Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation

Abstract

BackgroundInflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes. Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.AimTo identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.MethodsIn 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.ResultsSputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease. A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation. These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection. Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.ConclusionSputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations. The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways. Sputum TNF-α is a candidate marker for predicting airway bacterial infection.

The Role of Mean Platelet Volume in Chronic Obstructive Pulmonary Disease Exacerbation

“…This present inflammatory response, caused mostly by bacterial infections of lower airways, is higher than in the stable disease. 13 Potential mechanisms for this increased systemic inflammation in COPD exacerbation include: (1) spillover of inflammatory mediators from the pulmonary compartment; (2) an inflammatory reaction to tissue hypoxia; and (3) a reaction induced by the pro-inflammatory bacterial product lipopolysaccharide. 14 Several studies showed that inflammatory markers, such as circulating neutrophil numbers, C-reactive protein, fibrinogen, interleukin-6, interleukin-8, and soluble intercellular adhesion molecule 1, are increased during COPD exacerbation.…”

Significance of the Microbiome in Chronic Obstructive Pulmonary Disease

“…Numerous investigators have used various techniques to characterize the inflammatory response, including sputum analyses, bronchoalveolar lavage (BAL), bronchial biopsy, and blood markers. Several reports have confirmed an augmented inflammatory response in sputum, particularly during an AECOPD (14)(15)(16)(17)(18)(19); neutrophilic and eosinophilic inflammation have been described. In addition, a multitude of inflammatory mediators have been implicated (14-17, 19, 20).…”

Neutrophil Gelatinase-Associated Lipocalin: A New Biomarker for COPD Acute Exacerbation

“…During acute exacerbation, many inflammatory biomarkers and cells increase in blood and sputum [5]. Previous studies revealed that systemic biomarker levels increased and this was related to prognosis and mortality [13,15]. C-RP is the most sensitive acute inflammation indicator [5].…”

“…In addition to increase in difficulty of breathing, it must be accompanied by at least two of the things below for 24 hours or longer increase in coughing frequency or severity, increase in purulence or amount of sputum and wheeze [13]. Hospitalization criteria were made according to previous study [14].…”