Logo of thoraxThoraxVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Thorax. 2000 Feb; 55(2): 114–120.
PMCID: PMC1745686

Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations


BACKGROUND—Although it is presumed that exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased airway inflammation, there is little information available on inflammatory markers during an exacerbation and the relationship with severity or time course of recovery. A study was undertaken to investigate the sputum cell and cytokine characteristics of COPD when stable and during an exacerbation.
METHODS—Induced sputum samples from 57 patients with moderate to severe COPD were analysed (44 samples were taken during a stable period and 37 during an exacerbation). The patients recorded daily symptoms on diary cards. Cell counts and sputum levels of interleukin (IL)-6 and IL-8 were measured.
RESULTS—Patients with [gt-or-equal, slanted]3 exacerbations/year had higher median stable sputum levels of IL-6 (110 (95% CI 11 to 215) pg/ml) and IL-8 (6694 (95% CI 3120 to 11995) pg/ml) than those with [less-than-or-eq, slant]2 exacerbations/year (22 (95% CI 12 to 93) and 1628 (95% CI 607 to 4812) pg/ml, respectively). Median IL-6 levels were increased during exacerbations compared with stable conditions. The levels of IL-6 during exacerbations were related to the presence of a cold and to the total cell count and eosinophil and lymphocyte numbers, while IL-8 was positively correlated with all sputum cell counts. Sputum cell counts and cytokine levels during an exacerbation did not predict the size and duration of lung function changes in the exacerbation.
CONCLUSIONS—Patients with more frequent exacerbations have higher baseline sputum cytokine levels, which may predict the frequency of future exacerbations.

Full Text

The Full Text of this article is available as a PDF (91K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. 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. [PubMed]
  • Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987 Feb;106(2):196–204. [PubMed]
  • Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, Dolovich J. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992 Jan;47(1):25–29. [PMC free article] [PubMed]
  • 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 Dec;150(6 Pt 1):1646–1652. [PubMed]
  • Bhowmik A, Seemungal TA, Sapsford RJ, Devalia JL, Wedzicha JA. Comparison of spontaneous and induced sputum for investigation of airway inflammation in chronic obstructive pulmonary disease. Thorax. 1998 Nov;53(11):953–956. [PMC free article] [PubMed]
  • Keatings VM, Collins PD, Scott DM, Barnes PJ. 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. [PubMed]
  • Pitkin AD, Roberts CM, Wedzicha JA. Arterialised earlobe blood gas analysis: an underused technique. Thorax. 1994 Apr;49(4):364–366. [PMC free article] [PubMed]
  • Popov T, Gottschalk R, Kolendowicz R, Dolovich J, Powers P, Hargreave FE. The evaluation of a cell dispersion method of sputum examination. Clin Exp Allergy. 1994 Aug;24(8):778–783. [PubMed]
  • Pizzichini E, Pizzichini MM, Efthimiadis A, Hargreave FE, Dolovich J. Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. Eur Respir J. 1996 Jun;9(6):1174–1180. [PubMed]
  • Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB, Capron A. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 1991 Oct;88(4):561–571. [PubMed]
  • Cromwell O, Hamid Q, Corrigan CJ, Barkans J, Meng Q, Collins PD, Kay AB. Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. Immunology. 1992 Nov;77(3):330–337. [PMC free article] [PubMed]
  • Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. [PMC free article] [PubMed]
  • Wilson R. Bacterial infection and chronic obstructive pulmonary disease. Eur Respir J. 1999 Feb;13(2):233–235. [PubMed]
  • Gump DW, Phillips CA, Forsyth BR, McIntosh K, Lamborn KR, Stouch WH. Role of infection in chronic bronchitis. Am Rev Respir Dis. 1976 Apr;113(4):465–474. [PubMed]
  • Subauste MC, Jacoby DB, Richards SM, Proud D. Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J Clin Invest. 1995 Jul;96(1):549–557. [PMC free article] [PubMed]
  • Stockley RA. Lung infections. 1. Role of bacteria in the pathogenesis and progression of acute and chronic lung infection. Thorax. 1998 Jan;53(1):58–62. [PMC free article] [PubMed]
  • Khair OA, Devalia JL, Abdelaziz MM, Sapsford RJ, Tarraf H, Davies RJ. Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha and expression of ICAM-1 in cultured human bronchial epithelial cells. Eur Respir J. 1994 Dec;7(12):2109–2116. [PubMed]
  • Ball P, Harris JM, Lowson D, Tillotson G, Wilson R. Acute infective exacerbations of chronic bronchitis. QJM. 1995 Jan;88(1):61–68. [PubMed]
  • Ketelaars CA, Schlösser MA, Mostert R, Huyer Abu-Saad H, Halfens RJ, Wouters EF. Determinants of health-related quality of life in patients with chronic obstructive pulmonary disease. Thorax. 1996 Jan;51(1):39–43. [PMC free article] [PubMed]
  • Okubadejo AA, Jones PW, Wedzicha JA. Quality of life in patients with chronic obstructive pulmonary disease and severe hypoxaemia. Thorax. 1996 Jan;51(1):44–47. [PMC free article] [PubMed]
  • Pizzichini MM, Pizzichini E, Efthimiadis A, Chauhan AJ, Johnston SL, Hussack P, Mahony J, Dolovich J, Hargreave FE. Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study. Am J Respir Crit Care Med. 1998 Oct;158(4):1178–1184. [PubMed]
  • Denny FW., Jr The clinical impact of human respiratory virus infections. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 2):S4–12. [PubMed]
  • Pizzichini MM, Pizzichini E, Clelland L, Efthimiadis A, Mahony J, Dolovich J, Hargreave FE. Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment. Am J Respir Crit Care Med. 1997 May;155(5):1501–1508. [PubMed]
  • Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ. 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. [PubMed]
  • Albert RK, Martin TR, Lewis SW. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med. 1980 Jun;92(6):753–758. [PubMed]
  • Pizzichini E, Pizzichini MM, Gibson P, Parameswaran K, Gleich GJ, Berman L, Dolovich J, Hargreave FE. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1511–1517. [PubMed]
  • Kanner RE, Renzetti AD, Jr, Klauber MR, Smith CB, Golden CA. Variables associated with changes in spirometry in patients with obstructive lung diseases. Am J Med. 1979 Jul;67(1):44–50. [PubMed]

Articles from Thorax are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...