Allergy Asthma Immunol Res.  2013 Jul;5(4):181-188. 10.4168/aair.2013.5.4.181.

Relationship Between Atopy and Bronchial Hyperresponsiveness

  • 1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.


Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.


Allergic rhinitis; asthma; atopy; bronchial hyperresponsiveness; patients; population

MeSH Terms

Immunoglobulin E
Rhinitis, Allergic, Perennial
Immunoglobulin E


1. Crockcroft DW, Murdock KY, Berscheid BA. Relationship between atopy and bronchial responsiveness to histamine in a random population. Ann Allergy. 1984; 53:26–29.
2. Peat JK, Britton WJ, Salome CM, Woolcock AJ. Bronchial hyperresponsiveness in two populations of Australian schoolchildren. III. Effect of exposure to environmental allergens. Clin Allergy. 1987; 17:291–300.
3. Backer V, Ulrik CS, Hansen KK, Laursen EM, Dirksen A, Bach-Mortensen N. Atopy and bronchial responsiveness in random population sample of 527 children and adolescents. Ann Allergy. 1992; 69:116–122.
4. Burrows B, Sears MR, Flannery EM, Herbison GP, Holdaway MD. Relations of bronchial responsiveness to allergy skin test reactivity, lung function, respiratory symptoms, and diagnoses in thirteen-year-old New Zealand children. J Allergy Clin Immunol. 1995; 95:548–556.
5. Helenius IJ, Tikkanen HO, Sarna S, Haahtela T. Asthma and increased bronchial responsiveness in elite athletes: atopy and sport event as risk factors. J Allergy Clin Immunol. 1998; 101:646–652.
6. Peat JK, van den Berg RH, Green WF, Mellis CM, Leeder SR, Woolcock AJ. Changing prevalence of asthma in Australian children. BMJ. 1994; 308:1591–1596.
7. Forastiere F, Corbo GM, Dell'Orco V, Pistelli R, Agabiti N, Kriebel D. A longitudinal evaluation of bronchial responsiveness to methacholine in children: role of baseline lung function, gender, and change in atopic status. Am J Respir Crit Care Med. 1996; 153:1098–1104.
8. Kurukulaaratchy RJ, Matthews S, Arshad SH. Relationship between childhood atopy and wheeze: what mediates wheezing in atopic phenotypes? Ann Allergy Asthma Immunol. 2006; 97:84–91.
9. Sears MR, Burrows B, Herbison GP, Holdaway MD, Flannery EM. Atopy in childhood. II. Relationship to airway responsiveness, hay fever and asthma. Clin Exp Allergy. 1993; 23:949–956.
10. Plaschke P, Janson C, Norrman E, Björnsson E, Ellbjär S, Järvholm B. Association between atopic sensitization and asthma and bronchial hyperresponsiveness in swedish adults: pets, and not mites, are the most important allergens. J Allergy Clin Immunol. 1999; 104:58–65.
11. Yu J, Yoo Y, Kang H, Kim DK, Choi SH, Koh YY. The relationship between allergen sensitization and bronchial hyperresponsiveness in children aged 6-8 years. Pediatr Allergy Respir Dis. 2005; 15:344–351.
12. Kim BS, Jin HS, Kim HB, Lee SY, Kim JH, Kwon JW, Kim BJ, Yu J, Yoo S, Hong SJ. Airway hyperresponsiveness is associated with total serum immunoglobulin E and sensitization to aeroallergens in Korean adolescents. Pediatr Pulmonol. 2010; 45:1220–1227.
13. Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcock AJ. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy. 1993; 23:812–820.
14. Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med. 1991; 325:1067–1071.
15. Burrows B, Sears MR, Flannery EM, Herbison GP, Holdaway MD, Silva PA. Relation of the course of bronchial responsiveness from age 9 to age 15 to allergy. Am J Respir Crit Care Med. 1995; 152:1302–1308.
16. Omenaas E, Bakke P, Eide GE, Elsayed S, Gulsvik A. Serum house dust mite antibodies: predictor of increased bronchial responsiveness in adults of a community. Eur Respir J. 1996; 9:919–925.
17. Boulet LP, Cartier A, Thomson NC, Roberts RS, Dolovich J, Hargreave FE. Asthma and increases in nonallergic bronchial responsiveness from seasonal pollen exposure. J Allergy Clin Immunol. 1983; 71:399–406.
18. Prieto L, Bertó JM, Lopez M, Peris A. Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients. Clin Exp Allergy. 1993; 23:172–178.
19. Madonini E, Briatico-Vangosa G, Pappacoda A, Maccagni G, Cardani A, Saporiti F. Seasonal increase of bronchial reactivity in allergic rhinitis. J Allergy Clin Immunol. 1987; 79:358–363.
20. Di Lorenzo G, Mansueto P, Melluso M, Morici G, Norrito F, Esposito Pellitteri M, Di Salvo A, Colombo A, Candore G, Caruso C. Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season. Clin Exp Allergy. 1997; 27:1052–1059.
21. van der Heide S, de Monchy JG, de Vries K, Bruggink TM, Kauffman HF. Seasonal variation in airway hyperresponsiveness and natural exposure to house dust mite allergens in patients with asthma. J Allergy Clin Immunol. 1994; 93:470–475.
22. Riccioni G, Di Stefano F, De Benedictis M, Verna N, Cavallucci E, Paolini F, Di Sciascio MB, Della Vecchia R, Schiavone C, Boscolo P, Conti P, Di Gioacchino M. Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites. Allergy Asthma Proc. 2001; 22:5–9.
23. Custovic A, Taggart SC, Francis HC, Chapman MD, Woodcock A. Exposure to house dust mite allergens and the clinical activity of asthma. J Allergy Clin Immunol. 1996; 98:64–72.
24. Cockcroft DW, Ruffin RE, Dolovich J, Hargreave FE. Allergen-induced increase in non-allergic bronchial reactivity. Clin Allergy. 1977; 7:503–513.
25. Cartier A, Thomson NC, Frith PA, Roberts R, Hargreave FE. Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber. J Allergy Clin Immunol. 1982; 70:170–177.
26. Ketchell RI, D'Amato M, Jensen MW, O'Connor BJ. Contrasting effects of allergen challenge on airway responsiveness to cysteinyl leukotriene D(4) and methacholine in mild asthma. Thorax. 2002; 57:575–580.
27. Nelson HS, Szefler SJ, Jacobs J, Huss K, Shapiro G, Sternberg AL. The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program. J Allergy Clin Immunol. 1999; 104:775–785.
28. Kurt E, Bavbek S, Aksu O, Erekul S, Misirligil Z. The effect of natural pollen exposure on eosinophil apoptosis and its relationship to bronchial hyperresponsiveness in patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2005; 95:72–78.
29. Djukanović R, Feather I, Gratziou C, Walls A, Peroni D, Bradding P, Judd M, Howarth PH, Holgate ST. Effect of natural allergen exposure during the grass pollen season on airways inflammatory cells and asthma symptoms. Thorax. 1996; 51:575–581.
30. Oddera S, Silvestri M, Penna R, Galeazzi G, Crimi E, Rossi GA. Airway eosinophilic inflammation and bronchial hyperresponsiveness after allergen inhalation challenge in asthma. Lung. 1998; 176:237–247.
31. Imaoka H, Gauvreau GM, Watson RM, Strinich T, Obminksi GL, Howie K, Killian KJ, O'Byrne PM. Sputum inflammatory cells and allergen-induced airway responses in allergic asthmatic subjects. Allergy. 2011; 66:1075–1080.
32. Boner AL, Niero E, Antolini I, Valletta EA, Gaburro D. Pulmonary function and bronchial hyperreactivity in asthmatic children with house dust mite allergy during prolonged stay in the Italian Alps (Misurina, 1756 m). Ann Allergy. 1985; 54:42–45.
33. Benckhuijsen J, van den Bos JW, van Velzen E, de Bruijn R, Aalbers R. Differences in the effect of allergen avoidance on bronchial hyperresponsiveness as measured by methacholine, adenosine 5'-monophosphate, and exercise in asthmatic children. Pediatr Pulmonol. 1996; 22:147–153.
34. Platts-Mills TA, Tovey ER, Mitchell EB, Moszoro H, Nock P, Wilkins SR. Reduction of bronchial hyperreactivity during prolonged allergen avoidance. Lancet. 1982; 2:675–678.
35. Htut T, Higenbottam TW, Gill GW, Darwin R, Anderson PB, Syed N. Eradication of house dust mite from homes of atopic asthmatic subjects: a double-blind trial. J Allergy Clin Immunol. 2001; 107:55–60.
36. Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy? Thorax. 1999; 54:268–272.
37. Corrigan C. Mechanisms of intrinsic asthma. Curr Opin Allergy Clin Immunol. 2004; 4:53–56.
38. Kurukulaaratchy RJ, Fenn M, Matthews S, Arshad SH. Characterisation of atopic and non-atopic wheeze in 10 year old children. Thorax. 2004; 59:563–568.
39. Castro-Rodriguez JA, Navarrete-Contreras P, Holmgren L, Sanchez I, Caussade S. Bronchial hyperreactivity to methacholine in atopic versus nonatopic asthmatic schoolchildren and preschoolers. J Asthma. 2010; 47:929–934.
40. Lúdvíksdóttir D, Janson C, Björnsson E, Stålenheim G, Boman G, Hedenström H, Venge P, Gudbjörnsson B, Valtysdóttir S. Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjogren's syndrome. BHR Study Group. Bronchial hyperresponsiveness. Allergy. 2000; 55:259–265.
41. Harmanci K, Bakirtas A, Turktas I. Factors affecting bronchial hyperreactivity in asthmatic children. J Asthma. 2008; 45:730–734.
42. Suh DI, Lee JK, Kim CK, Koh YY. Methacholine and adenosine 5'-monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma. Pediatr Allergy Immunol. 2011; 22:e101–e106.
43. Mochizuki H, Shigeta M, Tokuyama K, Morikawa A. Difference in airway reactivity in children with atopic vs nonatopic asthma. Chest. 1999; 116:619–624.
44. Gruber W, Eber E, Steinbrugger B, Modl M, Weinhandl E, Zach MS. Atopy, lung function and bronchial responsiveness in symptom-free paediatric asthma patients. Eur Respir J. 1997; 10:1041–1045.
45. Ferrante E, Corbo GM, Valente S, Ciappi G. Associations between atopy, asthma history, respiratory function and non-specific bronchial hyperresponsiveness in unselected young asthmatics. Respiration. 1992; 59:169–172.
46. Currie GP, Jackson CM, Lee DK, Lipworth BJ. Determinants of airway hyperresponsiveness in mild asthma. Ann Allergy Asthma Immunol. 2003; 90:560–563.
47. Bakirtas A, Turktas I. Determinants of airway responsiveness to adenosine 5'-monophosphate in school-age children with asthma. Pediatr Pulmonol. 2006; 41:515–521.
48. van den Berge M, Meijer RJ, Kerstjens HA, de Reus DM, Koeter GH, Kauffman HF, Postma DS. PC(20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine. Am J Respir Crit Care Med. 2001; 163:1546–1550.
49. Lúdvíksdóttir D, Janson C, Högman M, Hedenström H, Björnsson E, Boman G. Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma. BHR-Study Group. Respir Med. 1999; 93:552–556.
50. Drews AC, Pizzichini MM, Pizzichini E, Pereira MU, Pitrez PM, Jones MH, Sly PD, Stein RT. Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children. Allergy. 2009; 64:1597–1601.
51. Erwin EA, Rönmark E, Wickens K, Perzanowski MS, Barry D, Lundbäck B, Crane J, Platts-Mills TA. Contribution of dust mite and cat specific IgE to total IgE: relevance to asthma prevalence. J Allergy Clin Immunol. 2007; 119:359–365.
52. Fowler SJ, Lipworth BJ. Relationship of skin-prick reactivity to aeroallergens and hyperresponsiveness to challenges with methacholine and adenosine monophosphate. Allergy. 2003; 58:46–52.
53. Takeda K, Shibasaki M, Takita H. Relation between bronchial responsiveness to methacholine and levels of IgE antibody against Dermatophagoides farinae and serum IgE in asthmatic children. Clin Exp Allergy. 1993; 23:450–454.
54. Martín-Muñoz F, Moreno-Ancillo A, Pestaña JA, Contreras-Porta J, Díaz-Peña JM, Ojeda JA. Atopy and bronchial hyperresponsiveness in pure extrinsic childhood asthma. J Investig Allergol Clin Immunol. 1997; 7:229–233.
55. Lombardi C, Passalacqua G, Ciprandi G, Scordamaglia A, Canonica GW. Relationship between degree of nonspecific hyperresponsiveness and number of positive skin tests in asthmatics. Monaldi Arch Chest Dis. 2000; 55:181–184.
56. Currie GP, Jackson CM, Lee DK, Lipworth BJ. Allergen sensitization and bronchial hyper-responsiveness to adenosine monophosphate in asthmatic patients. Clin Exp Allergy. 2003; 33:1405–1408.
57. Suh DI, Lee JK, Kim CK, Koh YY. Bronchial hyperresponsiveness to methacholine and adenosine 5'-monophosphate, and the presence and degree of atopy in young children with asthma. Clin Exp Allergy. 2011; 41:338–345.
58. Cardinale F, de Benedictis FM, Muggeo V, Giordano P, Loffredo MS, Iacoviello G, Armenio L. Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. Pediatr Allergy Immunol. 2005; 16:236–242.
59. Sacco O, Sale R, Silvestri M, Serpero L, Sabatini F, Raynal ME, Biraghi M, Rossi GA. Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites. Pediatr Allergy Immunol. 2003; 14:475–481.
60. Di Lorenzo G, Pacor ML, Mansueto P, Esposito Pellitteri M, Lo Bianco C, Ditta V, Leto-Barone MS, Napoli N, Di Fede G, Rini GB. Determinants of bronchial hyperresponsiveness in subjects with rhinitis. Int J Immunopathol Pharmacol. 2005; 18:715–722.
61. Mølgaard E, Thomsen SF, Lund T, Pedersen L, Nolte H, Backer V. Differences between allergic and nonallergic rhinitis in a large sample of adolescents and adults. Allergy. 2007; 62:1033–1037.
62. Koh YY, Lee MH, Kim CK, Min YG, Kim YK, Min KU, Kim YY. A familial predisposition in bronchial hyperresponsiveness among patients with allergic rhinitis. J Allergy Clin Immunol. 1998; 102:921–926.
63. Cuttitta G, Cibella F, La Grutta S, Hopps MR, Bucchieri S, Passalacqua G, Bonsignore G. Non-specific bronchial hyper-responsiveness in children with allergic rhinitis: relationship with the atopic status. Pediatr Allergy Immunol. 2003; 14:458–463.
64. Cibella F, Cuttitta G, La Grutta S, Hopps MR, Passalacqua G, Pajno GB, Bonsignore G. Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up. Allergy. 2004; 59:1074–1079.
65. Mete N, Sin A, Gulbahar O, Erdinc M, Sebik F, Kokuludag A. The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2004; 93:193–199.
66. Verdiani P, Di Carlo S, Baronti A. Different prevalence and degree of nonspecific bronchial hyperreactivity between seasonal and perennial rhinitis. J Allergy Clin Immunol. 1990; 86:576–582.
67. Kim CK, Choi SJ, Lee JK, Suh DI, Koh YY. Bronchial hyperresponsiveness to methacholine and adenosine monophosphate and the degree of atopy in children with allergic rhinitis. Ann Allergy Asthma Immunol. 2011; 106:36–41.
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