Asia Pac Allergy.  2014 Jan;4(1):19-24. 10.5415/apallergy.2014.4.1.19.

Airway remodelling in asthma: role for mechanical forces

• Manuyakorn W

• KMID: 2397121
• DOI: http://doi.org/10.5415/apallergy.2014.4.1.19

Abstract

Asthma is a chronic airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness and airflow obstruction. Airway structural changes or airway remodelling consist of epithelial injury, goblet cell hyperplasia, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. These changes were previously considered as a consequence of chronic airway inflammation. Even though inhaled corticosteroids can suppress airway inflammation, the natural history of asthma is still unaltered after inhaled corticosteroid treatment. As such there is increasing evidence for the role of mechanical forces within the asthmatic airway contributing to airway structural changes.

Keyword

Asthma; Airway remodelling; Mechanical forces

MeSH Terms

Adrenal Cortex Hormones
Airway Remodeling*
Asthma*
Goblet Cells
Hyperplasia
Inflammation
Muscle, Smooth
Natural History
Adrenal Cortex Hormones

Figure

• 

  Fig. 1 Airway structural changes in asthma. Panels A and B demonstrate epithelial injuries (white arrows) and increased thickness of airway smooth muscle (grey arrows). Panel C demonstrates subepithelial collagen deposition (red stain; black arrow). Reprinted from Al-Muhsen et al. [7], with permission of Elsevier.

Reference

1. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002; 360:1715–1721.

2. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008; 372:1107–1119.

3. Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006; 354:1998–2005.

4. Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, Bacharier LB, Lemanske RF Jr, Strunk RC, Allen DB, Bloomberg GR, Heldt G, Krawiec M, Larsen G, Liu AH, Chinchilli VM, Sorkness CA, Taussig LM, Martinez FD. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006; 354:1985–1997.

5. Murray CS, Woodcock A, Langley SJ, Morris J, Custovic A. IFWIN study team. Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study. Lancet. 2006; 368:754–762.

6. Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Silva PA, Poulton R. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003; 349:1414–1422.

7. Al-Muhsen S, Johnson JR, Hamid Q. Remodeling in asthma. J Allergy Clin Immunol. 2011; 128:451–462.

8. Turato G, Barbato A, Baraldo S, Zanin ME, Bazzan E, Lokar-Oliani K, Calabrese F, Panizzolo C, Snijders D, Maestrelli P, Zuin R, Fabbri LM, Saetta M. Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma. Am J Respir Crit Care Med. 2008; 178:476–482.

9. Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodelling in childhood asthma. Thorax. 2005; 60:389–394.

10. Bossley CJ, Fleming L, Gupta A, Regamey N, Frith J, Oates T, Tsartsali L, Lloyd CM, Bush A, Saglani S. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol. 2012; 129:974–982.e13.

11. Barbato A, Turato G, Baraldo S, Bazzan E, Calabrese F, Panizzolo C, Zanin ME, Zuin R, Maestrelli P, Fabbri LM, Saetta M. Epithelial damage and angiogenesis in the airways of children with asthma. Am J Respir Crit Care Med. 2006; 174:975–981.

12. Payne DN, Rogers AV, Adelroth E, Bandi V, Guntupalli KK, Bush A, Jeffery PK. Early thickening of the reticular basement membrane in children with difficult asthma. Am J Respir Crit Care Med. 2003; 167:78–82.

13. Saglani S, Payne DN, Zhu J, Wang Z, Nicholson AG, Bush A, Jeffery PK. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med. 2007; 176:858–864.

14. Tschumperlin DJ, Drazen JM. Chronic effects of mechanical force on airways. Annu Rev Physiol. 2006; 68:563–583.

15. Wang JH, Thampatty BP. An introductory review of cell mechanobiology. Biomech Model Mechanobiol. 2006; 5:1–16.

16. Savla U, Waters CM. Mechanical strain inhibits repair of airway epithelium in vitro. Am J Physiol. 1998; 274:L883–L892.

