Chronic Obstructive Pulmonary Disease Status Research Articles

Effectiveness of empagliflozin in patients with heart failure and COPD: Results from EMPEROR-Preserved and EMPEROR-Reduced

Abstract Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive syndromes that share numerous risk factors and clinical symptoms. We sought to analyse the relationship between COPD status and outcomes in patients receiving empagliflozin or placebo in the EMPEROR-Preserved and EMPEROR-Reduced trials. Methods and results We analyzed data of 9,718 patients, including 1,238 (12.7%) with COPD. Compared to patients without COPD, patients with COPD were more likely to be in NYHA class III (19.4 vs. 28.4%), to be male (62.4 vs. 69.0%), to have higher body mass index (29.0±5.7 vs. 29.5±6.1 kg/m2), to be white, to be smoker or ex-smoker (47.1 vs. 71.9%), to be older (69.6±10.5 vs. 72.1±8.7y, all p<0.0001), to have a longer duration of HF (5.0 vs. 5.4y, p=0.04), to have higher haemoglobin and high-sensitivity troponin T values (both p<0.01), and a trend towards more advanced kidney dysfunction. Patients with COPD exhibited a higher adjusted risk of reaching the primary endpoint of first HF hospitalization or CV death compared to those without COPD (adjusted hazard ratio [HR] 1.52, 95% confidence interval [95% CI] 1.28-1.80, p<0.0001). The favorable impact of empagliflozin on the primary outcome remained consistent regardless of COPD status at baseline (no COPD: HR 0.76, 95% CI 0.68-0.84, COPD: HR 0.82, 95% CI 0.66-1.03, p for interaction 0.50, Figure). The effects on HF hospitalizations, cardiovascular and all-cause mortality were not affected by COPD status. The Kansas City Cardiomyopathy Questionnaire showed similar improvement in patients with or without COPD treated with empagliflozin. The distribution of adverse events was comparable between patients receiving empagliflozin and those on placebo, irrespective of COPD status at baseline. Conclusions COPD is frequently encountered in patients with HF and associated with worse outcomes. Among patients with COPD, treatment with empagliflozin is associated with consistent efficacy on outcomes and improvement in quality of life as in patients without COPD.

Correlation between elderly patients with COPD and the impact on immunity in tuberculosis patients: A retrospective study.

The prevalence of chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) is increasing globally, yet their comprehensive impact on the immune system remains underexplored. This study aimed to provide a thorough assessment of the immune status of patients with COPD and tuberculosis (TB-COPD), including their pulmonary conditions, immune cell responses, and changes in lymphocyte subpopulations. A total of 151 patients with TB-COPD patients were included, and clinical data were compared between the TB-COPD group and a group of TB patients without COPD (TB-NCOPD). Lung imaging findings and peripheral blood immune cell levels were compared between the 2 groups. Flow cytometry was used to analyze the absolute counts of lymphocyte subpopulations. The incidence of pulmonary lobe lesions and cavitation in the TB-COPD group aged 70 years or older was significantly higher than that in the control group. At the immune cell level, patients with TB-COPD showed a significant reduction in total lymphocytes, CD4+ T lymphocytes and CD4+/CD8+ ratio. Regardless of COPD status, the CD4+ T cell count in the CMV-infected group was significantly lower than that in the uninfected group (P < .05). Additionally, the CD4+/CD8+ ratio in the COPD + TB CMV + group was significantly lower than that in the uninfected group. Analysis of lymphocyte subpopulations revealed a decrease in the counts of CD4+ T lymphocytes in patients with TB-COPD, potentially associated with the chronic inflammatory state induced by COPD. The one-month treatment outcomes showed that the improvement rate in the control group was 70.58%, which was significantly higher than the 38.92% in the COPD + TB group (P < .001). We observed a significant increase in the number of pulmonary cavity patients in the TB-COPD group, suggesting that COPD may be a potential risk factor for the formation of pulmonary cavities in patients with TB. At the immune cell level, TB-COPD patients showed a notable decrease in lymphocytes and CD4+ T lymphocytes, implying that COPD combined with pulmonary TB may significantly affect the immune system, leading to a reduction in the counts of key immune cells.

