non-COPD Controls Research Articles

Diagnostic value of interferon-γ release assay in patients with COPD complicated with pulmonary tuberculosis

BackgroundThe common diagnostic methods for tuberculosis have been showing reduced sensitivity among chronic obstructive pulmonary disease patients. This study was conducted to evaluate and analyse the diagnostic value of an interferon-γ release assay in COPD patients complicated with pulmonary tuberculosis.MethodsA nested case-control study was conducted on 123 COPD patients hospitalized at the Fifth Hospital of Shijiazhuang, Hebei Province, from January 2019 to June 2021. Thirty-one patients with active pulmonary tuberculosis complicated with COPD composed the observation group (Group A), 31 patients with nonactive pulmonary tuberculosis complicated with COPD composed the COPD control group (Group B), and 31 patients with active pulmonary tuberculosis not complicated with COPD composed the non-COPD control group (Group C). An interferon-γ release assay, a purified protein derivative of tuberculin (PPD) test, an anti-tuberculosis antibody test, a test of Mycobacterium tuberculosis by sputum smear microscopy and a test of Mycobacterium tuberculosis by PCR method were used to test patients in each group. The positive detection rates generated from the five test methods were compared and analysed.ResultsIn COPD patients complicated with active pulmonary tuberculosis, the differences in the percentage of patients with positive interferon-γ release between the PPD test, anti-tuberculosis antibody test, Mycobacterium tuberculosis by sputum smear microscopy and PCR test results were statistically significant.ConclusionIn patients with COPD complicated with active pulmonary tuberculosis, the percentage of patients who were positive according to the interferon-γ release assay was higher than that according to the sputum smear microscopy, PCR detection of Mycobacterium tuberculosis in sputum specimen, and detection of anti-tuberculosis antibodies. COPD-related complications did not affect the T-SPOT; the greater the T-SPOT value was, the greater the likelihood of active TB. For patients who are T-SPOT positive but clinically considered to have inactive tuberculosis, regular follow-ups should be performed to observe changes in the patient’s condition.

Computed tomography (CT) quantitative assessment of single lobe emphysema correlates with chronic obstructive pulmonary disease (COPD) severity: a cross-sectional study with retrospective data collection.

In the past, many researchers have studied the correlation between quantitative parameters of computed tomography (CT) and parameters of pulmonary function test (PFT) in patients with chronic obstructive pulmonary disease (COPD) with good results. Most of these studies have focused on the whole-lung level. In this study, we analyzed the biphasic CT lung volume parameters and the percentage of emphysema volume in different lobes of the lungs of patients with different grades of COPD and assessed their relationship with different lung function indices. We retrospectively collected patients who underwent PFTs at The First Affiliated Hospital of Guangzhou Medical University from 1 July 2019 to 27 January 2020, and underwent chest respiratory dual-phase CT scans within 1 week, including 112 non-COPD patients and 297 COPD patients. We quantified the biphasic CT lung volume parameters and the percentage of emphysema volume in different lobes using a pulmonary image analysis tool. One-way analysis of variance (ANOVA) and Kruskal-Wallis H method were used to compare the quantitative CT parameters of each lung lobe in different groups. The correlation between quantitative CT parameters of different lung lobes and lung function indices was assessed using multiple linear regression. Among the 3 biphasic CT lung volume parameters, only volume change/inspiratory lung volume (∆LV/LVin) in the non-COPD control, mildly to moderately severe, and severe to extremely severe groups had statistical differences in each lobe level (all P<0.05). Correlation was significant between LVin and different lung function indices and between low attenuation areas percent below the threshold of -950 in the inspiratory phase [low attenuation area below -950 in the inspiratory phase (%LAA-950in)] and lung function indices in the left lower lobe (all P<0.05). There was statistically significant correlation between expiratory lung volume and ∆LV/LVin and lung function indices in the right lower lung (all P≤0.001). In the remaining lobes, LVin, expiratory lung volume, ∆LV/LVin, and %LAA-950in correlated with only some of the lung function indices. The percentage of emphysema volume did not differ between lobes in the non-COPD control and severe to extremely severe COPD populations. LVin and %LAA-950in in the left upper lobe, expiratory lung volume and ∆LV/LVin in the right lower lobe were more reflective of the changes in lung function indices of the patients, whereas the correlation of the 3 biphasic CT lung volume parameters and the percentage of emphysema volume in the upper lobes of both lungs and the right middle lung with lung function indices was unclear.

