Cytokine Biomarkers of Exacerbations in Sputum From Patients With Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study

被引:2
作者
Budroni, Sonia [1 ]
Taccone, Marianna [1 ]
Stella, Maria [1 ]
Aprea, Susanna [1 ]
Schiavetti, Francesca [1 ]
Bardelli, Monia [1 ]
Lambert, Christophe [2 ]
Rondini, Simona [1 ,3 ]
Weynants, Vincent [4 ]
Contorni, Mario [1 ]
Wilkinson, Tom M. A. [5 ,6 ]
Brazzoli, Michela [1 ]
Rossi Paccani, Silvia [1 ]
机构
[1] GSK, Via Fiorentina 1, I-53100 Siena, Italy
[2] GSK, Wavre, Belgium
[3] GSK Vaccines Inst Global Hlth, Siena, Italy
[4] GSK, Rixensart, Belgium
[5] Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, England
[6] Southampton Gen Hosp, Natl Inst Hlth Res Southampton Biomed Res Ctr, Southampton Ctr Biomed Res, Southampton, England
关键词
biomarkers; chronic obstructive pulmonary disease; cytokine signature; exacerbation; sputum; PATHOGENS; COPD;
D O I
10.1093/infdis/jiae232
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background We determined the relationships between cytokine expression in sputum and clinical data to characterize and understand chronic obstructive pulmonary disease (COPD) exacerbations in people with COPD.Methods We measured 30 cytokines in 936 sputum samples, collected at stable state and exacerbation visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (ClinicalTrials.gov NCT01360398). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type.Results Of the cytokines, 17 were suitable for analysis. As for disease states, in exacerbation sputum samples, interleukin (IL) 17A, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, and IL-10 were significantly increased compared to stable state sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-alpha, IL-1 beta, and IL-1 alpha. IL-1 alpha, IL-1 beta, and TNF-alpha were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis.Conclusions Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1 alpha, IL-1 beta, or TNF-alpha. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types. Measuring 30 cytokines in 936 sputum samples from patients with chronic obstructive pulmonary disease, we observed significant increases (IL-17A, TNF-alpha, IL-1 beta, IL-10) between stable and exacerbation states. We also identified a combination of cytokines (IL-1 alpha, IL-1 beta, or TNF-alpha) as suitable biomarkers for bacteria-associated exacerbations.
引用
收藏
页码:e1112 / e1120
页数:9
相关论文
共 21 条
[1]   Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease [J].
Aaron, SD ;
Angel, JB ;
Lunau, M ;
Wright, K ;
Fex, C ;
Le Saux, N ;
Dales, RE .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 163 (02) :349-355
[2]   Acute Exacerbations of Chronic Obstructive Pulmonary Disease Identification of Biologic Clusters and Their Biomarkers [J].
Bafadhel, Mona ;
McKenna, Susan ;
Terry, Sarah ;
Mistry, Vijay ;
Reid, Carlene ;
Haldar, Pranabashis ;
McCormick, Margaret ;
Haldar, Koirobi ;
Kebadze, Tatiana ;
Duvoix, Annelyse ;
Lindblad, Kerstin ;
Patel, Hemu ;
Rugman, Paul ;
Dodson, Paul ;
Jenkins, Martin ;
Saunders, Michael ;
Newbold, Paul ;
Green, Ruth H. ;
Venge, Per ;
Lomas, David A. ;
Barer, Michael R. ;
Johnston, Sebastian L. ;
Pavord, Ian D. ;
Brightling, Christopher E. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2011, 184 (06) :662-671
[3]   Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations [J].
Barker, Bethan L. ;
Haldar, Koirobi ;
Patel, Hemu ;
Pavord, Ian D. ;
Barer, Michael R. ;
Brightling, Christopher E. ;
Bafadhel, Mona .
CHEST, 2015, 147 (01) :46-55
[4]   Targeting cytokines to treat asthma and chronic obstructive pulmonary disease [J].
Barnes, Peter J. .
NATURE REVIEWS IMMUNOLOGY, 2018, 18 (07) :454-466
[5]   Mediators of chronic obstructive pulmonary disease [J].
Barnes, PJ .
PHARMACOLOGICAL REVIEWS, 2004, 56 (04) :515-548
[6]   Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study [J].
Bourne, Simon ;
Cohet, Catherine ;
Kim, Viktoriya ;
Barton, Anna ;
Tuck, Andy ;
Aris, Emmanuel ;
Mesia-Vela, Sonia ;
Devaster, Jeanne-Marie ;
Ballou, W. Ripley ;
Clarke, Stuart ;
Wilkinson, Tom .
BMJ OPEN, 2014, 4 (03)
[7]   Chronic obstructive pulmonary disease [J].
Decramer, Marc ;
Janssens, Wim ;
Miravitlles, Marc .
LANCET, 2012, 379 (9823) :1341-1351
[8]   Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease [J].
Donaldson, GC ;
Seemungal, TAR ;
Bhowmik, A ;
Wedzicha, JA .
THORAX, 2002, 57 (10) :847-852
[9]  
Feng Y., 2022, Braz. J. Biol., V82, pe231134, DOI [10.1590/1519-6984.231134, 10.1590/1519-6984.231134]
[10]  
Gibson GJ., 2013, EUROPEAN LUNG WHITE, P155