Investigating the role of pentraxin 3 as a biomarker for bacterial infection in subjects with COPD

Background: Pentraxin 3 (PTX3) is an acute phase protein, involved in antibacterial resistance. Recent studies have shown PTX3 levels to be elevated in the presence of a bacterial infection and in a murine sepsis model. Objective: We aim to investigate if sputum PTX3 can be used as a biomarker for bacterial infection in subjects with COPD. Materials and methods: Sputum samples from 142 COPD patients (102 men) with a mean (range) age of 69 years (45–85) and mean (SD) post-bronchodilator percentage predicted forced expiratory volume in 1 second (FEV 1 ) of 50% (19) were analyzed for PTX3, using a commercial assay at stable state and during an exacerbation. Association with bacteria, from culture, quantitative real-time polymerase chain reaction (qPCR) and colony-forming units (CFU) was investigated. Results: The geometric mean (95% CI) PTX3 level at stable state was 50.5 ng/mL (41.4–61.7). PTX3 levels correlated with absolute neutrophil count in sputum ( r = 0.37; P , 0.01), but not FEV 1 or health status. There was a weak correlation between PTX3 and bacterial load (CFU: r = 0.29, P , 0.01; 16S qPCR: r = 0.18, P = 0.05). PTX3 was a poor predictor of bacterial colonization (defined as . 10 5 CFU/mL at stable state) with a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.59 and 95% confidence interval (CI) 0.43–0.76 ( P = 0.21). During an exacerbation, there was a modest increase in PTX3 (fold difference 0.15, 95% of difference 0.02–0.29; P = 0.02), and PTX3 fared better at identifying a bacteria-associated exacerbation (ROC AUC 0.65, 95% CI 0.52–0.78, P = 0.03). Conclusion: PTX3 is associated with bacterial infection in patients with COPD, but its utility as a biomarker for identifying a bacteria-associated exacerbation warrants further studies.

[1]  C. Garvey Recent updates in chronic obstructive pulmonary disease , 2016, Postgraduate medicine.

[2]  F. Dal-Pizzol,et al.  Pentraxin 3 sputum levels differ in patients with chronic obstructive pulmonary disease vs asthma. , 2015, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[3]  I. Pavord,et al.  Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function , 2015, International journal of chronic obstructive pulmonary disease.

[4]  R. Lutter,et al.  External validation of blood eosinophils, FENO and serum periostin as surrogates for sputum eosinophils in asthma , 2014, Thorax.

[5]  Feng Liu,et al.  Pentraxin 3 as a Prognostic Biomarker in Patients with Systemic Inflammation or Infection , 2014, Mediators of inflammation.

[6]  I. Pavord,et al.  Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations , 2014, Chest.

[7]  P. Garred,et al.  Pentraxin-3 Serum Levels Are Associated with Disease Severity and Mortality in Patients with Systemic Inflammatory Response Syndrome , 2013, PloS one.

[8]  M. Tosun,et al.  Pentraxin 3 as a Novel Biomarker of Inflammation in Chronic Obstructive Pulmonary Disease , 2013, Inflammation.

[9]  M. Kolácková,et al.  Pentraxin 3(PTX 3): An Endogenous Modulator of the Inflammatory Response , 2012, Mediators of inflammation.

[10]  Christopher E Brightling,et al.  Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. , 2011, American journal of respiratory and critical care medicine.

[11]  G. Joos,et al.  COPD is associated with reduced pulmonary interstitial expression of pentraxin-3 , 2011, European Respiratory Journal.

[12]  E. Jantunen,et al.  High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients , 2011, Haematologica.

[13]  Alberto Mantovani,et al.  Neutrophils in the activation and regulation of innate and adaptive immunity , 2011, Nature Reviews Immunology.

[14]  J. Laine,et al.  High Plasma Level of Long Pentraxin 3 (PTX3) Is Associated with Fatal Disease in Bacteremic Patients: A Prospective Cohort Study , 2011, PloS one.

[15]  M. Miravitlles,et al.  Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease , 2010, Respiratory research.

[16]  C. Garlanda,et al.  An integrated view of humoral innate immunity: pentraxins as a paradigm. , 2010, Annual review of immunology.

[17]  A. Mantovani,et al.  Increased levels of serum pentraxin 3, a novel cardiovascular biomarker, in patients with inflammatory rheumatic disease , 2010, Arthritis care & research.

[18]  M. Weatherall,et al.  Quality of life measured by the St George's Respiratory Questionnaire and spirometry , 2009, European Respiratory Journal.

[19]  T. Murphy,et al.  Infection in the pathogenesis and course of chronic obstructive pulmonary disease. , 2008, The New England journal of medicine.

[20]  O. Uzun,et al.  Role of bacteria in acute exacerbations of chronic obstructive pulmonary disease , 2008, International journal of chronic obstructive pulmonary disease.

[21]  J. Eason,et al.  Research Corner Outcomes in Cardiopulmonary Physical Therapy: Chronic Respiratory Disease Questionnaire (CRQ) , 2008, Cardiopulmonary physical therapy journal.

[22]  S. Hurd,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[23]  A. Nocker,et al.  Use of Propidium Monoazide for Live/Dead Distinction in Microbial Ecology , 2007, Applied and Environmental Microbiology.

[24]  S. Johnston,et al.  Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. , 2006, American journal of respiratory and critical care medicine.

[25]  A. Mantovani,et al.  Dual function of the long pentraxin PTX3 in resistance against pulmonary infection with Klebsiella pneumoniae in transgenic mice. , 2006, Microbes and infection.

[26]  A. Torres,et al.  Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. , 2005, Archives of internal medicine.

[27]  D. Honeybourne,et al.  Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD , 2004, European Respiratory Journal.

[28]  Dieter Klein,et al.  Quantification using real-time PCR technology : applications and limitations , 2002 .

[29]  I. Pavord,et al.  Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability. , 2001, Respiratory medicine.

[30]  T. Seemungal,et al.  Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations , 2000, Thorax.

[31]  F. Hargreave,et al.  Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. , 1996, The European respiratory journal.

[32]  J. Ruiz,et al.  Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. , 1995, American journal of respiratory and critical care medicine.

[33]  R. Stockley,et al.  Simple method for quantifying viable bacterial numbers in sputum. , 1995, Journal of clinical pathology.

[34]  N. Anthonisen,et al.  Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. , 1987, Annals of internal medicine.

[35]  D. Postma,et al.  Chronic obstructive pulmonary disease. , 2002, Clinical evidence.

[36]  S. Amyes,et al.  Antibiotic resistance in bacteria. , 1992 .