REVIEW
The role of induced sputum in asthma assessment
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1
2nd University Pneumonology Clinic, Athens
University Medical School, General University
Hospital of Athens “Attikon”
2
Respiratory Failure Centre Research
Laboratory, Athens Chest Diseases Hospital
“Sotiria”
3
4th University Internal Medicine Clinic, Athens
University Medical School, General University
Hospital of Athens “Attikon”
4
1st University Pneumonology Clinic, Athens
University Medical School, Athens Chest
Diseases Hospital “Sotiria”
Pneumon 2012;25(3):283-290
KEYWORDS
ABSTRACT
During recent years interest has been growing in the use of non-invasive methods for the assessment of airway inflammation in subjects with asthma. To date sputum induction is the only noninvasive measure of airway inflammation that has a clearly proven role in asthma management. Induced sputum cell count and mediator measurements have been particularly well validated. A variety of soluble mediators can be measured in the sputum supernatant of patients with asthma, including eosinophil-derived proteins, cytokines and remodelling-associated proteins. Sputum eosinophilia (i.e., >3%) is a classic feature of asthma, although a minority of patients present a non eosinophilic cellular pattern. The percentage of sputum eosinophils has proved to be useful in predicting short term response to inhaled corticosteroids, and there is scope for the application of other induced sputum markers in clinical practice. Sputum induction is a procedure that is generally well-tolerated and safe and a European Respiratory Society (ERS) Task Force has published a comprehensive review on sputum methodology. The widespread application of induced sputum in the investigation of asthma across the complete spectrum of disease severity, and mainly in moderate to severe asthma, has provided insight into the relationship between airway function and airway inflammation leading to the proposal of new disease phenotypes and the definition of which of these phenotypes respond to current treatment, offering an additional tool to guide the clinical management of patients with asthma.
REFERENCES (65)
1.
Global initiative for Asthma. Global strategy for asthma management and prevention. Gina reports 2009.
2.
Djukanovic R, Sterk PJ, Fahy JV, Hargreave FE. Standardised methodology of sputum induction and processing. Eur Respir J Suppl, 2002;37:1s-2s.
3.
Pin I, Gibson PG, Kolendwicz R, et al. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax 1992;47:25-29.
4.
Efthimiadis A, Spanevello A, Hamid Q, et al. Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation. Eur Respir J Suppl, 2002;37:19s-23s.
5.
Vignola AM, Rennar SI, Hargreave FE, et al. Standardised methodology of sputum induction and processing. Future directions. Eur Respir J Suppl 2002;37:51s-55s.
6.
Fahy JV, Liu J, Wong H, Boushey HA. Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects. Am Rev Respir Dis, 1993;147:1126-1131.
7.
Richter K, Jörres RA, Mucke M, Magnussen H. Sequentially induced sputum in patients with asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 1997;155:A821.
8.
Holz O, Jorres RA, Koschyk S, Speckin P, Welker L, Magnussen H. Changes in sputum composition during sputum induction in healthy and asthmatic subjects. Clin Exp Allergy, 1998;28:284- 292.
9.
Gershman NH, Liu H, Wong HH, Liu JT, Fahy JV. Fractional analysis of sequential induced sputum samples during sputum induction: evidence that different lung compartments are sampled at different time points. J Allergy Clin Immunol, 1999;104:322-328.
10.
Hunter CJ, Ward R, Woltmann G, Wardlaw AJ, Pavord ID. The safety and success rate of sputum induction using a low output ultrasonic nebulizer. Respir Med, 1999;93:345-348.
11.
Phipps PR, Gonda I, Anderson SD, Bailey D, Bautovich G. Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects. Eur Respir J, 1994;7:1474-1482.
12.
Belda J, Hussack P, Dolovich M, Efthimiadis A, Hargreave FE. Sputum induction: effect of nebulizer output and inhalation time on cell counts and fluid-phase measures. Clin Exp Allergy 2001; 31:1740-4.
13.
Pizzichini E, Pizzichini MM, Leigh R, Djukanovic R, Sterk, PJ. Safety of sputum induction. Eur Respir J Suppl 2002;37:9s-18s.
14.
Cianchetti S, Bacci E, Ruocco L, et al. Salbutamol pretreatment does not change eosinophil percentage and eosinophilic cationic protein concentration in hypertonic saline-induced sputum in asthmatic subjects. Clin. Exp. Allergy, 1999;29:712-718.
15.
Cianchetti S, Bacci E, Ruocco L, et al. Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects. Eur Respir J, 2004;24:1018-1024.
16.
Efthimiadis A, Jayaram L, Weston S, Carruthers S, Hargreave FE. Induced sputum: time from expectoration to processing. Eur Respir J, 2002;19:706-708.
17.
Cleland WW. Dithiothreitol, a new protective reagent for SH groups. Biochemistry, 1964;3:480-482.
18.
Efthimiadis A, Weston S, Carruthers S, Hussack P, Hargreave FE. Induced sputum: effect of filtration on the total and differential cell counts. Am J Respir Crit Care Med, 2000;161: A853.
19.
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;9:1174-1180.
20.
Pizzichini MM, Popov TA, Efthimiadis A, et al. Spontaneous and induced sputum to measure indices of airway inflammation in asthma. Am J Respir Crit Care Med, 1996;154:866-869.
21.
Pizzichini E, Pizzichini MM, Efthimiadis A, et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med, 1996;154:308-317.
22.
Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanovic R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med, 2000;161:9-16.
23.
Pavord ID, Pizzichini MM, Pizzichini E, Hargreave FE. The use of induced sputum to investigate airway inflammation. Thorax 1997;52:498–501.
24.
Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J. Allergy Clin. Immunol., 1995;95:843-852.
25.
In’t Veen JC, Smits HH, Hiernstra PS, Zwinderman AE, Sterk PJ, Bel EH. Lung function and sputum characteristics of patients with severe asthma during an induced exacerbation by double-blind steroid withdrawal. Am J Respir Crit Care Med, 1999;160:93-99.
26.
Pizzichini E, Pizzichini MM, Efthimiadis A, et al. Asthma and natural colds: inflammatory indices in induced sputum. A feasibility study. Am J Respir Crit Care Med, 1998;158:1178- 1184.
27.
Hunter CJ, Brightling CE, Woltmanw G, Wardlar AJ, Pavord ID. A comparison of the validity of different diagnostic tests in adults with asthma. Chest 2002;121:1051-1057.
28.
Green RH, Brightling C, Woltmann G, Parker D, Wardlaw AJ, Pavord ID. Analysis of induced sputum in adults with asthma. Identification of a subgroup with an isolated sputum neutrophilia and a poor response to inhaled corticosteroids. Thorax 2002;57(10):875-879.
29.
Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology, 2006;11:54-61.
30.
Kips JC, O’Connor BJ, Inmaan MD, Svensson K, Pauwels RA, O’Byrne PM. A long-term study of the anti-inflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma. Am J Respir Crit Care Med, 2000;161:996- 1001.
31.
Louis R, Bettiol J, Cataldo D, Sele J, Henquet M, Radermecker M. Effect of a 4-week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naïve asthmatics. Clin Exp Allergy, 2000;30:1151-1160.
32.
Pizzichini E, Leff JA, Reiss TF, et al. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized controlled trial. Eur Respir J, 1999;14:12-18.
33.
Parameswaran K, Leigh R, Hargreave FE. Sputum eosinophil count to assess compliance with corticosteroid therapy in asthma. J Allergy Clin Immunol, 1999;104:502-503.
34.
Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest 2001;119:1329-1336.
35.
Shaw DE, Berry MA, Hargadon B, et al. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest 2007;132:1871-1875.
36.
Kulkarni NS, Hollins F, Sutcliffe A, et al. Eosinophil protein in airway macrophages: a novel biomarker of eosinophilic inflammation in patients with asthma. J Allergy Clin Immunol, 2010;126:61-69.
37.
Foschino Barbaro MP, Costa VR, Resta O, et al. Menopausal asthma: a new biological phenotype? Allergy, 2010;65:1306- 1312.
38.
Todd DC, Armstrong S, D’Silva L, Allen CJ, Hargreave FE, Parameswaran K. Effect of obesity on airway inflammation: a cross-sectional analysis of body mass index and sputum cell counts. Clin Exp Allergy, 2007:37:1049-1054.
39.
Obata H, Dittrick M, Chan H, Chan-Yeung M. Sputum eosinophils and exhaled nitric oxide during late asthmatic reaction in patients with western red cedar asthma. Eur Respir J, 1999;13:489-495.
40.
Lemiere C, Pizzichini MM, Balkissoon R, et al. Diagnosing occupational asthma: use of induced sputum. Eur Respir J, 1999;13:482-488.
41.
Lemiere C. The use of sputum eosinophils in the evaluation of occupational asthma. Curr. Opin. Allergy Clin Immunol, 2004;4(2):81-5.
