High-risk Chronic Obstructive Pulmonary Disease Research Articles

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies

Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups. We examined two high-risk omics-defined groups in non-overlapping test sets (n=1133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined "high activity" (low PRS, high TRS) and "severe risk" (high PRS, high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signalling processes compared to a low-risk (low PRS, low TRS) subgroup. "High activity" but not "severe risk" participants had greater prospective FEV1 decline (COPDGene:-51mL/year; ECLIPSE:-40mL/year) and proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection. National Institutes of Health.

Five-Repetition Sit-to-Stand Test as Predictor of Mortality in High Risk COPD Patients

ObjectiveTo determine if adding performance on the five-repetition sit-to-stand test (5-STS) to chronic obstructive pulmonary disease (COPD) high-risk criteria, proposed by the Spanish COPD guidelines (GesEPOC), affects mortality prognosis. MethodsObservational study of COPD outpatients involved prospective follow-up for 5 years. Patients were classified based on 5-STS performance and risk criteria proposed by GesEPOC version 2021. Outcome measures were 5-year mortality timing and rate. Kaplan–Meier curves and univariate and multivariate Cox proportional-hazard analyses, analysis of variance, and univariate and multivariate linear and logistic regression models were used. ResultsOne hundred and thirty-seven patients were included. Mean age was 66±8.3 years, and 87.6% were men. Of them, 115 (83.9%) were classified as high risk, 43 (34.4%) of whom had poor performance on the 5-STS. Overall mortality at 5 years was 27% and was significantly higher in the high-risk (29.6%) compared with the low-risk (13.6%) group. Among high-risk patients, mortality at 5 years was significantly worse with poor 5-STS performance (60.5%) compared with non-poor performance (11.1%). Poor performance on the 5-STS was independently associated with increased 5-year mortality risk (HR 4.70; 95% CI: 1.96–11.27) in a model adjusted for history of heart disease and dyspnea. ConclusionAmong high-risk COPD patients, those with poor performance on the 5-STS have a significantly higher mortality at 5 years than those with non-poor 5-STS performance.

Factors Determining the Risk Level of Chronic Obstructive Lung Disease (COPD) in Smokers in Bandung City: A Secondary Data Analysis

Chronic obstructive pulmonary disease (COPD) is a major contributor to illness and death. COPD can result in the obstruction of airflow and disturbance of the respiratory system. These symptoms have a tendency to be enduring and progressively worse. In Indonesia, the number of persons affected by COPD is estimated to be 9.2 million, with smokers being the primary cause of COPD cases. Hence, the objective of this study was to determine the risk variables linked to the occurrence of COPD among smokers in Bandung City in 2022. This study employed a cross-sectional design, with a sample size of 189 smokers aged over 40 years in Bandung City. The participants were selected via total sampling. This study employed secondary research methodology, utilising chi-square and binary regression analysis for data analysis. The findings indicated that the prevalence of high-risk COPD cases in Bandung City in 2022 was 12.7%. An relationship was seen between age, smoking intensity, namely 20-30 packs of cigarettes per year, and level of physical activity. After controlling for age, physical activity, and degree of smoking, the primary cause of the increased risk of COPD was the consumption of 20-30 packs of cigarettes per year (PR= 11.34; 95% CI = 1.65 to 77.67). This study highlights the significance of lifestyle interventions, such as smoking cessation programmes and CERDIK's behaviours, in managing COPD.

Whole-course management of chronic obstructive pulmonary disease in primary healthcare: an internet of things-enabled prospective cohort study in China

BackgroundDespite substantial progress in reducing the global burden of chronic obstructive pulmonary disease (COPD), traditional methods to promote understanding and management of COPD are insufficient. We developed an innovative model...

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.

Early Diagnosis of High-Risk Chronic Obstructive Pulmonary Disease Based on Quantitative High-Resolution Computed Tomography Measurements.

Quantitative computed tomography (QCT) techniques, focusing on airway anatomy and emphysema, may help to detect early structural changes of COPD disease. This retrospective study aims to identify high-risk COPD participants by using QCT measurements. We enrolled 140 participants from the Second Affiliated Hospital of Shenyang Medical College who completed inspiratory high-resolution CT scans, pulmonary function tests (PFTs), and clinical characteristics recorded. They were diagnosed Non-COPD by PFT value of FEV1/FVC >70% and divided into two groups according percentage predicted FEV1 (FEV1%), low-risk COPD group: FEV1% ≥ 95%, high-risk group: 80% < FEV1% < 95%. The QCT measurements were analyzed by the Student's t-test (or Mann-Whitney U-test) method. Then, feature candidates were identified using the LASSO method. Meanwhile, the correlation between QCT measurements and PFTs was assessed by the Spearman rank correlation test. Furthermore, support vector machine (SVM) was performed to identify high-risk COPD participants. The performance of the models was evaluated in terms of accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-score, and area under the ROC curve (AUC), with p <0.05 considered statistically significant. The SVM based on QCT measurements achieved good performance in identifying high-risk COPD patients with 85.71% of ACC, 88.34% of SEN, 84.00% of SPE, 83.33% of F1-score, and 0.93 of AUC. Further, QCT measurements integration of clinical data improved the performance with an ACC of 90.48%. The emphysema index (%LAA-950) of left lower lung was negatively correlated with PFTs (P < 0.001). The airway anatomy indexes of lumen diameter (LD) were correlated with PFTs. QCT measurements combined with clinical information could provide an effective tool for an early diagnosis of high-risk COPD. The QCT indexes can be used to assess the pulmonary function status of high-risk COPD.

Patterns of care in the management of high-risk COPD in the US (2011–2019): an observational study for the CONQUEST quality improvement program

In this study, we compare management of patients with high-risk chronic obstructive pulmonary disease (COPD) in the United States to national and international guidelines and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). Patients were identified from the DARTNet Practice Performance Registry and categorized into three high-risk cohorts in each year from 2011 to 2019: newly diagnosed (≤12 months after diagnosis), already diagnosed, and patients with potential undiagnosed COPD. Patients were considered high-risk if they had a history of exacerbations or likely exacerbations (respiratory consult with prescribed medication). Descriptive statistics for 2019 are reported, along with annual trends. In 2019, 10% (n=16,610/167,197) of patients met high-risk criteria. Evidence of spirometry for diagnosis was low; in 2019, 81% (n=1228/1523) of patients newly diagnosed at high-risk had no record of spirometry/peak expiratory flow in the 12 months pre- or post-diagnosis and 43% (n=651/1523) had no record of COPD symptom review. Among those newly and already diagnosed at high-risk, 52% (n=4830/9350) had no evidence of COPD medication. Findings suggest inconsistent adherence to evidence-based guidelines, and opportunities to improve identification, documentation of services, assessment, therapeutic intervention, and follow-up of patients with COPD. This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit

ObjectiveThe aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. MethodsEPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. Results4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], peripheral blood eosinophilia>300mm3 [OR: 2.16 (1.10–4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15–4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41–2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29–7.41), p<0.011]. ConclusionsInhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy.

Effect of high-flow nasal cannula versus non-invasive ventilation in preventing re-intubation in high-risk chronic obstructive pulmonary disease patients: A randomised controlled trial.

Currently, a high-flow nasal cannula (HFNC) has been shown to improve extubation outcomes. However, there is a lack of evidence on the utilisation of HFNC in high-risk chronic obstructive pulmonary disease (COPD) patients. This study aimed to compare the effectiveness of HFNC versus non-invasive ventilation (NIV) in preventing re-intubation following planned extubation in high-risk COPD patients. In this prospective, randomised, controlled trial, 230 mechanically ventilated COPD patients at high risk for re-intubation who fulfilled the criteria for planned extubation were enrolled. Post-extubation blood gases and vital signs at 1, 24, and 48 hours were recorded. The primary outcome was the re-intubation rate within 72 hours. Secondary outcomes included post-extubation respiratory failure, respiratory infection, intensive care unit and hospital length of stay, and mortality rate at 60 days. 230 patients after planned extubation were randomly allocated to receive either HFNC (n = 120) or NIV (n = 110). Re-intubation within 72 hours was significantly lower in the high-flow group: 8 patients (6.6%) versus 23 patients (20.9%) in the NIV group {absolute difference, 14.3% [95% confidence interval (CI), 10.9-16.3]; P = 0.001}. The frequency of post-extubation respiratory failure was less in patients assigned to HFNC than in those allocated NIV (25% vs. 35.4%) [absolute difference, 10.4% (95% CI, 2.4-14.3); P = 0.001]. There was no significant difference between the two groups regarding reasons for respiratory failure after extubation. It was observed that the 60-day mortality rate was lower in patients who received HFNC than in those assigned to NIV (5% vs. 13.6%) [absolute difference, 8.6 (95% CI, 4.3 to 9.10); P = 0.001]. The use of HFNC after extubation appears to be superior to NIV in reducing the risk of re-intubation within 72 hours and 60-day mortality in high-risk COPD patients.

