GOLD Stage Research Articles

Severe Pulmonary Hypertension in COPD: Impact on Survival and Diagnostic Approach

Severe pulmonary hypertension (PH) is prognostically highly relevant in patients with COPD. The criteria for severe PH have been defined based on hemodynamic thresholds in right heart catheterization. Can noninvasive clinical tools predict severe PH in patients with COPD? How does the mortality risk change with increasing severity of airflow limitation and pulmonary vascular disease? We retrospectively analyzed all consecutive patients with COPD with suspected PH undergoing in-depth clinical evaluation, including right heart catheterization, in our PH clinic between 2005 and 2018. Clinical variables potentially indicative of severe PH or death were analyzed using univariate and stepwise multivariate logistic regression and Cox regression analysis adjusted for age and sex. We included 142 patients with median FEV1 of 55.0%predicted (interquartile range [IQR], 42.4%-69.4%predicted) and mean pulmonary arterial pressure of 35mmHg (IQR, 27-43mmHg). A multivariate model combining echocardiographic systolic pulmonary arterial pressure of≥ 56mmHg, N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels of≥ 650 pg/mL, and pulmonary artery (PA) to ascending aorta (Ao) diameter ratio on chest CT scan of≥ 0.93 predicted severe PH with high positive and negative predictive values (both 94%). After correction for age and sex, both airflow limitation (P= .002; Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-2 vsstage 3: hazard ratio [HR], 1.56 [95%CI, 0.90-2.71]; GOLD stages 1-2 vsstage 4: HR, 3.45 [95%CI, 1.75-6.79]) and PH severity (P= .012; HR, 1.85 [95%CI, 1.15-2.99]) remained associated independently with survival. The combination of GOLD stages 3 and 4 airflow limitation and severe PH showed the poorest survival (HR for death, 3.26 [95%CI, 1.62-6.57; P= .001] vsGOLD stages 1-2 combined with nonsevere PH). In patients with COPD, the combination of echocardiography, NT-proBNP level, and PA to Ao diameter ratio predicts severe PH with high sensitivity and specificity. The contribution of severe PH and severe airflow limitation to impaired survival is comparable.

Dysregulated circulating microRNA-126 in chronic obstructive pulmonary disease: linkage with acute exacerbation risk, severity degree, and inflammatory cytokines.

BackgroundMicroRNA‐126 (miR‐126) is engaged in respiratory diseases via regulating airway tissue injury and pulmonary inflammation, while its relation with chronic obstructive pulmonary disease (COPD) is not reported. The study aimed to evaluate the value of miR‐126 for estimating COPD acute exacerbation risk and its relation to disease severity and inflammatory cytokines in COPD patients.MethodsThis study was a case–control study. Seventy acute exacerbation COPD (AECOPD) patients, 70 stable COPD (SCOPD) patients, and 70 healthy controls (HCs) were consecutively recruited. Plasma miR‐126 expression was detected by reverse transcription quantitative polymerase chain reaction. Plasma tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and interleukin‐17 (IL‐17) in COPD patients were further determined by enzyme‐linked immunosorbent assay.ResultsMiR‐126 was higher in AECOPD patients compared to SCOPD patients and HCs (both P adj < 0.001). Receiver operating characteristic curves revealed miR‐126 distinguished AECOPD patients from SCOPD patients (area under curve (AUC): 0.805, 95%CI: 0.733–0.877) and HCs (AUC: 0.884, 95%CI: 0.829–0.939) and also distinguished SCOPD from HCs (AUC = 0.656, 95%CI: 0.566–0.747). MiR‐126 positively related to GOLD stage in both AECOPD patients (p < 0.001) and SCOPD patients (p < 0.001). Furthermore, miR‐126 positively linked with TNF‐α (p < 0.001), IL‐1β (p = 0.002), IL‐6 (p = 0.009), and IL‐17 (p < 0.001) levels in AECOPD patients; but miR‐126 only positively related to TNF‐α and IL‐17 levels (all p < 0.050), instead of IL‐1β or IL‐6 level (all p > 0.050) in SCOPD patients and HCs.ConclusionDysregulated circulating miR‐126 not only relates to COPD susceptibility and its acute exacerbation risk but also links with disease severity and inflammatory cytokines in COPD patients.

A Study of Red Blood Cell Disorders in Chronic Obstructive Pulmonary Disease Patients

Background: Chronic obstructive pulmonary disease (COPD) is a disease that affecting body systems especially the respiratory system, circulatory system and also hematopoietic system. Objectives: The primary objective of the present study was to determine the prevalence of anemia and polycythemia in COPD patients. The secondary objectives was to determine factors associated with anemia and polycythemia. Materials and Methods: The present study was a retrospective study. All medical records of COPD patients visiting the lung diseases clinic of HRH Princess Maha Chakri Sirindhorn Medical Center between January 1, 2016, and December 31, 2019, were reviewed. Complete blood count, biochemistry laboratory results, lung function test, 6-minute walking distance, frequency of exacerbations and admission were recorded. Results: One hundred twenty-five patients were enrolled. Patients in GOLD stage 1, 2, 3 and 4 were 41.2%, 47%, 9.8% and 2% respectively. Most of the patients were in group A (50.4%). In our study, the prevalence of anemia in COPD patients was 39.2% and none of the patients had polycythemia. There was no association between GOLD classification or group of COPD and anemia. When analyzed by multiple logistic regression, we found that the higher BMI showed a significantly lower risk of anemia than lower BMI (OR 0.877; 95% CI: 0.795 to 0.967) and the frequency of acute exacerbation correlated with anemic condition statistically significant (OR 1.402, 95% CI: 1.142 to 1.721). Anemia and frequency of exacerbation had&nbsp; very low level of positive correlation (r=0.282) at the significance level. Conclusion: Anemia was common comorbidity in COPD patients. Lower body mass index and frequency of exacerbation were significantly related to anemia. Keywords: Chronic obstructive pulmonary disease; Anemia; Polycythemia; Hemoglobin

Assessment of pulmonary functions and peripheral muscle strength of COPD patients in different GOLD stages

Purpose: The purpose of this research was to examine the respiratory functions, respiratory muscle strength and peripheral muscle strength of COPD patients with different GOLD stages and to evaluate their correlation with the duration and prognosis of the disease in COPD. Methods: Patient’s demographic information, clinical status, COPD Assessment Test score, mMRC Dyspnea Scale score, emergency and hospital admissions numbers in the last 3 months, number of exacerbation and hospitalizations in the last one year were recorded. Maximal mouth pressures were used for respiratory muscle strength. Peripheral muscle strength was evaluated with handgrip in the upper extremity. In the lower extremity knee extension and flexion strength were evaluated with a hand-held dynamometer. The findings of PFT performed during the regular hospital controls were obtained. GOLD stages of patients were determined according to GOLD combined assessment. Results: Total of 31 COPD cases (5 females, 26 males, age 64.80 ± 7.71 years), including nine in Group B, five in Group C and 17 in Group D, were included in our study. There were statistically significant, negative, moderate correlations between all patients' respiratory functions and disease duration (p <0.05; for FVC% r: -0.410; for FEV1% r: -0.569; for MEF25-75% r: -0.451). There was a statistically significant, moderate, negative correlation between knee extension strength and numbers of exacerbations and hospitalizations over the last 1 year (p <0.05). Conclusion: The results of the study suggest that non-respiratory symptoms and GOLD stages should also be considered in the planning of COPD follow-up and pulmonary rehabilitation programs. Clinical trial registration number (NCT04803656), 09.03.2021 (retrospectively registered).