Incidence of and risk factors for preoperative deep vein thrombosis in elderly patients with end-stage osteoarthritis following total knee arthroplasty: a retrospective cohort study

BackgroundDeep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty.MethodsWe retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values.ResultsThe incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P < 0.001) and 72.5 years for age (AUC, 0.668; P < 0.001).ConclusionAmong elderly patients with end-stage OA, venous ultrasonography to rule out DVT risk should be prioritized in those with a high D-dimer concentration (> 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).

Prevalence and Impact of Chronic Obstructive Pulmonary Disease in Ischemic Heart Disease: A Systematic Review and Meta-Analysis of 18 Million Patients.

The prevalence of chronic obstructive pulmonary disease (COPD) in patients with ischemic heart disease (IHD) remains uncertain, and its association with adverse outcomes is frequently overlooked. This study aimed to estimate the prevalence of COPD, and its impact on pharmacological treatment, and clinical outcomes in patients with IHD. A systematic literature search was conducted in Web of Science, Embase, and PubMed until November 20, 2023. All studies that reported the prevalence of COPD in IHD patients were included, and a random-effects model was employed to calculate the pooled prevalence. Data on cardiovascular risk factors/comorbidities, beta-blockers (BBs) prescription, acute phase outcomes [in-hospital mortality, major adverse cardiovascular events (MACE), acute heart failure (AHF), and cardiogenic shock], and long-term mortality were compared according to COPD status. A total of 82 eligible studies that reported the prevalence of COPD in 18 million IHD patients were included. The pooled prevalence of COPD was 12.0% [95% confidence intervals (CI): 9.9%-14.1%] in patients with IHD. In subgroup analysis, the prevalence of COPD was highest in North America (15.3%), followed by Europe (10.0%), and Asia (8.8%). In addition, COPD was associated with a higher burden of cardiovascular risk factors/comorbidities, but lower BBs prescription [odds ratio (OR) 0.50, 95% CI 0.38-0.66]. Moreover, COPD was linked to an increased risk of in-hospital mortality (OR 1.47, 95% CI 1.37-1.58), MACE (OR 1.81, 95% CI 1.44-2.27), AHF (OR 2.14, 95% CI 1.86-2.46), cardiogenic shock (OR 1.30, 95% CI 1.01-1.68), as well as long-term mortality (OR 1.99, 95% CI 1.80-2.20). This meta-analysis demonstrated that COPD is prevalent in IHD, involving 12.0% of IHD patients, and is linked to a lower prescription of BBs, an increased burden of comorbidities, and worse acute phase outcomes and long-term mortality.

Exploring the Promising Impact of Pulmonary Rehabilitation on Gait and Balance in Patients With COPD

Purpose: Chronic obstructive pulmonary disease (COPD) is commonly associated with respiratory difficulties, but it also presents with musculoskeletal problems. The objective of this systematic review and meta-analysis was to evaluate the effects of pulmonary rehabilitation (PR) on balance and gait in patients with COPD. Review Methods: We conducted a comprehensive search of 4 databases, including PubMed, Google Scholar, Science Direct, and Web of Science, from inception to November 2023. The review included studies reporting the association between COPD status and balance and gait using PR. Two independent reviewers examined the titles and abstracts, extracted the data using a standardized form, and assessed the risk of bias of the included articles. Summary: A total of 14 studies with 320 patients in the study groups and 188 controls were included in the analysis. The risk of bias in the included studies was medium to high. The results showed that PR non-statistically significantly improved balance, as demonstrated by moderate effect sizes in the Timed Up and Go (standardized mean difference [SMD] = 0.1: 95% CI, −1.41 to 1.69) and Berg Balance Scale (SMD = −0.39: 95% CI, −1.30 to 0.53). However, the impact of PR on gait function was less clear, with mixed results. The study findings highlight the positive but non-significant effects of PR on balance in individuals with COPD. The results suggest that PR programs could include exercises that target balance improvement to enhance the overall quality of patients. However, further research is needed to determine the optimal duration and intensity of these exercises to achieve maximum benefits for patients with COPD.

