scholarly journals Enhanced neutrophil response in chronic obstructive pulmonary disease

Thorax ◽  
2001 ◽  
Vol 56 (6) ◽  
pp. 432-437
Author(s):  
A Noguera ◽  
S Batle ◽  
C Miralles ◽  
J Iglesias ◽  
X Busquets ◽  
...  

BACKGROUNDNeutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs.METHODSCirculating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 andl-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFα). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR).RESULTSPatients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference –3.4 (95% CI of the difference –5.1 to –1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference –77 (95% CI of the difference –102 to –52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5)v 45 (3); mean difference –46 (95% CI of the difference –61 to –31), p<0.001) and after stimulation with TNFα (MFI 340 (15) v 263 (11); mean difference –77 (95% CI of the difference –119 to –34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation.CONCLUSIONSThese results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.

2020 ◽  
Author(s):  
Songming Zhuo ◽  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Wugen Zhan ◽  
...  

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.


2020 ◽  
Vol 3 (1) ◽  
pp. 2-8
Author(s):  
Robert A. Wise

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.


2018 ◽  
Vol 4 (4) ◽  
pp. 00080-2018 ◽  
Author(s):  
David I. Fielding ◽  
Justin Travers ◽  
Phan Nguyen ◽  
Michael G. Brown ◽  
Gunter Hartel ◽  
...  

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC.EDAC was identified at bronchoscopy as 75–100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC.38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls).These data show a new utility of IOS: detecting EDAC in patients with normal lung function.


1998 ◽  
Vol 274 (6) ◽  
pp. L908-L913 ◽  
Author(s):  
Víctor I. Peinado ◽  
Joan A. Barberà ◽  
Josep Ramírez ◽  
Federico P. Gómez ◽  
Josep Roca ◽  
...  

To investigate whether endothelial dysfunction of pulmonary arteries (PA) is present in patients with mild chronic obstructive pulmonary disease (COPD) and to what extent it is related to the morphological abnormalities of PA, we studied 41 patients who underwent lung resection. Patients were divided into the following groups: nonsmokers ( n = 7), smokers with normal lung function ( n = 13), and COPD ( n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh) and ADP. Structural abnormalities of PA were assessed morphometrically. PA of COPD patients developed lower maximal relaxation in response to ADP than both nonsmokers and smokers ( P < 0.05 each) and a trend to reduced relaxation in response to ACh ( P = 0.08). Maximal relaxation to ADP correlated with the degree of airflow obstruction ( r = 0.48, P < 0.01). Morphometrical analysis of PA revealed thicker intimas, especially in small arteries, in both smokers and COPD compared with nonsmokers ( P < 0.05 each). We conclude that endothelial dysfunction of PA is already present in patients with mild COPD. In these patients, as well as in smokers with normal lung function, small arteries show thickened intimas, suggesting that tobacco consumption may play a critical role in the pathogenesis of pulmonary vascular abnormalities in COPD.


2020 ◽  
pp. oemed-2020-106610
Author(s):  
Ting Wang ◽  
Wenqing Sun ◽  
Hongyan Wu ◽  
Yuxin Cheng ◽  
Yan Li ◽  
...  

ObjectivesSusceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker’s pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies.MethodsTo systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study.ResultsInterestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10−4) and lung function (rs4651005, OR=1.39, p=1.62×10−3; rs985256, OR=0.73, p=8.24×10−4 and rs6539952, OR=1.28, p=4.32×10−4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10−4), ANGPTL1 (rs4651005, p=5.4 ×10−7), SPATS2L (rs985256, p=1.1 ×10−5) and RP11-463O9.9 (rs6539952, p=7.1 ×10−6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis.ConclusionsThese results provided a deeper understanding of the genetic predisposition basis of CWP.


Author(s):  
SALVA FATIMA HEBA ◽  
SYED AAMIR ALI ◽  
MOHAMMED ALEEMUDDIN NAVEED ◽  
SALWA MEHRIN ◽  
MAARIA GULNAAZ ◽  
...  

Objectives: The objectives of the study were to estimate the relative impact of triple therapy on lung function, health status, and mortality risk compared with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) therapy in symptomatic chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations in an Indian clinical population. Methodology: The GLIMPSE (Lung Function, Health Status, and Mortality Risk Assessment in COPD using Triple Therapy) was as a prospective, parallel design, single-center observational study comparing 24 weeks of triple therapy (twice-daily combination of budesonide [BUD]-formoterol [FOR] [100/6 μg] and once-daily tiotropium [TIO] [9 μg]) with ICS/LABA (twice daily BUD-FOR [100/6 μg]). The primary outcome was the mean change in forced expiratory volume in the 1st s (FEV1%) predicted and COPD assessment test total score from baseline at week 24. Secondary outcomes were variation in dyspnea grade and BODE total score from baseline. Results: At week 24 in triple therapy (n=70) and ICS/LABA therapy (n=70), mean difference from baseline in FEV1% predicted were 5.40 (95% confidence interval [CI]: 1.29–9.50) and 1.90 (95% CI: –1.87–5.68) respectively, and mean difference in CAT total score from baseline was –5.10 units (95% CI: –3.49–−6.71) and –1.80 units (95% CI: –0.052–−3.548), respectively. In addition, there was a statistically significant reduction in dyspnea grading and BODE score with comparable adverse events in both groups. Conclusion: Overall, the results favored triple therapy over dual therapy in advanced symptomatic COPD patients.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095263
Author(s):  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Yan Shen ◽  
Wugen Zhan ◽  
...  

Objective The pathogenesis of chronic obstructive pulmonary disease (COPD) remains elusive. Here, we assessed the correlation between CD8+ T cell frequencies and autophagy in COPD patients. Methods Subjects were divided into three groups (n = 30 patients/group): (1) COPD patients in the stable phase; (2) smokers with normal lung function; and (3) non-smokers with normal lung function. Flow cytometry was used to enumerate CD8+ T cell subsets (CD8+, CD8+ effector, and CD8+ memory T cells) and quantitate T-cell apoptosis. RT-PCR and western blotting were used to measure levels of LC3 and p62. Results Frequencies of CD8+ T cell subsets and expression of p62 and LC3 II/I were significantly higher in COPD patients compared with the other two groups, while the rate of apoptosis was lower. In COPD patients, LC3 II/I and p62 expression were positively correlated with CD8+ T cell subset frequencies. Moreover, a significant correlation was observed between LC3 II/I and p62 expression and T cell subset frequencies. Conclusion Autophagy level is positively correlated with the frequencies of CD8+ T cells, suggesting that autophagy might be involved in COPD pathogenesis.


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