Skip to main content
Thorax logoLink to Thorax
. 2000 Sep;55(9):768–774. doi: 10.1136/thorax.55.9.768

Induced sputum in children: feasibility, repeatability, and relation of findings to asthma severity

N Wilson 1, P Bridge 1, A Spanevello 1, M Silverman 1
PMCID: PMC1745860  PMID: 10950896

Abstract

BACKGROUND—The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured.
METHODS—In a cross sectional study of children aged 5-15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10days.
RESULTS—A satisfactory sample (>500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold difference for eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant differences were found between asthma and healthy controls for the eosinophil differential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function.
CONCLUSIONS—Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma.



Full Text

The Full Text of this article is available as a PDF (146.9 KB).

Selected References

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

  1. Bland J. M., Altman D. G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307–310. [PubMed] [Google Scholar]
  2. Busse W., Banks-Schlegel S. P., Larsen G. L. Childhood- versus adult-onset asthma. Am J Respir Crit Care Med. 1995 May;151(5):1635–1639. doi: 10.1164/ajrccm.151.5.7735626. [DOI] [PubMed] [Google Scholar]
  3. Cai Y., Carty K., Henry R. L., Gibson P. G. Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children. Eur Respir J. 1998 Apr;11(4):848–853. doi: 10.1183/09031936.98.11040848. [DOI] [PubMed] [Google Scholar]
  4. Crimi E., Spanevello A., Neri M., Ind P. W., Rossi G. A., Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med. 1998 Jan;157(1):4–9. doi: 10.1164/ajrccm.157.1.9703002. [DOI] [PubMed] [Google Scholar]
  5. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992 Mar;145(3):669–674. doi: 10.1164/ajrccm/145.3.669. [DOI] [PubMed] [Google Scholar]
  6. Efthimiadis A., Pizzichini M. M., Pizzichini E., Dolovich J., Hargreave F. E. Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline. Eur Respir J. 1997 Jun;10(6):1336–1340. doi: 10.1183/09031936.97.10061336. [DOI] [PubMed] [Google Scholar]
  7. Ferguson A. C., Vaughan R., Brown H., Curtis C. Evaluation of serum eosinophilic cationic protein as a marker of disease activity in chronic asthma. J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):23–28. doi: 10.1016/s0091-6749(95)70148-6. [DOI] [PubMed] [Google Scholar]
  8. Gibson P. G., Wlodarczyk J. W., Hensley M. J., Gleeson M., Henry R. L., Cripps A. W., Clancy R. L. Epidemiological association of airway inflammation with asthma symptoms and airway hyperresponsiveness in childhood. Am J Respir Crit Care Med. 1998 Jul;158(1):36–41. doi: 10.1164/ajrccm.158.1.9705031. [DOI] [PubMed] [Google Scholar]
  9. Grootendorst D. C., Sont J. K., Willems L. N., Kluin-Nelemans J. C., Van Krieken J. H., Veselic-Charvat M., Sterk P. J. Comparison of inflammatory cell counts in asthma: induced sputum vs bronchoalveolar lavage and bronchial biopsies. Clin Exp Allergy. 1997 Jul;27(7):769–779. [PubMed] [Google Scholar]
  10. Grootendorst D. C., van den Bos J. W., Romeijn J. J., Veselic-Charvat M., Duiverman E. J., Vrijlandt E. J., Sterk P. J., Roldaan A. C. Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity. Eur Respir J. 1999 Mar;13(3):647–653. doi: 10.1183/09031936.99.13364799. [DOI] [PubMed] [Google Scholar]
  11. Iredale M. J., Wanklyn S. A., Phillips I. P., Krausz T., Ind P. W. Non-invasive assessment of bronchial inflammation in asthma: no correlation between eosinophilia of induced sputum and bronchial responsiveness to inhaled hypertonic saline. Clin Exp Allergy. 1994 Oct;24(10):940–945. doi: 10.1111/j.1365-2222.1994.tb02725.x. [DOI] [PubMed] [Google Scholar]
