Association between plasma interleukin-33 level and acute exacerbation of chronic obstructive pulmonary disease.
Joo Hyonsoo,Park Seoung Ju,Min Kyung Hoon,Rhee Chin Kook
BMC pulmonary medicine
BACKGROUND:The role of interleukin (IL)-33 in patients with chronic obstructive pulmonary disease (COPD) has not been well elucidated. The aim of this study is to analyze the association between plasma IL-33 level and acute exacerbation of COPD. METHODS:Plasma IL-33 was measured in 62 COPD patients during their stable state. Patients were prospectively followed up for 1 year. The expression of IL-33 was measured in lung tissue obtained from 38 patients who underwent surgery. RESULTS:The number of exacerbations was significantly higher in the high plasma IL-33 group compared with the low plasma IL-33 group. On Poisson regression analysis, high plasma IL-33 was associated with increased risk of exacerbation (incidence rate ratio = 2.166, P = 0.043). The expression of IL-33 in the lung was higher in COPD patients than in controls. The expression of IL-33 was significantly correlated with smoking pack years (R = 0.45, P < 0.01) and Forced expiratory volume in 1 s (%) (R = - 0.58, P < 0.01). CONCLUSION:The plasma level of IL-33 in patients with COPD was significantly associated with the risk of exacerbation in prospective follow up. The expression of IL-33 in the lung was positively correlated with smoking and negatively correlated with lung function.
10.1186/s12890-021-01423-8
Association Between IL-17 and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.
International journal of chronic obstructive pulmonary disease
Background: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. Methods:We searched databases such as PubMed, Web of Science, Cochrane Library and Embase to extract original research. Results: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; <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; <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; <0.001). Conclusion: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.
10.2147/COPD.S412626
Acute exacerbation of chronic obstructive pulmonary disease in United States emergency departments, 2010-2018.
BMC pulmonary medicine
OBJECTIVES:Little is known about the recent status of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the U.S. emergency department (ED). This study aimed to describe the disease burden (visit and hospitalization rate) of AECOPD in the ED and to investigate factors associated with the disease burden of AECOPD. METHODS:Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS), 2010-2018. Adult ED visits (aged 40 years or above) with AECOPD were identified using International Classification of Diseases codes. Analysis used descriptive statistics and multivariable logistic regression accounting for NHAMCS's complex survey design. RESULTS:There were 1,366 adult AECOPD ED visits in the unweighted sample. Over the 9-year study period, there were an estimated 7,508,000 ED visits for AECOPD, and the proportion of AECOPD visits in the entire ED population remained stable at approximately 14 per 1,000 visits. The mean age of these AECOPD visits was 66 years, and 42% were men. Medicare or Medicaid insurance, presentation in non-summer seasons, the Midwest and South regions (vs. Northeast), and arrival by ambulance were independently associated with a higher visit rate of AECOPD, whereas non-Hispanic black or Hispanic race/ethnicity (vs. non-Hispanic white) was associated with a lower visit rate of AECOPD. The proportion of AECOPD visits that were hospitalized decreased from 51% to 2010 to 31% in 2018 (p = 0.002). Arrival by ambulance was independently associated with a higher hospitalization rate, whereas the South and West regions (vs. Northeast) were independently associated with a lower hospitalization rate. The use of antibiotics appeared to be stable over time, but the use of systemic corticosteroids appeared to increase with near statistical significance (p = 0.07). CONCLUSIONS:The number of ED visits for AECOPD remained high; however, hospitalizations for AECOPD appeared to decrease over time. Some patients were disproportionately affected by AECOPD, and certain patient and ED factors were associated with hospitalizations. The reasons for decreased ED admissions for AECOPD deserve further investigation.
10.1186/s12890-023-02518-0
The role of CD8 + T lymphocytes in chronic obstructive pulmonary disease: a systematic review.
Williams Maya,Todd Ian,Fairclough Lucy C
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
OBJECTIVE AND DESIGN:This systematic review aims to establish the role of CD8 + T lymphocytes in COPD. METHODS:Forty-eight papers published in the last 15 years were identified for inclusion. RESULTS:CD8 + T-cells are increased in the lungs of patients with COPD (17 studies, 16 positive) whereas in the circulation, findings were inconclusive. Activation of CD8 + T-cells was enhanced in lungs (four studies, three positive) but cell phenotype was unclear. There was substantial evidence of a higher proportion of type 1 CD8 + (Tc1) cells in COPD (11 studies, 9 positive), though the population of type 2 (Tc2) cells was also increased (5 studies, 4 positive). CD8 + T-cells in COPD exhibited greater expression of cytotoxic proteins (five studies, five positive). Studies assessed a variety of questions so evidence was insufficient to draw firm conclusions. The role of CD8 + T-cells at acute exacerbation of COPD and also their contribution to alveolar destruction can only be hypothesised at this stage. CONCLUSIONS:Not only is the number of CD8 + T-cells increased in COPD, these cells have increased capacity to exert effector functions and are likely to contribute to disease pathogenesis. Several mechanisms highlighted show promise for future investigation to consolidate current knowledge.
10.1007/s00011-020-01408-z
Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease.
Qi Yu-Jing,Sun Xue-Jiao,Wang Zhe,Bin Yan-Fei,Li Ying-Hua,Zhong Xiao-Ning,Bai Jing,Deng Jing-Min,He Zhi-Yi
Chinese medical journal
BACKGROUND:The eosinophilic chronic obstructive pulmonary disease (COPD) is known to be more sensitive to corticosteroid. The sputum microbiome has been shown to affect COPD prognosis, but its role in acute exacerbations of eosinophilic COPD is unclear. This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD. METHODS:Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups. Patients with eosinophils ≥300 cells/μL in the peripheral venous blood were assigned to the eosinophilic group (Eos) and the rest to the non-eosinophilic group (Noneos). All patients received similar treatment including inhaled budesonide according to the guidelines. The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA (rRNA) method. The levels of interleukin (IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells. Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test. Categorical data were evaluated using Chi-squared test or Fisher's exact test. RESULTS:Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group. Prior to treatment, the alpha diversity (Shannon index) (2.65 ± 0.63 vs. 2.56 ± 0.54, t = 0.328, P = 0.747) and the structure of the sputum microbiome were similar in the Eos group and the Noneos group. After 7 days of treatment, alpha diversity increased in both groups, while the microbiome richness (Ace index) was significantly lower in the Eos group (561.87 ± 109.13 vs. 767.88 ± 148.48, t = -3.535, P = 0.002). At the same time, IL-6 (12.09 ± 2.85 pg/mL vs. 15.54 ± 2.45 pg/mL, t = -4.913, P < 0.001) and IL-8 (63.64 ± 21.69 pg/mL vs. 78.97 ± 17.13 pg/mL, t = -2.981, P = 0.004) decreased more significantly in the Eos group, and the percentages of inhibition of IL-8 at dexamethasone concentrations 10 to 10 mol/L were significantly higher in the Eos group than those in the Noneos group (all P < 0.05). CONCLUSIONS:The induced sputum microbiome richness decreased more significantly following treatment in the Eos patients compared to the Noneos patients. The lower plasma inflammatory factor levels and the higher percentage of inhibition of IL-8 might be due to higher corticosteroid sensitivity in Eos patients.
10.1097/CM9.0000000000000677
The Role of Regulatory T Cell in Nontypeable -Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Guan Xuewa,Lu Yanjiao,Wang Guoqiang,Gibson Peter,Chen Fang,Fang Keyong,Wang Ziyan,Pang Zhiqiang,Guo Yingqiao,Lu Junying,Yuan Yuze,Ran Nan,Wang Fang
Mediators of inflammation
Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation. The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable (NTHi), one of the most commonly isolated bacteria. Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance; however, their role in AECOPD is poorly understood. In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD. Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS). NTHi was administrated through intratracheal instillation for an acute exacerbation. Weight loss and lung function decline were observed in smoke-exposed mice. Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment. Expression levels of Tregs and Th17 cells with specific cytokines TGF-1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially. Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model. But this activity was suppressed after NTHi administration. Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD.
10.1155/2018/8387150
Long noncoding RNAs antisense noncoding RNA in the INK4 locus (ANRIL) correlates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in patients with chronic obstructive pulmonary disease.
Ge Jianli,Geng Shasha,Jiang Hua
Journal of clinical laboratory analysis
BACKGROUND:We aimed to assess the predictive value of long noncoding RNAs antisense noncoding RNA in the INK4 locus (lncRNAs ANRIL) for acute exacerbation of chronic obstructive pulmonary disease (COPD) and evaluate its correlation with inflammatory cytokines as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage in COPD patients. METHODS:A total of 136 acute exacerbations of COPD (AECOPD) patients, 138 stable COPD patients, and 140 healthy controls (HCs) were consecutively recruited, and plasma samples were collected. Real-time polymerase chain reaction was used to detect lncRNA ANRIL expression. Enzyme-linked immunosorbent assay was performed to detect inflammatory cytokines expressions. RESULTS:LncRNA ANRIL expression was lower in AECOPD patients compared with stable COPD patients and HCs (Both P < 0.001). Receiver operating characteristic curves revealed lncRNA ANRIL could distinguish AECOPD patients from HCs (area under curve (AUC):0.700, 95% CI: 0.638-0.762) and stable COPD patients (AUC: 0.659, 95% CI: 0.594-0.724). For inflammatory cytokines, lncRNA ANRIL expression was negatively correlated with TNF-α (P < 0.001), IL-1β (P = 0.015), IL-8 (P = 0.008), IL-17A (P = 0.002), and LTB-4 (P = 0.004) in AECOPD patients, while it was negatively correlated with TNF-α (P = 0.049), IL-1β (P = 0.005), IL-17A (P = 0.030), and LTB-4 (P = 0.011) in stable COPD patients. Furthermore, lncRNA ANRIL expression negatively correlated with GOLD stage in AECOPD patients (P = 0.001), but not in stable COPD patients (P = 0.131). CONCLUSION:LncRNA ANRIL associates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in COPD patients.
10.1002/jcla.22678
Detection of respiratory viruses and expression of inflammatory cytokines in patients with acute exacerbation chronic obstructive pulmonary disease in Mongolia China.