17. Tschumperlin DJ, Shively JD, Kikuchi T, Drazen JM. Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Am J Respir Cell Mol Biol. 2003; 28:142–149.

18. Chu EK, Cheng J, Foley JS, Mecham BH, Owen CA, Haley KJ, Mariani TJ, Kohane IS, Tschumperlin DJ, Drazen JM. Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2006; 35:628–638.

19. Park JA, Tschumperlin DJ. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am J Respir Cell Mol Biol. 2009; 41:459–466.

20. Chu EK, Foley JS, Cheng J, Patel AS, Drazen JM, Tschumperlin DJ. Bronchial epithelial compression regulates epidermal growth factor receptor family ligand expression in an autocrine manner. Am J Respir Cell Mol Biol. 2005; 32:373–380.

21. Park JA, Drazen JM, Tschumperlin DJ. The chitinase-like protein YKL-40 is secreted by airway epithelial cells at base line and in response to compressive mechanical stress. J Biol Chem. 2010; 285:29817–29825.

22. Park JA, Sharif AS, Tschumperlin DJ, Lau L, Limbrey R, Howarth P, Drazen JM. Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo. J Allergy Clin Immunol. 2012; 130:1375–1383.

23. Chapman KE, Sinclair SE, Zhuang D, Hassid A, Desai LP, Waters CM. Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005; 289:L834–L841.

24. Savla U, Sporn PH, Waters CM. Cyclic stretch of airway epithelium inhibits prostanoid synthesis. Am J Physiol. 1997; 273:L1013–L1019.

25. McAnulty RJ, Chambers RC, Laurent GJ. Regulation of fibroblast procollagen production: transforming growth factor-beta 1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein. Biochem J. 1995; 307:63–68.

26. McAnulty RJ, Hernández-Rodriguez NA, Mutsaers SE, Coker RK, Laurent GJ. Indomethacin suppresses the anti-proliferative effects of transforming growth factor-beta isoforms on fibroblast cell cultures. Biochem J. 1997; 321:639–643.

27. Liu M, Xu J, Souza P, Tanswell B, Tanswell AK, Post M. The effect of mechanical strain on fetal rat lung cell proliferation: comparison of two- and three-dimensional culture systems. In Vitro Cell Dev Biol Anim. 1995; 31:858–866.

28. Morishima Y, Nomura A, Uchida Y, Noguchi Y, Sakamoto T, Ishii Y, Goto Y, Masuyama K, Zhang MJ, Hirano K, Mochizuki M, Ohtsuka M, Sekizawa K. Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding. Am J Respir Cell Mol Biol. 2001; 24:1–11.

29. Swartz MA, Tschumperlin DJ, Kamm RD, Drazen JM. Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc Natl Acad Sci U S A. 2001; 98:6180–6185.

30. Choe MM, Sporn PH, Swartz MA. Extracellular matrix remodeling by dynamic strain in a three-dimensional tissue-engineered human airway wall model. Am J Respir Cell Mol Biol. 2006; 35:306–313.

31. Mourgeon E, Xu J, Tanswell AK, Liu M, Post M. Mechanical strain-induced posttranscriptional regulation of fibronectin production in fetal lung cells. Am J Physiol. 1999; 277:L142–L149.

32. Wang JH, Thampatty BP, Lin JS, Im HJ. Mechanoregulation of gene expression in fibroblasts. Gene. 2007; 391:1–15.

33. Le Bellego F, Perera H, Plante S, Chakir J, Hamid Q, Ludwig MS. Mechanical strain increases cytokine and chemokine production in bronchial fibroblasts from asthmatic patients. Allergy. 2009; 64:32–39.

34. Ludwig MS, Ftouhi-Paquin N, Huang W, Pagé N, Chakir J, Hamid Q. Mechanical strain enhances proteoglycan message in fibroblasts from asthmatic subjects. Clin Exp Allergy. 2004; 34:926–930.

35. Breen EC. Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. J Appl Physiol (1985). 2000; 88:203–209.

36. Manuyakorn W, Noto A, Haitchi H, Holgate S, Howarth P, Davies D. Cyclical mechanical stretch enhances the proinflammatory and profibrotic responses of bronchial fibroblasts. Allergy. 2010; 65:Suppl s92. 544.

37. Bishop JE, Mitchell JJ, Absher PM, Baldor L, Geller HA, Woodcock-Mitchell J, Hamblin MJ, Vacek P, Low RB. Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity. Am J Respir Cell Mol Biol. 1993; 9:126–133.

38. Sanchez-Esteban J, Wang Y, Cicchiello LA, Rubin LP. Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2002; 282:L448–L456.

39. Smith PG, Tokui T, Ikebe M. Mechanical strain increases contractile enzyme activity in cultured airway smooth muscle cells. Am J Physiol. 1995; 268:L999–L1005.

40. Hasaneen NA, Zucker S, Cao J, Chiarelli C, Panettieri RA, Foda HD. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs. FASEB J. 2005; 19:1507–1509.

41. Smith PG, Deng L, Fredberg JJ, Maksym GN. Mechanical strain increases cell stiffness through cytoskeletal filament reorganization. Am J Physiol Lung Cell Mol Physiol. 2003; 285:L456–L463.

42. Fairbank NJ, Connolly SC, Mackinnon JD, Wehry K, Deng L, Maksym GN. Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain. Am J Physiol Lung Cell Mol Physiol. 2008; 295:L479–L488.

43. Hasaneen NA, Zucker S, Lin RZ, Vaday GG, Panettieri RA, Foda HD. Angiogenesis is induced by airway smooth muscle strain. Am J Physiol Lung Cell Mol Physiol. 2007; 293:L1059–L1068.

44. Wang L, Paré PD. Deep inspiration and airway smooth muscle adaptation to length change. Respir Physiol Neurobiol. 2003; 137:169–178.

45. Matsumoto H, Niimi A, Tabuena RP, Takemura M, Ueda T, Yamaguchi M, Matsuoka H, Jinnai M, Chin K, Mishima M. Airway wall thickening in patients with cough variant asthma and nonasthmatic chronic cough. Chest. 2007; 131:1042–1049.

46. Niimi A, Torrego A, Nicholson AG, Cosio BG, Oates TB, Chung KF. Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol. 2005; 116:565–570.

47. Grainge CL, Lau LC, Ward JA, Dulay V, Lahiff G, Wilson S, Holgate S, Davies DE, Howarth PH. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011; 364:2006–2015.

48. Wang K, Liu CT, Wu YH, Feng YL, Bai HL, Ma ES, Wen FQ. Effects of formoterol-budesonide on airway remodeling in patients with moderate asthma. Acta Pharmacol Sin. 2011; 32:126–132.

49. Pavord ID, Jeffery PK, Qiu Y, Zhu J, Parker D, Carlsheimer A, Naya I, Barnes NC. Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol. J Allergy Clin Immunol. 2009; 123:1083–1089.

50. Milanese M, Crimi E, Scordamaglia A, Riccio A, Pellegrino R, Canonica GW, Brusasco V. On the functional consequences of bronchial basement membrane thickening. J Appl Physiol (1985). 2001; 91:1035–1040.

51. Niimi A, Matsumoto H, Takemura M, Ueda T, Chin K, Mishima M. Relationship of airway wall thickness to airway sensitivity and airway reactivity in asthma. Am J Respir Crit Care Med. 2003; 168:983–988.

52. Paganin F, Séneterre E, Chanez P, Daurés JP, Bruel JM, Michel FB, Bousquet J. Computed tomography of the lungs in asthma: influence of disease severity and etiology. Am J Respir Crit Care Med. 1996; 153:110–114.

53. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy. 2008; 38:872–897.