The concept of pre-COPD: development and feasibility in primary health care

BACKGROUND: Chronic obstructive pulmonary disease is often not diagnosed as a preventable disease. The primary physician needs a diagnostic tool to detect chronic obstructive pulmonary disease at an early stage.&#x0D; AIM: To develop the concept of early detection of chronic obstructive pulmonary disease through a diagnostic tool that stratifies patients according to the risk of disease development.&#x0D; MATERIALS AND METHODS: Random sample of persons 3570 years from the lists provided by 15 polyclinics of Saint Petersburg and Arkhangelsk (cross-sectional study, n = 2388). Cohort prospective study (respondents with fixed or variable obstruction, n = 167). All respondents were asked about demographic data, smoking history, risk factors, and the presence of symptoms. Spirometry with a bronchodilator was performed for all participants.&#x0D; RESULTS: Fixed obstruction was found in 6.8% of the participants in the first phase; obstruction was associated with male sex, smoking status over 10 packs/years, age over 55 years, chronic cough and shortness of breath. Of the 65 members of the cohort with variable obstruction, 23.1% had a fixed obstruction after a year, the risk factors of which were a smoking status of more than 10 packs/years, a night cough and forced expiratory volume in 1 second less than lower limit of normal.&#x0D; CONCLUSIONS: Based on the results of the two phases of the study, a diagnostic tool was developed for the early detection of chronic obstructive pulmonary disease in the general population by identifying a group of people with preserved lung function and high-risk chronic obstructive pulmonary disease factors.

Decreased Cardiac Autonomic Function is Associated with Higher Exacerbation Risk and Symptom Burden in Chronic Obstructive Pulmonary Disease.

Current measures of chronic obstructive pulmonary disease (COPD) severity, including lung function, do not fully explain symptom burden, and there is a need to identify predictors of exacerbation risk and morbidity. Autonomic dysfunction may be implicated in both cardiovascular and respiratory morbidity in COPD and convey risk for exacerbations. Heart rate variability (HRV) is a marker of cardiac autonomic function that is predictive of cardiovascular health and has promise as a non-invasive COPD biomarker. The CLEAN AIR Heart study provided an opportunity to investigate the association between HRV and COPD morbidity among former smokers with moderate-severe COPD. Eighty-five participants, contributing 305 HRV measurements, underwent repeated clinical assessments over 4 study periods that included a 24-Holter monitoring assessment of HRV. HRV measures of interest were standard deviation of normal-to-normal intervals, (SDNN) (overall HRV) and root-mean-square of successive differences (RMSSD) (parasympathetic function). Exacerbation risk was assessed using negative binomial models, and mixed-effects models analyzed associations between HRV and symptoms. Decreases in SDNN (incidence rate ratio [IRR]1.40; 95% confidence interval [CI] 1.13 to1.74) and RMSSD (IRR 1.60; 95% CI 1.07 to 2.37) were associated with severe exacerbation risk. Decreases in SDNN were associated with higher St George's Respiratory Questionnaire scores, COPD Assessment Test scores, and chronic bronchitis symptoms. Findings demonstrate that HRV is associated with COPD symptom burden and exacerbation risk. HRV may represent an important biomarker with the potential to identify high-risk COPD populations.

Characteristics Associated with Spirometry Guideline Adherence in VA Patients Hospitalized with Chronic Obstructive Pulmonary Disease.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends at least annual spirometry for patients with chronic obstructive pulmonary disease (COPD). Since spirometry acquisition is variable in clinical practice, identifying characteristics associated with annual spirometry may inform strategies to improve care for patients with COPD. We included veterans hospitalized for COPD at Veterans Health Administration (VHA) facilities from 10/2012 to 09/2015. Our primary outcome was spirometry within 1 year of COPD hospitalization. Patient demographics, health factors, and comorbidities as well as practice and geographic variables were identified using Corporate Data Warehouse; provider characteristics were obtained from the Survey of Healthcare Experiences of Patients. We used logistic regression with a random intercept to account for potential clustering within facilities. Spirometry was completed 1 year before or after hospitalization for 20,683/38,148 (54.2%) veterans across 114 facilities. Patients with spirometry were younger, (mean=67.2 years (standard deviation (SD)=9.3) vs. 69.4 (10.3)), more likely non-white (21.3% vs. 19.7%), and more likely to have comorbidities (p<0.0001 for asthma, depression, and post-traumatic stress disorder). Pulmonary clinic visit was most strongly associated with spirometry (odds ratio (OR)=3.14 [95% confidence interval 2.99-3.30]). There was no association for facility complexity. In a secondary analysis including provider-level data (3862 patients), results were largely unchanged. There was no association between primary care provider age, gender, or type (physician vs. advanced practice registered nurse vs. physician assistant) and spirometry. In a cohort of high-risk COPD patients, just over half completed spirometry within 1 year of hospitalization. Pulmonary clinic visit was most strongly associated with 1-year spirometry, though provider variables were not. Spirometry completion for high-risk COPD patients remains suboptimal and strategies to improve post-hospitalization care for patients not seen in pulmonary clinic should be developed to ensure guideline concordant care.

Re-Defining High Risk COPD with Parameter Response Mapping Based on Machine Learning Models.

PurposeTo explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.Patients and MethodsA total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.ResultsMachine learning-based PRM showed that consistency between PRM parameters and PFT was better able to distinguish high-risk COPD from the normal, with an AUC of 0.84 when the threshold was 72%. When the threshold was 80%, the AUC was 0.72 and when the threshold was 95%, the AUC was 0.64.ConclusionMachine learning-based PRM is feasible for redefining high-risk COPD, and setting the optimal FEV1% predicted value lays the foundation for redefining high-risk COPD diagnosis.

Human Exhalation CO2 Sensor Based on the PEI-PEG/ZnO/NUNCD/Si Heterojunction Electrode.

Gas sensors based on semiconductors have outstanding sensitivity compared with the oxide-based devices; however, the high operation temperature greatly hinders its development in practical applications. Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, and the patients with severe COPD with or without exacerbation tend to have airflow obstruction, which results in an increase of CO2 concentration and subsequent hypercapnic respiratory failure. At present, COPD detection relies on professional operation; however, the patients suffer great discomfort during the arterial blood sampling. All these facts reduce patient’s willingness to test their physical health. Thus, noninvasive monitoring of CO2 levels is crucial for the early diagnosis of high-risk COPD patients. A nitrogen-incorporated ultrananocrystalline diamond (NUNCD) film exhibits excellent properties in biosensing and polyetherimide-polyethylene glycol (PEI-PEG) polymer possesses a great capability of CO2 capturing. By incorporating NUNCD into PEI-PEG film, this work focuses on ameliorating the sensitivity and selectivity of the present semiconductor CO2 sensor. From the theoretical regression analyses of the experimental results, it is found that the excellent performance of the PEI-PEG/ZnO/NUNCD/Si electrode is contributed by two main reaction layers, the adsorption layer (PEI-PEG) and the electric transfer layer (ZnO/NUNCD). The selectivity is dominated by the PEI-PEG adsorption layer and the sensitivity is directly related to the changes in the work function of the ZnO/NUNCD interface. The high aspect ratio (>10) of the flower-like ZnO structure, growth from ZnO nanoparticles, can provide a more active adsorption area, as a result, extremely enhancing the sensitivity of the CO2 sensor.

Lung cancer screening in clinical practice: identification of high-risk chronic obstructive pulmonary disease patients.

