Granulocyte activation markers in induced sputum: Comparison between chronic obstructive pulmonary disease, asthma, and normal subjects

Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 03/1997; 155(2):449-53. DOI: 10.1164/ajrccm.155.2.9032177
Source: PubMed


Airway inflammation is present in asthma and is thought to play a significant part in the development of airflow obstruction. In chronic obstructive pulmonary disease (COPD), neutrophilic inflammation is present in the airway lumen, whereas the submucosa displays a lymphocytic infiltrate. Less is known about the nature and mechanisms of inflammation in COPD than in asthma. Induced sputum allows noninvasive sampling of respiratory tract secretions from patients and control subjects, allowing characterization of cells and measurement of soluble markers. We exploited this technique in order to compare the presence and quantify specific markers of eosinophil and neutrophil activation in subjects with asthma or COPD, and control subjects. Differential cell counts showed significantly higher neutrophil percentages in the patients with COPD compared with other groups, while patients with asthma had higher numbers of eosinophils. The neutrophil markers myeloperoxidase (MPO), from primary granules in neutrophils, and human neutrophil lipocalin (HNL), released from secondary granules, were elevated in patients with asthma and COPD compared with control subjects but markedly more so in COPD. The difference between COPD and asthma was more marked for HNL than for MPO suggesting that HNL may be a better marker for discriminating between these conditions. Concentrations of the eosinophil granule protein, eosinophil cationic protein (ECP), and the eosinophil granule-derived enzyme, eosinophil peroxidase (EPO) were raised in the patients with asthma and those with COPD.

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    • "Please cite this article in press as: A. Kumari et al., Lipopolysaccharide (LPS) exposure differently affects allergic asthma exacerbations and its amelioration by intranasal curcumin in mice, Cytokine (2015), linked to severe, chronic and sudden attacks of asthma [13]. Activated neutrophils can release metalloproteinase (MMP-9), elastase and myeloperoxidase (MPO) contributing to the asthma worsening [14]. Reactive oxygen species (ROS) released from activated neutrophils has long been known to induce epithelial cell inflammation by directly causing tissue injury. "
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    ABSTRACT: Lipopolysaccharide (LPS) is ubiquitous in the environment and can therefore, exacerbate allergic responses. Studies have suggested immunoregulatory effects of LPS according to route, dose and stage of exposure. Present study has examined whether dose and stage of LPS exposure (during sensitization and challenge with OVA) exacerbates airway inflammations, antigen specific-IgE level, histamine release, Th1/Th2 cytokine response. Further, anti-asthmatic potential of curcumin, through intranasal route has been evaluated for the first time in LPS induced airway inflammation in an ovalbumin (OVA)-challenged mouse asthma model. Balb/c mice were first sensitized with OVA on 1st and 8th day and exposed to two LPS doses (0.1/1.0μg) separately on 2nd day and then further exposed to LPS with OVA-aerosol (from 9 to 14day). Further, lower LPS dose (0.1μg) was chosen for OVA exposed mouse model of asthma exacerbation study. Intranasal curcumin was administered from 9th to 14th day before every LPS exposure. Exposure to LPS (0.1μg) exacerbates airway inflammations in terms of IgE level, Th2-cytokine response (IL-4 and IL-5), histamine release, EPO and MPO activities and oxidative stress. Intranasal curcumin has effectively ameliorated airway exacerbations whereas dexamethasone, a known glucocorticosteroid, was not promising as compared to intranasal curcumin. Schedule and dose of LPS exposure determines asthma exacerbations and intranasal curcumin could be better immunomodulatory agent in LPS exposed asthma exacerbations. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Cytokine
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    • "NGAL has rarely been investigated in body fluids other than blood and urine. NGAL measurement has been performed in phlegm in chronic obstructive pulmonary disease [16, 17] and in bronchoalveolar lavage [18]. In our study, serum and pleural NGAL were high in PPE and pneumonia, that is an acute infection. "
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    ABSTRACT: Background The protein neutrophil gelatinase-associated lipocalin (NGAL) is a mediator synthesized and released by neutrophils. Its physiological function is as yet unclear. Levels in blood increase in several inflammatory diseases. High serum values indicate poor prognosis for several diseases. Pleural effusion may appear as the result of various pathologies. The most common cause is heart failure (HF). Other common causes include parapneumonic (PPE) and malignant (MPE) pleural effusions, and pulmonary embolism. Tubercular effusion (TE) is commonly encountered in Turkey and similar developing countries. The purpose of this study was to investigate the effectiveness of NGAL, a current inflammation marker, in discriminating between different etiological diseases that cause pleural effusion. Methods The study was performed at the Recep Tayyip Erdoğan University Faculty of Medicine Chest Diseases Clinic. One hundred patients were included in the study, 25 with parapneumonic effusion, 25 with heart failure-related effusion, 25 with tubercular effusion and 25 with cancer-related effusion. NGAL was measured in patients’ serum and pleural fluids. Results Serum NGAL levels in PPE (171 ± 56 ng/ml) were significantly higher (p < 0.001) than those in HF (86 ± 31 ng/ml), CA (103 ± 42 ng/ml) and TE (63 ± 19 ng/ml). Pleural NGAL levels were also significantly higher in PPE compared to HF, MPE and TE (p < 0.001). Serum NGAL levels exhibited a positive correlation with white blood cell (WBC), neutrophil, C-reactive protein (CRP), sedimentation, serum LDH, creatinine, pleural leukocyte and pleural neutrophil numbers. The most significant correlation was between NGAL level and WBC (p < 0.001, r = 0.579). Both serum and pleural NGAL levels are highly effective in differentiating patients with PPE from those without PPE (AUC: 0.910 and 0.790, respectively). Conclusions NGAL can be used in the diagnosis of diseases with an acute inflammatory course. Serum and pleural NGAL levels can differentiate PPE from other diseases causing pleural fluid with high sensitivity and specificity.
    Full-text · Article · Sep 2014 · Multidisciplinary respiratory medicine
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    • "Four articles [14,15,17,51] compared MPO levels in COPD patients with asthmatics. The SMD of MPO levels between the two groups was 0.34 (95% CI -0.31 to 0.99, P = 0.301; I2 = 73.7%; random effects model). "
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    ABSTRACT: Airway inflammation, especially neutrophilic airway inflammation, is a cardinal pathophysiologic feature in chronic obstructive pulmonary disease (COPD) patients. The ideal biomarkers characterizing the inflammation might have important potential clinical applications in disease assessment and therapeutic intervention. Sputum myeloperoxidase (MPO) is recognized as a marker of neutrophil activity. The purpose of this meta-analysis is to determine whether sputum MPO levels could reflect disease status or be regulated by regular medications for COPD. Studies were identified by searching PubMed, Embase, the Cochrane Database, CINAHL and for relevant reports published before September 2012. Observational studies comparing sputum MPO in COPD patients and healthy subjects or asthmatics, or within the COPD group, and studies comparing sputum MPO before and after treatment were all included. Data were independently extracted by two investigators and analyzed using STATA 10.0 software. A total of 24 studies were included in the meta-analysis. Sputum MPO levels were increased in stable COPD patients when compared with normal controls, and this increase was especially pronounced during exacerbations as compared with MPO levels during the stable state. Theophylline treatment was able to reduce MPO levels in COPD patients, while glucocorticoid treatment failed to achieve the same result. Sputum MPO might be a promising biomarker for guiding COPD management; however, further investigations are needed to confirm this.
    Full-text · Article · Mar 2014
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