Chronic Obstructive Pulmonary Disease Cases Research Articles

Arsenic exposure and lung function decline in chronic obstructive pulmonary disease patients: The mediating influence of systematic inflammation and oxidative stress

Lung tissue is one of the target sites of arsenic (As). The goal of this investigation was to assess the associations of blood As concentration with pulmonary function indicators in patients with chronic obstructive pulmonary disease (COPD), as well as the roles of systemic inflammation and oxidative stress in this relationship. All 791 COPD patients were selected. Blood As concentration, and tumour necrosis factor-α (TNF-α) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected in the serum of COPD cases. Blood As was robustly related to pulmonary function parameters in an inverse dose-dependent manner. Multivariate linear regression analyses verified that a 1-unit increase of blood As was linked to declines of 0.263 L in FVC, 0.288 L in FEV1, 3.454 in FEV1/FVC%, and 0.538 in predicted FEV1%, respectively. The potential for pulmonary function decline gradually increased across the elevated tertiles of blood As. Nonsmokers were susceptible to As-induced pulmonary function reduction. Blood As was positively linked to the levels of TNF-α and 8-iso-PGF2α. Increased TNF-α and 8-iso-PGF2α partially mediated As-induced the reductions in FEV1 and FVC among COPD patients. As exposure is intensely linked to pulmonary function reduction. Systematic inflammation and oxidative stress partially mediate such associations in COPD patients.

Endothelin-1 Gene Polymorphism in Chronic Obstructive Pulmonary Disease: A Case-Control Study

Abstract
 Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common multifactorial disease which has heterogeneous pathogenesis. The most important risk factor is smoking. In addition to many pathogenic mechanisms taking part in inflammatory process, Our study group does research on the relation of COPD with single nucleotide gene polymorphism at ET-1 gene. In the current studies there being a high ratio of Endotelin-1 (ET-1) in BAL liquid of COPD cases made researchers think ET-1 may have an important role in pathogenesis of COPD. 
 Methods: This prospective case-control study included 89 patients admitted with COPD and 87 control patients. In our study, we search for the density of single nucleotide gene polymorphism (+134 insA/delA) in ET-1 gene in the 87 smoking COPD and 89 healthy cases. Allele ratio and genotype distribution, distribution amongst three genotype in the COPD patient and healthy control group was analyzed. In this study, for endothelin gene -3A/-4A (-138 insertion/deletion) polymorphism analysis, PCR-RFLP method was used. 
 Results: In comparison with the healthy group, the COPD group has higher ratio of ET-1 gene (+134 insA/delA) polymorphism (p< 0,001). 
 Conclusion: Endotelin-1 gene polymorphism (+134 insA/delA) significantly increased in the patients than healthy ones (p

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Study to find out about various risk factors responsible for repeat acute exacerbation of COPD, which cause readmission within 90 days after admission in hospital due to acute exacerbation of COPD

Background: Approximately 3.2 million global deaths occur each year due to chronic obstructive pulmonary disease (COPD), in which exacerbations of COPD remain a prevailing cause. Exacerbations requiring hospitalization are associated with high mortality, and mortality risk is increased with higher exacerbation frequencies. Aims and Objectives: This study aimed to prospectively identify the risk factors of COPD that cause readmission within 90 days after admission to the hospital due to acute exacerbations of COPD. Materials and Methods: An observational study conducted at the School of Pulmonary Excellence, NSCB Medical College, Jabalpur, from the duration of March 2021 to August 2022 with a sample size of 140 estimated through 56% prevalence of readmission rate in available literature. Study participants, including all patients, were readmitted within 90 days after admission due to acute exacerbation of COPD (post-bronchodilator FEV1/FVC <0.70). Data analysis was performed using IBM software SPSS 22.0 and statistical association with the confidence interval of 95% and P<0.05. Results: The majority of COPD cases were male (84%) and belonged to the 50–60 years of age group. There was a statistically significant (P=0.001) association between grades of dyspnea and readmission cases. Dyspnea among readmission patients was found to be 100%. The prevalence of CAT score >10 was 64% and <10 is 36% among readmission patients the association was highly significant and more exacerbation leads to more readmission. Conclusion: In the study, various clinical parameters were found statistically significant between the admission and readmission groups. These parameters were CAT score, previous hospitalization history, previous exacerbation history, SpO2, dyspnea grading, and co-morbidities. The lung function test was difficult to do due to many of readmitted patients were not in a condition to do spirometry.

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank.

To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.