Feng Y,Liu E
Brazilian journal of biology = Revista brasleira de biologia
Chronic obstructive pulmonary disease (COPD) was estimated to be the third cause of global mortality by 2020. Acute exacerbation COPD (AECOPD) is a sudden worsening of COPD symptoms and could be due to virus/bacterial infections and air pollution. Increased expression of inflammatory markers in patients with AECOPD is associated with viral infection. This study aimed to detect different viruses and analyze the expression of various inflammatory markers associated with AECOPD patients. Three hundred and forty-seven patients diagnosed with COPD according to GOLD criteria were included in this study. Swab samples and blood were collected for the detection of viruses by RT-PCR and expression of inflammatory markers, respectively. Of the swab samples, 113 (32.6%) of samples were positive for virus detection. Of these, HRV (39.8%) was the predominant virus detected followed by FluB (27.4%) and FluA (22.1%). The presence of HRV was significantly higher (p=0.044) among the other detected viruses. When compared to healthy controls the expression levels of TNF-α, IL-6 and IL-8 were significantly higher (p<0.05) in virus-positive patients. The IL-6 and IL-8 were the next predominantly expressed in markers among the samples. The higher expression rate of IL-8 was significantly (p<0.05) associated with patients having COPD GOLD III severity level and smoking history. Although HRV was the predominant virus detected the combined prevalence of Influenza A and B surpassing the rate of HRV. The high-level expression of well known inflammatory markers of AECOPD, TNF-α, IL-6 and IL-8 indicates a chronic severe illness. These markers play an important role and could be used as a marker for determining the severity of AECOPD.
10.1590/1519-6984.231134
Copeptin, C-reactive protein, and procalcitonin as prognostic biomarkers in acute exacerbation of COPD.
Stolz Daiana,Christ-Crain Mirjam,Morgenthaler Nils G,Leuppi Jörg,Miedinger David,Bingisser Roland,Müller Christian,Struck Joachim,Müller Beat,Tamm Michael
Chest
BACKGROUND:A novel approach to estimate the severity of COPD exacerbation and predict its outcome is the use of biomarkers. We assessed circulating levels of copeptin, the precursor of vasopressin, C-reactive protein (CRP), and procalcitonin as potential prognostic parameters for in-hospital and long-term outcomes in patients with acute exacerbation of COPD (AECOPD) requiring hospitalization. METHODS:Data of 167 patients (mean age, 70 years; mean FEV(1), 39.9 +/- 16.9 of predicted [+/- SD]) presenting to the emergency department due to AECOPD were analyzed. Patients were evaluated based on clinical, laboratory, and lung function parameters on hospital admission, at 14 days, and at 6 months. RESULTS:Plasma levels of all three biomarkers were elevated during the acute exacerbation (p < 0.001), but levels at 14 days and 6 months were similar (p = not significant). CRP was significantly higher in patients presenting with Anthonisen type I exacerbation (p = 0.003). In contrast to CRP and procalcitonin, copeptin on hospital admission was associated with a prolonged hospital stay (p = 0.002) and long-term clinical failure (p < 0.0001). Only copeptin was predictive for long-term clinical failure independent of age, comorbidity, hypoxemia, and lung functional impairment in multivariate analysis (p = 0.005). The combination of copeptin and previous hospitalization for COPD increased the risk of poor outcome (p < 0.0001). Long-term clinical failure was observed in 11% of cases with copeptin < 40 pmol/L and no history of hospitalization, as compared to 73% of patients with copeptin >/= 40 pmol/L and a history of hospitalization (p < 0.0001). CONCLUSIONS:We suggest copeptin as a prognostic marker for short-term and long-term prognoses in patients with AECOPD requiring hospitalization.
10.1378/chest.06-2336
Antimicrobial peptide levels are linked to airway inflammation, bacterial colonisation and exacerbations in chronic obstructive pulmonary disease.
Persson Louise J P,Aanerud Marianne,Hardie Jon A,Miodini Nilsen Roy,Bakke Per S,Eagan Tomas M,Hiemstra Pieter S
The European respiratory journal
Antimicrobial peptides (AMPs) are effectors of host defence against infection, inflammation and wound repair. We aimed to study AMP levels in stable chronic obstructive pulmonary disease (COPD) and during acute exacerbations of COPD (AECOPD), and to examine their relation to clinical parameters and inflammatory markers.The 3-year Bergen COPD Cohort Study included 433 COPD patients and 325 controls. Induced sputum was obtained and analysed for levels of the AMPs human cathelicidin (hCAP18/LL-37) and secretory leukocyte protease inhibitor (SLPI), and for the inflammatory markers interleukin (IL)-8, IL-6 and tumour necrosis factor-α (TNF-α) using immunoassays. Systemic hCAP18/LL-37 and vitamin D levels were also studied. Treating AMPs as response variables, non-parametric tests were applied for univariate comparison, and linear regression to obtain adjusted estimates. The risk of AECOPD was assessed by Cox proportional-hazard regression.Sputum AMP levels were higher in patients with stable COPD (n=215) compared to controls (n=45), and further changed during AECOPD (n=56), with increased hCAP18/LL-37 and decreased SLPI levels. Plasma hCAP18/LL-37 levels showed a similar pattern. In stable COPD, high sputum hCAP18/LL-37 levels were associated with increased risk of AECOPD, non-typeable colonisation, higher age, ex-smoking and higher levels of inflammatory markers.Altered levels of selected AMPs are linked to airway inflammation, infection and AECOPD, suggesting a role for these peptides in airway defence mechanisms in COPD.
10.1183/13993003.01328-2016
Correlations between serum amyloid A, C-reactive protein and clinical indices of patients with acutely exacerbated chronic obstructive pulmonary disease.
Lin Tian-Lai,Chen Wei-Wen,Ding Zhi-Rong,Wei Si-Can,Huang Ming-Lian,Li Cai-Hui
Journal of clinical laboratory analysis
BACKGROUND:To explore the correlations between SAA, CRP, and clinical indices of patients with acutely exacerbated chronic obstructive pulmonary disease (AECOPD). METHODS:A total of 120 patients with AECOPD and another 120 with remitted COPD were enrolled in an AECOPD group and a COPD remission group, respectively. Meanwhile, 120 healthy subjects were included as a control group. SAA, CRP, PCT, Fbg, IL-8, IL-6, TNF-α, and IP-10 levels were detected. FEV and FEV /FVC were measured. RESULTS:Compared with control group, the serum levels of SAA, CRP, PCT, Fbg, IL-8, IL-6, TNF-α, and IP-10 significantly increased in COPD remission group (P < 0.05). The levels of AECOPD group significantly exceeded those of COPD remission group (P < 0.05). The levels of AECOPD patients with different GOLD grades were significantly different (P < 0.05). AECOPD group had significantly lower FEV and FEV /FVC than those of COPD remission group (P < 0.05). The CAT score of AECOPD patients was (18.41 ± 2.55) points. The levels of SAA, CRP, PCT, Fbg, IL-8, IL-6, TNF-α, and IP-10 were negatively correlated with FEV and FEV /FVC, and positively correlated with CAT score. The area under receiver operating characteristic curve of SAA was largest (0.931). The cutoff values for SAA, CRP, PCT and Fbg were 18.68 mg/L, 14.70 mg/L, 0.39 μg/L, 3.91 g/L, 0.46 μg/L, 24.17 μg/L, 7.18 mg/L, and 83.19 ng/L, respectively. CONCLUSIONS:Serum levels of SAA, CRP, PCT, Fbg, IL-8, IL-6, TNF-α, and IP-10 in AECOPD patients were elevated, which may undermine pulmonary functions. SAA can be used as an effective index for AECOPD diagnosis and treatment.
10.1002/jcla.22831
Increased CTLA-4 T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease.
Tan Dino B A,Teo Teck-Hui,Setiawan Abdul M,Ong Nathanael E,Zimmermann Maja,Price Patricia,Kirkham Lea-Ann S,Moodley Yuben P
Immunology
Impaired T helper type 1 (Th1) function is implicated in the susceptibility of patients with chronic obstructive pulmonary disease (COPD) to respiratory infections, which are common causes of acute exacerbations of COPD (AECOPD). To understand the underlying mechanisms, we assessed regulatory T (Treg) cells and the expression of an inhibitory T-cell receptor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Cryopreserved peripheral blood mononuclear cells (PBMC) from patients with AECOPD (n = 17), patients with stable COPD (sCOPD; n = 24) and age-matched healthy non-smoking controls (n = 26) were cultured for 24 hr with brefeldin-A or monensin to detect intracellular or surface CTLA-4 (respectively) by flow cytometry. T cells in PBMC from AECOPD (n = 9), sCOPD (n = 14) and controls (n = 12) were stimulated with anti-CD3 with and without anti-CTLA-4 blocking antibodies and cytokines were quantified by ELISA. Frequencies of circulating T cells expressing intracellular CTLA-4 were higher in sCOPD (P = 0·01), whereas patients with AECOPD had more T cells expressing surface CTLA-4 than healthy controls (P = 0·03). Increased frequencies of surface CTLA-4 CD4 T cells and CTLA-4 Treg cells paralleled increases in plasma soluble tumour necrosis factor receptor-1 levels (r = 0·32, P = 0·01 and r = 0·29, P = 0·02, respectively) in all subjects. Interferon-γ responses to anti-CD3 stimulation were inversely proportional to frequencies of CD4 T cells expressing intracellular CTLA-4 (r = -0·43, P = 0·01). Moreover, CTLA-4 blockade increased the induction of interferon-γ, tumour necrosis factor-α and interleukin-6 in PBMC stimulated with anti-CD3. Overall, chronic inflammation may expand sub-populations of T cells expressing CTLA-4 in COPD patients and therefore impair T-cell function. CTLA-4 blockade may restore Th1 function in patients with COPD and so aid the clearance of bacterial pathogens responsible for AECOPD.
10.1111/imm.12725
[Correlation among the levels of C-reactive protein and interleukin-18, quality of life, and lung function in patients with chronic obstructive pulmonary disease].
Long Haiyan,Luo Hong,Chen Ping,Li Yan
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
OBJECTIVE:To determine the correlation among the levels of C-reactive protein (CRP) and interleukin-18 (IL-18), quality of life, and pulmonary function in patients with chronic obstructive pulmonary disease (COPD),and to evaluate George's respiratory questionnaire (SGRQ). METHODS:From October 2008 to March 2009, 39 patients with an acute exacerbation COPD (the AECOPD group), 21 patients with stable COPD (the COPD group), and 22 normal people (the control group) were enrolled in our study. The serum CRP level was measured with Beckman Coulter Immage and the IL-18 level was measured by ELISA. All subjects completed the SGRQ assessment and all patients with COPD accepted pulmonary function test. RESULTS:The serum levels of CRP and IL-18, and SGRQ scores in the AECOPD group were significant1y higher than those in the COPD group and the control group (P<0.01). The serum levels of CRP and IL-18 and SGRQ scores in the COPD group were significant1y higher than those in the control group (P<0.01). The serum levels of CRP and IL-18 in the AECOPD group and the COPD group were negatively correlated with FEV1% and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC). SGRQ scores in the AECOPD group and the COPD group were negatively correlated with FEV1% and FEV1/FVC. The serum levels of CRP, IL-18 in the AECOPD group and the COPD group were positively correlated with SGRQ scores. CONCLUSION:CRP and IL-18 are involved in the process of inflammatory reaction of COPD, which could be markers of the acute exacerbation period of COPD. The serum levels of CRP and IL-18 might be related to the lung dysfunction and the lower quality of life in the patients with COPD. SGRQ is an effective, susceptible, and feasible method to evaluate the quality of life in patients with COPD.
10.3969/j.issn.1672-7347.2011.11.010
Reduced rhinovirus-specific antibodies are associated with acute exacerbations of chronic obstructive pulmonary disease requiring hospitalisation.
Yerkovich Stephanie T,Hales Belinda J,Carroll Melanie L,Burel Julie G,Towers Michelle A,Smith Daniel J,Thomas Wayne R,Upham John W
BMC pulmonary medicine
BACKGROUND:Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are often linked to respiratory infections. However, it is unknown if COPD patients who experience frequent exacerbations have impaired humoral immunity. The aim of this study was to determine if antibodies specific for common respiratory pathogens are associated with AECOPD. METHODS:Plasma was obtained from COPD patients when clinically stable. AECOPD requiring hospitalisation were recorded. IgG1 antibodies to H. Influenzae outer membrane protein 6 (P6), pneumococcal surface protein C (PspC) and the VP1 viral capsid protein of rhinovirus were measured. RESULTS:COPD patients who had an AECOPD (n = 32) had significantly lower anti-VP1 IgG1 antibody levels when stable compared to COPD patients who did not have an AECOPD (n = 28, p = 0.024). Furthermore, the number of hospitalisations was inversely proportional to anti-VP1 antibody levels (r = -0.331, p = 0.011). In contrast, antibodies specific for P6 and PspC were present at similar concentrations between groups. Plasma IL-21, a cytokine important for B-cell development and antibody synthesis, was also lower in COPD patients who had an AECOPD, than in stable COPD patients (p = 0.046). CONCLUSION:Deficient humoral immunity specific for rhinoviruses is associated with AECOPD requiring hospitalisation, and may partly explain why some COPD patients have an increased exacerbation risk following respiratory viral infections.
10.1186/1471-2466-12-37
Levels of leptin and IL-6 in lungs and blood are associated with the severity of chronic obstructive pulmonary disease in patients and rat models.
Liang Rui,Zhang Wei,Song Ya-Mei
Molecular medicine reports
The aim of the present study was to compare leptin and interleukin (IL)-6 expression in patients and rat models with chronic obstructive pulmonary disease (COPD). Leptin and IL-6 levels were determined in patients with an acute exacerbation of COPD (AECOPD), stable COPD and in healthy controls. Rat models of COPD were developed, histological and immunohistochemical analyses were performed and leptin and IL-6 levels were determined. Leptin and IL-6 levels in the serum and sputum were higher in patients with AECOPD compared with stable COPD and control patients. In rats, leptin and IL-6 were expressed in bronchial epithelial and inflammatory cells, while leptin expression was observed in alveolar cells and IL-6 expression in blood vessel cells only. Serum levels of leptin and IL-6 were significantly higher in COPD1 and COPD2 rats compared with the control rats, and were even higher in COPD1 rats than COPD2 rats. In conclusion, leptin and IL-6 levels were demonstrated to be associated with the severity of COPD.
10.3892/mmr.2013.1377
Mechanisms by Which the MBD2/miR-301a-5p/CXCL12/CXCR4 Pathway Regulates Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
International journal of chronic obstructive pulmonary disease
Background:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction, and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray assay identified microRNA (miR)-301a-5p as being associated with progression of acute exacerbation of COPD (AE-COPD); however, the mechanism underlying COPD pathogenesis remains unknown. Methods:Samples of serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and patients with stable COPD (R-COPD) or with an acute exacerbation of COPD (AE-COPD). Human HULEC-5a and human bronchial epithelial (HBE) cells were transfected with methyl-CpG-binding domain protein 2 (MBD2), sh-MBD2, miR-301a-5p mimics or an inhibitor, and then stimulated with cigarette smoke extract (CSE). Conditioned medium co-culture assays were performed by adding the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into wells containing si-c-x-c motif chemokine receptor 4 (CXCR4)-transfected-lung fibroblasts or human leukemic THP-1 cell line macrophages. Transwell assays were performed to analyze cell migration. Results:Our analysis of clinical samples showed that decreased miR-301a-5p levels in patients with AE-COPD were positively correlated with levels of MBD2 expression, but negatively correlated with levels of chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) expression. MBD2 overexpression significantly promoted miR-301a-5p production, but suppressed CXCL12 production in HULEC-5a and HBE cells. CXCL12 was confirmed to be a direct target of miR-301a-5p. CXCR4 knockdown significantly enhanced the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of the miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of phospho-mitogen-activated protein kinase (p-MEK) and phospho-protein kinase B (p-AKT). Conclusion:In summary, the MBD2/miR-301a-5p/CXCL12/CXCR4 pathway was shown to affect the migration of lung fibroblasts and monocyte-derived macrophages, which may play an important role during COPD exacerbations.
10.2147/COPD.S261522
[The role of 4-hydroxynonenal in assessment of chronic obstructive pulmonary disease severity].
Liu Hu,Xu Jian-ying
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
OBJECTIVE:To measure the levels of 4-hydroxynonenal (4-HNE), TNF-α and IL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and stable COPD, and therefore to explore the role of 4-HNE in the assessment of COPD severity. METHODS:A total of 242 patients with AECOPD, 182 males and 60 females, age 54 - 89 (mean 72 ± 8) years, 57 outpatients with stable COPD, 55 males and 2 females, age 38 - 76 (mean 60 ± 8) years, and 67 healthy controls, 49 males and 18 females, age 42 - 86 (mean 66 ± 10) years, were included in the study. Based on whether there were respiratory failure, chronic pulmonary heart disease or a history of smoking, the patients with AECOPD were divided into different subgroups. Patients with stable COPD were divided into different subgroups based on lung function or whether there was a history of smoking. The serum 4-HNE, TNF-α and IL-6 concentrations were measured by using enzyme-linked immune sorbent assay (ELISA). RESULTS:The serum 4-HNE levels in patients with AECOPD or stable COPD (16 ± 4) mg/L, (15 ± 5) mg/L were higher than those in healthy controls (12 ± 4) mg/L (both P < 0.01). After control for age, the serum 4-HNE levels in patients with AECOPD were significantly higher than those in stable COPD (F = 7.93, P < 0.01). There were no differences in the serum 4-HNE among AECOPD patients of current smokers, non-smokers and ex-smokers (16 ± 4) mg/L, (17 ± 3) mg/L, (17 ± 4) mg/L. The serum 4-HNE in AECOPD patients with chronic pulmonary heart disease were particularly higher (17 ± 4) mg/L vs (15 ± 4) mg/L (F = 1.23, P < 0.01). There were no differences in the serum 4-HNE between stable COPD patients of current smokers and ex-smokers (14 ± 5) mg/L, (16 ± 4) mg/L (t = -1.44, P > 0.05). In patients with stable COPD, the serum 4-HNE levels were significantly correlated with FEV(1)% (r = -0.345, P < 0.01) and IL-6 (r = 0.363, P < 0.01). CONCLUSIONS:The serum levels of 4-HNE in COPD patients with different smoking status were all significantly elevated, particular in patients with acute exacerbation and with pulmonary heart disease. In patients with stable COPD, the 4-HNE levels were negatively correlated with FEV(1)% and positively with serum IL-6 levels. It may be a valuable biomarkers for the assessment of COPD severity.
Comparison of CRP, Procalcitonin, Neutrophil Counts, Eosinophil Counts, sTREM-1, and OPN between Pneumonic and Nonpneumonic Exacerbations in COPD Patients.
Canadian respiratory journal
Introduction:The patients with community-acquired pneumonia (CAP) and acute exacerbations of COPD (AECOPD) could have a higher risk of acute and severe respiratory illness than those without CAP in AECOPD. Consequently, early identification of pneumonia in AECOPD is quite important. Methods. 52 subjects with AECOPD + CAP and 93 subjects with AECOPD from two clinical centers were enrolled in this prospective observational study. The values of osteopontin (OPN), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), C-reactive protein (CRP), procalcitonin (PCT), eosinophil (EOS) counts, and neutrophil (Neu) counts in blood on the first day of admission and clinical symptoms were compared in AECOPD and AECOPD + CAP. In addition, subgroup analyses of biomarker difference were conducted based on the current use of inhaled glucocorticoids (ICS) or systemic corticosteroids (SCS). Results:Patients with AECOPD + CAP had increased sputum volume, sputum purulence, diabetes mellitus, and longer hospital stays than AECOPD patients ( < 0.05). A clinical logistic regression model showed among the common clinical symptoms, purulent sputum can independently predict pneumonia in AECOPD patients after adjusting for a history of diabetes. At day 1, AECOPD + CAP patients had higher values of Neu, CRP, PCT, and OPN, while serum sTREM-1 levels and EOS counts were similar in the two groups. CRP fared best at predicting AECOPD with CAP ( < 0.05 for the test of difference), while OPN had similar accuracy with Neu, PCT, and purulent sputum ( > 0.05 for the test of difference). Multivariate analysis, including clinical symptoms and biomarkers, suggested that CRP ≥15.8 mg/dL at day 1 was a only promising predictor of pneumonia in AECOPD. CRP and OPN were not affected by ICS or SCS. Conclusions:CRP ≥15.8 mg/dL is an ideal promising predictor of pneumonia in AECOPD, and its plasma level is not affected by ICS or SCS. The diagnostic performance of CRP is not significantly improved when combined with clinical symptoms or other markers (OPN, PCT, and Neu).
10.1155/2022/7609083
[Platelet factor 4 and β-thromboglobulin in blood plasma of patients with acute exacerbation of chronic obstructive pulmonary disease].
Wu Jing-feng,Yang Yuan-hua,Pang Bao-sen
Zhonghua yi xue za zhi
OBJECTIVE:To explore the role of platelet factor 4 (PF4) and β-thromboglobulin (β-TG) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS:A total of 71 AECOPD patients and 50 chronic obstructive pulmonary disease (COPD) patients within a stable stage were admitted into Beijing Chaoyang Hospital from January 2008 to June 2010. And another 40 healthy volunteers were selected as control group. The data of demographics, arterial blood gas analysis and pulmonary function parameters was collected and analyzed. The plasma levels of PF4 and β-TG were measured by enzyme-linked immunosorbent assay (ELISA). Platelet count was measured by hematology analyzer. Statistical analysis was used for PF4, β-TG and platelet count. Spearman rank correlation was used for correlation analysis. RESULTS:No differences in age and gender existed among the AECOPD, stable and control groups. The plasma level of PF4 in the AECOPD group (2.28 µg/L) was significantly higher than that of the stable group (2.01 µg/L) and control group (1.57 µg/L) (both P < 0.05). The level of β-TG in AECOPD was 2.32 µg/L and it was significantly higher than that of the stable group (1.85 µg/L) and control group (1.29 µg/L) (both P < 0.05). The differences in platelet counts were insignificant between the AEC OPD group ((196 ± 67) ×10(9)/L), stable group ((194 ± 50) ×10(9)/L) and control group ((190 ± 48) ×10(9)/L). AECOPD group was divided into moderate, severe and very severe groups by pulmonary function parameters. The levels of PF4 and β-TG in very severe group were significantly higher than those in moderate and severe groups (P < 0.05). A significant positive correlation was observed between PF4 and β-TG (r = 0.518, P < 0.01). The levels of PF4 and β-TG were negatively correlated with FEV1%, FEV1/FVC and PaO2 (all P < 0.05). CONCLUSION:Abnormal platelet activation exists in AECOPD. And the levels of PF4 and β-TG may reflect the severity of AECOPD and can be used as the markers of estimating prethrombotic state.
