Sputum Of Chronic Obstructive Pulmonary Disease Patients Research Articles

Association Between IL-17 and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by neutrophils airway infiltration. It is currently known that Interleukin-17 (IL-17) is an important pro-inflammatory factor. It can promote the accumulation of neutrophils and participate in the chronic inflammatory process of COPD. However, the value of IL-17 levels in the diagnosis and assessment of COPD remains controversial. In view of this, we conducted a systematic review and meta-analysis to assess its relevance. We searched databases such as PubMed, Web of Science, Cochrane Library and Embase to extract original research. A total of 10 studies with 2268 participants were included in this meta-analysis. The results showed that the level of serum IL-17 in patients with stable COPD was significantly higher than that in healthy controls (standard mean difference SMD, 1.59, 95% CI 0.84-2.34; p<0.001). Compared with the stable COPD group, the serum IL-17 level in acute exacerbation (AECOPD) was significantly higher (SMD, 1.78, 95% CI 1.22-2.33; p<0.001). The level of IL-17 in sputum of COPD patients was also higher than that of healthy controls (SMD, 2.03, 95% CI 0.74-3.31; p<0.001). Our results showed that IL-17 levels were elevated in serum and sputum in COPD patients compared with healthy controls, and IL-17 levels increased with disease progression. IL-17 serves as a potential biomarker to indicate the persistence of neutrophilic inflammation and exacerbation of COPD.

Informative laboratory biomarkers for the diagnosis of respiratory diseases of occupational etiology in modern conditions

Chronic obstructive pulmonary disease (COPD) is one of the most serious problems of modern healthcare in the world. COPD is a common disease, characterized by a variety of clinical and functional features of the disease and heterogeneity of the inflammatory response. The study aims to research a comprehensive analysis of laboratory examination in persons at high risk of COPD, including data from general clinical and bacteriological studies and highlighting priority, early changes in its composition. The researchers analyzed the results of laboratory studies of the mucous membranes of the upper respiratory tract in persons with an established diagnosis of chronic obstructive pulmonary disease. The work uses data from official reports of the Ministry of Health for 2020. When evaluating the general (native) analysis of sputum in COPD patients, the nature was determined by its cellular composition. Segmented neutrophils predominated among leukocytes in 41.18±5.37%, eosinophils in 8.24±3.00%, alveolar macrophages in 9.41±3.19%. We found that Streptococcus pyogenes, Staph. epidermidis, Enterococcus spp., Candida albicans prevailed among the isolated microorganisms during the exacerbation of this disease. The remaining types of microorganisms (Klebsiella pnemoniae, Enterobacter aeromonas, Escherichia coli) were represented by single strains. The results of studies on the cellular composition and microbial spectrum of sputum of patients with acute COPD, allow us to conclude that the most informative and significant are general clinical indicators (leukocytes, eosinophils), as well as isolated microorganisms Streptococcus pyogenes, Staph. epidermidis, Enterococcus spp, and yeast fungi of the genus Candida albicans. The data obtained made it possible to substantiate the role of reliable and easily reproducible biomarkers in determining the activity of the disease and the phenotype of COPD.

Erythromycin suppresses neutrophil extracellular traps in smoking-related chronic pulmonary inflammation

Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40+ and CD86+ mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.

Dynamic differences in dietary polyunsaturated fatty acid metabolism in sputum of COPD patients and controls

IntroductionDisturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis. ObjectivesHere we investigated if PUFA metabolism is disturbed in COPD patients. MethodsFree PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed. ResultsSignificantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling. ConclusionsOur findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.

Aspergillus fumigatus Detection and Risk Factors in Patients with COPD-Bronchiectasis Overlap.