MRNA expression insights: Unraveling the relationship between COPD and lung cancer.

Lung cancer is a prevalent form of cancer worldwide. A possible link between lung cancer and chronic obstructive pulmonary disease (COPD) has been suggested by recent studies. The objective of our research was to analyze the mRNA expression patterns in both situations, with a specific emphasis on their biological functions and the pathways they are linked to. Data on COPD mRNA expression was collected from the NCBI-GEO database, while information regarding lung cancer mRNA was acquired from The Cancer Genome Atlas database. To examine the association of COPD-related scores in lung cancer patients, we utilized the ssGSEA algorithm for single sample gene set enrichment analysis. The possible routes were examined through the utilization of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Risk models were developed using Coxand least absolute shrinkage and selection operator (LASSO) regression analyses. Moreover, a GSEA was performed to investigate significant pathways among various risk groups. After identifying 17 genes that were differentially expressed and linked to COPD, we found that they met the criteria of having a false discovery rate < 0.05 and an absolute log2 fold change > 0.585. By utilizing the ssGSEA algorithm, it became possible to classify individuals with lung cancer into two distinct groups based on their COPD status. Consequently, a seven-gene risk model was developed specifically for these patients. The risk score was determined by applying the given formula: risk score = AC022784.1 × 0.0423737993775888 + CRISP3× 0.0415322046890524 + MELTF × 0.0661848418476596 + MT2P1 × 0.111843227536117 + FAM83A-AS1 × 0.045295939710361 + ZNF506 × -0.309489953363417 + ITGA6 × 0.01813978449589. The risk model associated with COPD showed a notable connection with different immune cells found in the lung cancer sample, including macrophages of M0/M1/M2 types, hematopoietic stem cells, mast cells, NK T cells and regulatory T cells. Overexpression of crucial genes was seen to enhance cell proliferation and invasive potential in the lung cancer sample. In the lung cancer sample, it was observed that an increase in ZNF506 expression enhanced both cell proliferation and invasion. In conclusion, this study effectively examines the potential correlation between COPD and lung cancer. A prognostic model based on seven COPD-associated genes demonstrated robust predictive potential in the lung cancer sample. Our analysis offers comprehensive insights for lung cancer patients.

Vitamin D Status and Lung Function in Stable COPD: A Cross-Sectional Study

Chronic obstructive pulmonary disease (COPD) is a major global health concern characterized by progressive airflow limitation. Vitamin D deficiency has been linked to impaired lung function and increased inflammation, suggesting a potential role in COPD pathogenesis. This study aimed to investigate the relationship between vitamin D status and lung function in patients with stable COPD. A cross-sectional study was conducted involving 51 stable COPD patients. Spirometry was performed to assess lung function, and serum 25-hydroxyvitamin D [25(OH)D] levels were measured. The association between 25(OH)D levels and lung function parameters, including forced expiratory volume in one second (FEV1), was analyzed using Pearson correlation. The mean age of the participants was 64.05 ± 8.05 years, and all were male. The majority (47.1%) had severe airflow limitation (FEV1 &lt; 30% predicted). The mean 25(OH)D level was 27.57 ± 6.74 ng/mL, indicating insufficiency in most patients. No significant correlation was found between 25(OH)D levels and FEV1 (r = -0.131, p = 0.180). In conclusion, this study did not find a significant association between vitamin D status and lung function in stable COPD patients. Further research, including longitudinal studies and interventional trials, is needed to elucidate the complex relationship between vitamin D and COPD and to determine the potential benefits of vitamin D supplementation in this population.

The relationship between heart failure and smoking, and development of urethral stricture.

