scholarly journals Elevated levels of arginase activity are related to inflammation in patients with COPD exacerbation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marcel Jose Rodríguez-Guzmán ◽  
Germán Peces-Barba Romero ◽  
Sandra Pérez Rial ◽  
Cristina Serrano del Castillo ◽  
Miguel Ángel Palomero Rodríguez ◽  
...  

Abstract Introduction Within the pathogenesis of the chronic obstructive pulmonary disease (COPD) there are interactions between different inflammatory mediators that are enhanced during an exacerbation. Arginase is present in bronchial epithelial cells, endothelial, fibroblasts and alveolar macrophages, which make it a probable key enzyme in the regulation of inflammation and remodelling. We aimed to find a potential relationship between arginase activity, inflammatory mediators in COPD patients in stable phase and during exacerbations. Methods We performed a prospective, observational study of cases and controls, with 4 study groups (healthy controls, stable COPD, COPD during an exacerbation and COPD 3 months after exacerbation). We measured arginase, inflammation markers (IL-6, IL-8, TNF-∝, IFN-γ and C reactive protein), and mediators of immunity: neutrophils, monocytes, total TCD3 + lymphocytes (CD3ζ), CD4 + T cells, CD8 + T cells, NK cells. Results A total of 49 subjects were recruited, average age of 69.73 years (59.18% male). Arginase activity is elevated during an exacerbation of COPD, and this rise is related to an increase in IL-6 production. The levels of IL-6 and IL-8 remained elevated in patients with COPD at 3 months after hospital exacerbation. We did not find a clear relationship between arginase activity, immunity or with the degree of obstruction in COPD patients. Conclusions Arginase activity is elevated during an exacerbation of COPD, and it could be related to an increase in the production of IL-6. Levels of IL-6, IL-8, and arginase activity remain elevated in patients with COPD at 3 months after hospital exacerbation. Arginase activity could contribute to the development of COPD.

2021 ◽  
pp. 153537022110088
Author(s):  
Mingshan Xue ◽  
Yifeng Zeng ◽  
Runpei Lin ◽  
Hui-Qi Qu ◽  
Teng Zhang ◽  
...  

While there is no cure for chronic obstructive pulmonary disease (COPD), its progressive nature and the formidable challenge to manage its symptoms warrant a more extensive study of the pathogenesis and related mechanisms. A new emphasis on COPD study is the change of energy metabolism. For the first time, this study investigated the anaerobic and aerobic energy metabolic pathways in COPD using the metabolomic approach. Metabolomic analysis was used to investigate energy metabolites in 140 COPD patients. The significance of energy metabolism in COPD was comprehensively explored by the Global Initiative for Chronic Obstructive Lung Disease–GOLD grading, acute exacerbation vs. stable phase (either clinical stability or four-week stable phase), age group, smoking index, lung function, and COPD Assessment Test (CAT) score. Through comprehensive evaluation, we found that COPD patients have a significant imbalance in the aerobic and anaerobic energy metabolisms in resting state, and a high tendency of anaerobic energy supply mechanism that correlates positively with disease progression. This study highlighted the significance of anaerobic and low-efficiency energy supply pathways in lung injury and linked it to the energy-inflammation-lung ventilatory function and the motion limitation mechanism in COPD patients, which implies a novel therapeutic direction for this devastating 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.


2019 ◽  
Vol 54 (1) ◽  
pp. 1800174 ◽  
Author(s):  
Malcolm R. Starkey ◽  
Maximilian W. Plank ◽  
Paolo Casolari ◽  
Alberto Papi ◽  
Stelios Pavlidis ◽  
...  

Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death globally. The lack of effective treatments results from an incomplete understanding of the underlying mechanisms driving COPD pathogenesis.Interleukin (IL)-22 has been implicated in airway inflammation and is increased in COPD patients. However, its roles in the pathogenesis of COPD is poorly understood. Here, we investigated the role of IL-22 in human COPD and in cigarette smoke (CS)-induced experimental COPD.IL-22 and IL-22 receptor mRNA expression and protein levels were increased in COPD patients compared to healthy smoking or non-smoking controls. IL-22 and IL-22 receptor levels were increased in the lungs of mice with experimental COPD compared to controls and the cellular source of IL-22 included CD4+ T-helper cells, γδ T-cells, natural killer T-cells and group 3 innate lymphoid cells. CS-induced pulmonary neutrophils were reduced in IL-22-deficient (Il22−/−) mice. CS-induced airway remodelling and emphysema-like alveolar enlargement did not occur in Il22−/− mice. Il22−/− mice had improved lung function in terms of airway resistance, total lung capacity, inspiratory capacity, forced vital capacity and compliance.These data highlight important roles for IL-22 and its receptors in human COPD and CS-induced experimental COPD.


2020 ◽  
Vol 90 (1) ◽  
Author(s):  
Michele Vitacca ◽  
Cinzia Lastoria ◽  
Monica Delmastro ◽  
Domenico Fiorenza ◽  
Pasquale De Cata ◽  
...  

To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital admission with relapse due to exacerbation do not find adequate support in current guidelines. Here we describe the results of a recent clinical audit, including a systematic review of practices reported in literature and an open discussion comparing these to current real-life procedures. The process was dived into two 8-hour-audits 3 months apart in order to allow work on the field in between meeting and involved 13 participants (3 nurses, 1 physiotherapist, 2 internists and 7 pulmonologists). This document reports the opinions of the experts and their consensus, leading to a bundle of multidisciplinary statements on the use of inhaled drugs for hospitalized COPD patients. Recommendations and topics addressed include: i) monitoring and diagnosis during the first 24 h after admission; ii) treatment algorithm and options (i.e., short and long acting bronchodilators); iii) bronchodilator dosages when switching device or using spacer; iv) flow measurement systems for shifting to LABA+LAMA within 48 h; v) when nebulizers are recommended; vi) use of SMI to deliver LABA+LAMA when patient needs SABA <3 times/day independently from flow limitation; vii) use of DPI and pre-dosed MDI to deliver LABA+LAMA or TRIPLE when patient needs SABA <3 times/day, with inspiratory flow > 30 litres/min; viii) contraindication to use DPI; ix) continuation of LABA-LAMA when patient is already on therapy; x) possible LABA-LAMA dosage increase; xi) use of SABA and/or SAMA in addition to LABA+LABA; xii) use of SABA+SAMA restricted to real need; xiii) reconciliation of drugs in presence of comorbidities; xiv) check of knowledge and skills on inhalation therapy; xv) discharge bundle; xvi) use of MDI and SMI in tracheostomized patients in spontaneous and ventilated breathing.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Nailya Kubysheva ◽  
Larisa Postnikova ◽  
Svetlana Soodaeva ◽  
Viкtor Novikov ◽  
Tatyana Eliseeva ◽  
...  

The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.


2020 ◽  
Vol 7 ◽  
Author(s):  
Xuanqi Liu ◽  
Haiyan Ge ◽  
Xiumin Feng ◽  
Jingqing Hang ◽  
Fengying Zhang ◽  
...  

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammatory processes, and exacerbation of COPD represents a critical moment in the progression of COPD. Several biomarkers of inflammation have been proposed to have a predictive function in acute exacerbation. However, their use is still limited in routine clinical practice. The purpose of our study is to explore the prognostic efficacy of novel inflammatory hemogram indexes in the exacerbation among stable COPD patients.Method: A total of 275 stable COPD patients from the Shanghai COPD Investigation Comorbidity Program were analyzed in our study. Blood examinations, especially ratio indexes like platelet–lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio [systemic immune-inflammation index (SII)], and monocyte × neutrophil/lymphocyte ratio [systemic inflammation response index (SIRI)], lung function test, CT scans, and questionnaires were performed at baseline and routine follow-ups. Clinical characteristics and information of exacerbations were collected every 6 months. The relationship between hemogram indexes and diverse degrees of exacerbation was assessed by logistic regression. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the ability of hemogram indexes to predict exacerbation of COPD. Furthermore, the discrimination and accuracy of combined indexes were measured by ROC and calibration curve.Result: There was a significant positive correlation between PLR levels and total exacerbation of COPD patients in a stable stage in a year. Also, the predictive ability of PLR exceeded any other ratio indexes, with an AUC of 0.66. SII and SIRI ranked second only to PLR, with an AUC of 0.64. When combining PLR with other indexes (sex, COPD year, and St. George's Respiratory Questionnaire scores), they were considered as the most suitable panel of index to predict total exacerbation. Based on the result of the ROC curve and calibration curve, the combination shows optimal discrimination and accuracy to predict exacerbation events in COPD patients.Conclusion: The hemogram indexes PLR, SII, and SIRI were associated with COPD exacerbation. Moreover, the prediction capacity of exacerbation was significantly elevated after combining inflammatory hemogram index PLR with other indexes, which will make it a promisingly simple and effective marker to predict exacerbation in patients with stable COPD.