The role of Aspergillus fumigatus in the airways of chronic obstructive pulmonary disease (COPD) patients with bronchiectasis is currently unclear. We searched for a sensitive and noninvasive method for A. fumigatus detection in the sputum of COPD patients and addressed potential risk factors for its presence. Induced sputum samples of 18 COPD patients and 17 COPD patients with bronchiectasis were analyzed for the presence of A. fumigatus by culture, galactomannan detection, and PCR. Of the patients with COPD–bronchiectasis overlap, 23.5% had a positive culture for A. fumigatus versus 10.5% of COPD patients without bronchiectasis (p = 0.39). The median sputum galactomannan optical density index was significantly higher in patients with COPD and bronchiectasis compared with patients with COPD alone (p = 0.026) and ranged between the levels of healthy controls and A. fumigatus-colonized cystic fibrosis patients. Both the presence of bronchiectasis and the administration of systemic corticosteroids were associated with sputum galactomannan (p = 0.0028 and p = 0.0044, respectively) and showed significant interaction (p interaction = 0.022). PCR for Aspergillus was found to be a less sensitive method, but was critically dependent on the extraction technique. The higher sputum galactomannan levels suggest a more abundant presence of A. fumigatus in the airways of patients with COPD–bronchiectasis overlap compared with patients with COPD without bronchiectasis, particularly when systemic corticosteroids are administered.

Deficiency of innate-like T lymphocytes in chronic obstructive pulmonary disease

BackgroundBased on the phenotypic and functional characteristics unconventional T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells link the innate and adaptive immune responses. Up to now data are scarce about their involvement in pulmonary disorders including chronic obstructive pulmonary disease (COPD). This study explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral blood and sputum of stable and exacerbating COPD patients.MethodsBy means of multicolor flow cytometry frequencies of total iNKT and MAIT cells and their subsets were enumerated in peripheral blood and sputum samples of healthy controls, and COPD patients. In addition, gene expression of TCR for iNKT, MAIT cells, and CD1d, MR1 were assessed by qPCR in the study cohorts.ResultsPercentages of total iNKT and MAIT cells were dramatically dropped in blood, and reduced numbers of iNKT cells were observed in the sputum of COPD patients. Furthermore decreased DN and increased CD4+ iNKT subsets, while increased DN and decreased CD8+ MAIT subpopulations were measured in the blood of COPD patients. Reduced invariant TCR mRNA levels in COPD patients had confirmed these previous findings. The mRNA expression of CD1d and MR1 were increased in stable and exacerbating COPD patients; however both molecules were decreased upon antibiotic and systemic steroid treatments.ConclusionsOur results support the notion that both invariant T-cell populations are affected in COPD. Further detailed analysis of invariant T cells could shed more light into the complex interactions of these lymphocyte groups in COPD pathogenesis.

Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive inflammatory condition that has been linked to the dysregulation of many metabolic pathways including lipid biosynthesis. How lipid metabolism could affect disease progression in smokers with COPD remains unclear. We cross-examined the transcriptomics, proteomics, metabolomics, and phenomics data available on the public domain to elucidate the mechanisms by which lipid metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO) signaling network utilizing active/inactive, and functional/dysfunctional lipid-mediated signaling pathways to explore how lipid-metabolism could promote COPD pathogenesis in smokers. SpLiCO was further utilized to investigate signal amplifiers, distributers, propagators, feed-forward and/or -back loops that link COPD disease severity and hypoxia to disruption in the metabolism of sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations for dependency of molecules identified several important nodes in the network with modular regulatory and signal distribution activities. Our systems-based analyses indicate that arachidonic acid is a critical and early signal distributer that is upregulated by the sphingolipid signaling pathway in COPD, while hypoxia plays a critical role in the elevated dependency to glucose as a major energy source. Integration of SpLiCo and clinical data shows a strong association between hypoxia and the upregulation of sphingolipids in smokers with emphysema, vascular disease, hypertension and those with increased risk of lung cancer.