The NELSON study demonstrated a positive association between computed tomography scanning and reduced mortality associated with lung cancer. The COPD-LUCSS-DLCO is a tool designed to improve screening selection criteria of lung cancer for chronic obstructive pulmonary disease patients. The aim of this study was to examine and compare the discriminating value of both scores in a community-based cohort of chronic obstructive pulmonary disease patients. A retrospective study of chronic obstructive pulmonary disease patients followed in pulmonology consultation for a period of 10 years (2009-2019) was conducted. The NELSON criteria and COPD-LUCSS-DLCO score were calculated for each patient at the time of the study inclusion. The lung cancer incidence was calculated for each of the subgroups during the follow-up period. A total of 103 patients were included in the study (mean age 64.7±9.2 years, 88.3% male). Applying the COPD-LUCSS-DLCO score, high-risk patients have a 5.9-fold greater risk of developing lung cancer versus the low risk. In contrast, there was no significant association between NELSON selection criteria and lung cancer incidence. The area under the curve was 0.69 for COPD-LUCSS-DLCO and 0.59 for NELSON criteria. Comparing test results showed no differences. The use of the COPD-LUCSS-DLCO score in clinical practice can help to detect chronic obstructive pulmonary disease patients in greater risk of developing lung cancer with better performance than NELSON criteria. Therefore, models that include a risk biomarker strategy can improve selection criteria and consequently can enhance a better lung cancer prediction.

Testing for Vitamin D in High-Risk COPD in Outpatient Clinics in Spain: A Cross-Sectional Analysis of the VITADEPOC Study.

Background: Vitamin D deficiency has been associated with an accelerated deterioration in lung function and increased exacerbations in chronic obstructive pulmonary disease (COPD). 25(OH) vitamin D levels have been indicated as a potentially useful marker for adverse results related to COPD. Methods: VITADEPOC is a cross-sectional clinical study recruiting consecutive patients with high-risk COPD. The objective of our study was to investigate vitamin D determination frequency in patients with high-risk COPD in clinical practice at outpatient clinics in Spain and to describe the factors associated with vitamin D testing. We also aimed to determine the frequency of vitamin D deficiency in these patients. Results: Only 51 (44%) patients underwent vitamin D determination and 33 (28.4%) had received vitamin D supplements in clinical practice. The patients who underwent testing for vitamin D in clinical practice were more often women (58.8% vs. 26.2%, p < 0.001) with comorbidities such as osteoporosis (19.6% vs. 6.2%, p < 0.001) or chronic renal failure (7.8% vs. 0%, p < 0.001) and with exacerbator phenotype (55% vs. 32.3%, p = 0.015). A total of 63 (54.3%) patients had serum vitamin D levels <20 ng/mL at the inclusion visit. Of these, 29 (46%) had serum vitamin D levels <12 ng/mL (severe deficiency). Having a history of inhaled corticosteroids (OR 3.210, p < 0.016), being treated with a cycle of systemic corticosteroids (OR 2.149, p < 0.002), and having a lower physical activity level (OR 3.840, p < 0.004) showed a statistically significant positive association with vitamin D deficiency. Conclusion: The testing of vitamin D levels in patients with high-risk COPD treated at outpatient respiratory clinics in Spain is infrequent. However, when tested, a severe deficiency is detected in one in four patients. Efforts to optimize case detection in COPD are needed.

Statins in High-Risk Chronic Obstructive Pulmonary Disease Outpatients: No Impact on Time to First Exacerbation and All-Cause Mortality - The STATUETTE Cohort Study.

BackgroundStatins have, due to their anti-inflammatory properties, been suggested to potentially improve chronic obstructive pulmonary disease (COPD) outcomes. We aimed to investigate the effect of statins on time to first exacerbation and all-cause mortality in high-risk COPD outpatients.MethodsAll outpatients with COPD seen at the Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, Denmark in 2016 were identified and followed for 3.5 years in this retrospective, registry-based cohort study of time to first acute exacerbation of COPD (AECOPD) or death. AECOPD was defined as a rescue course of oral corticosteroid and/or hospital admission. The association was estimated using time-varying crude and multivariable Cox proportional hazard regression.ResultsThe cohort comprised 950 COPD outpatients, mean (SD) age 71 (11) years, and FEV1 44% predicted (IQR 33%; 57%). The annual exacerbation rate was 0.88 (1.68) and 211 patients (22%) had a history of hospital admission for AECOPD in the 12 months prior to index date. Three hundred and ninety-three patients (41.4%) were defined as statin users, with 131 (33.3%) having filled the first prescription for statin after index date. Statin use was not associated with reduced risk of AECOPD. When stratifying for moderate and severe exacerbations in a sub-analysis in the same model, statin use did not have an increased HR for exacerbation of either severity (HR = 1.02 (95% CI 0.85to 1.24; p = 0.811) and HR = 1.07 (95% CI 0.89 to 1.29; p = 0.492) respectively). Statin use was not associated with all-cause mortality (HR 1.05 (95% CI, 0.75 to 1.47, p = 0.777)).ConclusionWe did not find any association between statin use and risk of AECOPD or all-cause mortality. The result adds to the evidence that an aggressive approach with statin treatment upfront is not beneficial in COPD, unless prescribed according to current guidelines for cardiovascular diseases.

Is serum iron responsive protein-2 level associated with pulmonary functions and frequent exacerbator phenotype in COPD?

Chronic Obstructive Pulmonary Disease (COPD) exacerbations contribute to the overall severity in individual patients because they are associated with airway inflammation, pulmonary function loss, decreased quality of life and increased mortality. Although, identifying frequent exacerbator patients is important due to severe outcomes associated with frequent exacerbator phenotype in COPD patients there is no single biomarker which can differentiate this phenotype. Iron responding protein-2 (IRP2) is the protein product of IREB2 gene, which is a COPD susceptibility gene that regulates cellular iron homeostasis and has a key role in hypoxic conditions. Previous research indicates that IREB2 expression in lung tissue is associated with spirometric measurements and emphysema in COPD. In this study, our aim was to investigate whether serum IRP2 levels were associated with frequent exacerbator phenotype, to evaluate whether IRP2 levels in serum are associated with pulmonary functions and selected systemic inflammation biomarkers. Designed as a single tertiary care center based, crosssectional study, included high risk (GOLD C, D) COPD patients who admitted to outpatient clinic consecutively between December 2015 and July 2016. The study included 80 COPD patients. Serum IRP2 levels were negatively correlated with FEV1 ml (r= -0.25, p= 0.02) and body weight (r= -0.35, p= 0.002) but not with markers of systemic inflammation. COPD patients with at least one exacerbation history in the last year tended to have higher IRP2 levels than patients without any exacerbation [12.3 (IQR 25-75: 10.4- 17.1) vs 10.5 (IQR 25-75: 8.8-18.5), p= 0.06]. Serum IRP2 level is significantly correlated with FEV1 mL but not with FEV1 % predicted and cannot be used to differentiate frequent exacer bator patients. Although IREB2 gene expressions in lung tissue and bronchoalveolar lavage results have significant associations with emphysema and FEV1/FVC, FEV1 %predicted in COPD patients, our results suggests serum IRP2 level is not as promising.

Can Triple Inhaled Therapy Lower All-Cause Mortality for High-Risk COPD Patients?

Whether inhaled medications can lower mortality among patients with chronic obstructive pulmonary disease (COPD) has been debated for years. In a 2007

Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD in Chinese Population: A Prospective Cohort Study.

BackgroundIn China, the high prevalence and mortality rate of Chronic Obstructive Pulmonary Disease (COPD) and the poor intervention effect makes it into a heavy social burden. The main reason is that the current diagnosis of COPD mainly based on the static lung function, which is difficult for early intervention. Through matching a predictive model for high-risk groups of COPD that rewards FEV1 rapid decline as the core, we will establish the early warning model and prove its validity and socio-economic value.MethodsThis is a multi-center, prospective, cohort study. A total of 10,000 people aged 40∼75 without lung disease will be recruited and followed for 3 years. Some questionnaires such as St George’s Respiratory Questionnaire (SGRQ), income class, educational level, comorbidity, smoking habit, and biomass smoke exposure history will be collected. The baseline level of Interleukin 6 (IL-6), high-sensitivity C-reactive Protein (hs-CRP), microRNAs-23a (miR-23a) in peripheral blood and pH value in exhaled breath condensate (EBC) will be measured, lung spirometry will be tested in the first, second, and fourth years. Primary outcome is the incidence of COPD, multivariate regression analysis will be used to establish the predictive model for COPD in China.DiscussionWith the rapid decline of lung function as the core and the baseline inflammatory biomarkers in peripheral blood and pH of the exhaled breath condensate as affecting factors, a predictive model to achieve early detection of high-risk COPD groups will be established and promoted.Trial registrationThis study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018, https://register.clinicaltrials.gov.