2015 ◽  
Vol 3 (2) ◽  
pp. 67-70
Author(s):  
Rawshan Arra Khanam ◽  
Md Ashraful Haque ◽  
Mohammad Omar Faruq

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable, but progressive disease. Hospital admissions of patients with COPD are frequently due to acute exacerbations of COPD (AECOPD). AECOPD are very common, affecting about 20% of COPD patients. The bacterial infection plays an important role in the exacerbation of COPD patients. In addition, recent studies using molecular diagnostics indicate that a substantial proportion of AECOPD are associated with viral infection. Accurate methods to differentiate viral and bacterial respiratory infections to allow targeted antibiotic therapy would be beneficial. Acute phase reactants are capable of demonstrating the inflammation; however, they cannot be employed to make a difference between bacterial and nonbacterial causes of the inflammation. Recently, measurement of procalcitonin (PCT) levels appears to be useful in order to minimize this problem.Bangladesh Crit Care J September 2015; 3 (2): 67-70


2004 ◽  
Vol 72 (2) ◽  
pp. 818-823 ◽  
Author(s):  
Debby Bogaert ◽  
Paul van der Valk ◽  
Reshmi Ramdin ◽  
Marcel Sluijter ◽  
Evelyn Monninkhof ◽  
...  

ABSTRACT Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal colonization and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae. We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneumococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% confidence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were significantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-specific and functional antibodies in S. pneumoniae-positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is frequently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our findings demonstrate that COPD patients are able to mount a significant immune response to pneumococcal infection. COPD patients may therefore benefit from pneumococcal vaccination.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Tang ◽  
Xiaodan Li ◽  
Man Wang ◽  
Qi Zou ◽  
Shasha Zhao ◽  
...  

T cells and B cells participate in the pathogenesis of COPD. Currently, NK cells and NKT cells have gained increasing attention. In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS) were recruited, and their pulmonary function was assessed. The frequencies of CD3+T, CD4+T, CD8+T, B, NK, and NKT-like cells were determined using flow cytometry. The frequencies of spontaneous and inducible IFN-γ+or CD107a+NK and NKT-like cells as well as activating or inhibitory receptors were also detected. The potential association of lymphocyte subsets with disease severity was further analyzed. Significantly decreased numbers of CD3+and CD4+T cells, and the CD4+/CD8+ratio, but increased numbers of CD3−CD56+NK and CD3+CD56+NKT-like cells were observed in COPD patients compared to HNS. The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients. The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater. The frequency of CD158b+NK cells was negatively correlated with FEV1% prediction and FEV1/FVC. Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD.


Author(s):  
Ozlem Ediboglu

Mechanical ventilation is a lifesaving therapy in patients who have acute respiratory failure due to chronic obstructive pulmonary disease (COPD). Mechanical ventilaton either invasive or non-invasive has an important role in the management of acute exacerbation of COPD (AECOPD). AECOPD required hospitalizaton had increased mortality and poor prognosis. Ventilatory management success related to understanding physiopathology of the disease. Clinicians must be aware of deterioration of clinical signs of COPD patients. The most appropriate treatment should be performed at optimal time. Some COPD patients are at high risk for prolonged mechanical ventilation due to COPD is a progressive disease.


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