Elevated levels of circulating exosome in COPD patients are associated with systemic inflammation.
Tan Dino B A,Armitage Jesse,Teo Teck-Hui,Ong Nathanael E,Shin Heewoong,Moodley Yuben P
Respiratory medicine
Chronic obstructive pulmonary disease (COPD) is characterized by progressive pulmonary and systemic inflammation. Acute exacerbations of COPD (AECOPD) are associated with acute inflammation and infections and increase the rates of morbidity and mortality. Currently, neither the aetiology nor pathogenesis of AECOPD are entirely understood. Exosomes have been reported to regulate immunity and inflammation via specific intercellular communications through an array of macromolecules (e.g. microRNA and proteins) contained within these microvesicles. We evaluated the level of circulating exosomes in relation to systemic inflammation in patients with AECOPD (n = 20) or stable COPD (sCOPD; n = 20) in comparison to non-smoking healthy controls (n = 20). Exosomes in plasma were isolated by precipitation-based method, and quantified using a CD9 expression based enzyme-linked immunosorbent assay (ELISA). Plasma biomarkers of systemic inflammation, C-reactive protein (CRP), soluble tumour necrosis factor receptor-1 (sTNFR1) and interleukin (IL)-6 were also quantified using ELISA. Levels of plasma exosome were higher in AECOPD patients (p < 0.001) and sCOPD patients (p < 0.05) compared to controls. Plasma levels of CRP and sTNFR1 were highest in AECOPD, followed by sCOPD patients compared to healthy controls (p < 0.05). Plasma IL-6 was elevated in AECOPD (p < 0.05) and sCOPD patients (p < 0.01) compared to controls. The level of exosome correlated with the levels of CRP, sTNFR1 and IL-6 in plasma. Exosomes may therefore be involved in the inflammatory process of AECOPD. Further studies involving exosomal phenotyping and molecular characterization are required to fully understand their role in the pathophysiology of COPD.
10.1016/j.rmed.2017.04.014
ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway.
Jiang Min,Cai Ren,Wang Jing,Li Zheng,Xu Dan,Jing Jing,Zhang Fengbo,Li Fengsen,Ding Jianbing
Frontiers in immunology
This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP . The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased , and mRNA levels. results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD activated Notch-GATA3 signal pathway.
10.3389/fimmu.2021.685400
Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood.
Freeman Christine M,Martinez Carlos H,Todt Jill C,Martinez Fernando J,Han MeiLan K,Thompson Deborah L,McCloskey Lisa,Curtis Jeffrey L
Respiratory research
BACKGROUND:Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. METHODS:We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants. RESULTS:Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased. CONCLUSIONS:The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute. TRIAL REGISTRATION:NCT00281216 , ClinicalTrials.gov.
10.1186/s12931-015-0251-1
Role of TNF-α, sTNF-R55 and sTNF-R75 in inflammation of acute exacerbations of chronic obstructive pulmonary disease.
Zeng Mian,Wen Ying,Liu Ling-yun,Wang Hui,Guan Kai-pan,Huang Xiaomei
Respiration; international review of thoracic diseases
BACKGROUND:Although some recent studies have demonstrated the important role of tumor necrosis factor-α (TNF-α) and soluble TNF receptors (sTNF-R) in inflammation of chronic obstructive pulmonary disease, the exact roles of TNF-α and sTNF-R as well as their interaction remained unclear. OBJECTIVES:To study changes in levels of systemic and airway local TNF-α and sTNF-R (sTNF-R55, sTNF-R75) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and clarify the relationship between these mediators and airflow limitation in AECOPD patients. METHODS:TNF-α, sTNF-R55 and sTNF-R75 levels in induced sputum and plasma as well as lung functions were examined in 48 AECOPD patients before and after treatment. Samples from 28 healthy volunteers served as controls. RESULTS:Compared to healthycontrols, both pre- and posttreatment levels of TNF-α, sTNF-R55 and sTNF-R75 in induced sputum and plasma of COPD patients were higher. In patients with AECOPD, posttreatment TNF-α levels significantly decreased compared to pretreatment levels (0.6 ± 0.46 vs. 0.82 ± 0.35 µg/l in plasma, p < 0.01; 0.48 ± 0.27 vs. 0.82 ± 0.34 µg/l in sputum, p < 0.001). While posttreatment sTNF-R55 and sTNF-R75 levels increased in both kinds of samples, mediator levels in plasma and lung functions were unrelated (p > 0.05). sTNF-R55 and sTNF-R75 levels in induced sputum were positively correlated with lung functions (p < 0.05), while TNF-α levels were negatively correlated with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to FEV1 predicted value. CONCLUSIONS:Inflammatory and anti-inflammatory mediators were imbalanced in the airways of AECOPD patients. It was local inflammation but not systemic inflammation that was closely related to airflow limitation.
10.1159/000210263
Delayed resolution of inflammatory response compared with clinical recovery in patients with acute exacerbations of chronic obstructive pulmonary disease.
Mohan Anant,Prasad Dharmendra,Sharma Alpana,Arora Sneh,Guleria Randeep,Sharma Surendra K,Pandey Ravinder M
Respirology (Carlton, Vic.)
BACKGROUND AND OBJECTIVE:The temporal profile of inflammatory markers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and their relationship to clinical response are not well characterized. The aim was to assess the changes in levels of inflammatory markers in AECOPD and correlate these with clinical and laboratory indices of recovery. METHODS:Serum levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen were measured in patients with AECOPD within 24 h of hospitalization and pre-discharge (stable state). RESULTS:Ninety-seven patients were evaluated (79 males; mean (SD) age, 61.4 (10.3) years). Eighty eight (90.7%) were current or former smokers, with a median consumption of 15 (0-75) packs/year. The median duration of COPD was 8 (2-25) years. Forty-six patients (56.9%) required mechanical ventilation for a median of 5 days (1-34) while in hospital. The median duration of hospital stay was 13 days (1-77). At reassessment before planned discharge, the levels of dyspnoea, leucocyte counts, erythrocyte sedimentation rate, creatinine, partial pressure of oxygen, and albumin normalized. The levels of CRP, IL-6 and fibrinogen reduced significantly but did not reach the normal range. Changes in IL-6 and fibrinogen levels correlated significantly with the acute physiologic assessment and chronic health evaluation II score, smoking history, blood pressure and leucocyte counts. Baseline IL-6 and fibrinogen levels significantly predicted a prolonged duration of mechanical ventilation. CONCLUSIONS:During AECOPD, the inflammatory response lags behind clinical and biochemical improvement. Fibrinogen and IL-6 are potentially useful markers for monitoring clinical response following an acute episode.
10.1111/j.1440-1843.2012.02216.x
Sputum Cytokine Profiling in COPD: Comparison Between Stable Disease and Exacerbation.
International journal of chronic obstructive pulmonary disease
Purpose:Cytokines are extracellular signaling proteins that have been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we investigated cytokine expression both at the mRNA and protein level in the sputum of healthy individuals, stable COPD patients, and those experiencing a severe acute exacerbation (AECOPD) requiring hospitalization. Patients and Methods:Sputum was collected in 19 healthy controls, 25 clinically stable COPD patients, and 31 patients with AECOPD. In AECOPD patients sample collection was performed both at the time of hospital admission and at discharge following treatment. Sputum supernatant was analyzed by an antibody microarray detecting 120 cytokines simultaneously, while the mRNA expression of 14 selected cytokines in sputum cells was investigated by real-time PCR (qPCR). Results:Proteomic analysis identified interleukin (IL)-6 and growth-regulated oncogene (GRO)α as the only sputum cytokines that were differentially expressed between stable COPD patients and healthy controls. At the onset of AECOPD, several cytokines exhibited altered sputum expression compared to stable COPD. Recovery from AECOPD induced significant changes in the sputum cytokine protein profile; however, the length of hospitalization was insufficient for most cytokines to return to stable levels. With regard to gene expression analysis by qPCR, we found that bone morphogenetic protein (BMP)-4 was up-regulated, while IL-1α, monokine-induced by interferon-γ (MIG), and BMP-6 were down-regulated at the mRNA level in patients with AECOPD compared to stable disease. Conclusion:The sputum cytokine signature of AECOPD differs from that of stable COPD. Protein level changes are asynchronous with changes in gene expression at the mRNA level in AECOPD. The observation that the levels of most cytokines do not stabilize with acute treatment of AECOPD suggests a prolonged effect of exacerbation on the status of COPD patients.
10.2147/COPD.S364982
Reactive oxygen species in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbation of chronic obstructive pulmonary disease.
Vaitkus Mindaugas,Lavinskiene Simona,Barkauskiene Diana,Bieksiene Kristina,Jeroch Jolanta,Sakalauskas Raimundas
Inflammation
Chronic airway inflammation can be mediated by an enhanced neutrophil oxidative burst. However, the role of bacteria in the pathogenesis of chronic obstructive pulmonary disease (COPD) exacerbations is highly controversial. The aim of this study was to evaluate the production of reactive oxygen species (ROS) in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbations of COPD (AECOPD). A total of 40 patients with AECOPD, 10 healthy nonsmokers, and 10 "healthy" smokers were enrolled into the study. Peripheral blood and sputum samples were obtained during exacerbation and after recovery. Neutrophils were isolated by high-density gradient centrifugation and magnetic separation. ROS production by neutrophils was investigated after stimulation with phorbol-myristate-acetate and Staphylococcus aureus bacteria. ROS production by neutrophils was assessed as the mean fluorescent intensity using a flow cytometer. IL-8 levels in serum and induced sputum were determinant by ELISA. Spontaneous ROS production was significantly higher in neutrophils from the patients with bacterial AECOPD as compared with nonbacterial AECOPD and stable COPD (P <0.05). ROS production stimulated with PMA and with Staphylococcus aureus was significantly higher in neutrophils isolated from the patients with bacterial AECOPD as compared with nonbacterial and stable COPD (P <0.05). The serum and induced sputum IL-8 levels were significantly increased in the patients with bacterial AECOPD than nonbacterial AECOPD, stable COPS, and "healthy" smokers and nonsmokers (P <0.05) and higher in the induced sputum as the compared with serum in all studied groups (P <0.05). Enlarge CRP level was documented during AECOPD than in all other groups (P <0.05). A markedly increased ROS production in sputum neutrophils during bacterial AECOPD shows an inflammatory response reflecting enhanced local inflammation, which can be mediated by bacterial colonization.
