Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 2004 Oct;59(10):837–842. doi: 10.1136/thx.2003.019349

Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD

R O'Donnell 1, C Peebles 1, J Ward 1, A Daraker 1, G Angco 1, P Broberg 1, S Pierrou 1, J Lund 1, S Holgate 1, D Davies 1, D Delany 1, S Wilson 1, R Djukanovic 1
PMCID: PMC1746844  PMID: 15454648

Abstract

Background: Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease (COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria.

Methods: Sixty five subjects (11 healthy smokers, 44 smokers with stage 0–IV COPD, and 10 healthy non-smokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation.

Results: Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction (r = –0.64, p<0.001) than did inspiratory HRCT measurements (which reflect emphysema severity; r = –0.45, p<0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction (r = 0.55, p<0.001) but did not correlate with HRCT indicators of the severity of emphysema.

Conclusions: This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.

Full Text

The Full Text of this article is available as a PDF (133.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arakawa H., Webb W. R. Expiratory high-resolution CT scan. Radiol Clin North Am. 1998 Jan;36(1):189–209. doi: 10.1016/s0033-8389(05)70014-2. [DOI] [PubMed] [Google Scholar]
  2. Betsuyaku T., Nishimura M., Takeyabu K., Tanino M., Venge P., Xu S., Kawakami Y. Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Am J Respir Crit Care Med. 1999 Jun;159(6):1985–1991. doi: 10.1164/ajrccm.159.6.9809043. [DOI] [PubMed] [Google Scholar]
  3. Cosio M. G., Hale K. A., Niewoehner D. E. Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis. 1980 Aug;122(2):265–221. doi: 10.1164/arrd.1980.122.2.265. [DOI] [PubMed] [Google Scholar]
  4. Cosio M., Ghezzo H., Hogg J. C., Corbin R., Loveland M., Dosman J., Macklem P. T. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1978 Jun 8;298(23):1277–1281. doi: 10.1056/NEJM197806082982303. [DOI] [PubMed] [Google Scholar]
  5. Djukanović R., Wilson J. W., Lai C. K., Holgate S. T., Howarth P. H. The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):772–777. doi: 10.1164/ajrccm/143.4_Pt_1.772. [DOI] [PubMed] [Google Scholar]
  6. Eda S., Kubo K., Fujimoto K., Matsuzawa Y., Sekiguchi M., Sakai F. The relations between expiratory chest CT using helical CT and pulmonary function tests in emphysema. Am J Respir Crit Care Med. 1997 Apr;155(4):1290–1294. doi: 10.1164/ajrccm.155.4.9105069. [DOI] [PubMed] [Google Scholar]
  7. Finkelstein R., Fraser R. S., Ghezzo H., Cosio M. G. Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1666–1672. doi: 10.1164/ajrccm.152.5.7582312. [DOI] [PubMed] [Google Scholar]
  8. Gelb A. F., Hogg J. C., Müller N. L., Schein M. J., Kuei J., Tashkin D. P., Epstein J. D., Kollin J., Green R. H., Zamel N. Contribution of emphysema and small airways in COPD. Chest. 1996 Feb;109(2):353–359. doi: 10.1378/chest.109.2.353. [DOI] [PubMed] [Google Scholar]
  9. Gelb A. F., Schein M., Kuei J., Tashkin D. P., Müller N. L., Hogg J. C., Epstein J. D., Zamel N. Limited contribution of emphysema in advanced chronic obstructive pulmonary disease. Am Rev Respir Dis. 1993 May;147(5):1157–1161. doi: 10.1164/ajrccm/147.5.1157. [DOI] [PubMed] [Google Scholar]
  10. Gevenois P. A., De Vuyst P., Sy M., Scillia P., Chaminade L., de Maertelaer V., Zanen J., Yernault J. C. Pulmonary emphysema: quantitative CT during expiration. Radiology. 1996 Jun;199(3):825–829. doi: 10.1148/radiology.199.3.8638012. [DOI] [PubMed] [Google Scholar]
  11. Gevenois P. A., de Maertelaer V., De Vuyst P., Zanen J., Yernault J. C. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1995 Aug;152(2):653–657. doi: 10.1164/ajrccm.152.2.7633722. [DOI] [PubMed] [Google Scholar]
  12. Hale K. A., Ewing S. L., Gosnell B. A., Niewoehner D. E. Lung disease in long-term cigarette smokers with and without chronic air-flow obstruction. Am Rev Respir Dis. 1984 Nov;130(5):716–721. doi: 10.1164/arrd.1984.130.5.716. [DOI] [PubMed] [Google Scholar]
  13. Keatings V. M., Collins P. D., Scott D. M., Barnes P. J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996 Feb;153(2):530–534. doi: 10.1164/ajrccm.153.2.8564092. [DOI] [PubMed] [Google Scholar]
  14. Keatings V. M., Jatakanon A., Worsdell Y. M., Barnes P. J. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997 Feb;155(2):542–548. doi: 10.1164/ajrccm.155.2.9032192. [DOI] [PubMed] [Google Scholar]