To evaluate the relationship between heart failure (HF), chronic obstructive pulmonary disease (COPD), and smoking with the development of urethral stricture (US) by examining the patients who underwent transurethral prostate resection procedure, with and without the development of US in their follow-ups. Among the patients who underwent transurethral resection of the prostate, 50 patients who developed US during their follow-ups formed group 1, while a total of 50 patients who did not develop US and were selected by lot formed group 2. The relationship between the patients' data on HF, COPD and smoking status and the development of US was investigated. The mean number of cigarettes smoked was statistically significantly high in the group with stricture (p = 0.007). Furthermore, pulmonary function test parameters of patients such as forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were found to be statistically significantly higher in Group 2 (p < 0.001, p < 0.001, and p = 0.008, respectively). In the logistic regression analysis, being a smoker was found to be the strongest predictor (p = 0.032). Our study concluded that smoking, HF, and COPD significantly increase the risk of developing stricture after transurethral resection of the prostate.

Predictors of paroxysmal atrial fibrillation in patients with a cryptogenic stroke: Selecting patients for long-term rhythm monitoring

BackgroundAfter a cryptogenic stroke, patients often will require prolonged cardiac monitoring; however, the subset of patients who would benefit from long-term rhythm monitoring is not clearly defined. ObjectiveThe purpose of this study was to create a risk score by identifying significant predictors of atrial fibrillation (AF) using age, sex, comorbidities, baseline 12-lead electrocardiogram, short-term rhythm monitoring, and echocardiographic data and to compare it to previously published risk scores. MethodsPatients admitted to Montefiore Medical Center between May 2017 and June 2022 with a primary diagnosis of cryptogenic stroke or transient ischemic attack who underwent long-term rhythm monitoring with an implantable cardiac monitor were retrospectively analyzed. ResultsVariables positively associated with a diagnosis of clinically significant AF include age (P <.001), race (P = .022), diabetes status (P = .026), chronic obstructive pulmonary disease status (P = .012), presence of atrial runs (P = .003), number of atrial runs per 24 hours (P <.001), total number of atrial run beats per 24 hours (P <.001), number of beats in the longest atrial run (P <.001), left atrial enlargement (P = .007), and at least mild mitral regurgitation (P = .009). We created a risk stratification score for our population, termed the ACL score. The ACL score demonstrated superiority to the CHA2DS2-VASc score and comparability to the C2HEST score for predicting device-detected AF. ConclusionThe ACL score enables clinicians to better predict which patients are more likely to be diagnosed with device-detected AF after a cryptogenic stroke.

BMI moderates the relationship between depression and chronic obstructive pulmonary disease: A cross‑sectional survey

BackgroundPrior research has established a connection between depression and chronic obstructive pulmonary disease (COPD). However, the influence of age and BMI on this association remains unclear. ObjectivesWe used the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between depression and COPD, and to investigate whether age and Body mass index (BMI) act as moderators in this relationship. MethodsWe analyzed data from 10,940 participants in the NHANES database. Depression served as the independent variable. COPD status served as the outcome variable. We employed multivariable logistic regression to examine the relationship between depression and COPD. ResultsOf the 10,940 respondents surveyed, about 3.9 % had COPD and 8.5 % had depression. The prevalence of depression in COPD patients was significantly greater than the prevalence of overall respondents (21.1 % VS.8.5 %). We found that the association between depression and COPD was mediated by BMI status. Controlling for other covariates, the association between depression and COPD increased significantly. For the underweight group, the impact of depression on the risk of COPD was lower compared to the normal BMI group. ConclusionThis study confirms a significant association between depression and COPD, with BMI serving as a moderator. These findings enhance our understanding of the complex interplay between depression and COPD and underscore the importance of considering individual physical health characteristics in clinical assessments. The results have significant implications for clinical practice and public health policymaking.

Efficacy and safety of pembrolizumab as first-line treatment for advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease: protocol for a prospective, single-arm, single-center, phase II clinical trial.