Ultrasonic AccV: a potential indicator of peripheral arteriosclerosis in patients with chronic obstructive pulmonary disease

ObjectiveThis study aimed to investigate the risk factors for peripheral arteriosclerosis (PAS) and peripheral artery disease (PAD) in chronic obstructive pulmonary disease (COPD) patients and potential ultrasound indicators that could be used to improve detection.MethodOutpatients seeking care between January 1, 2017, and December 31, 2020, in The First Affiliated Hospital of China Medical University were prospectively recruited. Subjects were divided into COPD and non-COPD (control) groups, and the COPD group was further divided into PAD and non-PAD subgroup, at the same time, PAS and non-PAS subgroup. Indicators of PAD -ankle-brachial index (ABI), indicators of PAS- pulse wave velocity (PWV), and ultrasound indices -peak systolic blood flow velocity (PSV) and blood flow acceleration velocity (AccV) were compared.ResultSixty-nine (61.6%) of 112 enrolled subjects had COPD. COPD patients had higher age, and blood pressure (BP)lower than controls. Seventeen (24.6%) COPD patients had PAD, the prevalence of PAD increases with the decrease of lung function, and seven (16.3%) non-COPD patients had PAD, however, there was no significant statistical difference between COPD and non-COPD groups. Fifty (72.5%) COPD patients had PAS, and thirty-four (79.1%) non-COPD patients had PAS, however, there was also no significant difference. The PAS subgroup had higher age, body mass index(BMI), body fat percentage(BFP), lower FEV1 and FEV1/FVC, as well as higher levels of right brachial artery and left dorsalis pedis artery AccV. Factors that correlated with ABI were 6MWD, post-bronchodilator FEV1, FEV1/ FVC, and maximal middle expiratory flow between 75% and 25% of FVC. Age, BP, and 6MWD, but not pulmonary function, were associated with brachial-ankle PWV (baPWV). There was a positive correlation between baPWV and radial artery AccV bilaterally.ConclusionRadial artery AccV correlated well with baPWV, which suggests that ultrasound could be used to assess both morphological and functional changes in vessels, may serving as a better method to identify PAS in high-risk COPD patients.

Alternative Splicing Is a Major Factor Shaping Transcriptome Diversity in Mild and Severe Chronic Obstructive Pulmonary Disease.

The role of alternative splicing in chronic obstructive pulmonary disease (COPD) is still largely unknown. We aimed to investigate the differences in alternatively splicing events between patients with mild-to-moderate and severe COPD compared with non-COPD control subjects and to identify splicing factors associated with aberrant alternative splicing in COPD. For this purpose, we performed genome-wide RNA-sequencing analysis of bronchial brushings from 23 patients with mild-to-moderate COPD, 121 with severe COPD, and 23 non-COPD control subjects. We found a significant difference in the frequency of alternative splicing events in patients with mild-to-moderate and severe COPD compared with non-COPD control subjects. There were from two to eight times (depending on event type) more differential alternative splicing events in the severe than in the mild-to-moderate stage. The severe COPD samples showed less intron retention and more exon skipping. It is interesting that the transcript levels of the top 10 differentially expressed splicing factors were significantly correlated with the percentage of many alternatively spliced transcripts in severe COPD. The aberrant alternative splicing in severe COPD was predicted to increase the overall protein-coding capacity of gene products. In conclusion, we observed large and significant differences in alternative splicing between bronchial samples of patients with COPD and control subjects, with more events observed in severe than in mild-to-moderate COPD. The changes in the expression of several splicing factors correlated with prevalence of alternative splicing in severe COPD. Alternative splicing can indirectly impact gene expression by changing the relative abundance of protein-coding isoforms potentially influencing pathophysiological changes. The results provide a better understanding of COPD-related alternative splicing changes.