10.1007/s10753-013-9690-3
The Expression of IL-6, TNF-, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
Journal of immunology research
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-, and MCP-1 were elevated in VP and coinfection subjects ( < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls ( > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.
10.1155/2017/8539294
Comparative analysis of MCP-1 and TF in elderly patients with acute exacerbations of COPD and its clinical significance.
Wang Y,Zheng Y,Zhai Y-L,Liu F-Q,Ding N
European review for medical and pharmacological sciences
OBJECTIVE:This study was conducted to investigate the variation of monocyte chemoattrant protein-1 (MCP-1) and tissue factor (TF) in elderly patients with acutely exacerbated chronic obstructive pulmonary disease (AECOPD) and their clinical significance. PATIENTS AND METHODS:Serum specimens were obtained from 49 AECOPD. Patients and 30 health controls, with mean age of 76.1 ± 10.2 and 62.8 ± 6.5 years. Patients in AECOPD group were further grouped into two subgroups, with high or normal procaletonin (PCT) levels. Plasma TE, MCP-1 and PCT were qualified by enzyme-linked immunosorbent assay (ELISA). RESULTS:TF and MCP-1 were found to be higher in AECOPD patients than in health people (p < 0.01), and TF was linearly and positively related to MCP-1. In the subgroups TF was significantly higher in patients with higher PCT than those with normal PCT (p < 0.05). CONCLUSIONS:In AECOPD patients blood cells are activated to hypercoagulation state, particularly when their PCT level is high. Extrinsic pathway activated by TE plays important role in development of the hypercoagulation state. Our results indicate that plasma TF level was positively correlated to the level of MCP-1. This suggests that monitoring of plasma TF and MCP-1 levels in AECOPD patients could be a very useful way to prevent and cure blood hypercoagulability, cardiovascular and cerebrovascular thrombotic diseases.
Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Lung
BACKGROUND:As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS:This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS:Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION:Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.
10.1007/s00408-024-00702-5
The role of Th1/Th2 cytokines played in regulation of specific CD4 Th1 cell conversion and activation during inflammatory reaction of chronic obstructive pulmonary disease.
Sun J,Liu T,Yan Y,Huo K,Zhang W,Liu H,Shi Z
Scandinavian journal of immunology
CD4 Th1-CXCR3 signalling pathway may play a key role in chronic obstructive pulmonary disease (COPD). The aim of this study was to explore Th1/Th2 cytokines ratio differences in patients in different stages of COPD and to confirm the hypothesis that elastin exposure might serve as an antigen to initiate the stimulation of CD4 Th1-CXCR3 immune inflammation pathway. Patients of COPD in different stages and normal individuals were enrolled. Ten millilitres of peripheral blood was drawn from patients. The concentration of CXCR3, IFN-γ, IL-2, IL-4 and IL-13 in plasma was detected by ELISA. The Naïve CD4 T cells were isolated from the peripheral blood mononuclear cells, which were stimulated by elastin and collagen before determining the level of IFN-γ secretion by ELISPOT. Compared with control group, the concentration of CXCR3 in the acute exacerbation COPD (AECOPD) group was higher (P < .05). The concentration of IFN-γ and IL-2 in AECOPD group was lower than that in remission (P < .05). The concentration of IFN-γ in the AECOPD and remission was higher than that in controls (P < .05), while IL-2 was opposite (P < .01). The concentration of IL-4 and IL-13 in AECOPD group was higher than that in the controls (P < .05). The CD4 Th1 cells stimulated by the elastin as antigen secreted more IFN-γ than that by collagen (P < .01). CXCR3 was highly expressed in patients with COPD. There were different Th1/Th2 cytokines in different stages of COPD. The CD4+Th1-specific conversion and activation may be an initiator of COPD immune inflammatory response.
10.1111/sji.12674
Sputum inflammatory cell-based classification of patients with acute exacerbation of chronic obstructive pulmonary disease.
Gao Peng,Zhang Jie,He Xiaoyan,Hao Yuqiu,Wang Ke,Gibson Peter G
PloS one
BACKGROUND:Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from acute exacerbations (AECOPD) and display varying disease severity. However, there is no available biomarker for the classification of AECOPD. This study is aimed at investigating the sputum cellular profiles to classify patients with AECOPD. METHODS:A total of 83 patients with AECOPD and 26 healthy controls were recruited. Their demographic and clinical characteristics were recorded, and their lung function was examined. The phenotypes of sputum inflammatory cells were characterised, and the concentrations of sputum and serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) were measured. Based on the sputum inflammatory cell profiles, individual patients were categorized into one of the four subgroups with inflammatory eosinophilic, neutrophilic, paucigranulocytic, and mixed granulocytic AECOPD. Most AECOPD patients were reevaluated within 12-14 months after discharge. RESULTS:There were 10 (12%) eosinophilic, 36 (43%) neutrophilic, 5 (6%) mixed granulocytic, and 32 (39%) paucigranulocytic AECOPD patients. The patients with mixed granulocytic or neutrophilic AECOPD had a higher BODE score, more sputum inflammatory cells, lower lung function, and longer hospital stay, accompanied by higher concentrations of sputum MMP-9, IL-6 and CRP, and serum SAA, IL-6 and CRP. Notably, 83% of patients with neutrophilic AECOPD displayed evidence of bacterial infection and many of them responded poorly to standard therapies. In addition, patients with mixed granulocytic or neutrophilic stable COPD remained at lower lung functions and higher levels of inflammation. CONCLUSION:Patients with AECOPD display heterogeneous inflammation, and the profiles of sputum inflammatory cells may be used as valuable biomarkers for the classification of AECOPD patients.
10.1371/journal.pone.0057678
Inference of Cellular Immune Environments in Sputum and Peripheral Blood Associated with Acute Exacerbations of COPD.
Cellular and molecular bioengineering
INTRODUCTION:Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, with high associated costs. Most of the cost burden results from acute exacerbations of COPD (AE-COPD), events associated with heightened symptoms and mortality. Cellular mechanisms underlying AE-COPD are poorly understood, likely because they arise from dysregulation of complex immune networks across multiple tissue compartments. METHODS:To gain systems-level insight into cellular environments relevant to exacerbation, we applied data-driven modeling approaches to measurements of immune factors (cytokines and flow cytometry) measured previously in two different human tissue environments (sputum and peripheral blood) during the stable and exacerbated state. RESULTS:Using partial least squares discriminant analysis, we identified a unique signature of cytokines in serum that differentiated stable and AE-COPD better than individual measurements. Furthermore, we found that models integrating data across tissue compartments (serum and sputum) trended towards being more accurate. The resulting paracrine signature defining AE-COPD events combined elevations of proteins associated with cell adhesion (sVCAM-1, sICAM-1) and increased levels of neutrophils and dendritic cells in blood with elevated chemoattractants (IP-10 and MCP-2) in sputum. CONCLUSIONS:Our results supported a new hypothesis that AE-COPD is driven by immune cell trafficking into the lung, which requires expression of cell adhesion molecules and raised levels of innate immune cells in blood, with parallel upregulated expression of specific chemokines in pulmonary tissue. Overall, this work serves as a proof-of-concept for using data-driven modeling approaches to generate new insights into cellular processes involved in complex pulmonary diseases.
10.1007/s12195-019-00567-2
Circulating JNK pathway-associated phosphatase: A novel biomarker correlates with Th17 cells, acute exacerbation risk, and severity in chronic obstructive pulmonary disease patients.
Gao Wei,Gao Lianjun,Yang Feng,Li Zongjun
Journal of clinical laboratory analysis
BACKGROUND:JNK pathway-associated phosphatase (JKAP) involves in the regulation of inflammation, immunity, and lung injury. The current study aimed to investigate correlation of JKAP with Th1, Th17 cells, acute exacerbation risk, and disease severity in chronic obstructive pulmonary disease (COPD) patients. METHODS:Totally, 45 stable COPD (SCOPD) patients, 45 acute exacerbation COPD (AECOPD) patients, and 45 controls were enrolled. Serum was collected for JKAP, interferon-gamma (IFN-γ) (Th1 cytokine), and interleukin 17 (IL-17) (Th17 cytokine) detection. Besides, peripheral blood mononuclear cell from COPD patients was collected for evaluating Th1 and Th17 cells. RESULTS:JKAP was highest in controls followed by SCOPD patients and lowest in AECOPD patients (median: 105.673 vs. 75.374 vs. 41.807 pg/ml, p < 0.001). Meanwhile, receiver operating characteristic (ROC) curves revealed that JKAP differentiated the AECOPD patients from the controls (area under curve (AUC): 0.910 (95% confidence interval (CI): 0.849-0.970)) and AECOPD patients from SCOPD patients (AUC: 0.726 (95% CI: 0.622-0.830)). Moreover, JKAP positively correlated with FEV (%predicted) in AECOPD patients (r = 0.347 p = 0.019). Additionally, JKAP was negatively correlated with the GOLD stage in AECOPD patients (r = -0.344, p = 0.021) and SCOPD patients (r = -0.357, p = 0.016). Whereas, JKAP was not associated with other clinical features (all p > 0.05). Besides, JKAP was negatively linked with Th17 cells (r = -0.378, p = 0.010), IFN-γ (r = -0.358, p = 0.016), IL-17 (r = -0.414, p = 0.005) in AECOPD patients and Th17 cells (r = -0.342, p = 0.022), IL-17 (r = -0.299, p = 0.046) in SCOPD patients. CONCLUSION:Downregulated JKAP correlates with Th17 cells, higher acute exacerbation risk, and severity in COPD patients, indicating its underlying potency as a biomarker for COPD.
10.1002/jcla.24153
Inflammatory response in acute viral exacerbations of COPD.
Rohde G,Borg I,Wiethege A,Kauth M,Jerzinowski S,An Duong Dinh T,Bauer T T,Bufe A,Schultze-Werninghaus G
Infection
BACKGROUND:Respiratory viruses are important triggers of acute exacerbations of COPD (AE-COPD). However, the inflammatory response in virus-positive exacerbations is still not fully understood. METHODS:We investigated CRP, IL-6, IL-8, IL-10, IFN-gamma, blood and sputum cells in patients with acute exacerbation (n = 36) and in stable disease (n = 20) and correlated these parameters to virus detection in respiratory secretions. RESULTS:Similar to other studies we found a significant increase in systemic CRP and absolute numbers of blood leukocytes in AE-COPD patients. Sputum IL-6 levels and sputum eosinophils tended to be higher during exacerbation. In patients with detection of respiratory viruses in nasal lavage, local IL-6 production in sputum was significantly increased; FEV(1) was significantly decreased and both parameters were inversely correlated to each other. CONCLUSION:This study supports previous findings of both, increased local and systemic inflammation in acute exacerbation of COPD. In virus-associated exacerbations, IL-6 is significantly increased and negatively correlated to FEV1 indicating a relation between virus-induced inflammation and airway obstruction. However, regarding our finding and previous data, it is becoming increasingly clear that the mediators investigated so far do not permit identifying the etiology of AE-COPD. Hence, further studies are needed to better define the inflammatory response in AE-COPD in general and in viral exacerbations in particular.