DETECTION OF EXTENDED SPECTRUM BETA LACTAMASES-PRODUCING KLEBSIELLA PNEUMONIAE ISOLATES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASES PATIENTS

Objective: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide which includes chronic bronchitis and emphysema. 80% of acute exacerbation of COPD (AECOPD) are triggered by respiratory viruses, atypical bacteria, and aerobic Gram-positive and Gram-negative bacteria. The aim of our study was to analyze the prevalence and antimicrobial susceptibility testing of Klebsiella pneumoniae and detection of extended spectrum beta lactamases (ESBL)-producing K. pneumoniae isolates from COPD patients. Methods: Sputum samples received from seventy-five diagnosed cases of COPD from the department of General Medicine and Chest Medicine, TSRM MCH and RC, Trichy, from March 2022 to August 2022. Direct Gram stain was done for all sputum samples. The suitable sputum samples were cultured. The identification of organism and antimicrobial susceptibility testing was done by standard microbiological techniques. Results: Out of seventy-five cases, 64% were males and 36% were females. Forty-seven were sputum positive, and the prevalence of Gram- negative bacteria was 64%. K. pneumoniae was the most common bacteria isolated (42.2%), followed by Pseudomonas aeruginosa (15.5%). Antimicrobial susceptibility testing of K. pneumoniae was sensitive to imipenem (78.94%), aminoglycosides (78.94%), amoxycillin-clavulinic acid (63.15%), ciprofloxacin (57.89%), Piperacillin-Taxobactam (57.89%), and the phenotypic tests showed 13 (68%) isolates were ESBL producers. Conclusion: This study showed that K. pneumoniae and P. aeruginosa are the most common organisms associated with AECOPD and increased rate of ESBL producers were observed.

Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Association of MMP7 T > C Gene Variant (rs10502001) and Expression in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) have obstructed airflow through their lungs. Single nucleotide polymorphisms in matrix metalloproteinases (MMPs) genes and the risk of COPD have been the subject of numerous studies, with conflicting results. This investigation was conducted to determine whether the MMP7 (T>C) gene variant (rs10502001) was associated with an increased risk of COPD. A case-control study was conducted with 360 subjects (180 healthy controls and 180 COPD cases). The polymerase chain reaction (PCR)-restriction fragment length polymorphism method was used to genotype the SNP rs1050200. mRNA expression of MMP7 was performed using RT-PCR. The genotypic/allelic frequencies and carriage rates of rs10502001 (T>C) polymorphism were evaluated in 180 each of healthy controls and COPD cases. Cases have higher TC/CC genotype frequencies than controls. The "CC" genotype was found to be significantly associated with increased COPD risk (p = 0.016). The "C" allele frequency was higher in cases than in controls and showed significant association with COPD (p = 0.005). The carriage rate frequencies of T(-) and C(+) were significantly higher in cases than in controls (p = 0.031 and 0.047, respectively). MMP7 expression was significantly upregulated (p = 0.001) in COPD cases as compared with the controls. In addition, comparisons of MMP7 expression between the COPD cases with different genotypes showed that the "CC" genotype cases had significantly higher expression than those with "TT" genotype. The present findings showed statistically significant correlation of MMP7 (T>C) polymorphism and expression with COPD. Therefore, MMP7 responsible for degradation of elastin has been strongly linked to the progression of COPD.

The altered sputum microbiome profile in patients with moderate and severe COPD compared to the healthy group in the Indian population

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1&lt;80% predicted) and severe groups (FEV1&lt;50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson’s index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA&gt;2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonas and Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

Hospitalization costs of COPD cases and its associated factors: an observational study at two large public tertiary hospitals in Henan Province, China

BackgroundThe increasing prevalence of Chronic Obstructive Pulmonary Disease (COPD) has imposed a considerable economic burden. However, there remains a paucity of relevant evidence regarding the hospitalization costs of COPD cases. Therefore, in this study, we aimed to assess the hospitalization costs among COPD cases and investigate the factors that contribute to their costs in Henan Province, China.MethodsWe enrolled a total of 1697 cases who were discharged with a diagnosis of COPD from January 1, 2020 to December 31, 2020, into the study. Demographic and clinical characteristics of the cases were obtained from the hospital information system (HIS) of two large tertiary hospitals in Henan Province, China. The factors associated with hospitalization costs were examined using a multiple linear regression model.ResultsTotal hospitalization costs of 1697 COPD cases were $5,419,011, and the median was $1952 (IQR:2031). Out-of-pocket fees accounted for 43.95% of the total hospitalization costs, and the median was $938 (IQR:956). Multiple linear regression analysis revealed that hospitalization costs were higher among older cases, cases with more comorbidities, and cases with longer length of stay. Furthermore, hospitalization costs were higher in cases who paid through private expenses compared to those covered by Urban Employee Basic Medical Insurance. Additionally, we found that cases admitted through an outpatient clinic had higher hospitalization costs than those admitted through the emergency department.ConclusionHospitalization costs of COPD cases are substantial. Strategies to reduce hospitalization costs, such as shortening LOS, optimizing payment plans, and preventing or managing complications, should be implemented to alleviate the economic burden associated with COPD hospitalizations.

Association of World Trade Center (WTC) Occupational Exposure Intensity with Chronic Obstructive Pulmonary Disease (COPD) and Asthma COPD Overlap (ACO).

Reported associations between World Trade Center (WTC) occupational exposure and chronic obstructive pulmonary disease (COPD) or asthma COPD overlap (ACO) have been inconsistent. Using spirometric case definitions, we examined that association in the largest WTC occupational surveillance cohort. We examined the relation between early arrival at the 2001 WTC disaster site (when dust and fumes exposures were most intense) and COPD and ACO in workers with at least one good quality spirometry with bronchodilator response testing between 2002 and 2019, and no physician-diagnosed COPD before 9/11/2001. COPD was defined spirometrically as fixed airflow obstruction and ACO as airflow obstruction plus an increase of ≥ 400ml in FEV1 after bronchodilator administration. We used a nested 1:4 case-control design matching on age, sex and height using incidence density sampling. Of the 17,928 study participants, most were male (85.3%) and overweight or obese (84.9%). Further, 504 (2.8%) and 244 (1.4%) study participants met the COPD and ACO spirometric case definitions, respectively. In multivariable analyses adjusted for smoking, occupation, cohort entry period, high peripheral blood eosinophil count and other covariates, early arrival at the WTC site was associated with both COPD (adjusted odds ratio [ORadj] = 1.34, 95% confidence interval [CI] 1.01-1.78) and ACO (ORadj = 1.55, 95%CI 1.04-2.32). In this cohort of WTC workers, WTC exposure intensity was associated with spirometrically defined COPD and ACO. Our findings suggest that early arrival to the WTC site is a risk factor for the development of COPD or of fixed airway obstruction in workers with pre-existing asthma.

Comparison of the Arterial PaCO 2 Values and ETCO 2 Values Measured with Sidestream Capnography in Patients with a Prediagnosis of COPD Exacerbation.

Background Aim of this study is to investigate whether end-tidal carbon dioxide (ETCO 2 ) values can be used instead of partial pressure of carbon dioxide (PaCO 2 ) values in guiding treatment, and determining treatment benefits in patients that received a pre-diagnosis of chronic obstructive pulmonary disease (COPD) exacerbation at the emergency department. Methods This observational prospective study was conducted with patients who presented to the emergency department with the complaint of shortness of breath and were diagnosed with COPD exacerbation. ETCO 2 was measured with the sidestream method during blood gas analysis in patients with indications for this analysis. Measurements were repeated at hour 1 after treatment. Results The study included a total of 121 cases. There was a positive correlation between the PaCO 2 and ETCO 2 values measured before and after treatment ( r = 0.736, p < 0.01 and r = 0.883, p < 0.01, respectively). High ETCO 2 values were accompanied by high PaCO 2 values. When the measurements before and after treatment were evaluated using the Bland-Altman method, most of the result were within the limits of agreement (-4.9 and +31.4/- 2.6 and +9.4), with mean differences being calculated as 13.2 and 8.4, respectively. Conclusions Although ETCO 2 and PaCO 2 were statistically consistent according to the results of our study, due to the high averages of differences between these two parameters, the ETCO 2 value has limited clinical use in COPD cases compared to PaCO 2 . However, high ETCO 2 values may indicate that noninvasive mechanical ventilation should be included in the treatment of COPD cases without waiting for the results of blood gas analysis, and they can also be when needed for inpatient treatment.

Current Progress of COPD Early Detection: Key Points and Novel Strategies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approximately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients.

Major depressive disorder plays a vital role in the pathway from gastroesophageal reflux disease to chronic obstructive pulmonary disease: a Mendelian randomization study.