COPD: Iron Deficiency and Clinical Characteristics in Patients With and Without Chronic Respiratory Failure.

The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according to 3 well-known criteria for iron deficiency, its associations with clinical characteristics of COPD, and mortality. In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 were non-COPD controls, ferritin, transferrin saturation (TSat), and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses. The prevalence of iron deficiency in the study population was 10%-43% according to diagnostic criteria, and was consistently higher in individuals with COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with forced expiratory volume in 1 second (FEV1) (odds ratio [OR] 0.33 per liter increase), smoking (OR 3.2), and cardiovascular disease (OR 4.7). TSat < 20% was associated with body mass index (BMI) (OR 1.1 per kg/m2 increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV1 (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (hazard ratio [HR] 1.2-1.8). The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking, and cardiovascular disease, while TSat < 20% was associated with reduced levels of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.

Impact of COPD on mortality: An 8-year observational retrospective healthcare claims database cohort study

BackgroundChronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Here we present a large observational study on the association of COPD and exacerbations with mortality (AvoidEx Mortality). MethodsA real-world, observational cohort study with longitudinal analyses of German healthcare claims data in patients ≥40 years of age with a COPD diagnosis from 2011 to 2018 (n = 250,723) was conducted. Patients entered the cohort (index date) upon the first COPD diagnosis. To assess the impact of COPD on all-cause death, a propensity score-matched control group of non-COPD patients was constructed. The number and severity of exacerbations during a 12-month pre-index period were used to form subgroups. For each exacerbation subgroup the exacerbations during 12 months prior to death were analysed. ResultsCOPD increases the all-cause mortality risk by almost 60% (HR 1.57 (95% CI 1.55–1.59)) in comparison to matched non-COPD controls, when controlling for other baseline covariates. The cumulative risk of death after 8 years was highest in patients with a history of more than one moderate or severe exacerbation. Among all deceased COPD patients, 17.2% had experienced a severe, and 34.8% a moderate exacerbation, within 3 months preceding death. Despite increasing exacerbation rates towards death, more than the half of patients were not receiving any recommended pharmacological COPD therapy in the year before death. ConclusionOur study illustrates the impact of COPD on mortality risk and highlights the need for consequent COPD management comprising exacerbation assessment and treatment.

Loss of p73 Expression Contributes to Chronic Obstructive Pulmonary Disease.

Rationale: Multiciliated cell (MCC) loss and/or dysfunction is common in the small airways of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this contributes to COPD lung pathology. Objectives: To determine if loss of p73 causes a COPD-like phenotype in mice and explore whether smoking or COPD impact p73 expression. Methods: p73floxE7-E9 mice were crossed with Shh-Cre mice to generate mice lacking MCCs in the airway epithelium. The resulting p73Δairway mice were analyzed using electron microscopy, flow cytometry, morphometry, forced oscillation technique, and single-cell RNA sequencing. Furthermore, the effects of cigarette smoke on p73 transcript and protein expression were examined using invitro and invivo models and in studies including airway epithelium from smokers and patients with COPD. Measurements and Main Results: Loss of functional p73 in the respiratory epithelium resulted in a near-complete absence of MCCs in p73Δairway mice. In adulthood, these mice spontaneously developed neutrophilic inflammation and emphysema-like lung remodeling and had progressive loss of secretory cells. Exposure of normal airway epithelium cells to cigarette smoke rapidly and durably suppressed p73 expression invitro and invivo. Furthermore, tumor protein 73 mRNA expression was reduced in the airways of current smokers (n = 82) compared with former smokers (n = 69), and p73-expressing MCCs were reduced in the small airways of patients with COPD (n = 11) compared with control subjects without COPD (n = 12). Conclusions: Loss of functional p73 in murine airway epithelium results in the absence of MCCs and promotes COPD-like lung pathology. In smokers and patients with COPD, loss of p73 may contribute to MCC loss or dysfunction.

Reduced miR-513a-5p expression in COPD may regulate airway mucous cell hyperplasia through TFR1-dependent signaling.

Airway mucous cell metaplasia and mucous hypersecretion is one of the key characteristic pathophysiological status of chronic obstructive pulmonary disease (COPD). micro(mi)RNAs are acknowledged as non-encoding RNA molecules playing important roles in gene expression regulation. In this study, we searched the Gene Expression Omnibus (GEO) database for the differentially expressed miRNAs between COPD and non-COPD controls with bioinformatics analysis. Finally, we focused on miR-513a-5p and investigated the potential mechanism by which miR-513a-5p regulates airway mucous hypersecretion and goblet cell metaplasia. A dual-luciferase reporter assay was then showing that miR-513a-5p targeted the 3'-UTR of TFR1 and inhibited its expression in vitro. In vivo transfection demonstrated that TFR1 downregulation partially blocked MUC5AC hypersecretion and goblet cell hyperplasia in COPD model rats. In vitro study, CSE increased the intracellular expression and secretion of MUC5AC by BEAS-2B branchial epithelial cells in the BEAS-2B cell and THP-1 cell coculture system. Coculture with either miR-513a-5p mimic-pretreated or TFR1-deficient THP-1 cells attenuated intracellular MUC5AC expression in BEAS-2B cells exposed to CSE. ELISA demonstrated that transfection of TFR1 siRNA or pretreatment with miR-513a-5p mimic reduced the secretion of inflammatory factors that are responsible for airway goblet cell hyperplasia, such as IL-1β, IL-13, and IL-17, by THP-1 cells after CSE stimulation. Our findings supported that miR-513a-5p/TFR1 signaling axis might activate macrophages as well as promote airway inflammation and airway mucous cell hyperplasia in COPD.

A bronchial gene signature specific for severe COPD that is retained in the nose.

A subset of COPD patients develops advanced disease with severe airflow obstruction, hyperinflation and extensive emphysema. We propose that the pathogenesis in these patients differs from mild-moderate COPD and is reflected by bronchial gene expression. The aim of the present study was to identify a unique bronchial epithelial gene signature for severe COPD patients. We obtained RNA sequencing data from bronchial brushes from 123 ex-smokers with severe COPD, 23 with mild-moderate COPD and 23 non-COPD controls. We identified genes specific to severe COPD by comparing severe COPD to non-COPD controls, followed by removing genes that were also differentially expressed between mild-moderate COPD and non-COPD controls. Next, we performed a pathway analysis on these genes and evaluated whether this signature is retained in matched nasal brushings. We identified 219 genes uniquely differentially expressed in severe COPD. Interaction network analysis identified VEGFA and FN1 as the key genes with the most interactions. Genes were involved in extracellular matrix regulation, collagen binding and the immune response. Of interest were 10 genes (VEGFA, DCN, SPARC, COL6A2, MGP, CYR61, ANXA6, LGALS1, C1QA and C1QB) directly connected to fibronectin 1 (FN1). Most of these genes were lower expressed in severe COPD and showed the same effect in nasal brushings. We found a unique severe COPD bronchial gene signature with key roles for VEGFA and FN1, which was retained in the upper airways. This supports the hypothesis that severe COPD, at least partly, comprises a different pathology and supports the potential for biomarker development based on nasal brushes in COPD.