Study of the level of sputum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) in COPD patients

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of respiratory morbidity and mortality worldwide. One of the main hypotheses concerning the pathogenesis of emphysema, a key cause of morbidity and mortality in COPD, is the protease antiprotease imbalance. Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodeling associated with aberrant inflammation.This study examined changes in sputum as regards MMP-9, TIMP-1 and levels of inflammatory cells in COPD patients compared with sputum of healthy smokers and non smokers. MethodsForty patients were included in this study. FEV1 before and after salbutamol inhalation, MMP-9, TIMP-1 and inflammatory cell count in the sputum of COPD patients, healthy smokers and non- smokers were investigated. ResultsMMP-9 was significantly increased in both COPD patients (194.4±100.6), and healthy smokers (104.5±42.1) compared with healthy non smokers (34.5±36.1). TIMP-1 was increased more in healthy non-smokers (192.7±37.7) than COPD patients (115±55.5) and healthy smokers (145.3±35.1). MMP-9/TIMP-1 was high in COPD patients (1.7±0.9) and healthy smokers (0.7±0.3) compared with healthy non smokers (0.2±0.2). Mean sputum total leucocytic count (TLC) was highly statistically significantly different between the three groups. COPD group showed the highest means value while non smokers group showed the lowest one. ConclusionsCOPD is characterized by an imbalance between MMP-9 and TIMP-1 which may play an important role in the pathogenesis of tissue remodeling and airway obstruction.

CXCL8 (interleukin 8)--the key inflammatory mediator in chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic disease of the upper airways and it is the fourth cause of death in the Polish population. COPD is characterized by not fully reversible constriction of air flow, which is a consequence of inflammation caused by noxious fumes and gases, particularly tobacco smoke. It seems that among mediators of inflammation, chemokine CXCL8 (interleukin 8) may play a pivotal role. CXCL8 is a member of the chemokine family and is a major chemoattractant to neutrophils, which are responsible for inducing and sustaining the inflammatory state. It was shown that there is a correlation between the number of neutrophils in induced sputum in COPD patients, the CXCL8 level, and clinical outcome of the illness. Increased frequency of exacerbation may be a result of increased secretion of mucus caused by increased expression of genes encoding mucins (MUC5AC and MUCB), which is stimulated by high levels of CXCL8. Activation of the CXCL8-encoding gene depends on pro-inflammatory cytokines such as tumor necrosis factor, interleukin 1 and lipopolysaccharide which activate transcription factor NF-κB. Inhibitors of CXCL8 (such as N-acetyl-L-cysteine) cause a decrease of exacerbation frequency and clinical symptoms. The data presented in the review suggest that CXCL8 plays a major role in the inflammatory process leading to COPD.

IL-32 was involved in cigarette smoke-induced pulmonary inflammation in COPD.

Previous study has proven the overexpression of interleukin 32 (IL-32) in lungs with chronic obstructive pulmonary disease (COPD). But the soluble IL-32 levels and the role of IL-32 in smokers and COPD are still unclear. In this study, we enrolled 133 subjects who were divided into three groups: nonsmokers, control smokers and smokers with COPD. We detected the IL-32 levels in serum and induced sputum of all subjects. The pulmonary function, PaO2 and smoking exposure index were also collected. Moreover, macrophages were isolated and stimulated by cigarette smoke extraction (CSE). A special siRNA was used to suppress the IL-32 expression. There was no significant difference in IL-32 serum levels among the three groups. The IL-32 levels of induced sputum in COPD patients were markedly higher than control smokers and nonsmokers. The IL-32 levels in induced sputum of COPD patients were negatively correlated with forced expiratory volume (FEV1)/forced vital capacity and FEV1%. Moreover, a low concentration CSE could stimulate IL-32 expression and promote the release of several inflammatory factors (such as IL-6 and tumor necrosis factor-α). A special siRNA could significantly suppress the release of these inflammatory factors. This study revealed the critical role of IL-32 in pulmonary inflammation of COPD and smoker-associated diseases.

Expression of Interleukin (IL)-10, IL-17A and IL-22 in Serum and Sputum of Stable Chronic Obstructive Pulmonary Disease Patients

Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of chronic obstructive pulmonary disease (COPD), but their expression in COPD is uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the serum and sputum of COPD patients. Blood samples and induced sputum samples were collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD stages, it was inversely correlated with percentage of forced expiratory volume in the first second (FEV1%) reference and positively correlated with C-reactive protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively correlated with sputum neutrophils, and reversely correlated with sputum macraphages (p < 0.01); 3) serum and sputum IL-22 were significantly higher in COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was similar in severe COPD (stage III and IV), which were higher than those in the other groups (p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and healthy smokers, which were decreased compared to non-smokers. These data suggest that the increased level of IL-17A in serum and sputum plays important roles in the pathogenesis of COPD. The increased sputum IL-22 might also play important roles in the pathogenesis of COPD, while IL-10 secretion might be not only affected by COPD but also by cigarette smoke.

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Toll-Like Receptor (TLR2 and TLR4) Polymorphisms and Chronic Obstructive Pulmonary Disease

Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs was associated with FEV1 level. Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.

Heterogeneity of Bronchitis in Airway Diseases in Tertiary Care Clinical Practice

Sputum cell counts have identified inflammatory subtypes of bronchitis in relatively small numbers of subjects with asthma, chronic obstructive pulmonary disease (COPD) and chronic cough in research studies. The prevalence of different subtypes of bronchitis in routine clinical practice, however, has not been reported. To examine the heterogeneity of bronchitis and its relationship to the severity of airflow obstruction. A retrospective cross-sectional survey based on a computerized database of spontaneous or induced sputum cell counts examined in a large university tertiary respiratory outpatient clinic. The database contained 4232 consecutive sputum records from 2443 patients with chronic cough (39%), asthma (37%), asthma with COPD (9%), COPD (13%) and bronchiectasis (3%). Total and differential cell counts were obtained from 86% of successful sputum samples. Induced sputum provided more viable samples than spontaneous expectorate. Approximately one-third of patients with asthma and one-fifth of patients with COPD experience eosinophilic bronchitis. Asthmatic patients with moderate to severe airflow obstruction had a greater number of sputum eosinophils. There was a significantly higher number of total cell counts and percentage of neutrophils in the sputum of COPD patients with moderate and severe airflow obstruction than in those with mild airflow obstruction. There is heterogeneity in the cellularity of sputum in various airway diseases. Patients with clinically stable airway diseases may have high sputum cell counts. During exacerbations, more patients may experience neutrophilic bronchitis. Severity of airflow obstruction is associated with eosinophilic bronchitis in patients with asthma, and neutrophilic bronchitis in patients with nonasthmatic COPD.

3-chlorotyrosine in Sputum of COPD Patients: Relationship with Airway Inflammation

ABSTRACTThe airways of patients with chronic obstructive pulmonary disease (COPD) are associated with increased numbers of inflammatory cells, in particular neutrophils and macrophages. Contained within the primary granules of neutrophils is the heme enzyme called myeloperoxidase (MPO) that has been used as a biomarker of neutrophilic inflammation in COPD and other inflammatory diseases. MPO is the only enzyme in the body that produces hypochlorous acid (HOCl), which effectively chlorinates tyrosine residues in proteins. The presence of 3-chlorotyrosine (3Cl-Tyr) in sputum of COPD patients has yet to be established. Spontaneously produced sputum was collected from 14 stable COPD patients, and ultra-centrifuged to prepare sol phase samples for analysis. Sputum 3Cl-Tyr levels were measured using Mass Spectrometry (LC-MSMS). Sputum MPO activity was measured using a standard chromogenic substrate assay. The Spearman rank correlation was used to analyse the data. We report for the first time the measurement of 3Cl-Tyr in sputum from stable COPD patients. The sputum levels of 3Cl-Tyr correlated well with sputum MPO activity (r = 0.88; p < 0.0001). The presence of 3Cl-Tyr in the sputum of stable COPD patients suggests an active process related to MPO that may play a role in the pathophysiology of this disease.

The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial

BackgroundAirway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.MethodsThis was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4–14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.ResultsMean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM). The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006). Both treatments were well tolerated.ConclusionThe relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar. In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.Trial registrationTrial registration number NCT00379028

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 +/- 6.24%) in sputum whereas neutrophils (63.3 +/- 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 +/- 330.7 pg/ml) and plasma (716.6 +/- 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 +/- 105.2 pg/ml) and TNF-alpha (308.8 +/- 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 +/- 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

Nuclear Factor-κB (NF-κB) Activity and Levels of IL-6, IL-8 and TNF-α in Induced Sputum in the Exacerbation and Recovery of COPD Patients

Background : Exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with increased airway inflammation, and the is known to be an indicator of cellular activation and of inflammatory mediator production. This study was undertaken to investigate the change of cytokine characteristics and activity in induced sputum of COPD patients during exacerbation and recovery of the disease. Methods : Sputum induction was performed in 37 patients with COPD during exacerbation and during recovery and in 15 healthy subjects. Cell counts, levels of IL-6, IL-8 and in induced sputum and NF-kB activity in macrophage of induced sputum were measured. Results : Patients with COPD showed significantly increased levels of IL-6, IL-8 and (p activity in induced sputum(p activity and levels of IL-6 and tended to be decreased during recovery, but not siginificantly. Conclusion : Activation of and increased levels of IL-6, IL-8 and were thought to be associated with pathogenesis and exacerbations of COPD.

Platinum-Based, Leukocyte-Depleting Chemotherapy Does Not Alter Induced Sputum Markers of Neutrophilic Inflammation in COPD Patients with Unresectable Non-Small Cell Lung Cancer

Background: Neutrophilic inflammation is a major feature of chronic obstructive pulmonary disease (COPD), and several novel therapies aim at the suppression of neutrophils in COPD. Due to the abundance and redundancy of mediators involved in neutrophilic inflammation, there is an ongoing controversy about the feasibility of such anti-neutrophilic approaches. Systemic chemotherapy has broad side effects, including neutrophil toxicity. Objectives: In this observational study, we have measured cellular and neutrophil-related inflammatory markers in induced sputum of COPD patients with unresectable non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. Methods: 15 COPD/NSCLC patients were followed during their first course of chemotherapy with cisplatin (60 mg/m² days 1 and 7) and etoposide (100 mg/m² days 3, 4, and 5). Sputum induction was performed before, and 3 weeks after chemotherapy. Peripheral blood count, sputum total cells and differentials, and the concentrations of the inflammatory markers interleukin (IL)-8, and matrix metalloproteinase (MMP)-9 in sputum supernatant were analyzed. Results: Similar to COPD controls (n = 12), COPD/NSCLC patients had increased levels of absolute and relative sputum neutrophils, IL-8, and MMP-9 at baseline, when compared with healthy controls (n = 14, p < 0.001, all comparisons). After chemotherapy, there was a significant reduction in peripheral blood leukocytes (pre: 10,736 ± 550, post: 6,536 ± 1,064 cells/µl, p = 0.002) and log neutrophils (pre: 8.9 ± 0.09, post: 8.1 ± 0.2 cells/µl, p = 0.004), whereas log sputum neutrophils (pre: 0.3 ± 0.37, post: 0.18 ± 0.3 cells × 10⁶/ml, p = 0.1) , IL-8 (pre 15.9 ± 3.8, post: 17.7 ± 3.6 ng/ml, p = 0.7), and log MMP-9 (pre: 5.3 ± 0.57, post: 5.6 ± 0.7 ng/ml, p = 0.33) remained unchanged. Conclusion: A single course of platinum-based chemotherapy markedly decreases peripheral blood neutrophils, but has no effect on inflammatory patterns of induced sputum in COPD patients with unresectable NSCLC.