Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a combination of 3 different disorders, namely chronic asthma, chronic bronchitis and pulmonary emphysema, sometimes simultaneously present in the same subject. Objectives: The aim of our study was to compare sputum inflammatory markers in patients with different phenotypes of chronic airway obstruction. Methods: Forty-five subjects (forced expiratory volume in 1 s/vital capacity, FEV1/VC: 58.8 ± 12.2%; FEV1: 49.8 ± 11.5% of predicted) were classified as chronic asthma (n = 10) or COPD patients (n = 35); the latter were further divided into patients with prevalent chronic bronchitis (n = 24) or prevalent pulmonary emphysema (n = 11) according to clinical history and functional evaluation, and underwent sputum induction and analysis of inflammatory cell and soluble mediators. Results: Patients with chronic asthma showed higher sputum eosinophil percentages and eosinophilic cationic protein levels, and lower neutrophil percentages and neutrophil elastase levels than COPD patients. Neutrophil chemotactic activity in sputum supernatant was higher than the pool of normal subjects both in chronic asthma and COPD patients. No difference in sputum cell composition and levels of soluble mediators was observed between patients with chronic bronchitis and patients with pulmonary emphysema. Conclusions: The pattern of airway inflammation in induced sputum of patients with chronic asthma is different from that of COPD patients with a similar FEV1. Among COPD patients, however, the pattern of airway inflammation shows no difference between chronic bronchitis and patients with pulmonary emphysema, suggesting that these two clinically and functionally distinct phenotypes share a common inflammatory pattern as detected by induced sputum.

Journal Section:
Editor's choice
Keywords:
Chronic obstructive pulmonary disease, Induced sputum, Chronic asthma, Chronic bronchitis, Emphysema
1.
Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM: Global burden of COPD: systematic review and meta-analysis. Eur Respir J 2006;28:523–532.
2.
American Thoracic Society: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:s77–s121.
3.
Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008;31:1334–1356.
4.
Holgate ST: Pathogenesis of asthma. Clin Exp Allergy 2008;38:872–897.
5.
Fabbri LM, Romagnoli M, Corbetta L, Casoni G, Busljetic K, Turato G, Ligabue G, Ciaccia A, Saetta M, Papi A: Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:418–424.
6.
Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530–534.
7.
Keatings VM, Barnes PJ: Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med 1997;155:449–453.
8.
Burrows B, Bloom JW, Traver GA, Cline MG: The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N Engl J Med 1987;317:1309–1314.
9.
Boschetto P, Miniati M, Miotto D, Braccioni F, De Rosa E, Bononi I, Papi A, Saetta M, Fabbri LM, Mapp CE: Predominant emphysema phenotype in chronic obstructive pulmonary disease patients. Eur Respir J 2003;21:450–454.
10.
Boschetto P, Quintavalle S, Zeni E, Leprotti S, Potena A, Ballerin L, Papi A, Palladini G, Luisetti M, Annovazzi L, Iadarola P, De Rosa E, Fabbri LM, Mapp CE: Association between markers of emphysema and more severe chronic obstructive pulmonary disease. Thorax 2006;61:1037–1042.
11.
Papi A, Romagnoli M, Baraldo S, Braccioni F, Guzzinati I, Saetta M, Ciaccia A, Fabbri LM: Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1773–1777.
12.
Paggiaro PL, Chanez P, Holz O, Ind PW, Djukanović R, Maestrelli P, Sterk PJ: Sputum induction. Eur Respir J Suppl 2002;37:3s–8s.
13.
Cianchetti S, Bacci E, Bartoli ML, Ruocco L, Pavia T, Dente FL, Di Franco A, Vagaggini B, Paggiaro P: Can hypertonic saline inhalation influence preformed chemokine and mediator release in induced sputum of chronic obstructive pulmonary disease patients? Comparison with isotonic saline. Clin Exp Allergy 2007;37:1819–1826.
14.
Bacci E, Cianchetti S, Carnevali S, Bartoli ML, Dente FL, Di Franco A, Giannini D, Vagaggini B, Paggiaro PL: Induced sputum is a reproducible method to assess airway inflammation in asthma. Mediators Inflamm 2002;11:293–298.
15.
Lacoste JY, Bousquet J, Chanez P, Van Vyve T, Simony-Lafontaine J, Lequeu N, Vic P, Enander I, Godard P, Michel FB: Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease. J Allergy Clin Immunol 1993;92:537–548.
16.
Leckie MJ, Jenkins GR, Khan J, Smith SJ, Walker C, Barnes PJ, Hansel TT: Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+). Thorax 2003;58:23–29.