Ηeparan sulphate in infectious and non-infectious exacerbations of COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with worsening health outcomes and effective treatment of each episode is essential. In this study, we aimed to investigate if plasma levels of heparan sulphate (HS) are associated with the aetiology of AECOPD. COPD patients (N = 1189), GOLD grade II-IV, from a discovery cohort (N = 638) and from a validation cohort (N = 551), were included in the study. HS and heparanase (HSPE-1) were measured longitudinally in plasma at stable state, at AECOPD and at 4 weeks follow-up. Plasma HS was higher in patients with COPD as compared with non-COPD controls and was significantly increased at AECOPD as compared to stable state (p < 0.001) in the discovery and in the validation cohorts. Four distinct exacerbation groups were classified based on aetiology (no-infection/bacterial-infection/viral-infection/bacterial and viral coinfection) in the validation cohort. The fold-increase of HS from stable state to AECOPD was associated with the aetiology of exacerbation and was higher in cases with bacterial and viral coinfections. HSPE-1 was also significantly increased at AECOPD, however, there was no association of HSPE-1 levels with the aetiology of these events. The probability of having an infection at AECOPD was raised as HS levels increased from stable state to AECOPD. This probability was higher for bacterial infections than viral infections. The results of our study indicate that circulating levels of HS are increased at AECOPD and this increase may be associated with the aetiology of these events.

0871 Outcomes in Overlap Syndrome of COPD and OSA: A Secondary Data Analysis of STAGES

Abstract Introduction Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent, and termed Overlap Syndrome (OVS) when coexistent. Patient-reported outcomes (PROs) are impaired in both COPD and OSA alone, but their combined impact is unclear. We examined differences in the impact of COPD on PROs in adults with and without OSA. Methods Analyses included adults aged≥8 years with polysomnographic (PSG) data from the Stanford Technology Analytics and Genomics in Sleep (STAGES) study. We created sets of individuals with and without COPD, matched up to 1:5 on age±5 years, BMI±2.5 kg/m2, AHI±5 events/hour, and sex. Among all matched sets, we estimated the impact of COPD on fatigue (Fatigue Severity Scale), sleepiness (Epworth Sleepiness Scale), anxiety (Generalized Anxiety Disorder Questionnaire), depression (Personal Health Questionnaire-9), insomnia (Insomnia Severity Index), and function (Functional Outcomes of Sleep Questionnaire) using linear mixed effects models. We also examined whether the effect of COPD differed between those with (AHI≥10 events/hour) and without (AHI&amp;lt; 10 events/hour) OSA. Results Overall, 56 patients with COPD were matched to a total of 199 non-COPD controls (51.0% males). The sample was middle aged (55.8±11.8 years), overweight/obese (BMI 29.8±6.9 kg/m2), and had mild/moderate OSA (AHI 11.0±11.5 events/hour) on average; 26 (46.4%) of COPD cases had an AHI≥10. Among all patients, COPD was associated with worse PROs on average (p&amp;lt; 0.05 for all but ESS [p=0.070]). Among those with AHI&amp;lt; 10, there were no differences for any PRO between groups with and without COPD. However, COPD was associated with worse values of all PROs among those with OSA, including fatigue (mean [95% CI] difference = 9.8 [2.9, 16.7], p=0.006), sleepiness (2.8 [0.01, 5.7], p=0.050), anxiety (3.6 [1.1, 6.0], p=0.005), depression (4.4 [1.8, 7.0], p=0.001), insomnia (4.8 [2.0, 7.6], p=0.001) and function (-3.3 [-5.2, -1.5], p=0.001). Conclusion The effect of COPD on PROs is modified by OSA, with worse outcomes among those with OVS compared to OSA alone, but no impact of COPD among those without OSA. Identification of adults with OVS through early screening is crucial to prompt treatment of disease and reduce symptom burden. Support (if any) T32HL07713 P01 HL094307

A proteomics approach to identify COPD-related changes in lung fibroblasts.

Lung fibroblasts are implicated in abnormal tissue repair in chronic obstructive pulmonary disease (COPD). The exact mechanisms are unknown and comprehensive analysis comparing COPD- and control fibroblasts is lacking. The aim of this study is to gain insight into the role of lung fibroblasts in COPD pathology using unbiased proteomic and transcriptomic analysis. Protein and RNA were isolated from cultured parenchymal lung fibroblasts of 17 patients with stage IV COPD and 16 non-COPD controls. Proteins were analyzed using LC-MS/MS and RNA through RNA sequencing. Differential protein and gene expression in COPD was assessed via linear regression, followed by pathway enrichment, correlation analysis, and immunohistological staining in lung tissue. Proteomic and transcriptomic data were compared to investigate the overlap and correlation between both levels of data. We identified 40 differentially expressed (DE) proteins and zero DE genes between COPD and control fibroblasts. The most significant DE proteins were HNRNPA2B1 and FHL1. Thirteen of the 40 proteins were previously associated with COPD, including FHL1 and GSTP1. Six of the 40 proteins were related to telomere maintenance pathways, and were positively correlated with the senescence marker LMNB1. No significant correlation between gene and protein expression was observed for the 40 proteins. We hereby describe 40 DE proteins in COPD fibroblasts including previously described COPD proteins (FHL1, GSTP1) and new COPD research targets like HNRNPA2B1. Lack of overlap and correlation between gene and protein data supports the use of unbiased proteomics analysis and indicates that different types of information are generated with both methods.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile.

Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. Sprague-Dawley rats were classified into five groups: non-COPD/rest (n = 8), non-COPD/exercise (n = 7), COPD/rest (n = 7), COPD/medium exercise (n = 10), and COPD/intensive exercise (n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ± 15.33 g (P = 0.0005). The oxidative muscle fibers proportion was lower (P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity (P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease.

The pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) is implicated in airway inflammation, oxidative stress, protease/anti-protease and emphysema. Abnormally expressed non-coding RNAs (ncRNAs) play a vital role in regulation of COPD occurrence and progression. The regulatory mechanisms of the circRNA/lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) networks might facilitate our cognition of RNA interactions in COPD. This study aimed to identified novel RNA transcripts and constructed the potential ceRNA networks of COPD patients. Total transcriptome sequencing of the tissues from patients with COPD (COPD) (n = 7) and non-COPD control subjects (Normal) (n = 6) was performed, and the expression profiles of differentially expressed genes (DEGs), including mRNAs, lncRNAs, circRNAs, and miRNAs, were analyzed. The ceRNA network was established based on the miRcode and miRanda databases. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Gene set variation analysis (GSVA) were implemented for functional enrichment analysis of DEGs. Finally, CIBERSORTx was extracted to analyze the relevance between hub genes and various immune cells.The Starbase and JASPAR databases were used to construct hub-RNA binding proteins (RBPs) and lncRNA-transcription factor (TF) interaction networks. A total of 1,796 mRNAs, 2,207 lncRNAs, and 11 miRNAs showed differentially expression between the lung tissue samples from the normal and COPD groups. Based on these DEGs, lncRNA/circRNA-miRNA-mRNA ceRNA networks were constructed respectively. In addition, ten hub genes were identified. Among them, RPS11, RPL32, RPL5, and RPL27A were associated with the proliferation, differentiation, and apoptosis of the lung tissue. The biological function revealed that TNF-α via NF-kB and IL6/JAK/STAT3 signaling pathways were involved in COPD. Our research constructed the lncRNA/circRNA-miRNA-mRNA ceRNA networks, filtrated ten hub genes may regulate the TNF-α/NF-κB, IL6/JAK/STAT3 signally pathways, which indirectly elucidated the post-transcriptional regulation mechanism of COPD and lay the foundation for excavating the novel targets of diagnosis and treatment in COPD.

From Differential DNA Methylation in COPD to Mitochondria: Regulation of AHRR Expression Affects Airway Epithelial Response to Cigarette Smoke.

Cigarette smoking causes hypomethylation of the gene Aryl Hydrocarbon Receptor Repressor (AHRR), which regulates detoxification and oxidative stress-responses. We investigated whether AHRR DNA methylation is related to chronic obstructive pulmonary disease (COPD) and studied its function in airway epithelial cells (AECs). The association with COPD was assessed in blood from never and current smokers with/without COPD, and in AECs from ex-smoking non-COPD controls and GOLD stage II-IV COPD patients cultured with/without cigarette smoke extract (CSE). The effect of CRISPR/Cas9-induced AHRR knockout on proliferation, CSE-induced mitochondrial membrane potential and apoptosis/necrosis in human bronchial epithelial 16HBE cells was studied. In blood, DNA methylation of AHRR at cg05575921 and cg21161138 was lower in smoking COPD subjects than smoking controls. In vitro, AHRR DNA methylation at these CpG-sites was lower in COPD-derived than control-derived AECs only upon CSE exposure. Upon AHRR knockout, we found a lower proliferation rate at baseline, stronger CSE-induced decrease in mitochondrial membrane potential, and higher CSE-induced late apoptosis/necroptosis. Together, our results show lower DNA methylation of AHRR upon smoking in COPD patients compared to non-COPD controls. Our data suggest that higher airway epithelial AHRR expression may lead to impaired cigarette smoke-induced mitochondrial dysfunction and apoptosis/necroptosis, potentially promoting unprogrammed/immunogenic cell death.

A More Intense Examination of the Intensity of Physical Activity in People Living with Chronic Obstructive Pulmonary Disease: Insights from Threshold-Free Markers of Activity Intensity.

Physical activity (PA) intensity of people living with chronic obstructive pulmonary disease (COPD) is typically evaluated using intensity thresholds developed in younger, healthier populations with greater exercise capacity and free from respiratory symptoms. This study therefore compared (i) PA differences between COPD and non-COPD controls using both traditional intensity thresholds and threshold-free metrics that represent the volume and intensity of the whole PA profile, and (ii) explored the influence of exercise capacity on observed differences. Moderate-to-vigorous physical activity (MVPA), average acceleration (proxy for volume, mg) and intensity distribution of activity were calculated for 76 individuals with COPD and 154 non-COPD controls from wrist-worn ActiGraph accelerometry. PA profiles representing the minimum intensity (acceleration, mg) during the most active accumulated 5–960 min were plotted. Estimated VO2peak and relative intensity were derived from the incremental shuttle walk test distance. Compared to the non-COPD control group, individuals with COPD recorded fewer MVPA minutes (59 vs. 83 min/day), lower overall waking activity (29.1 vs. 36.4 mg) and a poorer waking intensity distribution (−2.73 vs. −2.57). Individuals with COPD also recorded a lower absolute intensity (acceleration, mg) for their most active 5–960 min, but higher intensity relative to their estimated exercise capacity derived from the ISWT. People with COPD have a lower volume and absolute intensity of PA than controls but perform PA at a higher relative intensity. There is a need to move away from absolute intensity thresholds, and towards personalised or relative-intensity thresholds, to reflect reduced exercise capacity in COPD populations.

Pre-clinical prediction of coronary atherosclerosis in copd by carotid artery intima media thickness

Aim and Introduction: To determine the association between Coronary atherosclerosis in Chronic Obstructive Pulmonary Disease and Carotid Artery Intima Media Thickness. The objective of the present case control study is to determine the association between carotid atherosclerosis in COPD patients and cardiovascular morbidity. Material and methods. It was a prospective case-control observational study. 50 COPD patients and 50 age- and gender-matched non-COPD controls were studied. Carotid artery USG scanning was carried out using B-mode duplex USG for measurement of carotid artery intima - media thickness. Results. CIMT was found to be more common in COPD group patients (78%) as compared to non-COPD group patients (26%) (P value = 0.000). The mean CIMT is 1.04 0.41 mm in the COPD group and 0.71 0.24 in the COPD group with a P value of 0.0001. The mean CIMT in Gold 3 was the highest (1.10 0.48 mm), followed by Gold 4 (1.05 0.46 mm) and the minimum in Gold 1 (0.73 0.00 mm). Conclusion. Our study shows that COPD is associated with increased CIMT, which is a preclinical predictor of coronary atherosclerosis and cardiovascular risk. However, further studies are needed.

Factors associated with coronary heart disease in COPD patients and controls.

COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p<0.01), whereas 55.9% of the COPD patients had a CaSc>100 compared to 31.6% of the controls (p<0.01). In a multivariable model adjusting for sex, age, body composition, pack-years, CRP, cholesterol/blood pressure lowering medication use and diabetes mellitus, the OR (95% CI) for having significant stenosis was 1.80 (0.86-3.78) in COPD patients compared with controls. In a similar model, the OR (95% CI) for having CaSc>100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.

Sexual Health in COPD: A Systematic Review and Meta-Analysis.

COPD has a profound impact on the lives of patients and their partners, but the influence on physical, psychological and social aspects of sexual health has not been reviewed systematically. Searches for studies of the impact of COPD on sexual health were conducted independently by two authors in the databases of PubMed, PsycINFO, Embases, CINAHL, Web of Science, Scopus and The Cochrane Library. English-language quantitative and qualitative studies assessing one or more aspects of sexual health in patients diagnosed with COPD were narratively reviewed and, when possible, subjected to meta-analytic evaluation. A total of 31 studies, including 4 qualitative, were included. Twelve studies assessing erectile dysfunction with the International Index of Erectile Function were subjected to meta-analysis. The pooled prevalence of erectile dysfunction was 74% (95% CI: 68–80%) in a total of 1187 patients with COPD, compared with 56% (37–73%) in 224 age-matched, non-COPD controls. The sexual health outcomes assessed in the remaining studies varied considerably, compromising the comparability of the results. None of the qualitative studies had sexual health as their primary focus. Compared with non-COPD individuals, erectile dysfunction appears to be more prevalent among patients with COPD, but more studies including non-COPD controls are needed to confirm this finding. In addition, the impact of COPD on other physical, psychological and social aspects of sexual health remains unclear due to the lack of comparable assessment methods and study designs.

Circulating Complement C1q as a Novel Biomarker is Associated with the Occurrence and Development of COPD.

PurposeIncreasing evidence has shown that the immune response interacts with the chronic inflammatory response and gives rise to the occurrence and development of COPD. Complement component 1q (C1q), as a subcomponent of the C1 complex, could be involved in innate and adaptive immunity. Our study aimed to investigate the relationship between C1q and the clinical characteristics of COPD subjects.Patients and MethodsSerum C1q levels were measured in 203 COPD subjects and 191 non-COPD controls. Correlations between C1q and the characteristics of COPD were analyzed using Spearman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. All 203 COPD subjects were followed up for 1 year for future acute exacerbations.ResultsThere were significant reductions in serum C1q levels in COPD subjects compared to non-COPD controls. Moreover, serum C1q levels were obviously positively correlated with the FEV1/FVC ratio and predicted FEV1% but had a weakly negative correlation with the %LAA-950 and the percentage of neutrophils in peripheral blood. Using a cutoff value of 137.150 mg/l as the boundary in ROC analysis, the sensitivity and specificity were 65.9% and 76.0%, respectively. The 1-year follow-up results showed that C1q levels less than 137.150 mg/l were negatively related to the time to the next severe exacerbation and the time to death.ConclusionCirculating C1q levels may be a novel biomarker not only related to the pulmonary function of COPD but also having great potential to predict the risk of COPD deterioration in the future. However, further prospective trials are needed to clarify the influences of C1q on the pathogenesis of COPD.