10.1007/s15010-008-7327-5
Correlation between TNF- -308 and +489 Gene Polymorphism and Acute Exacerbation of Chronic Obstructive Pulmonary Diseases.
Yu Suyun,Xue Min,Yan Zhijun,Song Bin,Hong Haiping,Gao Xiwen
BioMed research international
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is becoming a common respiratory disease, leading to increased morbidity and mortality worldwide. Tumor necrosis factor-alpha (TNF-) is a powerful proinflammatory cytokine involved in the pathogenesis of AECOPD. Therefore, we proposed a close correlation between the TNF- polymorphism [-308G/A (rs1800629), +489G/A (rs1800610)] and the disease progress of patients with AECOPD. Comparison of the TNF- genotypes between the 198 AECOPD diagnosed patients groups and 195 healthy peoples suggested their significant differences of the three genotypes (AA, GA, GG) distribution for TNF- -308 ( < 0.05), but no differences of that for TNF- +489. We found that patients with TNF- -308 GA/AA genotypes showed smaller adjacent arterial diameter, thicker bronchial wall, higher bronchial artery ratio, higher bronchial wall grading, and higher frequency of acute exacerbations than those with TNF- -308 GG genotype. Patients with TNF- +489 GA/AA genotypes showed the same AECOPD properties as patients with TNF- -308 except for the high frequency of acute exacerbations. Further experiment showed that the TNF- -308 and+489 gene polymorphisms could affect the expression level of TNF- in macrophages, suggesting the involvement of the macrophage population in disease regulation of AECOPD patients with TNF- -308G/A and+489G/A genotype heterogeneity. In conclusion, the TNF- -308 G/A genotype was related to AECOPD susceptibility and progress, while the TNF- +489G/A genotype was related to AECOPD progress, but not AECOPD susceptibility.
10.1155/2021/6661281
Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1β concentrations and acute exacerbation of chronic obstructive pulmonary disease.
Immunobiology
BACKGROUND:The relationship between C3a-C3aR, IL-1β, and the acute exacerbation of chronic obstructive pulmonary disease is still unclear. This study aims to explore the expression levels of C3aR in peripheral blood WBCs and the concentrations of C3a, C3aR, and IL-1β in plasma in healthy controls and patients with chronic obstructive pulmonary disease (COPD). METHODS:WBCs C3aR level in the peripheral blood, the concentrations of C3a, C3aR, and IL-1β in plasma were measured in 60 patients with acute exacerbation of COPD (AECOPD), 30 patients with stable COPD (SCOPD), and 30 healthy controls. The baseline characteristics and clinical data collected from enrolled patients, including age, gender, laboratory indicators, and lung function. We analyzed the correlation between C3a, C3aR, IL-1β, and lung function indicators (forced expiratory volume in the first second as a percentage of predicted value, FEV%pred) in the AECOPD group. RESULTS:The white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP) of patients in COPD were higher than in healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD were higher than in SCOPD and healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3aR, and IL-1β in AECOPD combined with respiratory failure were higher than in the non-respiratory failure group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD with high-risk were higher than in the low-risk group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD were negatively correlated with FEVpred%. The peripheral blood WBCs C3aR mRNA, the plasma C3a and C3aR in AECOPD were positively correlated with IL-1β. CONCLUSION:The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in COPD patients were significantly related to the risk of disease deterioration. The C3a-C3aR axis may be involved in airway inflammation in patients with COPD.
10.1016/j.imbio.2021.152164
High Blood Eosinophil and YKL-40 Levels, as Well as Low CXCL9 Levels, are Associated with Increased Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Peng Junnan,Yu Qian,Fan Shulei,Chen Xingru,Tang Rui,Wang Daoxin,Qi Di
International journal of chronic obstructive pulmonary disease
Background:Readmission after hospital discharge is common among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Predictive biomarkers of readmission would facilitate stratification strategies and individualized prognosis. Therefore, this study aimed to investigate the utility of type 2 biomarkers (eosinophils, periostin, and YKL-40) and a type 1 biomarker (CXCL9) in predicting readmission events in patients with AECOPD. Methods:This is a prospective observational study design. Blood levels of eosinophils, periostin, YKL-40, and CXCL9 were measured at admission. The clinical outcomes were 12-month COPD-related readmission, time to COPD-related readmission, and number of 12-month COPD-related readmissions. These outcomes were analyzed using logistic and Cox regression models and Spearman's rank test. Results:A total of 123 patients were included, of whom 51 had experienced at least one readmission for AECOPD. High levels of eosinophils (≥200 cells/μL or 2% of the total white blood cell count, adjusted odds ratio [aOR] =3.138, =0.009) and YKL-40 (≥14.5 ng/mL, aOR =2.840, =0.015), as well as low CXCL9 levels (≤30.1 ng/mL, aOR =2.551, =0.028), were associated with an increased COPD-related readmission. The highest relative readmission rate was observed in patients with both high eosinophil and YKL-40 levels. Moreover, high eosinophil and YKL-40 levels were associated with a shorter time to first COPD-related readmission and an increased number of 12-month COPD-related readmissions. Conclusion:High blood eosinophil and YKL-40 levels, as well as low CXCL9 levels, have predictive utility for the 12-month COPD-related readmission rate. Using eosinophils and YKL-40 together allows more precise identification of patients at high risk of COPD-related readmission.
10.2147/COPD.S294968
Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease.
Yin Tiping,Zhu Zhaoqin,Mei Zhoufang,Feng Jingjing,Zhang Wanju,He Yanchao,Shi Jindong,Qian Ling,Liu Yi,Huang Qihui,Hu Yunwen,Jie Zhijun
The clinical respiratory journal
OBJECTIVE:To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection. METHODS:This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty-one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus-positive (+) group and AECOPD virus-negative (-) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum. RESULTS:A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus- group. However, serum concentrations of interferon-inducible protein-10 (IP-10) and interferon-gamma (IFN-γ) in virus+ AECOPD patients were significantly higher than those in the virus- AECOPD, stable COPD and healthy control groups (P < .05). CONCLUSION:Viral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP-10 and IFN-γ levels might be value to indicate viral infection in AECOPD.
10.1111/crj.12656
Correlations of IL-1β and vitamin D with CAT score in patients with acute exacerbation of chronic obstructive pulmonary disease.
Cellular and molecular biology (Noisy-le-Grand, France)
This study was to analyze the correlations of IL-1β and vitamin D (VitD) with chronic obstructive pulmonary disease assessment test (CAT) score in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). For this purpose, a total of 65 patients with chronic obstructive pulmonary disease (COPD) treated in our hospital between June 2020 and June 2022 were enrolled and assigned to a research group, and 40 healthy individuals who underwent physical examination in our hospital over the same time spanning were enrolled into the control group. The 65 COPD patients were further grouped into a stability group (30 cases) and an exacerbation group (35 cases). The two groups were compared in the levels of 25-hydroxyvitamin D (25(OH)D), interleukin-1β (IL-1β) and blood gas indexes (arterial carbon dioxide partial pressure (PaCO2) and arterial partial pressure of oxygen (PaO2). The modified Medical Research Council Dyspnea Scale (mMRC) and the CAT were adopted for evaluation of the stability group and exacerbation group. The correlations of IL-1β and 25(OH)D with mMRC and CAT scores were analyzed. The diagnostic value of IL-1β and VitD in patients in different stages was analyzed through receiver operating characteristic (ROC) curves. Results showed that the control group showed greatly lower IL-1β and PaCO2 levels and higher 25(OH)D and PaO2 levels than the research group (all P<0.05). The stability group got greatly lower mMRC and CAT scores than the exacerbation group (both P<0.05). IL-1β had positive correlations with mMRC and CAT scores, while 25(OH)D had negative correlations with them (P<0.05). According to ROC curve-based analysis, IL-1β and 25(OH)D had areas under the curves of 0.814 and 0.583, respectively, in diagnosing the acute exacerbation period, and had specificities of 56.67% and 43.33%, respectively and sensitivities of 97.14% and 74.29%, respectively. In conclusion, patients with COPD have increased IL-1 β and VitD deficiency, so VitD can be properly supplemented during treatment, and the levels of inflammatory factors should be paid close attention to at all times. IL-1 β and VitD can be regarded as novel ideas for the diagnosis and treatment of COPD, which may further improve the effect of COPD prevention and treatment.
10.14715/cmb/2023.69.15.4
Increased serum IL‑41 associated with acute exacerbation of chronic obstructive pulmonary disease.
Experimental and therapeutic medicine
Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD.
10.3892/etm.2024.12601
IL-17A and the Promotion of Neutrophilia in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Roos Abraham B,Sethi Sanjay,Nikota Jake,Wrona Catherine T,Dorrington Michael G,Sandén Caroline,Bauer Carla M T,Shen Pamela,Bowdish Dawn,Stevenson Christopher S,Erjefält Jonas S,Stampfli Martin R
American journal of respiratory and critical care medicine
RATIONALE:Nontypeable Haemophilus influenzae (NTHi) causes acute exacerbation of chronic obstructive pulmonary disease (AECOPD). IL-17A is central for neutrophilic inflammation and has been linked to COPD pathogenesis. OBJECTIVES:We investigated whether IL-17A is elevated in NTHi-associated AECOPD and required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. METHODS:Experimental studies with cigarette smoke and NTHi infection were pursued in gene-targeted mice and using antibody intervention. IL-17A was measured in sputum collected from patients with COPD at baseline, during, and after AECOPD. MEASUREMENTS AND MAIN RESULTS:Exacerbated airway neutrophilia in cigarette smoke-exposed mice infected with NTHi was associated with an induction of IL-17A. In agreement, elevated IL-17A was observed in sputum collected during NTHi-associated AECOPD, compared with samples collected before or after the event. NTHi-exacerbated neutrophilia and induction of neutrophil chemoattractants over the background of cigarette smoke, as observed in wild-type mice, was absent in Il17a(-/-) mice and in mice treated with a neutralizing anti-IL-17A antibody. Further studies revealed that IL-1 receptor (R)1 signaling was required for IL-17A-dependent neutrophilia. Moreover, deficiency or therapeutic neutralization of IL-17A did not increase bacterial burden or delay bacterial clearance. CONCLUSIONS:IL-17A is induced during NTHi-associated AECOPD. Functionally, IL-1R1-dependent IL-17A is required for NTHi-exacerbated pulmonary neutrophilia induced by cigarette smoke. Targeting IL-17A in AECOPD may thus be beneficial to reduce neutrophil recruitment to the airways.