The first-line standard treatment option for patients with NSCLC complicated with Chronic obstructive pulmonary disease (COPD) is still unclear and relies on the treatment option of NSCLC alone. To date, a limited number of retrospective studies have explored the efficacy and safety of immunotherapy in patients with NSCLC complicated with COPD. We therefore designed this study to further explore the efficacy and safety of first-line immunotherapy in patients with NSCLC complicated with COPD. This study was designed as a single-armed, single-center, prospective, phase II clinical study. It will include 30 advanced (stage IV) NSCLC combined with COPD primary treatment subjects. Each subject's diagnosis will be confirmed by clinical, radiographic, pathologic, and pulmonary function evaluation. A fixed dose of 200 mg pembrolizumab will be administered by intravenous infusion on day1 every 3 weeks (Q3W). The management of stable and acute exacerbations of COPD include home oxygen therapy, and the use of conventional medications are also administered. Imaging evaluation will be performed every 6 weeks for 6 months from the first pembrolizumab dose and approximately every 12 weeks thereafter until disease progression or early withdrawal. COPD status will be evaluated every 3 months by pulmonary function, GOLD grading, mMRC score, CAT score, ABCD grouping, and AECOPD severity. The primary outcome is Progression-free survival. The secondary outcome measures include objective response rate, overall survival, rate of acute exacerbations of COPD (times/year), lung function, mMRC score, CAT score, impact of treatment on patient's health-related quality of life, antibiotic use (including duration and classes), and adverse events associated with immune checkpoint inhibitors. Exploratory endpoint is to explore the association between COPD grade and the degree of immune cell (CD4+ T lymphocytes and CD8+ T lymphocytes) infiltration, as well as the association between COPD grade and the efficacy of immune checkpoint inhibitors. ClinicalTrials.gov, identifier NCT05578222.

A Kano model-based demand analysis and perceived barriers of pulmonary rehabilitation interventions for patients with chronic obstructive pulmonary disease in China.

Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view. In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted. Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration. This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future.

Stable COPD Picture through Exhaled Breath Condensate, Questionnaires and Tests. A Proof of Concept Study

Background: Changes in lung structures persist in stable Chronic Obstructive Pulmonary Disease (COPD), but their correlation with the clinical picture remains unclear. The purpose of this study was to assess the stable COPD picture via the relationship between exhaled breath condensate (EBC) particle concentration and the Saint George Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and six-minute walking test (6 MWT). Methods: 12 stable COPD and 12 healthy subjects participated in the study. The EBC was collected with Rtube and analyzed using the Accusizer FxNano. Particle concentration was measured and correlated with the findings of the tools used to assess the health status and functional profile of COPD. The results’ analysis was performed with the Spearman’s test and the Mann-Whitney U - test. Results: The COPD group presented a worse picture of health status and functional profile compared to the healthy group. Correlations were observed between components of the SGRQ and CAT. The two groups presented similar levels of EBC particle concentrations, but the number of small particles was higher in COPD subjects. A correlation of the EBC particle concentration with the activity and total score of the SGRQ was only observed in the healthy group. Conclusion: The total particle number was similar in the COPD and healthy groups. A few correlations between the EBC particles and tools used were also observed. The use of EBC particle concentration to monitor COPD status cannot be claimed with confidence because of the small sample size. Further research is necessary, particularly in large-scale groups.

Palliative Care Among Lung Cancer Patients With and Without COPD: A Population-Based Cohort Study.

