Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

Pathophysiology of Chronic Obstructive Pulmonary Disease

만성폐쇄성폐질환의 병태생리

  • Kim, Hyun Kuk (Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lee, Sang-Do (Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center)
  • 김현국 (울산대학교 의과대학 서울아산병원 내과학교실) ;
  • 이상도 (울산대학교 의과대학 서울아산병원 내과학교실)
  • Published : 2005.07.30
Download PDF
⟨ Previous Next ⟩

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic progressive disease, characterized by irreversible airflow limitation, with a partially reversible component. The pathological abnormalities of COPD are associated with lung inflammation, imbalances of proteinase and antiproteinase, and oxidative stress, which are induced by noxious particles and gases in susceptible individuals. The physiological changes of COPD are mucus hypersecretion, ciliary dysfunction, airflow limitation, pulmonary hyperinflation, gas exchange abnormalities, pulmonary hypertension, cor pulmonale and systemic effects. The airflow limitation principally results from an increase in the resistance of the small conducting airways and a decrease in pulmonary elastic recoil due to emphysematous lung destruction. This article provides a general overview of the pathophysiology of COPD.

COPD는 비가역적인 기류제한을 특징으로 하는 질병의 상태이다. 이러한 기류제한은 유해입자나 가스등에 대한 폐의 비정상적인 염증반응과 관련되어 있고 자연경과 중 지속적으로 진행하는 양상을 띤다. 비정상적인 염증반응 및 단백분해효소와 항단백분해효소간의 불균형과 산화 스트레스 등의 기전에 의해 점액의 과분비, 섬모의 기능장애, 소기도의 섬유화와 협착, 폐실질의 파괴, 폐혈관손상 등이 발생한다. 이러한 병리학적 변화에 의해 기류제한이 발생하고 가스교환 장애, 폐고혈압, 폐성심, 전신적인 염증이나 골격근의 기능장애 등이 유발된다. COPD 환자의 일반적인 증상인 기침, 객담, 호흡곤란 등은 이러한 병태생리학적 변화로 설명할 수 있다.

Keywords

References

  1. Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:1256-76 https://doi.org/10.1164/ajrccm.163.5.2101039
  2. Mullen JB, Wright JL, Wiggs BR, Pare PD, Hogg JC. Reassessment of inflammation of airway in chronic bronchitis. BMJ 1985;291:1235-9
  3. Cosio M, Ghezzo H, Hogg JC, Corbin R, Loveland M, Dosman J, et al. The relation between structural changes in small airways and pulmonary-function tests. N Engl J Med 1978;298:1277-81 https://doi.org/10.1056/NEJM197806082982303
  4. Matsuba K, Thurlbeck WM. The number and dimensions of small airways in emphysematous lungs. Am J Pathol 1972;67:265-75
  5. Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstructive lung disease. N Engl J Med 1968;278:1355-60 https://doi.org/10.1056/NEJM196801042780102
  6. Kuwano K, Bosken CH, Pare PD, Bai TR, Wiggs BR, Hogg JC. Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993;148:1220-5
  7. Matsuba K, Wright JL, Wiggs BR, Pare PD, Hogg JC. The changes in airways structure associated with reduced forced expiratory volume in one second. Eur Respir J 1989;2:834-9
  8. Dayman H. Mechanics of airflow in health and emphysema. J Clin Invest 1951;30:1175-90
  9. Butler J, Caro CG, Alkaler R, Dubois AB. Physiological factors affecting airway resistance in normal subjects and in patients with obstructive airways disease. J Clin Invest 1960;39:584-91 https://doi.org/10.1172/JCI104071
  10. Mead J. Turner JM, Macklem PT, Little JB. Significance of the relationship between lung recoil and maximum expiratory flow. J Appl Physiol 1967;22:95-108
  11. Burnett D, Stockley RA. Serum and sputum alpha 2 macroglobulin in patients with chronic obstructive airways disease. Thorax 1981;36:512-6 https://doi.org/10.1136/thx.36.7.512
  12. Lane DJ, Howell JB, Giblin B. Relation between airways obstruction and $CO_{2}$ tension in chronic obstructive airways disease. Br Med J 1968;3:707-9 https://doi.org/10.1136/bmj.3.5620.707
  13. Rodriguez-Roisin R, MacNee W. Pathophysiology of chronic obstructive pulmonary disease. In: Postma DS, Siafakas MN, editors. Management of chronic obstructive pulmonary disease. Eur Respir Monograph 1998. p. 107-26
  14. McLean A, Warren PM, Gillooly M, MacNee W, Lamb D. Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer. Thorax 1992;47:144-9 https://doi.org/10.1136/thx.47.3.144
  15. Barbera JA, Riverola A, Roca J, Ramirez J, Wagner PD, Ros D, et al. Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;149:423-9 https://doi.org/10.1164/ajrccm.149.2.8306040
  16. MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease: part two. Am J Respir Crit Care Med 1994;150:1158-68 https://doi.org/10.1164/ajrccm.150.4.7921453
  17. Knighton DR, Hunt TK, Scheuenstuhl H, Halliday BJ, Werb Z, Banda MJ. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 1983;221:1283-5
  18. Biernacki W, Flenley DC, Muir AL, MacNee W. Pulmonary hypertension and right ventricular function in patients with COPD. Chest 1988;94:1169-75 https://doi.org/10.1378/chest.94.1.5
  19. Rahman I, Morrison D, Donaldson K, MacNee W. Systemic oxidative stress in asthma, COPD, and smokers. Am J Respir Crit Care Med 1996;154:1055-60
  20. Schols AM, Buurman WA, Staal van den Brekel AJ, Dentener MA, Wouters EF. Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 1996;51:819-24 https://doi.org/10.1136/thx.51.8.819
  21. Sauleda J, Garcia-Palmer FJ, Gonzalez G, Palou A, Agusti AG. The activity of cytochrome oxidase is increased in circulating lymphocytes of patients with chronic obstructive pulmonary disease, asthma, and chronic arthritis. Am J Respir Crit Care Med 2000;161:32-5 https://doi.org/10.1164/ajrccm.161.1.9906062
  22. Sauleda J, Garcia-Palmer F, Wiesner RJ, Tarraga S, Harting I, Tomas P, et al. Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1413-7 https://doi.org/10.1164/ajrccm.157.5.9710039
  23. American Thoracic Society and European Respiratory Society. Skeletal muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:S1-40
  24. Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1791-7 https://doi.org/10.1164/ajrccm.157.6.9705017
  25. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-12 https://doi.org/10.1056/ENEJMicm010514
  26. Wasserman K, Hansen JE, Sue DY, Casaburi R, Whipp BJ. Chapter 1. Exercise testing and interpretation: an overview. In: Wasserman K, Hansen JE, Sue DY, Casaburi R, Whipp BJ, editors. Principles of exercise testing and interpretation. 2nd ed. Philadelphia: Williams & Wilkins; 1994. p.1-8
  27. Killian KJ, Leblanc P, Martin DH, Summers E, Jones NL, Campbell EJ. Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation. Am Rev Respir Dis 1992;146:935-40
  28. Vandenbergh E, van de Woestijne KP, Gyselen A. Weight changes in the terminal stages of chronic obstructive pulmonary disease: relation to respiratory function and prognosis. Am Rev Respir Dis 1967;95:556-66
  29. Schols AM, Soeters PB, Dingemans AM, Mostert R, Frantzen PJ, Wouters EF. Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147:1151-6 https://doi.org/10.1164/ajrccm/147.5.1151
  30. Engelen MP, Schols AM, Lamers RJ, Wouters EF. Different patterns of chronic tissue wasting among patients with chronic obstructive pulmonary disease. Clin Nutr 1999;18:275-80 https://doi.org/10.1016/S0261-5614(99)80043-0
  31. Baarends EM, Schols AM, Pannemans DL, Westerterp KR, Wouters EF. Total free living energy expenditure in patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:549-54 https://doi.org/10.1164/ajrccm.155.2.9032193
  32. Jounieaux V, Mayeux I. Oxygen cost of breathing in patients with emphysema or chronic bronchitis in acute respiratory failure. Am J Respir Crit Care Med 1995;152:2181-4
  33. Mannix ET, Manfredi F, Farber MO. Elevated $O_{2}$ cost of ventilation contributes to tissue wasting in COPD. Chest 1999;115:708-13 https://doi.org/10.1378/chest.115.3.708
  34. Ferreira IM, Brooks D, Lacasse Y, Goldstein RS. Nutritional support for individuals with COPD: a meta-analysis. Chest 2000;117:672-8 https://doi.org/10.1378/chest.117.3.672
  35. Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003;21:347-60 https://doi.org/10.1183/09031936.03.00405703
  36. Di Francia M, Barbier D, Mege JL, Orehek J. Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;150:1453-5
  37. de Godoy I, Donahoe M, Calhoun WJ, Mancino J, Rogers RM. Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients. Am J Respir Crit Care Med 1996;153:633-7 https://doi.org/10.1164/ajrccm.153.2.8564110
  38. Takabatake N, Nakamura H, Abe S, Hino T, Saito H, Yuki H, et al. Circulating leptin in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1215-9
  39. Riancho JA, Gonzalez Macias J, Del Arco C, Amado JA, Freijanes J, Anton MA. Vertebral compression fractures and mineral metabolism in chronic obstructive lung disease. Thorax 1987;42:962-6 https://doi.org/10.1136/thx.42.12.962
  40. Praet JP, Peretz A, Rozenberg S, Famaey JP, Bourdoux P. Risk of osteoporosis in men with chronic bronchitis. Osteoporos Int 1992;2:257-61 https://doi.org/10.1007/BF01624152
  41. Iqbal F, Michaelson J, Thaler L, Rubin J, Roman J, Nanes MS. Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function. Chest 1999;116:1616-24 https://doi.org/10.1378/chest.116.6.1616
  42. Leech JA, Dulberg C, Kellie S, Pattee L, Gay J. Relationship of lung function to severity of osteoporosis in women. Am Rev Respir Dis 1990;141:68-71 https://doi.org/10.1164/ajrccm/141.1.68
  43. McEvoy CE, Ensrud KE, Bender E, Genant HK, Yu W, Griffith JM, et al. Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:704-9 https://doi.org/10.1164/ajrccm.157.3.9703080
  44. Halpern MT, Schmier JK, van Kerkhove MD, Watkins M, Kalberg CJ. Impact of long-term inhaled corticosteroid therapy on bone mineral density: results of a meta-analysis. Ann Allergy Asthma Immunol 2004;92:201-7 https://doi.org/10.1016/S1081-1206(10)61548-7
  45. Saetta M, di Stefano A, Maestrelli P, Turato G, Ruggieri MP, Roggeri A, et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med 1994;150:1646-52 https://doi.org/10.1164/ajrccm.150.6.7952628
  46. Saetta M, di Stefano A, Maestrelli P, Turato G, Mapp CE, Pieno M, et al. Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis. Clin Exp Allergy 1996;26:766-74
  47. Pizzichini MM, Pizzichini E, Efthimiadis A, Clelland L, Mahony JB, Dolovich J, et al. Markers of inflammation in induced sputum in acute bronchitis caused by Chlamydia pneumoniae. Thorax 1997;52:929-31 https://doi.org/10.1136/thx.52.10.929
  48. Pizzichini E, Pizzichini MM, Gibson P, Parameswaran K, Gleich GJ, Berman L, et al. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med 1998;158:1511-7 https://doi.org/10.1164/ajrccm.158.5.9804028
  49. Maestrelli P, Saetta M, di Stefano A, Calcagni PG, Turato G, Ruggieri MP, et al. Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage. Am J Respir Crit Care Med 1995;152:1926-31
  50. Turner MO, Hussack P, Sears MR, Dolovich J, Hargreave FE. Exacerbations of asthma without sputum eosinophilia. Thorax 1995;50:1057-61 https://doi.org/10.1136/thx.50.Suppl_1.S5
  51. Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 1995;95:843-52 https://doi.org/10.1016/S0091-6749(06)81011-0
  52. Barbera JA, Roca J, Ferrer A, Felez MA, Diaz O, Roger N, et al. Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1997;10:1285-91
  53. Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary diseases. Am J Respir Crit Care Med 2000;161:1608-13 https://doi.org/10.1164/ajrccm.161.5.9908022
  54. Schmidt GA, Hall JB. Acute or chronic respiratory failure: assessment and management of patients with COPD in the emergency setting. JAMA 1989;261:3444-53 https://doi.org/10.1001/jama.261.23.3444
  55. Rodriguez-Roisin R. Pulmonary gas exchange in acute respiratory failure. Eur J Anaesthesiol 1994;11:5-13