Background: Observational studies have shown a bidirectional association between chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), but it is not clear whether this association is causal. In our previous study, we found that depression was a hot topic of research in the association between COPD and GERD. Is major depressive disorder (MDD) a mediator of the association between COPD and GERD? Here, we evaluated the causal association between COPD, MDD, and GERD using Mendelian randomization (MR) study. Methods: Based on the FinnGen, United Kingdom Biobank, and Psychiatric Genomics Consortium (PGC) databases, we obtained genome-wide association study (GWAS) summary statistics for the three phenotypes from 315,123 European participants (22,867 GERD cases and 292,256 controls), 462,933 European participants (1,605 COPD cases and 461,328 controls), and 173,005 European participants (59,851 MDD cases and 113,154 controls), respectively. To obtain more instrumental variables to reduce bias, we extracted relevant single-nucleotide polymorphisms (SNPs) for the three phenotypes from published meta-analysis studies. Bidirectional MR and expression quantitative trait loci (eQTL)-MR were performed using the inverse variance weighting method to assess the causal association between GERD, MDD, and COPD. Results: There was no evidence of a causal effect between GERD and COPD in the bidirectional MR analysis [forward MR for GERD on COPD: odds ratios (OR) = 1.001, p = 0.270; reverse MR for COPD on GERD: OR = 1.021, p = 0.303]. The causal effect between GERD and MDD appeared to be bidirectional (forward MR for GERD on MDD: OR = 1.309, p = 0.006; reverse MR for MDD on GERD: OR = 1.530, p < 0.001), while the causal effect between MDD and COPD was unidirectional (forward MR for MDD on COPD: OR = 1.004, p < 0.001; reverse MR for COPD on MDD: OR = 1.002, p = 0.925). MDD mediated the effect of GERD on COPD in a unidirectional manner (OR = 1.001). The results of the eQTL-MR were consistent with those of the bidirectional MR. Conclusion: MDD appears to play a vital role in the effect of GERD on COPD. However, we have no evidence of a direct causal association between GERD and COPD. There is a bidirectional causal association between MDD and GERD, which may accelerate the progression from GERD to COPD.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans

BackgroundTreatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover...

Vitamin D status and chronic obstructive pulmonary disease risk: a prospective UK Biobank study

BackgroundLow vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to...

Associationsof diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study.

To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose-response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose-response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]). Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.

The altered lung microbiome dynamics in patients with moderate and severe COPD compared to the healthy group in the Indian population

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1&lt;80% predicted) and severe groups (FEV1&lt;50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson’s index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA&gt;2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonas and Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

Cognitive decline and risk of dementia in older adults after diagnosis of chronic obstructive pulmonary disease

Cognitive screening has been proposed for older adults diagnosed with chronic obstructive pulmonary disease (COPD). Therefore, we examined the change over time in cognitive function and the risk of incident dementia in older adults after COPD diagnosis. A sample of 3,982 participants from the population-based cohort study Good Aging in Skåne was followed for 19 years, and 317 incident COPD cases were identified. The cognitive domains of episodic memory, executive function, and language were assessed using neuropsychological tests. Mixed models for repeated measures and a Cox model were implemented. Participants performed, on average, worse over time on all neuropsychological tests after COPD diagnosis in comparison to those without COPD, although statistical significance differences were only observed for episodic memory and language. The groups had a comparable risk of developing dementia. In conclusion, our results indicate that cognitive screening in the early stages of COPD may be of limited clinical relevance.

Mitochondrial Rieske iron-sulfur protein is a crucial molecule in COPD-associated pulmonary hypertension

Pulmonary hypertension (PH) often occurs in chronic obstructive pulmonary disease (COPD) and is the major cause of death in COPD patients. Molecular mechanisms for PH in COPD remain poorly understood, and clinical treatments are neither specific nor effective. Cigarette and e-cigarette smoking (CS) account for up to 90% of COPD cases, in which nicotine is the major active component and causes COPD-like cellular responses; moreover, hypoxia is a known key factor in the development of PH. In this study, we aim to develop a PH in COPD animal model and determine the underlying molecular mechanisms. Our findings revealed that co-exposure of nicotine (or CS) and hypoxia synergistically elevated PH (i.e., right ventricular pressure and weight) compared to nicotine, CS, or hypoxia alone. We also found that mitochondrial reactive oxygen species ([ROS] m ), assessed using mitochondrial-specific ROS indicator MitoSOX, was significantly increased in pulmonary artery smooth muscle cells (PASMCs) from CS patients with COPD compared to normal PASMCs from non-CS patients. The increased [ROS] m was blocked by lentiviral short hairpin RNA (shRNA)-mediated knockdown of Rieske iron-sulfur protein (RISP) in mitochondrial complex III. More importantly, SMC-specific RISP gene knockout blocked nicotine/hypoxia exposure-induced PA remodeling and hypertension, whereas SMC-specific RISP overexpression exacerbated PH in mice. We further discovered that RISP regulated DNA damage following nicotine/hypoxia co-exposure via ataxia telangiectasia-mutated (ATM) signaling. RISP also mediated nuclear factor (NF)-κB inflammatory signaling. Together, our studies for the first time demonstrate that nicotine/hypoxia co-exposure leads to RISP-dependent [ROS] m , ATM-mediated DNA damage-dependent NF-κB-associated inflammation, PA vasoremodeling and PH in COPD in a sex-dependent manner. Moreover, RISP, ATM, and NF-κB may serve as novel and effective molecular targets in treating COPD and its associated PH. NIH R01 HL122865, NIH R03AG070784, and NIH R01 HL108232 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.