  12. Johnston S. L., Sanderson G., Pattemore P. K., Smith S., Bardin P. G., Bruce C. B., Lambden P. R., Tyrrell D. A., Holgate S. T. Use of polymerase chain reaction for diagnosis of picornavirus infection in subjects with and without respiratory symptoms. J Clin Microbiol. 1993 Jan;31(1):111–117. doi: 10.1128/jcm.31.1.111-117.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koller D. Y., Herouy Y., Götz M., Hagel E., Urbanek R., Eichler I. Clinical value of monitoring eosinophil activity in asthma. Arch Dis Child. 1995 Nov;73(5):413–417. doi: 10.1136/adc.73.5.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koller D. Y., Herouy Y., Götz M., Hagel E., Urbanek R., Eichler I. Clinical value of monitoring eosinophil activity in asthma. Arch Dis Child. 1995 Nov;73(5):413–417. doi: 10.1136/adc.73.5.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. O'Byrne P. M., Gauvreau G. M., Wood L. J. Pharmacologic modulation of airway inflammation. Allergy. 1998;53(45 Suppl):41–47. doi: 10.1111/j.1398-9995.1998.tb04938.x. [DOI] [PubMed] [Google Scholar]
  16. Piacentini G. L., Bodini A., Costella S., Vicentini L., Mazzi P., Sperandio S., Boner A. L. Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children. Eur Respir J. 1999 Jun;13(6):1386–1390. doi: 10.1183/09031936.99.13613919. [DOI] [PubMed] [Google Scholar]
  17. Pin I., Gibson P. G., Kolendowicz R., Girgis-Gabardo A., Denburg J. A., Hargreave F. E., Dolovich J. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992 Jan;47(1):25–29. doi: 10.1136/thx.47.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pin I., Radford S., Kolendowicz R., Jennings B., Denburg J. A., Hargreave F. E., Dolovich J. Airway inflammation in symptomatic and asymptomatic children with methacholine hyperresponsiveness. Eur Respir J. 1993 Oct;6(9):1249–1256. [PubMed] [Google Scholar]
  19. Pizzichini E., Pizzichini M. M., Efthimiadis A., Evans S., Morris M. M., Squillace D., Gleich G. J., Dolovich J., Hargreave F. E. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308–317. doi: 10.1164/ajrccm.154.2.8756799. [DOI] [PubMed] [Google Scholar]
  20. Pizzichini E., Pizzichini M. M., Efthimiadis A., Hargreave F. E., 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. doi: 10.1183/09031936.96.09061174. [DOI] [PubMed] [Google Scholar]
  21. Ronchi M. C., Piragino C., Rosi E., Stendardi L., Tanini A., Galli G., Duranti R., Scano G. Do sputum eosinophils and ECP relate to the severity of asthma? Eur Respir J. 1997 Aug;10(8):1809–1813. doi: 10.1183/09031936.97.10081809. [DOI] [PubMed] [Google Scholar]
  22. Rosier M. J., Bishop J., Nolan T., Robertson C. F., Carlin J. B., Phelan P. D. Measurement of functional severity of asthma in children. Am J Respir Crit Care Med. 1994 Jun;149(6):1434–1441. doi: 10.1164/ajrccm.149.6.8004295. [DOI] [PubMed] [Google Scholar]
  23. Spanevello A., Migliori G. B., Sharara A., Ballardini L., Bridge P., Pisati P., Neri M., Ind P. W. Induced sputum to assess airway inflammation: a study of reproducibility. Clin Exp Allergy. 1997 Oct;27(10):1138–1144. [PubMed] [Google Scholar]
  24. Twaddell S. H., Gibson P. G., Carty K., Woolley K. L., Henry R. L. Assessment of airway inflammation in children with acute asthma using induced sputum. Eur Respir J. 1996 Oct;9(10):2104–2108. doi: 10.1183/09031936.96.09102104. [DOI] [PubMed] [Google Scholar]
  25. Vanto T., Koskinen P. Serum eosinophil cationic protein in the evaluation of asthma severity in children. Allergy. 1998 Apr;53(4):415–419. doi: 10.1111/j.1398-9995.1998.tb03915.x. [DOI] [PubMed] [Google Scholar]
  26. Venge P. Serum measurements of eosinophil cationic protein (ECP) in bronchial asthma. Clin Exp Allergy. 1993 Jun;23 (Suppl 2):3-7, discussion 15-22. doi: 10.1111/j.1365-2222.1993.tb00372.x. [DOI] [PubMed] [Google Scholar]
  27. in 't Veen J. C., de Gouw H. W., Smits H. H., Sont J. K., Hiemstra P. S., Sterk P. J., Bel E. H. Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma. Eur Respir J. 1996 Dec;9(12):2441–2447. doi: 10.1183/09031936.96.09122441. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES