Inflammation In Chronic Obstructive Pulmonary Disease Patients Research Articles

FDG-PET/CT-based respiration-gated lung segmentation and quantification of lung inflammation in COPD patients

Objective and results descriptionThe study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a surrogate marker of inflammation in COPD. Patients treated with anti-inflammatory Liraglutide were compared to placebo and correlated with inflammatory markers. 27 COPD-patients (14 receiving Liraglutide treatment and 13 receiving placebo) underwent 4D-respiratory-gated FDG-PET/CT before and after treatment. Two raters independently segmented the lungs from CT images and measured activity in whole lung, mean standard uptake values (SUVmean) corrected for lean-body-mass in the phase-matched PET images of the whole segmented lung volume, and total lesion glycolysis (TLG; SUVmean multiplied by volume). Inter-rater reliability was analyzed with Bland-Altman analysis and correlation plots. We found no differences in metabolic activity in the lungs between the two groups as a surrogate of pulmonary inflammation, and no changes in inflammation markers. The purpose of the research and brief summary of main findings. The degree of and changes in pulmonary inflammation in chronic obstructive pulmonary disease (COPD) may be difficult to ascertain. Measuring metabolic activity as a surrogate marker of inflammation by FDG-PET/CT may be useful, but data on its use in COPD including reproducibility is still limited, especially with respiration-gated technique, which should improve quantification in the lungs. We assessed several quantitative measures of metabolic activity and correlated them with inflammation markers, and we assessed reproducibility of the methods. We found no differences in metabolic activity between the two groups (before and after 40 weeks treatment with Liraglutide vs. placebo). Bland-Altman analysis showed good agreement between the two raters.Trial registrationThe study was conducted between February 2018 and March 2020 at the Department of Pulmonary Diseases at Hospital South West Jutland and Lillebaelt Hospital, Denmark, and registered from March 2018 at clinicaltrials.gov with trial registration number NCT03466021.

A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) often associated with cigarette smoking. However, increasing evidence suggests that non-smoking COPD is much higher than previously thought. This study aims to identify a nonsmoking COPD biomarker and examined its value in diagnosis and prediction of acute exacerbation. A total of 35 stable COPD patients, 70 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients and 35 healthy control subjects were included. Plasma α 2 macroglobulin (A2M) and matrix metalloproteinase-9 (MMP-9) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method on all participants. Their association with clinical characteristics and lung function parameters were determined by regression analysis. Receiver operating characteristic (ROC) curve was used to determine the diagnostic sensitivity and specificity. Correlation coefficients were evaluated using Pearson's correlation. Plasma A2M concentration was decreased and MMP-9 concentration, MMP-9/A2M ratio were elevated in stable COPD patients compared with control groups. And MMP-9 expression was significantly higher in AECOPD patients. A2M level was increased in AECOPD patients with infection compared with those without. In addition, there was no statistical difference in A2M levels between smokers and nonsmokers COPD or healthy control subjects. Furthermore, A2M, MMP-9 and MMP-9/A2M were correlated with forced expiratory volume in one second (FEV1)%, FEV1/ forced vital capacity (FVC), CAT and mMRC score in COPD patients, but had no correlation with fraction of exhaled nitric oxide (FeNO) and concentration of alveolar nitric oxide (CaNO). A2M is altered in peripheral blood of COPD patients and correlated with severity and infection. Moreover, there was no significant correlation between the change in A2M and smoking, FeNO and CaNO, suggesting A2M may reflect the overall rather than local inflammation in COPD patients and serve as a potential biomarker for nonsmoking COPD patients.

COPD, diabetes, lymphopenia, and increased LDH cause higher mortality in hospitalized COVID-19 patients.

COPD, diabetes, lymphopenia, and increased LDH cause higher mortality in hospitalized COVID-19 patients.

Changes in Blood Markers of Oxidative Stress, Inflammation and Cardiometabolic Patients with COPD after Eccentric and Concentric Cycling Training.

Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. This study examined the effects of 12-week eccentric (ECC) and concentric (CONC) cycling training on plasma markers of cardiometabolic health, oxidative stress, and inflammation in COPD patients. A randomized trial in which moderate COPD was allocated to ECC (n = 10; 68.2 ± 10.0 year) or CONC (n = 10; 71.1 ± 10.3 year) training groups. Participants performed 12-week ECC or CONC training, 2-3 sessions per week, 10 to 30 min per session. Before and after training, peak oxygen consumption, maximal power output (VO2peak and POmax), and time-to-exhaustion (TTE) tests were performed. Plasma antioxidant and oxidative markers, insulin resistance, lipid profile, and systemic inflammation markers were measured before and after training at rest. VO2peak, POmax and TTE remained unchanged after ECC and CONC. CONC induced an increase in antioxidants (p = 0.01), while ECC decreased antioxidant (p = 0.02) markers measured at rest. CONC induced lesser increase in oxidative stress following TTE (p = 0.04), and a decrease in insulin resistance (p = 0.0006) compared to baseline. These results suggest that CONC training induced an increase in insulin sensitivity, antioxidant capacity at rest, and lesser exercise-induced oxidative stress in patients with moderate COPD.

Metabolic syndrome in patients with COPD: Causes and pathophysiological consequences.

Decreased physical activity significantly increases the probability of prevalent metabolic syndrome (MetS) with substantial impact on the expected course of COPD. Our research aims to assess the metabolic consequences of chronic obstructive pulmonary disease (COPD) and evaluate the prevalence of MetS and its interrelations with age, sex, comorbidities, drug intake, degree of decreased lung function, nutritional status, physical activity and quality of life. A cross-sectional study was performed on a random sample (n = 401) at the Department of Pulmonary Rehabilitation of the National Koranyi Institute of Pulmonology from March 1, 2019 to March 1, 2020 in Budapest, Hungary. Anthropometric and respiratory function tests and laboratory parameters of all patients were registered. MetS occurred in 59.1% of COPD patients with significant gender difference (male: 49.7% female: 67.6%). Concerning BMI, the prevalence of MetS was higher with BMI≥25 kg m-2 (P < 0.0001). Patients with this syndrome had significantly worse FEV1%pred (43 (30-56) vs. 47 (36-61); P = 0.028), lower quality of life (CAT: 26 (21-32) vs. 24.5 (19-29); P = 0.049) and significantly more frequent exacerbations (2 (1-3) vs.1 (0-2); P < 0.05), than patients without MetS. The prevalence of comorbidities were higher in overweight/obese patients (BMI> 25 kg m-2). In COPD patients MetS negatively affect respiratory function and quality of life and promotes exacerbations of the disease. MetS is related to nutritional status and the level of systemic inflammation in COPD patients.

The strong correlation between ADAM33 expression and airway inflammation in chronic obstructive pulmonary disease and candidate for biomarker and treatment of COPD

Airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is an amplified response of the normal immune system that occurs as a result of chronic irritation by toxic substances, such as cigarette smoke. This leads to the characteristic pathological changes in the inflammatory cells of COPD patients. ADAM33 has been reported to be involved in the pathogenesis of COPD in East Asia by affecting airway inflammation and other immune responses. The aim of this study was to determine the potential role of ADAM33 (mRNA and soluble levels) as a biomarker of inflammation in COPD patients. This is a case control study using consecutive sampling. The COPD case and control (non-COPD) groups comprised 37 and 29 patients, respectively. We used univariate analysis to assess differences in the parameters between the groups and bivariate analysis to non-parametrically compare these parameters between the two groups. We observed significantly higher mRNA levels of ADAM33 in the COPD patients (10.39 ± 1.76) as compared to that in the non-COPD individuals (6.93 ± 0.39; P < 0.001). The levels of soluble ADAM33 were also significantly higher in the COPD patients (2.188 ± 1.142 ng/ml) compared to the non-COPD individuals (0.487 ± 0.105 ng/ml; P < 0.001). The mRNA and soluble ADAM33 levels were significantly higher in COPD patients compared to those in the parameter-matched non-COPD individuals. Thus, ADAM33 is a potential biomarker and treatment for inflammation in COPD patients.

Aryl Hydrocarbon Receptor Defect Attenuates Mitogen-Activated Signaling through Leucine-Rich Repeats and Immunoglobulin-like Domains 1 (LRIG1)-Dependent EGFR Degradation.

Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27Kip1 or the impairment in mitogenic signal transduction driven by the epidermal growth factor (EGF) and EGF receptor (EGFR). We found that the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a repressor of EGFR, was induced in the absence of AHR in vitro and in vivo. The LRIG1 tends to degrade via a proteasome dependent manner by interacting with AHR in wild-type cells. Either LRIG1 or a disintegrin and metalloprotease 17 (ADAM17) were accumulated in AHR-defective cells, consequently accelerating the degradation of EGFR, and attenuating the response to mitogenic stimulation. We also affirmed low AHR but high LRIG1 levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients. This might partially elucidate the sluggish tissue repairment and developing inflammation in COPD patients.

A Novel Processing-Free Method for RNAseq Analysis of Spontaneous Sputum in Chronic Obstructive Pulmonary Disease.

Background: Assessments of airways inflammation in patients with chronic obstructive pulmonary disease (COPD) require semi-invasive procedures and specialized sample processing know-how. In this study we aimed to set up and validate a novel non-invasive processing-free method for RNA sequencing (RNAseq) of spontaneous sputum samples collected from COPD patients.Methods: Spontaneous sputum samples were collected and stabilized, with or without selection of plugs and with or without the use of a stabilizer specifically formulated for downstream diagnostic testing (PrimeStore® Molecular Transport Medium). After 8 days storage at ambient temperature RNA was isolated according to an optimized RNAzol® method. An average percentage of fragments longer than 200 nucleotides (DV200) >30% and an individual yield >50 ng were required for progression of samples to sequencing. Finally, to assess if the transcriptome generated would reflect a true endotype of COPD inflammation, the outcome of single-sample gene-set enrichment analysis (ssGSEA) was validated using an independent set of processed induced sputum samples. Results: RNA extracted from spontaneous sputum using a stabilizer showed an average DV200 higher than 30%. 70% of the samples had a yield >50 ng and were submitted to downstream analysis. There was a straightforward correlation in terms of gene expression between samples handled with or without separation of plugs. This was also confirmed by principal component analysis and ssGSEA. The top ten enriched pathways resulting from spontaneous sputum ssGSEA were associated to features of COPD, namely, inflammation, immune responses and oxidative stress; up to 70% of these were in common within the top ten enriched pathways resulting from induced sputum ssGSEA.Conclusion: This analysis confirmed that the typical COPD endotype was represented within spontaneous sputum and supported the current method as a non-invasive processing-free procedure to assess the level of sputum cell inflammation in COPD patients by RNAseq analysis.

(−)-Epicatechin ameliorates cigarette smoke-induced lung inflammation via inhibiting ROS/NLRP3 inflammasome pathway in rats with COPD

Chronic obstructive pulmonary disease (COPD) with increased morbidity and mortality is a worldwide healthcare challenge closely associated with cigarette smoking (CS). Currently, there is no effective therapeutic strategy to control inflammation in COPD patients. The present study tested the protective effects of (−)-Epicatechin (EC), a type of flavonoid, on CS-induced COPD and the underlying mechanism. Also, EC repressed the production of reactive oxygen species (ROS) and improved human bronchial epithelial cell viability after cigarette smoke extract (CSE) treatment. Further studies demonstrated that EC promotes ubiquitin-mediated Keap1 degradation by upregulating tripartite motif-containing protein 25 (TRIM25) expression and enhances the nuclear localization of Nrf2 protein. Also, EC dramatically inhibits the activation of NLRP3 inflammasome and reduces the CSE-induced pyroptosis, as indicated by decreasing lactate dehydrogenase release and the number of caspase-1-positive cells. Importantly, Nrf2 knockdown reversed the protective effect of EC on human bronchial epithelial cells, at least partially. Consistent with the results in vitro, EC inhibits the activation of NLRP3 inflammasome and relieves the CS-induced lung inflammation, as evident from decreased interleukin (IL)-1β and IL-18 secretion in a COPD rat model. In conclusion, this study revealed the protective effect of EC on experimental COPD rats and elucidated the mechanism of EC promoting Nrf2 activity, which might provide a novel therapeutic strategy for COPD.

N-Acetylcysteine Improves Inflammatory Response in COPD Patients by Regulating Th17/Treg Balance through Hypoxia Inducible Factor-1α Pathway.

Introduction This study was aimed to investigate the effects of N-acetylcysteine (NAC) on chronic obstructive pulmonary disease (COPD) and the change of Th17/Treg cytokine imbalance. Material and Methods. A total of 121 patients with stable COPD at the stage of C or D were consecutively enrolled and randomly divided into 2 groups. Patients in the treatment group received NAC granules (0.2 g × 10 bags, 0.4 g each time, 3 times/d) for half a year. The control group was treated with the same amount of placebo therapy. The peripheral blood of the patient was collected and the cytokine, T lymphocyte subsets were detected. Results We found the oral administration of NAC could regulate Th17/Treg balance to resist inflammation in COPD patients. Serum testing showed that the proportion of Treg in CD4+ T cells has increased and the Th17/Treg ratio has decreased during the NAC treatment. In vitro studies, we found that NAC regulated Th17/Treg balance through Hypoxia Inducible Factor-1α pathway. Conclusions Our result could provide new diagnosis and treatment for elderly patients with COPD from the perspective of immunity ideas.

Effects of the Health Belief Model-Based Intervention on Anxiety, Depression, and Quality of Life in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition. COPD causes a heavy burden on the patients through negative impacts on the quality of life and psychological health. The health belief model (HBM) is proposed and modified by several social psychologists and is confirmed to have benefits in the recovery of various diseases. This research aimed to explore the effects of the HBM-based intervention on anxiety, depression, and quality of life in COPD patients entering pulmonary rehabilitation (PR). Methods: This research was conducted at the Tianjin Rehabilitation Recuperate Center of Chinese PLA in 2019. A total of 136 COPD patients were randomized into the intervention group and the control group. In the control group, patients received the PR program. In the intervention group, patients received both PR program and the HBM-based intervention. Quality of life was measured by the COPD assessment test. The outcomes of anxiety and depression were measured by the Hospital Anxiety and Depression Scale. Results: The HBM-based intervention decreased both anxiety and depression scores among COPD patients. The COPD assessment test score was declined by the HBM-based intervention, which also decreased the serum levels of interleukin-6 and C-reactive protein in COPD patients entering PR. Conclusion: The HBM-based intervention alleviates anxiety and depression, enhances quality of life, and inhibits inflammation in COPD patients entering PR.

Susceptibility of individuals with lung dysfunction to systemic inflammation associated with ambient fine particle exposure: A panel study in Beijing

BackgroundThe underlying mechanism on the susceptibility of chronic obstructive pulmonary disease (COPD) patients to air pollution has yet to be clarified. ObjectivesBased on the COPD in Beijing (COPDB) study, we examined whether lung dysfunction contributed to pollutant-associated systemic inflammation in COPD patients. MethodsProinflammatory biomarkers including interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) were measured in serum samples collected from 53 COPD and 82 healthy participants. Concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), carbonaceous components in PM2.5, and PM size distribution were continuously monitored. Linear mixed effects models were used to examine the associations of biomarker differences with particle exposure, between COPD and healthy participants, and across subgroups with different levels of lung dysfunction. ResultsCOPD patients showed higher differences in IL-8 and TNFα levels associated with exposure to measured pollutants, comparing to healthy controls. In advanced analysis, particle-associated differences in IL-8 and TNFα levels were higher in participants with poorer lung ventilation and diffusion capacity, and higher ratio of residual volume. For example, an interquartile range increase in average PM2.5 concentration 2 weeks before visits was associated with a 15.7% difference in IL-8 level in participants with the lowest ratio of measured value to predicted value of forced expiratory volume in 1 s (FEV1%pred) (65.2%), and the association decreased monotonically with increasing FEV1%pred. Associations between differences in TNFα level and average ultrafine particle concentration 1 week before visits increased gradually with increasing ratio of measured value to predicted value of residual volume/total lung capacity. ConclusionsCOPD patients, especially those with poorer lung function, are more susceptible to systemic inflammation associated with fine particle exposure.

Elevated sputum IL-36 levels are associated with neutrophil-related inflammation in COPD patients.

Interleukin (IL)-36, including IL-36α, IL-36β, and IL-36γ in the IL-1 family, are agonists of their receptors. IL-36 expression is associated with inflammation, including lung infection in humans. However, there is no information on its role in the inflammation of different types of chronic obstructive pulmonary disease (COPD). This study focused on the sputum IL-36α, IL-36β, and IL-36γ levels in stable COPD patients and their relationship with lung function and other cytokines in different inflammatory types of COPD patients. Sputum specimens were collected from 73 stable COPD patients and 20 age- and gender-matched healthy controls. The levels of sputum IL-36α, IL-36β, and IL-36γ and other cytokines were quantified and sputum cells were characterized. The potential relationship between the levels of sputum IL-36α, IL-36β, or IL-36γ and lung functional measures, inflammatory cells, and cytokines was analyzed. In comparison with the healthy controls, sputum IL-36α and IL-36γ levels significantly increased in COPD (106.8pg/mL vs. 76.9pg/mL P=.001, 397.9pg/mL vs. 359.5pg/mL P=.006). The sputum IL-36α and IL-36γ levels were significantly higher in the neutrophilic and mixed granulocytic types than that in the eosinophilic and paucigranulocytic types of COPD patients. The sputum IL-36α levels were positively correlated with sputum IL-36γ levels and the numbers of sputum neutrophils, and the sputum IL-36γ levels were positively correlated with the numbers of sputum lymphocytes in COPD patients. Elevated levels of sputum IL-36α and IL-36γ were detected in COPD patients and may provide insights into the inflammatory pathways in neutrophilic COPD.

Low Vitamin D Status Is Associated with Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1-2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.

Association Between Interleukin-6 Blood Level and Chronic Obstructive Pulmonary Disease Severity

Chronic obstructive pulmonary disease (COPD) is known as a chronic inflammatory disease that not only occurs in the lung, but also affects the systemic. A continuous chronic inflammation in COPD patients will have an increased proinflammatory cytokines, both in COPD patients’ respiratory tract and blood. Interleukin-6 (IL-6) is one of proinflammatory cytokines that increases with COPD progression. IL-6 level examination in COPD patient’s blood as a systemic inflammation indicator is convenient and quick. The research aimed to measure IL-6 level in COPD patient’s serum, to determine COPD severity level, and to analyze correlation between IL-6 and severity level. The research is an observational analytic study using cross sectional design. The samples were 38 non-exacerbated COPD outpatients who visited Lung Unit at Dr. Soetomo Teaching Hospital, Surabaya, Indonesia and met inclusion and exclusion criteria. The study found no significant correlation between IL-6, COPD severity level, COPD obstruction, first forced expiratory volume (FEV1), and FEV1/forced vital capacity (FVC), withp&gt; 0.05. There was a significant correlation between IL-6 level, body mass index (BMI), and COPD assessment test (CAT) score, withp&lt; 0.05, while there was no significant difference of IL-6 level between high-risk and low-risk patients, withp= 0.066 (p&gt; 0.05). Moreover, there was a significant difference of IL-6 level between group A and D, withp= 0.040 (p&lt; 0.05). There were no significant correlation and difference between COPD severities, COPD obstruction, FEV1, FVC, FEV1/FEC ratio, smoking duration with stable IL-6.

Lung function and systemic inflammation associated with short-term air pollution exposure in chronic obstructive pulmonary disease patients in Beijing, China

BackgroundExposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China.MethodsWe enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up.ResultsA total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L).ConclusionAcute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.

S.19.01 Between love and rage: oxytocin and vasopressin modulate female aggression

We hypothesized that particulate matter (PM) gamma activity (gamma radiation associated with PM) is associated with systemic effects.Examine short-term relationships between ambient and indoor exposures to PM gamma activities with systemic inflammation and endothelial activation in chronic obstructive pulmonary disease (COPD) patients.In 85 COPD patients from Eastern Massachusetts, USA from 2012 to 2014, plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured seasonally up to four times. We used US EPA RadNet data measuring ambient gamma radiation attached to PM adjusted for background radiation, and estimated in-home gamma radiation exposures using the ratio of in-home-to-ambient sulfur in PM2.5. Linear mixed-effects regression models were used to determine associations between moving averages of PM gamma activities through the week before phlebotomy with these biomarkers. We explored ambient and indoor PM2.5, black carbon (BC), and NO2 as confounders.Ambient and indoor PM gamma activities measured as energy spectra classes 3 through 9 were positively associated with CRP and IL-6. For example, averaged from phlebotomy day through previous 6 days, each IQR increase in indoor PM gamma activity for each spectra class, was associated with an CRP increase ranging from 7.45% (95%CI: 2.77, 12.4) to 13.4% (95%CI: 5.82, 21.4) and for ambient exposures were associated with an increase of 8.75% (95%CI: −0.57, 18.95) to 14.8% (95%CI: 4.5, 26.0). Indoor exposures were associated with IL-6 increase of 3.56% (95%CI: 0.31, 6.91) to 6.46% (95%CI:1.33, 11.85) and ambient exposures were associated with an increase of 0.03% (95%CI: −6.37, 6.87) to 3.50% (95%CI: −3.15, 10.61). There were no positive associations with sVCAM-1. Sensitivity analyses using two-pollutant models showed similar effects.Our results demonstrate that short-term exposures to environmental PM gamma radiation activities were associated with systemic inflammation in COPD patients.

Systemic inflammation in COPD in relation to smoking status

&#x0D; &#x0D; &#x0D; Background and aims: Smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) that has been recently defined as a systemic pul- monary inflammatory disease. However, the impact of smok- ing itself on systemic inflammation in COPD patients has not yet been well established. The aim of our study was to inves- tigate the association between inflammatory markers and smoking status.&#x0D; Material and methods: We compared 202 current smokers, 61 ex-smokers and 57 never-smokers, all COPD patients. Assessments included medical history, spirometry, alpha-1 antitrypsin (AAT) genotyping, serum AAT, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and soluble tumor necrosis factor receptor (sTNFR)-1 and sTNFR-2 concentra- tions.&#x0D; Results: AAT and CRP concentrations in smokers (1.75 ± 0.51 g/L and 14.4 [9.5–20.5] mg/L) and ex-smokers (1.69 ± 0.43 g/L and 12.3 [8.7–16.3] mg/L) were higher than in never-smokers (1.49 ± 0.38 g/L and 5.1 [2.5–8.7] mg/L; p &lt; 0.05). sTNFR-1 level was higher in smokers than ex-smokers or never-smok- ers (241.2 pg/mL [145.3–349.4] vs. 213.7 pg/mL [147.1– 280.3] and 205.2 pg/mL [125–275]; p &lt; 0.05).&#x0D; Conclusions: Our data confirm that smoking is associated with increased levels of AAT, CRP, and sTNFR-1 in COPD patients, an array of systemic inflammation markers that continue to be active even after smoking cessation.&#x0D; &#x0D; &#x0D;

Short-term exposures to particulate matter gamma radiation activities and biomarkers of systemic inflammation and endothelial activation in COPD patients

BackgroundWe hypothesized that particulate matter (PM) gamma activity (gamma radiation associated with PM) is associated with systemic effects. ObjectiveExamine short-term relationships between ambient and indoor exposures to PM gamma activities with systemic inflammation and endothelial activation in chronic obstructive pulmonary disease (COPD) patients. MethodsIn 85 COPD patients from Eastern Massachusetts, USA from 2012 to 2014, plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured seasonally up to four times. We used US EPA RadNet data measuring ambient gamma radiation attached to PM adjusted for background radiation, and estimated in-home gamma radiation exposures using the ratio of in-home-to-ambient sulfur in PM2.5. Linear mixed-effects regression models were used to determine associations between moving averages of PM gamma activities through the week before phlebotomy with these biomarkers. We explored ambient and indoor PM2.5, black carbon (BC), and NO2 as confounders. ResultsAmbient and indoor PM gamma activities measured as energy spectra classes 3 through 9 were positively associated with CRP and IL-6. For example, averaged from phlebotomy day through previous 6 days, each IQR increase in indoor PM gamma activity for each spectra class, was associated with an CRP increase ranging from 7.45% (95%CI: 2.77, 12.4) to 13.4% (95%CI: 5.82, 21.4) and for ambient exposures were associated with an increase of 8.75% (95%CI: −0.57, 18.95) to 14.8% (95%CI: 4.5, 26.0). Indoor exposures were associated with IL-6 increase of 3.56% (95%CI: 0.31, 6.91) to 6.46% (95%CI:1.33, 11.85) and ambient exposures were associated with an increase of 0.03% (95%CI: −6.37, 6.87) to 3.50% (95%CI: −3.15, 10.61). There were no positive associations with sVCAM-1. Sensitivity analyses using two-pollutant models showed similar effects. ConclusionsOur results demonstrate that short-term exposures to environmental PM gamma radiation activities were associated with systemic inflammation in COPD patients.

Short-term Exposures to Particulate Matter Gamma Radiation Activities and Biomarkers of Systemic Inflammation and Endothelial Activation in COPD Patients

Abstract Background We hypothesized that particulate matter (PM) gamma activity (gamma radiation associated with PM) is associated with systemic effects. Objective Examine short-term relationships between ambient and indoor exposures to PM gamma activities with systemic inflammation and endothelial activation in chronic obstructive pulmonary disease (COPD) patients. Methods In 85 COPD patients from Eastern Massachusetts, USA from 2012 to 2014, plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured seasonally up to four times. We used US EPA RadNet data measuring ambient gamma radiation attached to PM adjusted for background radiation, and estimated in-home gamma radiation exposures using the ratio of in-home-to-ambient sulfur in PM2.5. Linear mixed-effects regression models were used to determine associations between moving averages of PM gamma activities through the week before phlebotomy with these biomarkers. We explored ambient and indoor PM2.5, black carbon (BC), and NO2 as confounders. Results Ambient and indoor PM gamma activities measured as energy spectra classes 3 through 9 were positively associated with CRP and IL-6. For example, averaged from phlebotomy day through previous 6 days, each IQR increase in indoor PM gamma activity for each spectra class, was associated with an CRP increase ranging from 7.45% (95%CI: 2.77, 12.4) to 13.4% (95%CI: 5.82, 21.4) and for ambient exposures were associated with an increase of 8.75% (95%CI: −0.57, 18.95) to 14.8% (95%CI: 4.5, 26.0). Indoor exposures were associated with IL-6 increase of 3.56% (95%CI: 0.31, 6.91) to 6.46% (95%CI:1.33, 11.85) and ambient exposures were associated with an increase of 0.03% (95%CI: −6.37, 6.87) to 3.50% (95%CI: −3.15, 10.61). There were no positive associations with sVCAM-1. Sensitivity analyses using two-pollutant models showed similar effects. Conclusions Our results demonstrate that short-term exposures to environmental PM gamma radiation activities were associated with systemic inflammation in COPD patients.