10.1164/rccm.201409-1689OC
ILC2s Induce Adaptive Th2-Type Immunity in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Jiang Min,Liu Huifang,Li Zheng,Wang Jing,Zhang Fengbo,Cao Kaixiu,Li Fengsen,Ding Jianbing
Mediators of inflammation
To investigate the effect of ILC2s on Th2-type adaptive immunity during the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the study enrolled healthy people, stable COPD patients, and AECOPD patients. Flow cytometry was used to detect Th1, Th2, and ILC2 in the peripheral blood and CD80 and MHC II levels on ILC2. The mRNA levels of , , and of ILC2s were detected by RT-PCR. In addition, ILC2s from the peripheral blood of AECOPD patients were cocultured with CD4 T cells from the peripheral blood of healthy controls. Cytokine levels in serum of the three groups and the in vitro coculture supernatants were measured by ELISA. Compared with the stable COPD group or the healthy control group, Th2 in the peripheral blood of AECOPD group increased dramatically, inducing an increase of Th2/Th1 ratio in AECOPD patients. Meanwhile, the level of IL-4 in the serum of this group was also increased. However, we also detected ILC2s in the peripheral blood of the AECOPD group and found that it was also increased, alone with the increased , , and mRNA levels. We also found that the CD80 and MHC II on ILC2 were significantly upregulated and the proportion of MHC II ILC2 cells was significantly positively correlated with the proportion of Th2 cells in AECOPD patients. To further demonstrate the effect of ILC2 on Th2 cells, we cocultured ILC2 with CD4 T cells in vitro, which also showed a significant increase of Th2 ratio as well as Th2-associated cytokines IL-4, IL-5, and IL-13. However, we found that this effect of ILC2s on Th2 cells could be inhibited by the addition of anti-MHC II. The Th2/Th1 balance shifts to Th2 in AECOPD. ILC2s may function as APC by the upregulation of MHC II and regulate adaptive immunity shift to Th2-type response in AECOPD.
10.1155/2019/3140183
Circulating miR-146a/b correlates with inflammatory cytokines in COPD and could predict the risk of acute exacerbation COPD.
Medicine
The aim of this study was to investigate the predicting value of miR-146a/b for acute exacerbation chronic obstructive pulmonary disease (AECOPD) and COPD, and to explore their associations with inflammatory cytokines in AECOPD and stable COPD patients.One hundred six AECOPD, 122 stable COPD patients, and 110 health volunteers with age and sex matched to total COPD patients (AECOPD and stable COPD) were enrolled. Blood samples were collected from all participants. Relative expression of miR-146a/b was determined by real-time polymerase chain reaction. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), leukotriene B4 (LTB-4) expression in serum from AECOPD and stable COPD patients were assessed using commercial ELISA kit.Serum levels of miR-146a and miR-146b were down regulated in AECOPD patients compared with stable COPD patients and HCs. miR-146a and miR-146b are of good values for predicting the risk of AECOPD in HCs with AUC of 0.702 and 0.715. Additionally, miR-146a and miR-146b could distinguish AECOPD from stable COPD patients with AUC of 0.670 and 0.643. In AECOPD patients, levels of miR-146a in AECOPD patients were negatively associated with TNF-α, IL-6, IL-8, and LTE-4 expression. In stable COPD patients, miR-146a expressions were negatively correlated with TNF-α, IL-1β, IL-6, IL-8, and LTE-4 levels. And, the expressions of miR-146b in AECOPD patients were negatively associated with IL-1β and LTB-4 expression. While in stable COPD patients, miR-146b expressions were only negatively correlated with TNF-α level.In conclusion, miR-146a and miR-146b were negatively correlated with inflammatory cytokines, and could be promising biomarkers for predicting the risk of AECOPD in stable COPD patients and healthy individuals.
10.1097/MD.0000000000009820
NLRP3 Inflammasome Involves in the Acute Exacerbation of Patients with Chronic Obstructive Pulmonary Disease.
Wang Huaying,Lv Chun'er,Wang Shi,Ying Huajuan,Weng Yuesong,Yu Wanjun
Inflammation
The NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein complex, produces the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which may contribute to the development of airway inflammation in chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the correlation between circulating and local airway NLRP3 inflammasome activation with acute exacerbation of COPD (AECOPD). mRNA levels of NLRP3, Caspase (Casp)-1, apoptosis-associated speck-like protein containing CARD (ASC), IL-18, and IL-1β in peripheral blood mononuclear cells (PBMCs) and bronchial tissues were determined by real-time PCR in 32 smokers, 65 patients with AECOPD, 50 COPD patients in recovery stage, and 30 COPD patients in stable stage. The levels of IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) supernatants were measured by ELISA. The load of six common pathogens in BALF samples were determined by real-time PCR. The potential correlation between the mRNA levels of NLRP3, Casp-1, ASC, IL-18 or IL-1β and the load of pathogens was evaluated individually. Significantly higher mRNA levels of NLRP3, Casp-1, ASC, IL-18, IL-1β and higher levels of IL-18 and IL-1β were found in patients with AECOPD than in smokers. These NLRP3 inflammasome mediators were significantly decreased when COPD patients in the same group became clinical stable. The increased mRNA levels of NLRP3 inflammasomes in bronchial tissues were positively correlated with the load of the six common pathogens in the lower respiratory tract. We conclude that systemic and local airway NLRP3 inflammasome activation is associated with the acute exacerbation, which might be predictive factors of the acute exacerbation and clinical outcomes in COPD patients.
10.1007/s10753-018-0780-0
Serum inflammatory factor and cytokines in AECOPD.
Jia Tie-Gang,Zhao Jian-Qing,Liu Jian-Hua
Asian Pacific journal of tropical medicine
OBJECTIVE:To explore the serum levels of IL-32, MMP-9,PCT and CRP in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS:A total of 50 patients with AECOPD and 45 cases with acute asthma attack admitted from October 2013 to August 2014 were selected, and the serum levels of IL-32, MMP-9, PCT and CRP were determined and compaed by using Double antibody sandwich Enzyme linked immunosorbent assay, immunofluorescence double antibody sandwich assay and immunoturbidimetry assay. RESULTS:Serum levels of IL-32, MMP-9, PCT and CRP were significantly higher in AECOPD group than acute asthma attack group (P<0.05). IL-32 and MMP-9 were negatively correlated with lung function. MMP-9 in AECOPD patients was increased more significantly. CONCLUSIONS:Serum levels of IL-32 and MMP-9 were negatively correlated with lung function, and the worse the lung function is, the more significant the increase is.
10.1016/S1995-7645(14)60177-2
Clinical value of IL-13 and ECP in the serum and sputum of eosinophilic AECOPD patients.
Li Ting,Gao Li,Ma Hong-Xia,Wei Yang-Yang,Liu Yue-Hua,Qin Ke-Ru,Wang Wen-Tao,Wang Hai-Long,Pang Min
Experimental biology and medicine (Maywood, N.J.)
IMPACT STATEMENT:Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an inevitable trend in the development of the disease and eosinophils (EOS) participate in inflammation process. It is important to explore some relatively simple biomarkers in AECOPD which are useful to recognize the disease. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of IL-13 and ECP in the serum and sputum were measured. The levels of IL-13 and ECP in sputum in the eosinophilic group were higher than those in the noneosinophilic group. Moreover, the noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. IL-13 and ECP are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies.
10.1177/1535370220931765
Comparative Study of Cytokine Levels in Different Respiratory Samples in Mild-to-Moderate AECOPD Patients.
Lung
BACKGROUND:Matrix metalloproteinase-12 (MMP-12) and Tissue inhibitor of metalloproteinase-4 (TIMP-4) play important roles in the pathophysiology of chronic obstructive pulmonary disease (COPD). Subjects of many previous studies were patients with severe and very severe COPD. However, there are comparatively few studies on patients with mild-to-moderate COPD. Our aim was to measure MMP-12 and TIMP-4 levels and to compare its levels in various materials in patients with mild-to-moderate acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We also compared which of the two materials of these biomarkers was better correlated with disease severity and DODE index. METHODS:A total of 39 patients with AECOPD and 25 control subjects were enrolled in our study. MMP-12 and TIMP-4 in different respiratory samples were detected by ELISA. RESULTS:Expression levels of MMP-12 in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) and TIMP-4 in BALF were significantly higher in AECOPD patients than that in healthy subjects (P < 0.001). However, there was no significant difference in TIMP-4 level in EBC of AECOPD patients compared to healthy subjects (P = 0.0527). The levels of MMP-12 in BALF and EBC and TIMP-4 in BAFL of AECOPD patients were significantly correlated with FEV% predicted (P < 0.001). However, in AECOPD patients, there was no significant correlation between TIMP-4 levels in EBC and BODE index (r = 0.4175, P = 0.0559). CONCLUSION:During mild-to-moderate AECOPD, the levels of MMP-12 and TIMP-4 in BALF were better correlated with FEV% predicted and BODE index than that in EBC, indicating that they may be new target interventions for pharmacology to prevent and/or treat AECOPD.
10.1007/s00408-019-00263-y
Influenza a virus triggers acute exacerbation of chronic obstructive pulmonary disease by increasing proinflammatory cytokines secretion via NLRP3 inflammasome activation.
Journal of inflammation (London, England)
BACKGROUND:Influenza A virus (IAV) triggers acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but the molecular mechanisms remain unclear. In this study, we investigated the role of IAV induced NLRP3 inflammasome activation to increase airway inflammation response in the progression of AECOPD. METHODS:Human bronchial epithelial cells were isolated and cultured from normal and COPD bronchial tissues and co-cultured with IAV. The NLRP3 inflammasome associated genes were identified using RNA sequencing, and the expressions of NLRP3 inflammasome components were measured using qRT-PCR and western blot after cells were transfected with siRNA and treated with MCC950. Moreover, IAV-induced COPD rat models were established to confirm the results; 37 AECOPD patients were included to measure the serum and bronchoalveolar lavage fluid (BALF) of interleukin (IL)-18 and IL-1β. RESULTS:Increased levels of NLRP3 inflammasome components were not seen until 6 h post-inoculation in normal cells. However, both cell groups reached peak NLRP3 level at 12 h post-inoculation and maintained it for up to 24 h. ASC, Caspase-1, IL-1β and IL-18 were also elevated in a similar time-dependent pattern in both cell groups. The mRNA and protein expression of the NLRP3 inflammasome components were decreased when COPD cells treated with siRNA and MCC950. In COPD rats, the NLRP3 inflammasome components were elevated by IAV. MCC950 alleviated lung damage, improved survival time, and reduced NLRP3 inflammasome components expression in COPD rats. Additionally, the serum and BALF levels of IL-1β and IL-18 were increased in AECOPD patients. CONCLUSIONS:NLRP3 inflammasome is activated in COPD patients as a pre-existing condition that is further exacerbated by IAV infection.