Lung cancer patients with chronic obstructive pulmonary disease (COPD) may have greater palliative care needs due to poor prognosis and symptom burden. We sought to compare the provision of timely palliative care and symptom burden by COPD status. We performed a retrospective, population-based cohort study of individuals diagnosed with lung cancer in Ontario, Canada (2009-2019) using health administrative databases and cancer registries. The impact of COPD on the probability of receiving palliative care was determined accounting for dying as a competing event, overall and stratified by stage. The provision of palliative care for patients with severe symptoms (Edmonton Symptom Assessment Scale score ≥ 7), location of the first palliative care visit and symptom severity were compared by COPD status. A total of 74,993 patients were included in the study (48% of patients had available symptom data). At the time of lung cancer diagnosis, 50% of patients had COPD. Stage I-III patients with COPD were more likely to receive palliative care (adjusted Hazard Ratio (HR)s: 1.05-1.31) with no difference for stage IV (1.02, 95% CI: 1.00-1.04). Despite having severe symptoms, very few patients with early-stage disease received palliative care (Stage I: COPD-23% vs. no COPD-18%, SMD=0.12). Most patients (84%) reported severe symptoms and COPD worsened symptom burden, especially among early-stage patients. COPD impacts the receipt of palliative care and symptom burden for patients with early-stage lung cancer. Many patients with severe symptoms did not receive palliative care, suggesting unmet needs among this vulnerable population.

Chest MRI and CT Predictors of 10-Year All-Cause Mortality in COPD

Pulmonary imaging measurements using magnetic resonance imaging (MRI) and computed tomography (CT) have the potential to deepen our understanding of chronic obstructive pulmonary disease (COPD) by measuring airway and parenchymal pathologic information that cannot be provided by spirometry. Currently, MRI and CT measurements are not included in mortality risk predictions, diagnosis, or COPD staging. We evaluated baseline pulmonary function, MRI and CT measurements alongside imaging texture-features to predict 10-year all-cause mortality in ex-smokers with (n = 93; 31 females; 70 ± 9years) and without (n = 69; 29 females, 69 ± 9years) COPD. CT airway and vessel measurements, helium-3 (3He) MRI ventilation defect percent (VDP) and apparent diffusion coefficients (ADC) were quantified. MRI and CT texture-features were extracted using PyRadiomics (version2.2.0). Associations between 10-year all-cause mortality and all clinical and imaging measurements were evaluated using multivariable regression model odds-ratios. Machine-learning predictive models for 10-year all-cause mortality were evaluated using area-under-receiver-operator-characteristic-curve (AUC), sensitivity and specificity analyses. DLCO (%pred) (HR = 0.955, 95%CI: 0.934-0.976, p < 0.001), MRI ADC (HR = 1.843, 95%CI: 1.260-2.871, p < 0.001), and CT informational-measure-of-correlation (HR = 3.546, 95% CI: 1.660-7.573, p = 0.001) were the strongest predictors of 10-year mortality. A machine-learning model trained on clinical, imaging, and imaging textures was the best predictive model (AUC = 0.82, sensitivity = 83%, specificity = 84%) and outperformed the solely clinical model (AUC = 0.76, sensitivity = 77%, specificity = 79%). In ex-smokers, regardless of COPD status, addition of CT and MR imaging texture measurements to clinical models provided unique prognostic information of mortality risk that can allow for better clinical management.Clinical Trial Registration: www.clinicaltrials.gov NCT02279329

Initial alpha-1 antitrypsin screening in Turkish patients with chronic obstructive pulmonary disease.

Alpha-1 antitrypsin (AAT) deficiency is associated with several types of pathology, and the reported effects of mutations in the ATT-encoding gene vary worldwide. No Turkish study has yet appeared. We thus explored the AAT status of Turkish patients with chronic obstructive pulmonary disease (COPD). This prospective cross-sectional study included outpatients and inpatients treated from June 2021 to June 2022. Serum AAT levels were checked, and dry blood samples were subjected to genetic analysis. : Genetic mutations were found in 21 (3.52%) of 596 patients with prior and new COPD diagnoses treated in our pneumonology outpatient department. The mean serum AAT level was 114.80 mg/dL (minimum 19, maximum 209; standard deviation 27.86 mg/dL). The most frequent mutation was M/Plowell (23.8%, n = 5), followed by M/S (23.8%, n = 5), M/I (19%, n = 4), M/Malton (14.3%, n = 3), Z/Z (9.5%, n = 2), M/Z (4.8%, n = 1), and Kayseri/Kayseri (4.8%, n = 1). Thoracic computed tomography revealed that 85.7% (n = 18) of all patients had emphysema, 28.5% (n = 6) had bronchiectasis, and 28.5% (n = 6) had mass lesions. Of the emphysema patients, 55% (n = 10) had only upper lobe emphysema, and 83.3% (n = 15) had emphysema in additional areas, but statistical significance was lacking (p > 0.05). In patients with emphysema and normal serum AAT levels, genetic analyses may reveal relevant heterozygous mutations, which are commonly ignored. Most clinicians focus on lower lobe emphysema. Evaluations of such patients might reveal AAT mutations that are presently overlooked because they are not considered to influence COPD status.

Pre-diagnostic prescribing patterns in dyspnoea patients with as-yet-undiagnosed lung cancer: A longitudinal study of linked primary care and cancer registry data

IntroductionPatients with as-yet undiagnosed lung cancer (LC) can present to primary care with non-specific symptoms such as dyspnoea, often in the context of pre-existing chronic obstructive pulmonary disease (COPD). Related medication prescriptions pre-diagnosis might represent opportunities for earlier diagnosis, but UK evidence is limited. Consequently, we explored prescribing patterns of relevant medications in patients who presented with dyspnoea in primary care and were subsequently diagnosed with LC. MethodLinked primary care (Clinical Practice Research Datalink) and National Cancer Registry data were used to identify 5434 patients with incident LC within a year of a dyspnoea presentation in primary care between 2006 and 2016. Primary care prescriptions relevant to dyspnoea management were examined: antibiotics, inhaled medications, oral steroids, and opioid analgesics. Poisson regression models estimated monthly prescribing rates during the year pre-diagnosis. Variation by COPD status (52 % pre-existing, 36 % COPD-free, 12 % new-onset) was examined. Inflection points were identified indicating when prescribing rates changed from the background rate. Results63 % of patients received 1 or more relevant prescriptions 1–12 months pre-diagnosis. Pre-existing COPD patients were most prescribed inhaled medications. COPD-free and new-onset COPD patients were most prescribed antibiotics. Most patients received 2 or more relevant prescriptions. Monthly prescribing rates of all medications increased towards time of diagnosis in all patient groups and were highest in pre-existing COPD patients. Increases in prescribing activity were observed earliest in pre-existing COPD patients 5 months pre-diagnosis for inhaled medications, antibiotics, and steroids, ConclusionResults indicate that a diagnostic window of appreciable length exists for potential earlier LC diagnosis in some patients. Lung cancer diagnosis may be delayed if early symptoms are misattributed to COPD or other benign conditions.

Increased Lung Cancer Risk and Associated Risk Factors in Tuberculosis Survivors: A Korean Population-Based Study.

Few studies have comprehensively evaluated the risk of lung cancer in tuberculosis survivors with consideration of smoking status and chronic obstructive pulmonary disease (COPD). Furthermore, little is known about lung cancer risk factors in tuberculosis survivors. This population-based cohort study enrolled tuberculosis survivors (n = 75 467) between 2010 and 2017 and 1:1 age- and sex-matched controls. Subjects were followed up for 1 year from the date of tuberculosis diagnosis to the date of the incident lung cancer, death, or December 2018, whichever came first. The risk of lung cancer was evaluated according to smoking and COPD status. We also evaluated the risk factors for lung cancer and developed an individualized lung cancer prediction model for tuberculosis survivors. During a median follow-up duration of 4.8 years, the incident lung cancer risk was 1.72-fold higher in tuberculosis survivors than in the controls. Among tuberculosis survivors, those who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio, 6.78) compared with never-smoker, non-tuberculosis-infected controls. tuberculosis survivors with COPD had a higher risk (2.43) than non-COPD, non-tuberculosis-infected controls. Risk factors for lung cancer in tuberculosis survivors were pulmonary tuberculosis, age >60 years, smoking, and the presence of COPD or asthma. The individualized lung cancer risk model showed good discrimination (concordance statistic = 0.827). Previous tuberculosis infection is an independent risk factor regardless of smoking status or amount and COPD. Closer monitoring of tuberculosis survivors, especially heavy smokers or those with COPD, is needed for early lung cancer diagnosis.

Childhood Cigarette Smoking and Risk of Chronic Obstructive Pulmonary Disease in Older U.S. Adults.

Rationale: It is not certain the extent to which childhood smoking adds chronic obstructive pulmonary disease (COPD) risk independent of lifetime cigarette exposure. Objectives: We examined the association between age started smoking cigarettes regularly, current smoking status, smoking history, and risk of COPD. Methods: Cross-sectional survey of U.S. adults ⩾40 years old in the 2020 National Health Interview Survey. Respondents who were ever cigarette smokers were asked when they began smoking regularly. Multivariable analysis assessed self-report of COPD diagnosis as a function of age started smoking (<15 yr vs. ⩾15 yr) adjusting for current smoking, cigarette pack-years, and covariates. Measurements and Main Results: Overall, 7.1% reported that they had COPD, 2.6% for never-smokers compared with 23.1% and 11.6% for smoking onset <15 and ⩾15 years, respectively. Persons who began smoking regularly at <15 years of age had higher pack-years of smoking (median, 29 vs. 15, respectively), and higher smoking intensity (median, 20 cigarettes/d for <15 yr vs. 10 cigarettes/d for ⩾15 yr for current smokers). In the multivariable analysis, the relative risk for COPD among childhood smokers was 1.41 (95% confidence interval, 1.22-1.63) compared with later-onset smokers. Substituting smoking duration for pack-years confounded the association between current smoking and COPD but did not change the childhood smoking estimate. In a stratified analysis, higher risk for childhood smoking was found at all current smoking intensity levels. Conclusions: Among adults aged ⩾40 years, one-fifth of childhood smokers have COPD. Lifetime cigarette smoking explained some but not all of the higher risk. If replicated, this suggests a lung development window of enhanced vulnerability to cigarette smoking.

All-Cause, Cardiovascular and Respiratory Mortality in People with Type 2 Diabetes and Chronic Obstructive Pulmonary Disease (COPD) in England: A Cohort Study Using the Clinical Practice Research Datalink (CPRD).

Type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD) are common non-communicable diseases. Both have an inflammatory nature and similar risk factors, and there is overlap and interaction between them. To date, there is a lack of research on outcomes in people that have both conditions. The aim of this study was to investigate whether the presence of COPD in people with T2D was associated with an increased risk of all-cause, respiratory-cause and cardiovascular-cause mortality. A three-year cohort study (2017-19) was done using the Clinical Practice Research Datalink Aurum database. The study population was 121,563 people with T2D aged ≥40. The exposure was COPD status at baseline. Incident rates for all-cause, respiratory-cause and cardiovascular-cause mortality were calculated. Poisson models for each outcome were fitted to estimate rate ratios for COPD status adjusted for age, sex, Index of Multiple Deprivation, smoking status, body mass index, prior asthma and cardiovascular disease. COPD was present in 12.1% people with T2D. People with COPD had a higher all-cause mortality rate (448.7 persons per 1000 person years) compared with people without COPD (296.6 persons per 1000 person years). People with COPD also had substantially higher respiratory mortality incidence rates and moderately raised cardiovascular mortality rates. Fully adjusted Poisson models showed that people with COPD had a 1.23 (95% CI 1.21, 1.24) times higher rate of all-cause mortality as compared with those without COPD and a 3.03 (95% CI 2.89, 3.18) times higher rate of respiratory-cause mortality. There was no evidence of an association with cardiovascular mortality after adjusting for existing cardiovascular disease. Co-morbid COPD in people with T2D was associated with increased mortality overall and particularly from respiratory causes. People with both COPD and T2D are a high-risk group who would benefit from particularly intensive management of both conditions.