IL-10 producing regulatory B cells are decreased in blood from smokers and COPD patients

BackgroundTwo opposing B cell subsets have been defined based on their cytokine profile: IL-6 producing effector B cells (B-effs) versus IL-10 producing regulatory B cells (B-regs) that respectively positively or negatively regulate immune responses. B-regs are decreased and/or impaired in many autoimmune diseases and inflammatory conditions. Since there is increasing evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD, the aim of this study was to investigate the presence and function of B-regs in COPD.MethodsFirst, presence of IL-10 producing regulatory B cells in human lung tissue was determined by immunohistochemistry. Secondly, quantification of IL-10 + B-regs and IL-6 + B-effs in peripheral blood mononuclear cells (PBMCs) from healthy controls, smokers without airflow limitation, and COPD patients (GOLD stage I-IV) was performed by flow cytometry. Thirdly, we exposed blood-derived B cells from COPD patients in vitro to cigarette smoke extract (CSE) and quantified IL-10 + B-regs and IL-6 + B-effs. Furthermore, we aimed at restoring the perturbed IL10 production by blocking BAFF. Fourthly, we determined mRNA expression of transcription factors involved in IL-10 production in FACS sorted memory- and naive B cells upon exposure to medium or CSE.ResultsThe presence of IL-10 producing regulatory B cells in parenchyma and lymphoid follicles in lungs was confirmed by immunohistochemistry. The percentage of IL-10 + B-regs was significantly decreased in blood-derived memory B cell subsets from smokers without airflow limitation and patients with COPD, compared to never smokers. Furthermore, the capacity of B cells to produce IL-10 was reduced upon in vitro exposure to CSE and this could not be restored by BAFF-blockade. Finally, upon CSE exposure, mRNA levels of the transcription factors IRF4 and HIF-1α, were decreased in memory B cells.ConclusionDecreased numbers and impaired function of B-regs in smokers and patients with COPD might contribute to the initiation and progression of the disease.

Computed tomography-based body composition measures in COPD and their association with clinical outcomes: A systematic review.

BackgroundComputed tomography (CT) is commonly utilized in chronic obstructive pulmonary disease (COPD) for lung cancer screening and emphysema characterization. Computed tomography-morphometric analysis of body composition (muscle mass and adiposity) has gained increased recognition as a marker of disease severity and prognosis. This systematic review aimed to describe the CT-methodology used to assess body composition and identify the association of body composition measures and disease severity, health-related quality of life (HRQL), cardiometabolic risk factors, respiratory exacerbations, and survival in patients with COPD.MethodsSix databases were searched (inception-September 2021) for studies evaluating adult COPD patients using thoracic or abdominal CT-muscle or adiposity body composition measures. The systematic review was conducted in accordance with the PRISMA guidelines.ResultsTwenty eight articles were included with 15,431 COPD patients, across all GOLD stages with 77% males, age range (mean/median 59–78 years), and BMI range 19.8–29.3 kg/m2. There was heterogeneity in assessment of muscle mass and adiposity using thoracic (n = 22) and abdominal (n = 8) CT-scans, capturing different muscle groups, anatomic locations, and adiposity compartments (visceral, subcutaneous, and epicardial). Low muscle mass and increased adiposity were associated with increased COPD severity measures (lung function, exercise capacity, dyspnea) and lower HRQL, but were not consistent across studies. Increased visceral adiposity (n = 6) was associated with cardiovascular disease or risk factors (hypertension, hyperlipidemia, and diabetes). Low muscle CSA was prognostic of respiratory exacerbations or mortality in three of six studies, whereas the relationship with increased intermuscular adiposity and greater mortality was only observed in one of three studies.ConclusionThere was significant variability in CT-body composition measures. In several studies, low muscle mass was associated with increased disease severity and lower HRQL, whereas adiposity with cardiovascular disease/risk factors. Given the heterogeneity in body composition measures and clinical outcomes, the prognostic utility of CT-body composition in COPD requires further study.

Prevalence of metabolic syndrome in chronic obstructive pulmonary disease and its correlation with severity of disease.

ABSTRACTIntroduction:The understanding of chronic obstructive pulmonary disease (COPD) has changed considerably over the past decade. The metabolic syndrome (MS) represents a cluster of risk factors that increases the risk for developing various noncommunicable diseases. In COPD, it is associated with worsening respiratory symptoms, increasing lung function impairment, pulmonary hypertension, and increasing hospitalizationsAims:To determine the prevalence of MS in patients with COPD and correlate it with disease severityMethodology:The present study was a cross-sectional observational study. Patients confirmed by spirometry to have COPD were included in the study. All demographic data and anthropometric, radiological, and laboratory parameters were recorded. The definition stated by modified NCEP ATP III criteria proposed by the AHA/NHLB (2005) was followed to identify patients with MS. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 20 for WindowsResults:A total of 76 patients were included in the study. MS was recorded in 42.1% of COPD cases. The average number of exacerbations and hospitalizations due to COPD in MS cases (1.38 ± 1.95 and 0.97 ± 1.51) were more than the patients without MS (1.27 ± 1.30 and 0.68 ± 0.96). The majority of patients with MS exhibited grade 3 dyspnea based on modified medical research council grading (MMRC). MS was commonest in patients with GOLD stage III disease. High serum triglyceride level was observed in an increasing trend (25%, 30%, 35.5%, and 75%) in GOLD stages I, II, III, and IV, respectivelyConclusion:Patients with MS present with more severe disease and frequent exacerbations. All COPD patients should be screened for MS at the primary level.

SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD - Possible Implications for Interstitial Fibrosis.

BackgroundSmokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19.MethodsThis cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 were never-smoking normal controls (NC). Immunostaining for ACE2, Furin, and TMPRSS2 was performed and analysed for percent expression in small airway epithelium (SAE) and counts for positively and negatively stained type 2 pneumocytes and alveolar macrophages (AMs) were done using Image ProPlus V7.0. Furthermore, primary small airway epithelial cells (pSAEC) were analysed by immunofluorescence after exposure to cigarette smoke extract (CSE).ResultsACE2, Furin, and TMPRSS2 expression significantly increased in SAE and type 2 pneumocytes in all the subjects (except Furin for NLFS) compared to NC (p < 0.001). Similar significance was observed for ACE2 positive AM (p < 0.002), except COPD-ES, which decreased in ACE2 positive AMs (p < 0.003). Total type 2 pneumocytes and AMs significantly increased in the pathological groups compared to NC (p < 0.01), except SAD (p = 0.08). However, AMs are significantly reduced in COPD-ES (p < 0.003). Significant changes were observed for tissue co-expression of Furin and TMPRSS2 with ACE2 in SAE, type 2 pneumocytes and AMs. These markers also negatively correlated with lung function parameters, such as FEV1/FVC % predicted, FEF25-75%, DLCO% predicted. A strong co-localisation and expression for ACE2 (p < 0.0001), Furin (p < 0.01), and TMPRSS2 (p < 0.0001) was observed in pSAEC treated with 1% CSE than controls.DiscussionThe increased expression of ACE2, TMPRSS2 and Furin, in the SAE, type 2 pneumocytes and AMs of smokers and COPD are detrimental to lung function and proves that these patient groups could be more susceptible to severe COVID-19 infection. Increased type 2 pneumocytes suggest that these patients are vulnerable to developing post-COVID-19 interstitial pulmonary fibrosis or fibrosis in general. There could be a silently developing interstitial pathology in smokers and patients with COPD. This is the first comprehensive study to report such changes.

The genesis of Xindian gold deposit, Liaodong Peninsula, NE China: Constraints from zircon U–Pb ages, S–Pb isotopes, and pyrite trace element chemistry

AbstractThe Xindian deposit is a medium tonnage (&gt;5 tonnes of Au) quartz vein‐type gold deposit located on the south‐central part of the Liaodong Peninsula, China. A total of 37 auriferous quartz veins are hosted within the Paleoproterozoic metamorphic rocks of the Gaixian Formation and Late Triassic porphyritic biotite granite. Mineral paragenesis indicates that gold mineralization took place in three stages: early milky quartz‐pyrite stage, main gray quartz‐polymetallic sulfide and gold stage, and late quartz‐calcite‐pyrite stage. Silicification and pyritization are spatially and temporally associated with the main mineralization stage. Zircon U–Pb dating from dikes that predate and postdate the mineralization constrain the timing of mineralization to the Early Cretaceous, between 127.2 and 120.9 Ma. High‐precision in‐situ S isotope analyses yielded δ34S values for pyrite, sphalerite and galena of 10.1–11.0‰, 10.3–10.5‰, and 8.6–8.8‰, respectively, indicating that S was derived from the multiple sources. In‐situ Pb isotope analyses resulted in 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb ratios of 38.207–38.634, 15.598–15.668, and 18.027–18.143, respectively, for pyrite and galena, suggesting Pb derivation from a mixture of Gaixian Formation metamorphic rocks and other potential sources. In‐situ LA‐ICP‐MS trace element mapping and spot analyses show that the inner core of the pyrite (Py‐ic) formed early and is generally enriched in Au, As, Co, Ni, Bi, and Te, the outer core of the pyrite (Py‐oc) contains less Co, Ni, As, and Au, but more Cu, Pb, and Zn, whereas the rim of the pyrite (Py‐r) is enriched in Ag, Sn, Sb, Cu, Pb, and Zn. Trace element signatures of pyrite reveal that the mineralizing fluid was initially of magmatic‐hydrothermal origin, and subsequently modified by intensive interaction with the wall rock (Gaixian Formation). Our results consistently demonstrate that the Xindian gold deposit is resulted from fluid–rock interaction between the Early Cretaceous magmatic‐hydrothermal fluids and Gaixian Formation metamorphic wall rocks that enriched the metal budget of the mineralizing fluid. Then the addition of meteoric water significantly changed the physical and chemical conditions of the mineralizing fluid, triggering gold precipitation in the Xindian deposit. The results of our study expand the Early Cretaceous gold metallogenic models in the Liaodong Peninsula, highlighting the importance of the Gaixian Formation for regional gold mineralization.

Prevalence of depression and anxiety among chronic obstructive pulmonary disorder patients and its impact on the severity of the disease

Background: There is high prevalence of anxiety and depression in chronic obstructive pulmonary disease (COPD) patients, leading to habits such as smoking. Aims and Objectives: This study aims to relate quantitatively, the contribution of anxiety and depression on prognosis, smoking, and stage of the disease. Materials and Methods: This cross-sectional study was conducted over a period of 3 months on 50 male COPD patients, aged 40–70 years. Patients were recruited to participate in the study after obtaining informed consent and were administered a questionnaire. They were subjected for detailed clinical examination, chest-X ray. CAT, BODE, GOLD stage, MADRS, and HAM-A were calculated and submitted for statistical analysis. Results: Depression had more influence on smoking rather than anxiety. There was no contributing influence by age. Conclusion: Clinicians should be encouraged to concentrate more on addressing depression rather than anxiety.

Correlation of Six-Minute Walk Test and COPD Assessment Test (CAT) Scores with Spirometric Indices in Chronic Obstructive Pulmonary Disease Patients

Background: For chronic obstructive pulmonary disease spirometry assessment of post-bronchodilator FEV1 is critical for establishing the diagnosis, staging of the disease, predicting the outcome, and planning treatment. The six-minute walk test (6MWT) is an endurance test used to evaluate functional status of patients with cardiopulmonary disorders. CAT score is a well-established tool for determining the impact of COPD on one's health. Objective: To find out correlation between spirometric indices FEV1, FVC, FEV1/FVC, 6MWT and CAT Scores in COPD patients. Design: Cross sectional study Setting: Conducted from September 2019 to September 2021, for a period of 24 months in a tertiary care hospital in India Materials and Methods: In this study, the correlation between spirometric indices FEV1, FVC, FEV1/FVC, 6MWT and CAT Scores was analyzed in 100 patients diagnosed with COPD. Main outcome measures: 6MWT, CAT Scores and Spirometry values in COPD Sample size: 100 Results: Most patients were males(75%) between the ages of 61-70(36%). Majority were in Stage 3 COPD(55%), followed by stage 2 of GOLD staging(25%). Most of them had CAT score range of 21–30(51%), followed by 10–20(48%) and on 6MWT majority walked a distance of 301-400 meters(43%), followed by &gt; 400 meters(35%). The pulse rate and mean systolic blood pressure increased while mean SpO2 decreased post-6WMT with a statistically significant difference(P&lt;.001). The correlation of 6MWT and spirometry parameters shows there was a strong positive correlation of FEV1, FVC, and FEV1/FVC with 6MWT and correlation of CAT score and spirometry parameters shows there was a strong positive correlation of FEV1, FVC, and FEV1/FVC with 6MWT with a statistically significant difference (P&lt;.0001). There was a strong negative correlation between 6MWT and CAT score with a statistically significant difference (P&lt;.0001) Conclusion: The 6MWT and CAT score can be used as an effective alternative to determine the severity of COPD, according to the findings of this study especially in rural settings where access to spirometry is limited. Limitations: Majority of the individuals in our study had mild–moderate COPD severity, emphasizing that the 6MWT's validity and efficacy should be assessed in all COPD grades. Conflict of interest: None

The Relationship between C-Reactive Protein and COPD Patients

Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable chronic inflammatory respiratory disease that affects 210 million people globally. Due to inflammation the resultant IL6 increases the level of C-REACTIVE PROTEIN (CRP) from hepatocytes. This study was conducted to evaluate the association of C-Reactive Protein in COPD patients. The study also includes the key role of C-reactive protein (CRP) in assessing the acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD), which has proven to be more valuable. This was a prospective study conducted over a period of three months between February 2021 and April 2021 at the department of General Medicine in Saveetha Medical College Hospital, Chennai. In a study of 50 patients, 25 were patients with COPD and 25 were a control group of healthy people. High Sensitivity C-Reactive Protein (hs-CRP), blood gases, spirometry, Body Mass Index (BMI), 6 Minute Walk Distance (6MWD) and GOLD stage of severity were measured. The serum hs-CRP was then evaluated for any correlation with the predictors of outcomes of COPD subjects. hs-CRP levels were higher in patients with COPD than in healthy individuals (4.82 / 0.8 mgl). A correlation was found between hs-CRP and the following variables:&#x0D; FEV1 (r = -0.813; p &lt; 0.01), 6MWD (r = -0.876; p &lt; 0.01), GOLD stage (r = 0.797; p &lt; 0.01) and evaluated. This study revealed that there is certain increase in hs-CRP in COPD patients due to inflammation. It acts not only as an inflammatory diagnostic marker, but also plays a role as predictor for the outcome of the disease and reducing the mortality rate.

Circulating JNK pathway-associated phosphatase: A novel biomarker correlates with Th17 cells, acute exacerbation risk, and severity in chronic obstructive pulmonary disease patients.

BackgroundJNK 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.MethodsTotally, 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.ResultsJKAP 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 FEV1 (%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.ConclusionDownregulated JKAP correlates with Th17 cells, higher acute exacerbation risk, and severity in COPD patients, indicating its underlying potency as a biomarker for COPD.

Upper airway symptoms and Small Airways Disease in Chronic Obstructive Pulmonary Disease, COPD

BackgroundSmall Airways Disease (SAD) is a recognised part of the pathology in Chronic Obstructive Pulmonary Disease (COPD) and contributes to the symptom burden in the disease. Upper airway symptoms in COPD is an emerging field of study, and in this study, we sought to examine the co-existence of SAD and upper airways symptoms in a cohort of COPD patients MethodsWe investigated a cohort of patients with COPD for the presence of SAD with three different modalities. We performed High-Resolution CT (HRCT) with Parametric Response Mapping (PRM) analysis and recorded distribution of emphysema (PRMEmph) and functional Small Airways Disease (PRMfSAD). We measured central and peripheral lung resistance using Impulse Oscillometry (IOS) and recorded R5Hz, R20Hz, R5-R20Hz, X5, Fres and Ax. Static lung function parameters were obtained using Body Plethysmography.Data on upper and lower airway symptoms were evaluated using the Upper Airway subdomain of the 22 items Sino Nasal Outcome Test (SNOT22nasal) and the COPD Assessment Test (CAT), respectively. FindingsWe recruited a total of 112 patients. (female sex: 58%, Age 68 (±8) years, FEV1%predicted: 53% (±16%), GOLD stage: A: 23%, B: 55%, C:1% D: 21%). Forty-five (40%) were classified as having high upper airway symptoms (UAS), defined as SNOT22nasal ≥6. Eighty-seven per cent showed signs of SAD using IOS (R5-R20Hz > 0.07 kPa/L/s). No significant differences were found between UAS groups in IOS, PRM or Body Plethysmography parameters. ConclusionIn patients with COPD, the prevalence of small airways disease was very high, but no association between upper airway symptoms and small airways disease was demonstrated.

Association of Total Airway Count on Computed Tomography with Pulmonary Function Decline in Early-Stage COPD: A Population-Based Prospective Cohort Study.

BackgroundIt has been found that the degree of terminal bronchiole destruction is associated with the severity of COPD. However, total airway count (TAC) of CT-visible and its relationship with COPD lung function severity and pulmonary function decline remains controversial. The present study aimed to determine whether TAC is significantly reduced in early-stage COPD (GOLD stage I–II) compared with healthy control subjects and whether TAC is associated with annual decline in pulmonary function in Chinese patients with early-stage COPD.MethodsA total of 176 participants were enrolled in this study, of which 139 participants had undergone at least two spirometry measurements within 7 years (average 5.5 [standard deviation 0.8] years) after baseline data acquisition. CT-visible TAC was measured by summing all airway segments using semi-automated software. Average lumen diameter, average inner area, emphysema index, air trapping, and inspiratory Pi10 were also measured. Multivariable linear analysis was performed to evaluate variables that were significantly related to pulmonary function parameters and to evaluate the correlation between TAC and annual decline in longitudinal pulmonary function.ResultsCompared with healthy control subjects, CT-visible TAC was significantly reduced by 51% in GOLD II and by 31% in GOLD I after adjustment. TAC had the greatest impact on pre-bronchodilator FEV1, pre-bronchodilator FVC, post-bronchodilator FEV1, and post-bronchodilator FEV1/FVC (both p<0.001) among all CT indicators measured. TAC has the best correlation with inspiratory Pi10 (ρ=−0.751, p<0.001), an evaluation indicator of the degree of airway remodeling. TAC was independently associated with annual decline in pre-bronchodilator FEV1 (p=0.023), post-bronchodilator FEV1 (p=0.018), and post-bronchodilator FEV1/FVC (p<0.001).ConclusionThis finding suggests that CT-visible TAC may be an evaluation indicator of the degree of airway remodeling, and was diminished in greater COPD lung function severity, and independently associated with disease progression. Early-stage COPD patients have already occurred lung structural changes and early intervention may be needed to ameliorate the progression of disease.Clinical Trial RegistrationChiCTR-OO-14004264.

Study of Levels of Plasma Fibrinogen and its Association with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease

COPD has been recognized as a component of the systemic inflammatory syndrome. A commonly used indicator of the severity and progression of the disease in COPD is expiratory volume per second (FEV1). However, it is weakly associated with symptoms and administration difficulties in elderly patients. Therefore, there is a need for other markers that are better and easy to apply to sick and elderly patients. Plasma fibrinogen can be used as a marker of disease severity. Aim: To estimate the plasma fibrinogen level in patients with COPD and Relationship of levels of plasma fibrinogen with the severity of chronic obstructive pulmonary disease using the BODE classification and GOLD staging. Place and Duration: In the Medicine Unit-II of Jinnah Hospital Lahore for one-year duration from August 2020 to August 2021. Methods: In this cross-sectional study, 110 COPD patients were assessed by measuring plasma fibrinogen correlated with disease severity using the GOLD scale, BODE index and the 6-minute walk test. Results: Plasma fibrinogen is present in all COPD patients. A significant correlation was observed between the BODE index (r = 0.69, p &lt;0.001), gold grading (r = 0.95, p &lt;0.001) and plasma fibrinogen levels. Most of the 110 subjects (34.5%) were Grade II, then Grade III 30.9%, 18.1% Grade IV and 14.5% Grade I. In our study, it was found that the average level of fibrinogen increased with the increase in the GOLD stage, which was statistically significant, and the p value was 0.01. Conclusions: Plasma fibrinogen levels are significantly higher in COPD and can be used as a marker correlating with disease severity in COPD. Keywords: COPD; plasma fibrinogen; GOLDEN stage; BODE index.

Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD

Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets. Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations? We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations. Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations. Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations. ClinicalTrials.gov; No.: NCT01969344; URL: www. gov.

127 ‘BONE HEALTH AND FRACTURE RISK ASSESSMENT IN COPD EXACERBATIONS DURING HOSPITALISATION- ROOM FOR IMPROVEMENT?’

Abstract Background COPD increases the risk of osteoporosis and international guidelines recommend that such patients undergo fracture risk assessment, referral for densitometry and appropriate management. We aimed to identify if patients admitted to our hospital with COPD exacerbation underwent assessment and were prescribed bone protection medication. Methods All admissions with COPD exacerbation to an Irish level 2 hospital between July 2020 and July 2021 were identified. The discharge summaries were screened for information regarding the presence of fracture risk and bone health assessment. Discharge prescriptions were examined for calcium, vitamin d and anti-osteoporosis medications. Radiology reports were screened for fragility fractures. Results Between July 2020–2021, there were 3,840 presentations to the medical assessment unit. Forty-six patients were admitted with a diagnosis of COPD exacerbation, mean age 72 (56% female). Seventy eight percent were classified as having GOLD Stage D disease with 28% receiving long term oxygen therapy. Mean number of hospitalisations per year per patient was 1.91 ± 1.2. Forty-three percent had laboratory evidence of bone health assessment during admission. Only 50% of patients were discharged on vitamin d replacement; 22% on calcium supplementation and 4% on osteoporotic medications. Regarding previous fractures, 9% had evidence of fragility fracture described on radiology reports, this was not mentioned on any hospital discharge letter. Conclusion This study suggests that opportunities for bone health assessment and intervention may be under recognised in COPD patients. Ways to improve this may include proformas and visual aids to prompt assessment and documentation of bone health, further education to increase awareness and greater access to densitometry resources in the community. In conclusion, this study highlights that further attention to patients’ bone health assessment and commencement of appropriate treatment is warranted. Admission to hospital or clinic review for such patients provide important opportunities for intervention.

Detection of mineralization stages using zonality and multifractal modeling based on geological and geochemical data in the Au-(Cu) intrusion-related Gouzal-Bolagh deposit, NW Iran

The objective of this paper is to detect various gold and copper mineralization stages according to surface lithogeochemical data utilizing zonality index and spectrum-area (S-A) multifractal modeling along with geological data in the Au-(Cu) intrusion-related Gouzal-Bolagh deposit, northwestern Iran. Gold mineralization at Gouzal-Bolagh consists of quartz-sulfide veins within the Paleocene batholithic granitoid complex, which has intruded into the Mesozoic and older metamorphic rocks and shales. Considering the mineralization type, a zonality index was determined as (Au + Cu)/(As + Sb). Au, Cu, and zonality index values were categorized by the S-A multifractal model and the log–log plots. Moreover, multifractal modeling of the zonality index in correlation with geological (specifically mineralographical) data shows that there are three stages for mineralization including Pre-, main and post-mineralization (supergene enrichment). The main stage of mineralization formed from two sub-stages:A (Quartz vein and veinlet sulfidation), B (Quartz sulfide brecciation). In addition, various stages of mineralization contain zonality index values of < 31.8, 31.8–507.3, 507.3–758.3, 758.3–1628.7 and >1628.7 for background, pre-mineralization, sub-stages A, B and supergene, respectively. The background is a granitic batholith containing silicic mineralized veins with a NE-SW trend. Results obtained by this study demonstrate that there are major occurrences of gold and copper mineralization in the sulfidation and brecciation sub-stages, respectively.

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease

BackgroundDysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.MethodsWe carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.ResultsWe observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.ConclusionThese data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.