10.1186/s12950-022-00305-y
Predictive Value of GDF-15 and sST2 for Pulmonary Hypertension in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
International journal of chronic obstructive pulmonary disease
Objective:To confirm whether growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) are indicators of pulmonary hypertension in acute exacerbation of chronic obstructive pulmonary disease (AECOPD-PH). Methods:All patients admitted to the hospital with AECOPD between July 2020 and October 2021 were enrolled. The patients were then categorized into AECOPD and AECOPD-PH groups according to PH probability, and the differences in GDF-15 and sST2 serum levels in the AECOPD and AECOPD-PH groups were compared. Correlation analysis was carried out to explore the association between GDF-15 and sST2 serum levels and the length of hospital stay of patients with AECOPD-PH. Receiver operating characteristic curve analysis was used to assess the clinical significance of GDF-15 and sST2 in predicting patients with AECOPD-PH. Results:Included in this study were 126 patients with AECOPD, including 69 with AECOPD and 57 with AECOPD-PH. The serum levels of GDF-15 and sST2 in the AECOPD-PH group were significantly higher than those in the AECOPD group ( < 0.05). There was no significant correlation between the length of hospital stay in AECOPD-PH patients and GDF-15 and sST2 serum levels ( > 0.05). The area under the curves of GDF-15, sST2, and GDF-15 + sST2 for predicting AECOPD-PH and AECOPD-PH patients with poor prognosis were >0.60 and 0.70, respectively. The optimal cutoff values of GDF-15 and sST2 for predicting AECOPD-PH were 1125.33 pg/mL and 80.68 ng/mL and 1309.72 pg/mL and 59.10 ng/mL for predicting AECOPD-PH patients with poor prognosis, respectively. Conclusion:GDF-15 and sST2 levels may be useful in the prediction of AECOPD-PH.
10.2147/COPD.S429334
Enhanced prothrombotic and proinflammatory activity of circulating extracellular vesicles in acute exacerbations of chronic obstructive pulmonary disease.
Respiratory medicine
BACKGROUND:Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are associated with a high rate of cardiovascular events. Thromboinflammation (the interplay between coagulation and inflammation) is probably involved in these events. Extracellular vesicles (EV) increase during AE-COPD, but their role in thromboinflammation in COPD is still unknown. We investigated EV-associated prothrombotic and proinflammatory activity in COPD. METHODS:Patients with AE-COPD, stable COPD (sCOPD) and age- and sex-matched subjects (controls) were enrolled. AE-COPD patients were evaluated at hospital admission and 8 weeks after discharge (recovery; longitudinal arm). In a cross-sectional arm, AE-COPD were compared with sCOPD and controls. EV-mediated prothrombotic activity was tested by measuring the concentration of EV-associated phosphatidylserine, as assessed by a prothrombinase assay, and tissue factor, as assessed by a modified one-stage clotting assay (EV-PS and EV-TF, respectively). Synthesis of interleukin-8 (IL-8) and C-C motif chemokine ligand-2 (CCL-2) by cells of the human bronchial epithelial cell line 16HBE incubated with patients' EV was used to measure EV-mediated proinflammatory activity. RESULTS:Twenty-five AE-COPD (median age [interquartile range] 74.0 [14.0] years), 31 sCOPD (75.0 [9.5] years) and 12 control (67.0 [3.5] years) subjects were enrolled. In the longitudinal arm, EV-PS, EV-TF, IL-8 and CCL-2 levels were all significantly higher at hospital admission than at recovery. Similarly, in the cross-sectional arm, EV-PS, EV-TF and cytokines synthesis were significantly higher in AE-COPD than in sCOPD and controls. CONCLUSIONS:EV exert prothrombotic and proinflammatory activities during AE-COPD and may therefore be effectors of thromboinflammation, thus contributing to the higher cardiovascular risk in AE-COPD.
10.1016/j.rmed.2024.107563
Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD.
Cytokine
BACKGROUND:The pathogenesis and treatment strategies for chronic obstructive pulmonary disease (COPD) require further exploration. Abnormal neutrophil inflammation and the overexpression of neutrophil extracellular traps (NETs) are closely associated with acute exacerbations of COPD (AECOPD). Siglec-9, a specific receptor expressed on neutrophils that inhibits their function, prompted us to investigate its relationship with NETs found in induced sputum and the severity of the disease. METHODS:We collected clinical data from patients with AECOPD and assessed the expression of Siglec-9 in peripheral blood neutrophils and the presence of NETs in induced sputum. We then observed the correlation between Siglec-9, the inflammatory response, and the severity of AECOPD. RESULTS:We observed an increase in the expression of Siglec-9 in the peripheral blood neutrophils of patients with AECOPD. Concurrently, these patients exhibited more severe clinical symptoms, higher systemic inflammation levels, and a reduced quality of life compared to those with induced sputum NET expression. Further subgroup analysis of AECOPD patients with high Siglec-9 expression revealed worsened quality of life and more severe inflammation, particularly in indicators such as the BODE index, CRP, peripheral blood neutrophil count, IL-6, IL-8, TNF-α expression, and others. Furthermore, we noted a significant increase in NET-specific expression in the sputum of patients with high Siglec-9 expression levels. In comparison to patients with low Siglec-9 expression, those with high expression experienced more systemic inflammatory reactions and a lower quality of life. Correlation analysis of the aforementioned indicators revealed that the expression ratio of Siglec-9 in the peripheral blood of patients correlated with lung function, quality of life, and NETs in the induced sputum of patients with AECOPD. CONCLUSION:The increased expression of Siglec-9 in peripheral blood neutrophils of AECOPD patients leads to elevated NET expression in induced sputum, exacerbating the systemic inflammatory response and worsening lung function and quality of life in these patients.
10.1016/j.cyto.2024.156558
Changes in Th1/Th2-producing cytokines during acute exacerbation chronic obstructive pulmonary disease.
Wei Bing,Sheng Li Chun
The Journal of international medical research
Objective This study aimed to explore cytokine serum levels and the ratio of type 1 T helper (Th1)/Th2 cells in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total 245 patients diagnosed with AECOPD and 193 patients who progressed to stable COPD after the initiation of treatment in hospital were selected, while a further 50 healthy individuals served as controls. All patients with COPD were diagnosed using Global Initiative for Chronic Obstructive Lung Disease criteria. Serum concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-10, IL-17, and immunoglobulin (Ig)E were measured using enzyme-linked immunosorbent assays. Results AECOPD patients had higher levels of IL-2, IFN-γ, IL-4, IL-10, IL-17, and IgE than those with stable COPD or controls. Intriguingly, the ratios of Th1/Th2 and IL-17/IgE were lower in AECOPD patients compared with the other two groups. These data suggest that AECOPD patients produce more IgE and have more differentiated Th2 cells than other groups. Conclusion Our findings suggest that an imbalance of circulating CD4 T cell subsets correlates with AECOPD, and that a shift of Th1/Th2 and IL-17/IgE ratios may be caused by increased Th2 cell production.
10.1177/0300060518781642
Inflammasome signalling pathway in the regulation of inflammation - its involvement in the development and exacerbation of asthma and chronic obstructive pulmonary disease.
Postepy dermatologii i alergologii
Inflammasomes are multiprotein oligomers, whose main function is the recruitment and activation of caspase-1, which cleaves the precursor forms of interleukin (IL)-1β and IL-18, generating biologically active cytokines. Activation of inflammasome is an essential component of the innate immune response, and according to recent reports it is involved in epithelial homeostasis and type 2 T helper cell (Th2) differentiation. In recent years, the contribution of inflammasome dependent signalling pathways to the development of inflammatory diseases became a topic of multiple research studies. Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent obstructive lung diseases. Recent studies have focused on inflammatory aspects of asthma and COPD development, demonstrating the key role of inflammasome-dependent processes. Factors responsible for activation of inflammasome complex are similar in both asthma and COPD and include bacteria, viruses, cigarette smoke, and particulate matter. Some recent studies have revealed that NLRP3 inflammasome plays a crucial role, particularly in the development of acute exacerbations of COPD (AECOPD). Activation of NLRP3 inflammasome has been linked with neutrophilic severe steroid-resistant asthma. Although most of the studies on inflammasomes in asthma and COPD focused on the NLRP3 inflammasome, there are scarce scientific reports linking other inflammasomes such as AIM2 and NLRP1 with obstructive lung diseases. In this mini review we focus on the role of molecular pathways associated with inflammasome in the most prevalent lung diseases such as asthma and COPD. Furthermore, we will try to answer the question of whether inhibition of inflammasome can occur as a modern therapy in these diseases.
10.5114/ada.2022.118077
Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.
Respiratory research
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD). METHODS:A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated. RESULTS:A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = - 0.367, P = 0.009) and proportion of Th2 cells (r = - 0.655, P < 0.0001). CONCLUSIONS:The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity. TRIAL REGISTRATION:China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx .
10.1186/s12931-022-02058-x
Diagnostic and Prognostic Value of Inflammatory Parameters Including Neopterin in the Setting of Pneumonia, COPD, and Acute Exacerbations.
Pizzini Alex,Lunger Fabian,Sahanic Amra,Nemati Nada,Fuchs Dietmar,Weiss Günter,Kurz Katharina,Bellmann-Weiler Rosa
COPD
Acute exacerbations and community-acquired pneumonia (CAP) are severe complications in patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed inflammatory parameters in serum including C-reactive protein (CRP), procalcitonin (PCT), and serum neopterin (NPT) to determine their potential to differentiate between patients with CAP+COPD and with acute exacerbations of COPD (AECOPD) without pneumonia. 102 (39 women and 63 men) patients were included in this retrospective study, of whom 48 presented with CAP without underlying COPD, 20 with CAP+COPD and 34 with AECOPD. CRP, PCT, and blood counts were determined by routine automated tests, and NPT concentrations were determined by ELISA. The ratios of CRP to NPT levels were calculated. Upon patient admission, CRP, PCT, and NPT levels were significantly higher in patients with CAP compared to those in AECOPD patients. CRP/NPT ratio was lower in AECOPD compared to CAP (+/-COPD) patients. Positive correlations were found between duration of hospitalization and CRP levels and the CRP/NPT ratio at study entry. Patients who were readmitted within 30 days tended to have higher NPT levels at initial presentation. Patients under ongoing corticosteroid treatment presented with lower inflammatory parameters. The CRP/NPT-ratio was suited well to discriminate between AECOPD and CAP on the basis of COPD, a CRP/NPT cutoff of 0.346 provided a sensitivity of 65% and a specificity of 79%. The combinatory use of inflammatory patterns might help to differentiate patients with AECOPD from those with CAP on the basis of COPD.
10.1080/15412555.2016.1266317