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. 2001 Jan;56(1):36–41. doi: 10.1136/thorax.56.1.36

Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD

S Gompertz 1, D Bayley 1, S Hill 1, R Stockley 1
PMCID: PMC1745913  PMID: 11120902

Abstract

BACKGROUND—Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation.
METHODS—Airway inflammation (spontaneous sputum sol phase myeloperoxidase (MPO), elastase, leukotriene (LT)B4, interleukin (IL)-8, secretory leukoprotenase inhibitor (SLPI), protein leakage) and serum levels of C reactive protein (CRP) were compared in 40 patients with stable, smoking related COPD, divided into those with frequent (⩾3/year) or infrequent (⩽2/year) exacerbations according to the number of primary care consultations during the preceding year. The comparisons were repeated after excluding eight otherwise clinically indistinguishable patients who had tubular bronchiectasis on the HRCT scan.
RESULTS—Patients with frequent (n=12) and infrequent (n=28) exacerbations were indistinguishable in terms of their clinical, pulmonary function, and sputum characteristics, CRP concentrations, and all of their bronchial inflammatory parameters (p>0.05). The patients without evidence of tubular bronchiectasis (n=32) were equally well matched but the sputum concentrations of SLPI were significantly lower in the frequent exacerbators (n=8) in this subset analysis (p<0.05).
CONCLUSIONS—There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in affected individuals.



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Selected References

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  1. Anthonisen N. R., Manfreda J., Warren C. P., Hershfield E. S., Harding G. K., Nelson N. A. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987 Feb;106(2):196–204. doi: 10.7326/0003-4819-106-2-196. [DOI] [PubMed] [Google Scholar]
  2. Berry R. B., Shinto R. A., Wong F. H., Despars J. A., Light R. W. Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. Chest. 1989 Dec;96(6):1241–1246. doi: 10.1378/chest.96.6.1241. [DOI] [PubMed] [Google Scholar]
  3. Bhowmik A., Seemungal T. A., Sapsford R. J., Wedzicha J. A. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 2000 Feb;55(2):114–120. doi: 10.1136/thorax.55.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burge P. S., Calverley P. M., Jones P. W., Spencer S., Anderson J. A., Maslen T. K. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000 May 13;320(7245):1297–1303. doi: 10.1136/bmj.320.7245.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Confalonieri M., Mainardi E., Della Porta R., Bernorio S., Gandola L., Beghè B., Spanevello A. Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease. Thorax. 1998 Jul;53(7):583–585. doi: 10.1136/thx.53.7.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gaga M., Bentley A. M., Humbert M., Barkans J., O'Brien F., Wathen C. G., Kay A. B., Durham S. R. Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis. Thorax. 1998 Aug;53(8):685–691. doi: 10.1136/thx.53.8.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gompertz S., Stockley R. A. Inflammation--role of the neutrophil and the eosinophil. Semin Respir Infect. 2000 Mar;15(1):14–23. doi: 10.1053/srin.2000.0150014. [DOI] [PubMed] [Google Scholar]
  8. Hill A. T., Bayley D. L., Campbell E. J., Hill S. L., Stockley R. A. Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency. Eur Respir J. 2000 May;15(5):886–890. doi: 10.1034/j.1399-3003.2000.15e12.x. [DOI] [PubMed] [Google Scholar]
  9. Hill A. T., Bayley D., Stockley R. A. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med. 1999 Sep;160(3):893–898. doi: 10.1164/ajrccm.160.3.9901091. [DOI] [PubMed] [Google Scholar]
  10. Hill A. T., Campbell E. J., Hill S. L., Bayley D. L., Stockley R. A. Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med. 2000 Sep;109(4):288–295. doi: 10.1016/s0002-9343(00)00507-6. [DOI] [PubMed] [Google Scholar]
  11. Holmes W. F., Macfarlane J. T., Macfarlane R. M., Lewis S. The influence of antibiotics and other factors on reconsultation for acute lower respiratory tract illness in primary care. Br J Gen Pract. 1997 Dec;47(425):815–818. [PMC free article] [PubMed] [Google Scholar]
  12. Ketelaars C. A., Schlösser M. A., Mostert R., Huyer Abu-Saad H., Halfens R. J., Wouters E. F. Determinants of health-related quality of life in patients with chronic obstructive pulmonary disease. Thorax. 1996 Jan;51(1):39–43. doi: 10.1136/thx.51.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Llewellyn-Jones C. G., Harris T. A., Stockley R. A. Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema. Am J Respir Crit Care Med. 1996 Feb;153(2):616–621. doi: 10.1164/ajrccm.153.2.8564107. [DOI] [PubMed] [Google Scholar]
  14. O'Brien C., Guest P. J., Hill S. L., Stockley R. A. Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care. Thorax. 2000 Aug;55(8):635–642. doi: 10.1136/thorax.55.8.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paggiaro P. L., Dahle R., Bakran I., Frith L., Hollingworth K., Efthimiou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. Lancet. 1998 Mar 14;351(9105):773–780. doi: 10.1016/s0140-6736(97)03471-5. [DOI] [PubMed] [Google Scholar]
  16. Pavord I. D. Sputum induction to assess airway inflammation: is it an inflammatory stimulus? Thorax. 1998 Feb;53(2):79–80. doi: 10.1136/thx.53.2.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pye A., Stockley R. A., Hill S. L. Simple method for quantifying viable bacterial numbers in sputum. J Clin Pathol. 1995 Aug;48(8):719–724. doi: 10.1136/jcp.48.8.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sallenave J. M., Shulmann J., Crossley J., Jordana M., Gauldie J. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol. 1994 Dec;11(6):733–741. doi: 10.1165/ajrcmb.11.6.7946401. [DOI] [PubMed] [Google Scholar]
  19. Seemungal T. A., Donaldson G. C., Paul E. A., Bestall J. C., Jeffries D. J., Wedzicha J. A. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1418–1422. doi: 10.1164/ajrccm.157.5.9709032. [DOI] [PubMed] [Google Scholar]
  20. Stockley R. A., Burnett D. Alpha,-antitrypsin and leukocyte elastase in infected and noninfected sputum. Am Rev Respir Dis. 1979 Nov;120(5):1081–1086. doi: 10.1164/arrd.1979.120.5.1081. [DOI] [PubMed] [Google Scholar]
  21. Stănescu D., Sanna A., Veriter C., Kostianev S., Calcagni P. G., Fabbri L. M., Maestrelli P. Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax. 1996 Mar;51(3):267–271. doi: 10.1136/thx.51.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thompson W. H., Nielson C. P., Carvalho P., Charan N. B., Crowley J. J. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):407–412. doi: 10.1164/ajrccm.154.2.8756814. [DOI] [PubMed] [Google Scholar]
  23. Tomee J. F., Koëter G. H., Hiemstra P. S., Kauffman H. F. Secretory leukoprotease inhibitor: a native antimicrobial protein presenting a new therapeutic option? Thorax. 1998 Feb;53(2):114–116. doi: 10.1136/thx.53.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yamamoto C., Yoneda T., Yoshikawa M., Fu A., Tokuyama T., Tsukaguchi K., Narita N. Airway inflammation in COPD assessed by sputum levels of interleukin-8. Chest. 1997 Aug;112(2):505–510. doi: 10.1378/chest.112.2.505. [DOI] [PubMed] [Google Scholar]

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