Allergy Asthma Immunol Res.  2010 Oct;2(4):209-214. 10.4168/aair.2010.2.4.209.

Overlap Between Asthma and COPD: Where the Two Diseases Converge

• Kim SR
• Rhee YK

• KMID: 2260381
• DOI: http://doi.org/10.4168/aair.2010.2.4.209

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are traditionally recognized as distinct diseases, with some clearly separate characteristic. Asthma originates in childhood, is associated with allergies and eosinophils, and is best treated by targeting inflammation, whereas COPD occurs in adults who smoke, involves neutrophils, and is best treated with bronchodilators and the removal of risk factors. However, the distinction between the two is not always clear. Patients with severe asthma may present with fixed airway obstruction, and patients with COPD may have hyperresponsiveness and eosinophilia. Recognizing and understanding these overlapping features may offer new insight into the mechanisms and treatment of chronic airway inflammatory diseases.

Keyword

Asthma; COPD; overlap; exacerbation; remodeling

MeSH Terms

Adult
Airway Obstruction
Asthma
Bronchodilator Agents
Eosinophilia
Eosinophils
Humans
Hypersensitivity
Inflammation
Neutrophils
Pulmonary Disease, Chronic Obstructive
Risk Factors
Smoke
Bronchodilator Agents
Smoke

Reference

1. Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol. 2010. 120:76–85.

2. Boulet LP, Turcotte H, Hudon C, Carrier G, Maltais F. Clinical, physiological and radiological features of asthma with incomplete reversibility of airflow obstruction compared with those of COPD. Can Respir J. 1998. 5:270–277.

3. Fabbri LM, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, Ligabue G, Ciaccia A, Saetta M, Papi A. Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003. 167:418–424.

4. Jeffery PK. Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2004. 1:176–183.

5. Guerra S. Overlap of asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2005. 11:7–13.

6. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009. 64:728–735.

7. Mahler DA, Donohue JF, Barbee RA, Goldman MD, Gross NJ, Wisniewski ME, Yancey SW, Zakes BA, Rickard KA, Anderson WH. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest. 1999. 115:957–965.

8. Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek TJ Jr, Kesten S, Towse L. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002. 122:47–55.

9. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2009. Bethesda: National Institutes of Health, National Heart, Lung, and Blood Institute;(NIH publication; no. 02-3659).

10. National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. 2007. Bethesda: National Institutes of Health;(NIH publication; no. 07-4051).

11. Soriano JB, Davis KJ, Coleman B, Visick G, Mannino D, Pride NB. The proportional Venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom. Chest. 2003. 124:474–481.

12. Marsh SE, Travers J, Weatherall M, Williams MV, Aldington S, Shirtcliffe PM, Hansell AL, Nowitz MR, McNaughton AA, Soriano JB, Beasley RW. Proportional classifications of COPD phenotypes. Thorax. 2008. 63:761–767.

13. Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997. 156:737–743.

14. Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanovic R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000. 161:9–16.

15. Saetta M, Di Stefano A, Maestrelli P, Turato G, Ruggieri MP, Roggeri A, Calcagni P, Mapp CE, Ciaccia A, Fabbri LM. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med. 1994. 150:1646–1652.

16. Chanez P, Vignola AM, O'Shaugnessy T, Enander I, Li D, Jeffery PK, Bousquet J. Corticosteroid reversibility in COPD is related to features of asthma. Am J Respir Crit Care Med. 1997. 155:1529–1534.

17. Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest. 1999. 104:985–993.

18. Welte T, Groneberg DA. Asthma and COPD. Exp Toxicol Pathol. 2006. 57:Suppl 2. 35–40.

19. Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, Bellettato CM, Papi A, Corbetta L, Zuin R, Sinigaglia F, Fabbri LM. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002. 165:1404–1409.

20. Matheson JM, Lemus R, Lange RW, Karol MH, Luster MI. Role of tumor necrosis factor in toluene diisocyanate asthma. Am J Respir Cell Mol Biol. 2002. 27:396–405.

21. Noguchi E, Yokouchi Y, Shibasaki M, Inudou M, Nakahara S, Nogami T, Kamioka M, Yamakawa-Kobayashi K, Ichikawa K, Matsui A, Arinami T. Association between TNFA polymorphism and the development of asthma in the Japanese population. Am J Respir Crit Care Med. 2002. 166:43–46.

22. Bousquet J, Lacoste JY, Chanez P, Vic P, Godard P, Michel FB. Bronchial elastic fibers in normal subjects and asthmatic patients. Am J Respir Crit Care Med. 1996. 153:1648–1654.

23. Atkinson JJ, Senior RM. Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol. 2003. 28:12–24.

24. Elias JA, Zhu Z, Chupp G, Homer RJ. Airway remodeling in asthma. J Clin Invest. 1999. 104:1001–1006.

25. James AL, Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur Respir J. 2007. 30:134–155.

26. Bourdin A, Serre I, Flamme H, Vic P, Neveu D, Aubas P, Godard P, Chanez P. Can endobronchial biopsy analysis be recommended to discriminate between asthma and COPD in routine practice? Thorax. 2004. 59:488–493.

27. Vestbo J, Prescott E. Update on the "Dutch hypothesis" for chronic respiratory disease. Thorax. 1998. 53:Suppl 2. S15–S19.

28. Lange P, Parner J, Vestbo J, Schnohr P, Jensen G. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med. 1998. 339:1194–1200.

29. Mauad T, Dolhnikoff M. Pathologic similarities and differences between asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2008. 14:31–38.

30. Lamblin C, Gosset P, Tillie-Leblond I, Saulnier F, Marquette CH, Wallaert B, Tonnel AB. Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med. 1998. 157:394–402.

31. Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol. 1995. 95:843–852.

32. Wark PA, Johnston SL, Moric I, Simpson JL, Hensley MJ, Gibson PG. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J. 2002. 19:68–75.

33. Tsokos M, Paulsen F. Expression of pulmonary lactoferrin in sudden-onset and slow-onset asthma with fatal outcome. Virchows Arch. 2002. 441:494–499.

34. Zhu J, Qiu YS, Majumdar S, Gamble E, Matin D, Turato G, Fabbri LM, Barnes N, Saetta M, Jeffery PK. Exacerbations of bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants. Am J Respir Crit Care Med. 2001. 164:109–116.

35. Siva R, Green RH, Brightling CE, Shelley M, Hargadon B, McKenna S, Monteiro W, Berry M, Parker D, Wardlaw AJ, Pavord ID. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007. 29:906–913.

36. Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose M. Airway cytokine expression measured by means of protein array in exhaled breath condensate: correlation with physiologic properties in asthmatic patients. J Allergy Clin Immunol. 2006. 118:84–90.

37. Bullens DM, Truyen E, Coteur L, Dilissen E, Hellings PW, Dupont LJ, Ceuppens JL. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res. 2006. 7:135.

38. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J, Chakir J. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001. 108:430–438.

39. Wong CK, Ho CY, Ko FW, Chan CH, Ho AS, Hui DS, Lam CW. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol. 2001. 125:177–183.

40. Barczyk A, Pierzchala W, Sozañska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 2003. 97:726–733.

41. Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007. 4:512–521.

42. Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007. 370:758–764.

43. Stein RT, Holberg CJ, Sherrill D, Wright AL, Morgan WJ, Taussig L, Martinez FD. Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study. Am J Epidemiol. 1999. 149:1030–1037.

44. Vonk JM, Jongepier H, Panhuysen CI, Schouten JP, Bleecker ER, Postma DS. Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. Thorax. 2003. 58:322–327.

45. Wright JL, Churg A. Advances in the pathology of COPD. Histopathology. 2006. 49:1–9.

46. Mauad T, Silva LF, Santos MA, Grinberg L, Bernardi FD, Martins MA, Saldiva PH, Dolhnikoff M. Abnormal alveolar attachments with decreased elastic fiber content in distal lung in fatal asthma. Am J Respir Crit Care Med. 2004. 170:857–862.

47. James AL, Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur Respir J. 2007. 30:134–155.

48. Spurzem JR, Rennard SI. Pathogenesis of COPD. Semin Respir Crit Care Med. 2005. 26:142–153.

49. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Elias JA. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest. 2000. 106:1081–1093.

50. Kraft M, Djukanovic R, Wilson S, Holgate ST, Martin RJ. Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med. 1996. 154:1505–1510.

51. Kraft M, Martin RJ, Wilson S, Djukanovic R, Holgate ST. Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Am J Respir Crit Care Med. 1999. 159:228–234.

52. Sutherland ER, Martin RJ, Bowler RP, Zhang Y, Rex MD, Kraft M. Physiologic correlates of distal lung inflammation in asthma. J Allergy Clin Immunol. 2004. 113:1046–1050.

53. Sumi Y, Hamid Q. Airway remodeling in asthma. Allergol Int. 2007. 56:341–348.

54. Bosken CH, Wiggs BR, Pare PD, Hogg JC. Small airway dimensions in smokers with obstruction to airflow. Am Rev Respir Dis. 1990. 142:563–570.

55. Nagai A, West WW, Thurlbeck WM. The National Institutes of Health Intermittent Positive-Pressure Breathing trial: pathology studies. II. Correlation between morphologic findings, clinical findings, and evidence of expiratory air-flow obstruction. Am Rev Respir Dis. 1985. 132:946–953.

56. Wright JL, Lawson LM, Pare PD, Wiggs BJ, Kennedy S, Hogg JC. Morphology of peripheral airways in current smokers and ex-smokers. Am Rev Respir Dis. 1983. 127:474–477.

57. Kerstjens HA, Brand PL, Quanjer PH, van der Bruggen-Bogaarts BA, Koetër GH, Postma DS. Dutch CNSLD Study Group. Variability of bronchodilator response and effects of inhaled corticosteroid treatment in obstructive airways disease. Thorax. 1993. 48:722–729.

58. Tashkin DP, Altose MD, Connett JE, Kanner RE, Lee WW, Wise RA. The Lung Health Study Research Group. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996. 153:1802–1811.

59. van Schayck CP. Is lung function really a good parameter in evaluating the long-term effects of inhaled corticosteroids in COPD? Eur Respir J. 2000. 15:238–239.

60. Weir DC, Burge PS. Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction. Thorax. 1993. 48:309–316.

61. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000. 320:1297–1303.

62. Calverley PM, Burge PS, Spencer S, Anderson JA, Jones PW. Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Thorax. 2003. 58:659–664.

63. Kuwano K, Bosken CH, Paré PD, Bai TR, Wiggs BR, Hogg JC. Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1993. 148:1220–1225.

64. Lambert RK, Wiggs BR, Kuwano K, Hogg JC, Paré PD. Functional significance of increased airway smooth muscle in asthma and COPD. J Appl Physiol. 1993. 74:2771–2781.

65. Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001. 344:350–362.

66. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004. 350:2645–2653.

67. Saetta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001. 163:1304–1309.

68. Lee M, Goodbourn S. Signalling from the cell surface to the nucleus. Essays Biochem. 2001. 37:71–85.

69. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000. 356:2144–2148.

70. Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov. 2003. 2:717–726.

71. Adcock IM, Chung KF, Caramori G, Ito K. Kinase inhibitors and airway inflammation. Eur J Pharmacol. 2006. 533:118–132.

72. Zhou Y, Schneider DJ, Blackburn MR. Adenosine signaling and the regulation of chronic lung disease. Pharmacol Ther. 2009. 123:105–116.

73. Caruso M, Tringali G, Polosa R. Evidence for a functional contribution of adenosine signalling in inflammatory airway diseases. Immunol Endocr Metab Agents Med Chem. 2007. 7:286–297.

74. Polosa R, Blackburn MR. Adenosine receptors as targets for therapeutic intervention in asthma and chronic obstructive pulmonary disease. Trends Pharmacol Sci. 2009. 30:528–535.