17.
Dente FL, Carnevali S, Bartoli ML, Cianchetti S, Bacci E, Di Franco A, Vagaggini B, Paggiaro P: Profiles of proinflammatory cytokines in sputum from different groups of severe asthmatic patients. Ann Allergy Asthma Immunol 2006;97:312–320.
18.
Little SA, MacLeod KJ, Chalmers GW, Love JG, McSharry C, Thomson NC: Association of forced expiratory volume with disease duration and sputum neutrophils in chronic asthma. Am J Med 2002;112:446–452.
19.
Balzano G, Stefanelli F, Iorio C, De Felice A, Melillo EM, Martucci M, Melillo GL: Eosinophilic inflammation in stable chronic obstructive pulmonary disease. Relationship with neutrophils and airway function. Am J Respir Crit Care Med 1999;160:1486–1492.
20.
Zhu J, Qiu YS, Majumdar S, Gamble E, Matin D, Turato G, Fabbri LM, Barnes N, Saetta M, Jeffery PK: Exacerbations of bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants. Am J Respir Crit Care Med 2001;164:109–116.
21.
Spanevello A, Confalonieri M, Sulotto F, Romano F, Balzano G, Migliori GB, Bianchi A, Michetti G: Induced sputum cellularity. Reference values and distribution in normal volunteers. Am J Respir Crit Care Med 2000;162:1172–1174.
22.
Fujimoto K, Kubo K, Yamamoto H, Yamaguchi S, Matsuzawa Y: Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema. Chest 1999;115:697–702.
23.
Chanez P, Vignola AM, O’Shaugnessy T, Enander I, Li D, Jeffery PK, Bousquet J: Corticosteroid reversibility in COPD is related to features of asthma. Am J Respir Crit Care Med 1997;155:1529–1534.
24.
Beeh KM, Kornmann O, Buhl R, Culpitt SV, Giembycz MA, Barnes PJ: Neutrophil chemotactic activity of sputum from patients with COPD: role of interleukin 8 and leukotriene B<sub>4</sub>. Chest 2003;123:1240&ndash;1247.
25.
Milne ENC, Pistolesi M: Detecting and quantifying chronic bronchitis and emphysema; in Milne ENC, Pistolesi M (eds): Reading the Chest Radiograph. A Physiologic Approach. St Louis, Mosby, 1993, pp 267&ndash;310.
26.
Miniati M, Filippi E, Falaschi F, Carrozzi L, Milne EN, Sostman HD, 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;151:1359&ndash;1367.
27.
Sitkauskiene B, Sakalauskas R, Malakauskas K, Lotvall J: Reversibility to a &beta;<sub>2</sub>-agonist in COPD: relationship to atopy and neutrophil activation. Respir Med 2003;97:591&ndash;598.
28.
Kostikas K, Gaga M, Papatheodorou G, Karamanis T, Orphanidou D, Loukides S: Leukotriene B<sub>4</sub> in exhaled breath condensate and sputum supernatant in patients with COPD and asthma. Chest 2005;127:1553&ndash;1559.
29.
Calverley PM, Burge PS, Spencer S, Anderson JA, Jones PW: Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Thorax 2003;58:659&ndash;664.
30.
Fabbri L, Pauwels RA, Hurd SS: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD Executive Summary updated 2003. COPD 2004;1:105&ndash;141.
31.
Confalonieri M, Mainardi E, Della Porta R, Bernorio S, Gandola L, Begh&egrave; B, Spanevello A: Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease. Thorax 1998;53:583&ndash;585.
32.
Yildiz F, Kaur AC, Ilgazli A, Celikoglu M, Kacar Ozkara S, Paksoy N, Ozkarakas O: Inhaled corticosteroids may reduce neutrophilic inflammation in patients with stable chronic obstructive pulmonary disease. Respiration 2000;67:71&ndash;76.
33.
Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ: Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med 1997;155:542&ndash;548.
34.
Liu J, Sandrini A, Thurston MC, Yates DH, Thomas PS: Nitric oxide and exhaled breath nitrite/nitrates in chronic obstructive pulmonary disease patients. Respiration 2007;74:617&ndash;623.
35.
Snoeck-Stroband JB, Lapperre TS, Gosman MM, Boezen HM, Timens W, ten Hacken NH, Sont JK, Sterk PJ, Hiemstra PS; Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) Study Group: Chronic bronchitis sub-phenotype within COPD: inflammation in sputum and biopsies. Eur Respir J 2008;31:70&ndash;77.
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