Higher Risk Of Chronic Obstructive Pulmonary Disease Research Articles

The Role of Active and Passive Smoking in Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A 12-year Prospective Study in China.

There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all Ptrend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (Ptrend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), β (95% CI) = 0.17 (- 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)]. Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention.

“Occupational exposure to charcoal smoke and dust, a major risk factor for COPD: a multiregional cross-sectional study in the Democratic Republic of Congo”

Occupational exposure to charcoal smoke and dust is a threat to workers respiratory system. What is the prevalence of chronic obstructive pulmonary disease (COPD) in charcoal workers as compared to farmers in rural areas of Democratic Republic of Congo (DRC)? This cross-sectional, comparative, and multi-site study was performed in the charcoal-producing provinces of South-Western DRC. We randomly included charcoal workers and compared them to farmers (18 to 70 years old). Air quality indexes, anthropometric, physical activity, sociodemographic characteristics, and related medical events data were recorded. A Lung function questionnaire was used to assess respiratory symptoms (RS) and spirometry was performed. COPD was defined as the presence of RS for more than 3 months with a FEV1/FVC ratio below the lower limit of normal. The prevalence of COPD was calculated, and logistic regression was used to identify COPD-associated factors. We included 485 subjects between August 2020 and July 2021. Charcoal Producers (CP, n = 229) were compared with farmers (n = 118), and charcoal saleswomen (CS, n = 72) were compared to vegetable saleswomen (VS, n = 66). Respective groups were similar in age, job seniority, height, and weight. The air was more polluted at charcoal workplaces. The prevalence of COPD was higher in CP than in farmers (39.7% vs 14.4%; P < 0.0001), and in CS compared to VS (40.3% vs 13.6%; P < 0.0001). Being a charcoal worker was independently associated with COPD in the CP and farmers group: adjusted OR, 3.54 (95% CI, 1.94-6.46), and, in the saleswomen group: 7.85 (95% CI, 2.85-21.5), where it was also independently associated with young age: 0.85 (0.80-0.93) and monthly income: 0.88 (0.83-0.96). In rural areas of DRC, producing or selling charcoal is associated with a higher risk of COPD.

Altered levels of IFN-γ, IL-4, and IL-5 depend on the TLR4 rs4986790 genotype in COPD smokers but not those exposed to biomass-burning smoke.

Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 (TLR4) single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the TLR4 gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels. We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA. The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG. The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.

SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPD.

Determining SNP-SNP interaction of the disease has become important for further investigation of pathogenesis and experimental research. Although many studies have been published on the effect of MMPs gene polymorphisms on chronic obstructive pulmonary disease (COPD), there is a lack of information on SNP-SNP and SNP-environment interactions. This study aimed to investigate the interaction between the polymorphisms of MMP1, MMP2, MMP9 and MMP12 genes and its combined effect with smoking on the risk of developing COPD. Totally 181 COPD patients and 292 healthy individuals were involved. Blood samples from the participants were tested for genotyping and data were collected through questionnaires. Genotyping was performed with nested allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP-SNP and SNP-environment interactions were investigated using multifactor dimensionality reduction and logistic regression analysis. The result showed that participants with high nicotine dependence and heavy smokers had a higher risk of COPD than non-smokers. Also, G/G genotype (cOR = 5.83; 95% CI, 1.19-28.4, p = 0.029) of MMP2 rs243864 and T/T genotype (cOR = 1.79; 95% CI, 1.16-2.76, p = 0.008) of MMP12 rs652438 independently contributes to the susceptibility of COPD. For SNP-SNP interaction, the positive interaction between rs243864 G/G genotype of MMP2 and rs652438 T/T genotype of MMP12 was found, and the combination of risk genotypes has a high risk of COPD (OR = 12.92; 95% CI, 1.46-114.4, p = 0.021). Moreover, the combination of T/T genotype of MMP12 rs652438 and smoking-related factors increases the risk of COPD approximately 4.5 to 6-fold. The results suggests that there is a combination of MMP2, MMP12, and smoking-related factors may increase the risk of developing COPD.

Risk of Chronic Obstructive Pulmonary Disease and Receipt of a Breathing Test in 26 States and the District of Columbia, 2017–2018

Risk of Chronic Obstructive Pulmonary Disease and Receipt of a Breathing Test in 26 States and the District of Columbia, 2017–2018

The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study.

The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis-COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.

P1119 Increased risk of chronic respiratory disease among individuals with Inflammatory Bowel Disease in a prospective cohort study

