated with obstruction in children with severe asthma. Allergy. 2008;63:533–541
  22. Lambert RK, Codd SL, Alley MR, Pack RJ. Physical determinants of bronchial mucosal folding. J Appl Physiol. 1994;77:1206–1216
  23. Pratusevich VR, Seow CY, Ford LE. Plasticity in canine airway smooth muscle. J Gen Physiol. 1995;105:73–94
  24. Bai TR. On the terminology for describing the length-force relationship and its changes in airway smooth muscle. J Appl Physiol. 2004;97:2029–2034
  25. Wang L, Pare PD, Seow CY. Plasticity in skeletal, cardiac, and smooth muscle: selected contribution: effect of chronic passive length change on airway smooth muscle length-tension relationship. J Appl Physiol. 2001;90:734–740
  26. Pellegrino R, Sterk P, Sont J, Brusaco V. Assessing the effect of deep inhalation on airway calibre: a novel approach to lung function in bronchial asthma and COPD. Eur Respir J. 1998;12:1219–1227
  27. Chetta A, Zanini A, Foresi A, Del Donno M, Castagnaro A, D'Ippolito R, et al. Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone. Am J Respir Crit Care Med. 2003;167:751–757
  28. Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. Am J Respir Crit Care Med. 1999;159:1043–1051
  29. Little SA, Sproule MW, Cowan MD, Macleod KJ, Robertson M, Love JG, et al. High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity. Thorax. 2002;57:247–253
  30. Kasahara K, Shiba K, Ozawa T, Okuda K, Adachi M. Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax. 2002;57:242–246
  31. Saglani S, Papaioannou G, Khoo L, Ujita M, Jeffery P, Owens C, et al. Can HRCT be used as a marker of airway remodelling in children with difficult asthma?. Respir Res. 2006;7:46
  32. Niimi A, Matsumoto H, Amitani R, Nakano Y, Sakai H, Takemura M, et al. Effect of short-term treatment with inhaled corticosteroid on airway wall thickening in asthma. Am J Med. 2004;116:725–731
  33. Capraz F, Kunter E, Cermik H, Ilvan A, Pocan S. The effect of inhaled budesonide and formoterol on bronchial remodeling and HRCT features in young asthmatics. Lung. 2007;185:89–96
  34. Gono H, Fujimoto K, Kawakami S, Kubo K. Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. Eur J Respir Dis. 2003;22:965–971
  35. Niimi A, Matsumoto H, Amitani R, Nakano Y, Mishima M, Minakuchi M, et al. Airway wall thickness in asthma assessed by computed tomography. Relation to clinical indices. Am J Respir Crit Care Med. 2000;162:1518–1523
  36. Boulet L, Belanger M, Carrier G. Airway responsiveness and bronchial-wall thickness in asthma with or without fixed airflow obstruction. Am J Respir Crit Care Med. 1995;152:865–871
  37. Nakano Y, Whittall K, Kalloger S, Coxson H, Pare P. Development and validation of human airway analysis algorithm using multidetector row CT. Proceedings of SPIE. 2002;4683:460–469
  38. Brown NJ, Salome CM, Berend N, Thorpe CW, King GG. Airway distensibility in adults with asthma and healthy adults, measured by forced oscillation technique. Am J Respir Crit Care Med. 2007;176:129–137
  39. Brown RH, SN, Mudge B, Diemer FB, Permutt S, Togias A. High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma. Am J Respir Crit Care Med 2001;163:994-1001.
  40. Ward C, Johns DP, Bish R, Pais M, Reid DW, Ingram C, et al. Reduced airway distensibility, fixed airflow limitation, and airway wall remodeling in asthma. Am J Respir Crit Care Med. 2001;164:1718–1721
  41. Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, et al. Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest. 2003;112:1029–1036
  42. Bosse Y, Thompson C, Audette K, Stankova J, Rola-Pleszczynski M. Interleukin-4 and interleukin-13 enhance human bronchial smooth muscle cell proliferation. Int Arch Allergy Immunol. 2008;146:138–148
  43. Amrani Y, Tliba O, Choubey D, Huang CD, Krymskaya VP, Eszterhas A, et al. IFN-gamma inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway. Am J Physiol Lung Cell Mol Physiol. 2003;284:L1063–L1071
  44. Hakonarson H, Maskeri N, Carter C, Grunstein M. Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999;103:1077–1087
  45. Elshaw SR, Henderson N, Knox A, Watson S, Buttle D, Johnson S. Matrix metalloproteinase expression and activity in human airway smooth muscle cells. Br J Pharmacol. 2004;142:1318–1324
  46. Liang K-C, Lee C-W, Lin W-N, Lin C-C, Wu C-B, Luo S-F, et al. Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-kappaB signaling pathways in human tracheal smooth muscle cells. J Cell Physiol. 2007;211:759–770
  47. Cox G, Thomson NC, Rubin AS, Niven RM, Corris PA, Siersted HC, et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med. 2007;356:1327–1337

 Supported by the Richard and Edith Strauss Canada Foundation, Canadian Institutes of Health Research.

 Disclosure of potential conflict of interest: H. Coxson has served as a consultant/advisor board member for GlaxoSmithKline and has received research support fro GlaxoSmithKline, Spiration, and Wyeth. C. Lemière has received research support from the National Institute for Occupational Safety and Health and the Institut de Recherche Robert-Sauvé en Santé et Sécurité du Travail and has served as an advisor to GlaxoSmithKline, AstraZeneca, and Novartis. P. Ernst has received speaker's fees from or served on an advisory board for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, and Nycomed. Q. Hamid has received research support from the McGill University Health Center Strauss Foundation. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)00637-X

doi: 10.1016/j.jaci.2009.03.049

The Journal of Allergy and Clinical Immunology
Volume 124, Issue 1 , Pages 45-51.e4 , July 2009

Article Tools

* Image Usage & Resolution