42.
Lemiere C. Induced sputum and exhaled nitric oxide as noninvasive markers of airway inflammation from work exposures. Curr. Opin. Allergy Clin Immunol 2007;7(2):133-7.
43.
Anees W, Huggins V, Pavord ID, Robertson AS, Burge PS. Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants. Thorax 2002;57(3):231-236.
44.
Leigh R, Hargreave FE. Occupational neutrophilic asthma. Can Respir J, 1999;6:205-208.
45.
Efthimiadis A, Pizzichini MM, Pizichini E, Dolovich J, Hargreave FE. Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiotreithol vs phosphatebuffered saline. Eur Respir J, 1997;10:1336–1340.
46.
Erin EM, Jenkins GR, Kon OM, et al. Optimized dialysis and protease inhibition of sputum dithiothreitol supernatants. Am J Respir Crit Care Med, 2008;177:132-141.
47.
Dente FL, Carnevali S, Bartoli ML, et al. Profiles of proinflammatory cytokines in sputum from different groups of severe asthmatic patients. Ann Allergy Asthma Immunol, 2006;97:312- 320.
48.
Hemelaers L, Henket M, Sele J, Bureau F, Louis R. Cysteinylleukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics. Allergy 2006;61:136-139.
49.
Profita M, Gagliardo R, Di Giorgi R, et al. Biochemical interaction between effects of beclomethasone dipropionate and salbutamol or formoterol in sputum cells from mild to moderate asthmatics. Allergy, 2005;60:323-329.
50.
Quaedvlieg V, Henket M, Sele J, Louis R. Cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics. Clin Exp Immunol, 2006;143:161-166.
51.
Manise M, Schleich F, Gusbin N, et al. Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity. Allergy, 2010;65:889-896.
52.
Kodric M, Shah AN, Fabbri LM, Confalonieri M. An investigation of airway acidification in asthma using induced sputum: a study of feasibility and correlation. Am J Respir Crit Care Med, 2007;175:905-910.
53.
Sugiura H, Komaki Y, Koarai A, Ichinose M. Nitrative stress in refractory asthma. J Allergy Clin Immunol, 2008;121:355-360.
54.
Maisi P, Prikk K, Sepper R, et al. Soluble membrane-type 1 matrix metalloproteinase (MT1-MMP) and gelatinase A (MMP-2) in induced sputum and bronchoalveolar lavage fluid of human bronchial asthma and bronchiectasis. APMIS, 2002;110;771- 782.
55.
Suzuki R, Kato T, Miyazaki Y, et al. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in sputum from patients with bronchial asthma. J Asthma, 2001;38:477- 484.
56.
Vignola AM, Riccobono L, Mirabella A, et al. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am J Respir Crit Care Med, 1998;158:1945-1950.
57.
Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest, 2002;122:1543-1552.
58.
Nomura A, Uchida Y, Sakamoto T, et al. Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-beta. Clin Exp Allergy, 2002;32:860-865.
59.
Yamaguchi M, Niimi A, Matsumoto H, et al. Sputum levels of transforming growth factor-beta1 in asthma: relation to clinical and computed tomography findings. J Investig Allergol Clin Immunol, 2008;18:202-206.
60.
Asai K, Kanazawa H, Kamoi H, Shiraishi S, Hirata K, Yoshikawa J. Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients. Clin Exp Allergy, 2003;33:595- 599.
61.
Delimpoura V, Bakakos P, Tseliou E, et al. Increased levels of osteopontin in sputum supernatant in severe refractory asthma. Thorax 2010;65:782-786.
62.
Schleich FN, Seidel L, Sele J, et al. Exhaled nitric oxide thresholds associated with a sputum eosinophil count >=3% in a cohort of unselected patients with asthma. Thorax, 2010;65:1039-1044.
63.
Tseliou E, Bessa V, Hillas G, et al. Exhaled nitric oxide and exhaled breath condensate pH in severe refractory asthma. Chest, 2010;138:107-113.
64.
Simpson JL, Wood LG, Gibson PG. Inflammatory mediators in exhaled breath, induced sputum and saliva. Clin Exp Allergy, 2005;35:1180-1185.
65.
Hillas G, Kostikas K, Mantzouranis K, et al. Exhaled Nitric Oxide and Exhaled Breath Condensate pH as predictors of sputum cell counts in optimally treated smoking asthmatics. Respirology 2011;16(5):811-8.