  15. Knudson R. J., Standen J. R., Kaltenborn W. T., Knudson D. E., Rehm K., Habib M. P., Newell J. D. Expiratory computed tomography for assessment of suspected pulmonary emphysema. Chest. 1991 Jun;99(6):1357–1366. doi: 10.1378/chest.99.6.1357. [DOI] [PubMed] [Google Scholar]
  16. Kubo K., Eda S., Yamamoto H., Fujimoto K., Matsuzawa Y., Maruyama Y., Hasegawa M., Sone S., Sakai F. Expiratory and inspiratory chest computed tomography and pulmonary function tests in cigarette smokers. Eur Respir J. 1999 Feb;13(2):252–256. doi: 10.1034/j.1399-3003.1999.13b06.x. [DOI] [PubMed] [Google Scholar]
  17. Kubo K., Eda S., Yamamoto H., Fujimoto K., Matsuzawa Y., Maruyama Y., Hasegawa M., Sone S., Sakai F. Expiratory and inspiratory chest computed tomography and pulmonary function tests in cigarette smokers. Eur Respir J. 1999 Feb;13(2):252–256. doi: 10.1034/j.1399-3003.1999.13b06.x. [DOI] [PubMed] [Google Scholar]
  18. LEOPOLD J. G., GOUGH J. The centrilobular form of hypertrophic emphysema and its relation to chronic bronchitis. Thorax. 1957 Sep;12(3):219–235. doi: 10.1136/thx.12.3.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Louis R., Lau L. C., Bron A. O., Roldaan A. C., Radermecker M., Djukanović R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000 Jan;161(1):9–16. doi: 10.1164/ajrccm.161.1.9802048. [DOI] [PubMed] [Google Scholar]
  20. Miller R. R., Müller N. L., Vedal S., Morrison N. J., Staples C. A. Limitations of computed tomography in the assessment of emphysema. Am Rev Respir Dis. 1989 Apr;139(4):980–983. doi: 10.1164/ajrccm/139.4.980. [DOI] [PubMed] [Google Scholar]
  21. Miniati M., Filippi E., Falaschi F., Carrozzi L., Milne E. N., Sostman H. D., Pistolesi M. Radiologic evaluation of emphysema in patients with chronic obstructive pulmonary disease. Chest radiography versus high resolution computed tomography. Am J Respir Crit Care Med. 1995 May;151(5):1359–1367. doi: 10.1164/ajrccm.151.5.7735585. [DOI] [PubMed] [Google Scholar]
  22. Müller N. L., Staples C. A., Miller R. R., Abboud R. T. "Density mask". An objective method to quantitate emphysema using computed tomography. Chest. 1988 Oct;94(4):782–787. doi: 10.1378/chest.94.4.782. [DOI] [PubMed] [Google Scholar]
  23. O'Shaughnessy T. C., Ansari T. W., Barnes N. C., Jeffery P. K. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med. 1997 Mar;155(3):852–857. doi: 10.1164/ajrccm.155.3.9117016. [DOI] [PubMed] [Google Scholar]
  24. Pare P. D., Brooks L. A., Bates J., Lawson L. M., Nelems J. M., Wright J. L., Hogg J. C. Exponential analysis of the lung pressure-volume curve as a predictor of pulmonary emphysema. Am Rev Respir Dis. 1982 Jul;126(1):54–61. doi: 10.1164/arrd.1982.126.1.54. [DOI] [PubMed] [Google Scholar]
  25. Peleman R. A., Rytilä P. H., Kips J. C., Joos G. F., Pauwels R. A. The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J. 1999 Apr;13(4):839–843. doi: 10.1034/j.1399-3003.1999.13d24.x. [DOI] [PubMed] [Google Scholar]
  26. Retamales I., Elliott W. M., Meshi B., Coxson H. O., Pare P. D., Sciurba F. C., Rogers R. M., Hayashi S., Hogg J. C. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med. 2001 Aug 1;164(3):469–473. doi: 10.1164/ajrccm.164.3.2007149. [DOI] [PubMed] [Google Scholar]
  27. Saetta M., Ghezzo H., Kim W. D., King M., Angus G. E., Wang N. S., Cosio M. G. Loss of alveolar attachments in smokers. A morphometric correlate of lung function impairment. Am Rev Respir Dis. 1985 Oct;132(4):894–900. doi: 10.1164/arrd.1985.132.4.894. [DOI] [PubMed] [Google Scholar]
  28. Saetta M., Turato G., Facchini F. M., Corbino L., Lucchini R. E., Casoni G., Maestrelli P., Mapp C. E., Ciaccia A., Fabbri L. M. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med. 1997 Nov;156(5):1633–1639. doi: 10.1164/ajrccm.156.5.9701081. [DOI] [PubMed] [Google Scholar]
  29. Soejima K., Yamaguchi K., Kohda E., Takeshita K., Ito Y., Mastubara H., Oguma T., Inoue T., Okubo Y., Amakawa K. Longitudinal follow-up study of smoking-induced lung density changes by high-resolution computed tomography. Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1264–1273. doi: 10.1164/ajrccm.161.4.9905040. [DOI] [PubMed] [Google Scholar]
  30. Turato Graziella, Zuin Renzo, Miniati Massimo, Baraldo Simonetta, Rea Federico, Beghé Bianca, Monti Simonetta, Formichi Bruno, Boschetto Piera, Harari Sergio. Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. Am J Respir Crit Care Med. 2002 Jul 1;166(1):105–110. doi: 10.1164/rccm.2111084. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES