Allergy Asthma Immunol Res.  2010 Jul;2(3):165-171. 10.4168/aair.2010.2.3.165.

A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis

• Holgate ST

• KMID: 2133803
• DOI: http://doi.org/10.4168/aair.2010.2.3.165

Abstract

The original concept of asthma being primarily a disease of airways smooth muscle drove the development of bronchodilator drugs. However when it was realised that airway inflammation underpinned the disordered airway function, this gave way to the development of controller therapies such as inhaled cromones and corticosteroids. More recently the discovery of complex interconnecting cytokine and chemokine networks has stimulated the development of biologics with varying success. With the recognition that airway wall "remodelling" is present early in asthma inception and is in part driven by aberrant epithelial-mesenchymal communication both genetic and environmental factors beyond allergen exposure such as virus infection and air pollution are being seen as being increasingly important not only in asthma exacerbations but in the origins of asthma and its evolution into different sub-phenotypes. This brings us round full circle to once again considering that the origins of asthma lie in defects in the formed elements of the airway; the epithelium, smooth muscle, and vasculature. Over the last 25 years Professor You Young Kim has engaged in the exciting discovery science of allergy and asthma and has made an enormous contribution in bringing Korea to the forefront of disease management and research, a position that both he and his colleagues can justly be proud of.

Keyword

Asthma; airway inflammation; airway remodeling; infection; epithelial-mesenchymal trophic unit; ADAM33

MeSH Terms

Adrenal Cortex Hormones
Air Pollution
Airway Remodeling
Asthma
Biological Agents
Disease Management
Epithelium
Hypersensitivity
Inflammation
Korea
Muscle, Smooth
Viruses
Adrenal Cortex Hormones
Biological Agents

Figure

• 

  Fig. 1 Prof. You Young Kim (right) and the author. This photograph was taken during Prof. Kim's overseas Research Fellowship at Southampton University, UK in 1983.

Reference

1. Sakula A. Henry hyde salter (1823-71): A biographical sketch. Thorax. 1985. 40:887–888.

2. Vyas H, Krishnaswamy G. Paul ehrlich's "Mastzellen"--from aniline dyes to DNA chip arrays: A historical review of developments in mast cell research. Methods Mol Biol. 2006. 315:3–11.

3. McEwen BJ. Eosinophils: A review. Vet Res Commun. 1992. 16:11–44.

4. Osler W. The Principles and Practice of Medicine. 1892. 1st ed. NY: D. Appleton and Company;497–501.

5. Pearce N. The use of beta agonists and the risk of death and near death from asthma. J Clin Epidemiol. 2009. 62:582–587.

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

7. Ovary Z. From prausnitz-kustner to passive cutaneous anaphylaxis and beyond. Chem Immunol. 1990. 49:90–120.

8. Ishizaka K, Ishizaka T. Mechanisms of reaginic hypersensitivity and IgE antibody response. Immunol Rev. 1978. 41:109–148.

9. Austen KF. Reaction mechanisms in the release of mediators of immediate hypersensitivity from human lung tissue. Fed Proc. 1974. 33:2256–2262.

10. Durham SR, Carroll M, Walsh GM, Kay AB. Leukocyte activation in allergen-induced late-phase asthmatic reactions. N Engl J Med. 1984. 311:1398–1402.

11. Holgate ST. Reflections on the mechanism(s) of action of sodium cromoglycate (intal) and the role of mast cells in asthma. Respir Med. 1989. 83:Suppl A. 25–31.

12. Turner-Warwick M. Corticosteroid aerosols: The future? Postgrad Med J. 1974. 50:suppl 4. 80–84.

13. Djukanovic R, Wilson JW, Britten KM, Wilson SJ, Walls AF, Roche WR, Howarth PH, Holgate ST. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992. 145:669–674.

14. Burge PS, Efthimiou J, Turner-Warwick M, Nelmes PT. Double-blind trials of inhaled beclomethasone diproprionate and fluocortin butyl ester in allergen-induced immediate and late asthmatic reactions. Clin Allergy. 1982. 12:523–531.

15. Cockcroft DW. The bronchial late response in the pathogenesis of asthma and its modulation by therapy. Ann Allergy. 1985. 55:857–862.

16. Soter NA, Austen KF. The diversity of mast cell-derived mediators: Implications for acute, subacute, and chronic cutaneous inflammatory disorders. J Invest Dermatol. 1976. 67:313–319.

17. Kim YY, Holgate ST, Church MK. Inhibition of histamine release from dispersed human lung and tonsillar mast cells by nicardipine and nifedipine. Br J Clin Pharmacol. 1985. 19:631–638.

18. Kay AB. Cell-mediated immune response in asthma. Agents Actions Suppl. 1989. 28:365–373.

19. Wasserman SI. Mediators of immediate hypersensitivity. J Allergy Clin Immunol. 1983. 72:101–119.

20. Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992. 326:298–304.

21. Lambrecht BN, Hammad H. Biology of lung dendritic cells at the origin of asthma. Immunity. 2009. 31:412–424.

22. Maestrelli P, Boschetto P, Fabbri LM, Mapp CE. Mechanisms of occupational asthma. J Allergy Clin Immunol. 2009. 123:531–542.

23. Kim YK, Son JW, Kim HY, Park HS, Lee MH, Cho SH, Min KU, Kim YY. New occupational allergen in citrus farmers: Citrus red mite (panonychus citri). Ann Allergy Asthma Immunol. 1999. 82:223–228.

24. Kim YK, Son JW, Kim HY, Park HS, Lee MH, Cho SH, Min KU, Kim YY. Citrus red mite (Panonychus citri) is the most common sensitizing allergen of asthma and rhinitis in citrus farmers. Clin Exp Allergy. 1999. 29:1102–1109.

25. Lee MH, Cho SH, Park HS, Bahn JW, Lee BJ, Son JW, Kim YK, Koh YY, Min KU, Kim YY. Citrus red mite (panonychus citri) is a common sensitizing allergen among children living around citrus orchards. Ann Allergy Asthma Immunol. 2000. 85:200–204.

26. Kim KM, Kwon HS, Jeon SG, Park CH, Sohn SW, Kim DI, Kim SS, Chang YS, Kim YK, Cho SH, Min KU, Kim YY. Korean ginseng-induced occupational asthma and determination of IgE binding components. J Korean Med Sci. 2008. 23:232–235.

27. Corne J, Djukanovic R, Thomas L, Warner J, Botta L, Grandordy B, Gygax D, Heusser C, Patalano F, Richardson W, Kilchherr E, Staehelin T, Davis F, Gordon W, Sun L, Liou R, Wang G, Chang TW, Holgate S. The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: Efficacy, safety, and pharmacokinetics. J Clin Invest. 1997. 99:879–887.

28. Holgate ST, Chuchalin AG, Hebert J, Lotvall J, Persson GB, Chung KF, Bousquet J, Kerstjens HA, Fox H, Thirlwell J, Cioppa GD. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004. 34:632–638.

29. Fahy JV, Fleming HE, Wong HH, Liu JT, Su JQ, Reimann J, Fick RB Jr, Boushey HA. The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med. 1997. 155:1828–1834.

30. Holgate S, Smith N, Massanari M, Jimenez P. Effects of omalizumab on markers of inflammation in patients with allergic asthma. Allergy. 2009. 64:1728–1736.

31. Eckman JA, Sterba PM, Kelly D, Alexander V, Liu MC, Bochner BS, Macglashan DW Jr, Saini SS. Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge. J Allergy Clin Immunol. 2009. 125:889–895.

32. Cho SH, Seo JY, Choi DC, Yoon HJ, Cho YJ, Min KU, Lee GK, Seo JW, Kim YY. Pathological changes according to the severity of asthma. Clin Exp Allergy. 1996. 26:1210–1219.

33. Kaminska M, Foley S, Maghni K, Storness-Bliss C, Coxson H, Ghezzo H, Lemiere 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. 124:45–51.

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

35. 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.

36. Djukanovic R, Lai CK, Wilson JW, Britten KM, Wilson SJ, Roche WR, Howarth PH, Holgate ST. Bronchial mucosal manifestations of atopy: A comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls. Eur Respir J. 1992. 5:538–544.

37. Sohn SW, Chang YS, Lee HS, Chung DH, Lee CT, Kim YH, Kim YK, Min KU, Kim YY, Cho SH. Atopy may be an important determinant of subepithelial fibrosis in subjects with asymptomatic airway hyperresponsiveness. J Korean Med Sci. 2008. 23:390–396.

38. Holgate ST. Epithelium dysfunction in asthma. J Allergy Clin Immunol. 2007. 120:1233–1244.

39. Polosa R, Puddicombe SM, Krishna MT, Tuck AB, Howarth PH, Holgate ST, Davies DE. Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects. J Allergy Clin Immunol. 2002. 109:75–81.

40. Hamilton LM, Puddicombe SM, Dearman RJ, Kimber I, Sandstrom T, Wallin A, Howarth PH, Holgate ST, Wilson SJ, Davies DE. Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium. Eur Respir J. 2005. 25:978–985.

41. Puddicombe SM, Torres-Lozano C, Richter A, Bucchieri F, Lordan JL, Howarth PH, Vrugt B, Albers R, Djukanovic R, Holgate ST, Wilson SJ, Davies DE. Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium. Am J Respir Cell Mol Biol. 2003. 28:61–68.

42. Cohen L, E X, Tarsi J, Ramkumar T, Horiuchi TK, Cochran R, DeMartino S, Schechtman KB, Hussain I, Holtzman MJ, Castro M. Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med. 2007. 176:138–145.

43. Burgel PR, Nadel JA. Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Respir J. 2008. 32:1068–1081.

44. Hamilton LM, Torres-Lozano C, Puddicombe SM, Richter A, Kimber I, Dearman RJ, Vrugt B, Aalbers R, Holgate ST, Djukanovic R, Wilson SJ, Davies DE. The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma. Clin Exp Allergy. 2003. 33:233–240.

45. Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: Insights from clinical studies. Proc Am Thorac Soc. 2009. 6:256–259.

46. Chalmers GW, MacLeod KJ, Thomson L, Little SA, McSharry C, Thomson NC. Smoking and airway inflammation in patients with mild asthma. Chest. 2001. 120:1917–1922.

47. de Boer WI, Sharma HS, Baelemans SM, Hoogsteden HC, Lambrecht BN, Braunstahl GJ. Altered expression of epithelial junctional proteins in atopic asthma: Possible role in inflammation. Can J Physiol Pharmacol. 2008. 86:105–112.

48. Cookson W. The immunogenetics of asthma and eczema: A new focus on the epithelium. Nat Rev Immunol. 2004. 4:978–988.

49. O'Regan GM, Sandilands A, McLean WH, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008. 122:689–693.

50. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009. 124:3–20.

51. Tieu DD, Kern RC, Schleimer RP. Alterations in epithelial barrier function and host defense responses in chronic rhinosinusitis. J Allergy Clin Immunol. 2009. 124:37–42.

52. Runswick S, Mitchell T, Davies P, Robinson C, Garrod DR. Pollen proteolytic enzymes degrade tight junctions. Respirology. 2007. 12:834–842.

53. Gershwin LJ. Effects of allergenic extracts on airway epithelium. Curr Allergy Asthma Rep. 2007. 7:357–362.

54. Hole AM, Draper A, Jolliffe G, Cullinan P, Jones M, Taylor AJ. Occupational asthma caused by bacillary amylase used in the detergent industry. Occup Environ Med. 2000. 57:840–842.

55. Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L, Symington P, O'Toole S, Myint SH, Tyrrell DA, Holgate ST. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995. 310:1225–1229.

56. Sears MR, Johnston NW. Understanding the september asthma epidemic. J Allergy Clin Immunol. 2007. 120:526–529.

57. Miller EK, Edwards KM, Weinberg GA, Iwane MK, Griffin MR, Hall CB, Zhu Y, Szilagyi PG, Morin LL, Heil LH, Lu X, Williams JV. A novel group of rhinoviruses is associated with asthma hospitalizations. J Allergy Clin Immunol. 2009. 123:98–104.

58. Wark PA, Johnston SL, Bucchieri F, Powell R, Puddicombe S, Laza-Stanca V, Holgate ST, Davies DE. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005. 201:937–947.

59. Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, Kebadze T, Mallia P, Stanciu LA, Parker HL, Slater L, Lewis-Antes A, Kon OM, Holgate ST, Davies DE, Kotenko SV, Papi A, Johnston SL. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006. 12:1023–1026.

60. Lee HR, Kim MH, Lee JS, Liang C, Jung JU. Viral interferon regulatory factors. J Interferon Cytokine Res. 2009. 29:621–627.

61. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee WM, Shult PA, Reisdorf E, Carlson-Dakes KT, Salazar LP, DaSilva DF, Tisler CJ, Gern JE, Lemanske RF Jr. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008. 178:667–672.

62. Kotaniemi-Syrjanen A, Reijonen TM, Korhonen K, Waris M, Vainionpaa R, Korppi M. Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age. Pediatr Int. 2008. 50:506–510.

63. Rate A, Upham JW, Bosco A, McKenna KL, Holt PG. Airway epithelial cells regulate the functional phenotype of locally differentiating dendritic cells: implications for the pathogenesis of infectious and allergic airway disease. J Immunol. 2009. 182:72–83.

64. Upham JW, Zhang G, Rate A, Yerkovich ST, Kusel M, Sly PD, Holt PG. Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing. J Allergy Clin Immunol. 2009. 124:707–713.

65. Esnault S, Rosenthal LA, Wang DS, Malter JS. Thymic stromal lymphopoietin (TSLP) as a bridge between infection and atopy. Int J Clin Exp Pathol. 2008. 1:325–330.

66. Collison LW, Vignali DA. Interleukin-35: odd one out or part of the family? Immunol Rev. 2008. 226:248–262.

67. Bisset LR, Schmid-Grendelmeier P. Chemokines and their receptors in the pathogenesis of allergic asthma: Progress and perspective. Curr Opin Pulm Med. 2005. 11:35–42.

68. Holgate ST, Davies DE, Lackie PM, Wilson SJ, Puddicombe SM, Lordan JL. Epithelial-mesenchymal interactions in the pathogenesis of asthma. J Allergy Clin Immunol. 2000. 105:193–204.

69. Holgate ST, Davies DE. Rethinking the pathogenesis of asthma. Immunity. 2009. 31:362–367.

70. Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K, Walsh A, Liu Z, Hayward B, Folz C, Manning SP, Bawa A, Saracino L, Thackston M, Benchekroun Y, Capparell N, Wang M, Adair R, Feng Y, Dubois J, FitzGerald MG, Huang H, Gibson R, Allen KM, Pedan A, Danzig MR, Umland SP, Egan RW, Cuss FM, Rorke S, Clough JB, Holloway JW, Holgate ST, Keith TP. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature. 2002. 418:426–430.

71. Holgate ST, Yang Y, Haitchi HM, Powell RM, Holloway JW, Yoshisue H, Pang YY, Cakebread J, Davies DE. The genetics of asthma: ADAM33 as an example of a susceptibility gene. Proc Am Thorac Soc. 2006. 3:440–443.

72. Lee JY, Park SW, Chang HK, Kim HY, Rhim T, Lee JH, Jang AS, Koh ES, Park CS. A disintegrin and metalloproteinase 33 protein in patients with asthma: Relevance to airflow limitation. Am J Respir Crit Care Med. 2006. 173:729–735.

73. Puxeddu I, Pang YY, Harvey A, Haitchi HM, Nicholas B, Yoshisue H, Ribatti D, Clough G, Powell RM, Murphy G, Hanley NA, Wilson DI, Howarth PH, Holgate ST, Davies DE. The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma. J Allergy Clin Immunol. 2008. 121:1400–1406.