Abstract Background Cross-sectional evidence suggests a higher burden of chronic respiratory diseases in people with inflammatory bowel disease (IBD), but there is a lack of prospective evidence to clarify the direction of their associations. This study aimed to investigate the association of IBD with the risk of two major chronic respiratory diseases, chronic obstructive pulmonary disease (COPD) and asthma. Methods We included 430,414 participants from UK Biobank and followed them from recruitment (2006-2010) to 2021. COPD and asthma cases were obtained from inpatient data and death register. Using Cox proportional hazards models, we estimated the multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) of developing COPD and asthma in participants with IBD compared with IBD-free groups. We also investigated the association among Crohn's disease (CD) and ulcerative colitis (UC) with the risk of COPD and asthma. Results Over a median follow-up of 143 months, there were 11,196 incident COPD and 9831 asthma cases. The adjusted HRs of developing COPD (HR=1.54, 95% CI: 1.33-1.79) and asthma (HR=1.52, 95% CI: 1.29-1.79) were higher for those with IBD when compared with IBD-free participants. Participants with CD and UC were also found to have a higher risk of COPD (CD: HR=1.71; 95% CI: 1.36-2.15; UC: HR=1.45; 95% CI: 1.20-1.75) and asthma (CD: HR=1.73; 95%CI: 1.33-2.25; UC: HR=1.41; 95%CI: 1.15-1.73) when compared with those free of IBD (Table 1). Conclusion This study suggested that individuals with IBD have a higher risk of developing COPD and asthma, highlighting the importance of preventing chronic respiratory diseases among IBD patients.

Female reproductive histories and the risk of chronic obstructive pulmonary disease

BackgroundFemale reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess...

Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants

BackgroundLittle is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition.MethodsA total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS.ResultsThe cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference.ConclusionsLong-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT.

To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters. A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA. The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P<0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P<0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P<0.05). The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.

Developing Climate Change and Health Impact Monitoring with eHealth at the South East Asia Community Observatory and Health and Demographic Surveillance Site, Malaysia (CHIMES).

Malaysia is projected to experience an increase in heat, rainfall, rainfall variability, dry spells, thunderstorms, and high winds due to climate change. This may lead to a rise in heat-related mortality, reduced nutritional security, and potential migration due to uninhabitable land. Currently, there is limited data regarding the health implications of climate change on the Malaysian populace, which hinders informed decision-making and interventions. This study aims to assess the feasibility and reliability of using sensor-based devices to enhance climate change and health research within the SEACO health and demographic surveillance site (HDSS) in Malaysia. We will particularly focus on the effects of climate-sensitive diseases, emphasizing lung conditions like chronic obstructive pulmonary disease (COPD) and asthma. In our mixed-methods approach, 120 participants (>18 years) from the SEACO HDSS in Segamat, Malaysia, will be engaged over three cycles, each lasting 3 weeks. Participants will use wearables to monitor heart rate, activity, and sleep. Indoor sensors will measure temperature in indoor living spaces, while 3D-printed weather stations will track indoor temperature and humidity. In each cycle, a minimum of 10 participants at high risk for COPD or asthma will be identified. Through interviews and questionnaires, we will evaluate the devices' reliability, the prevalence of climate-sensitive lung diseases, and their correlation with environmental factors, like heat and humidity. We anticipate that the sensor-based measurements will offer a comprehensive understanding of the interplay between climate-sensitive diseases and weather variables. The data is expected to reveal correlations between health impacts and weather exposures like heat. Participant feedback will offer perspectives on the usability and feasibility of these digital tools. Our study within the SEACO HDSS in Malaysia will evaluate the potential of sensor-based digital technologies in monitoring the interplay between climate change and health, particularly for climate-sensitive diseases like COPD and asthma. The data generated will likely provide details on health profiles in relation to weather exposures. Feedback will indicate the acceptability of these tools for broader health surveillance. As climate change continues to impact global health, evaluating the potential of such digital technologies is crucial to understand its potential to inform policy and intervention strategies in vulnerable regions.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population

IntroductionThe aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population. MethodsThis was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression. ResultsWe studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03–1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30–1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82–5.77), with a population attributable fraction for COPD of 8.2%. ConclusionsOccupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers.

An explainable artificial intelligence framework for risk prediction of COPD in smokers

BackgroundSince the inconspicuous nature of early signs associated with Chronic Obstructive Pulmonary Disease (COPD), individuals often remain unidentified, leading to suboptimal opportunities for timely prevention and treatment. The purpose of this study was to create an explainable artificial intelligence framework combining data preprocessing methods, machine learning methods, and model interpretability methods to identify people at high risk of COPD in the smoking population and to provide a reasonable interpretation of model predictions.MethodsThe data comprised questionnaire information, physical examination data and results of pulmonary function tests before and after bronchodilatation. First, the factorial analysis for mixed data (FAMD), Boruta and NRSBoundary-SMOTE resampling methods were used to solve the missing data, high dimensionality and category imbalance problems. Then, seven classification models (CatBoost, NGBoost, XGBoost, LightGBM, random forest, SVM and logistic regression) were applied to model the risk level, and the best machine learning (ML) model’s decisions were explained using the Shapley additive explanations (SHAP) method and partial dependence plot (PDP).ResultsIn the smoking population, age and 14 other variables were significant factors for predicting COPD. The CatBoost, random forest, and logistic regression models performed reasonably well in unbalanced datasets. CatBoost with NRSBoundary-SMOTE had the best classification performance in balanced datasets when composite indicators (the AUC, F1-score, and G-mean) were used as model comparison criteria. Age, COPD Assessment Test (CAT) score, gross annual income, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), anhelation, respiratory disease, central obesity, use of polluting fuel for household heating, region, use of polluting fuel for household cooking, and wheezing were important factors for predicting COPD in the smoking population.ConclusionThis study combined feature screening methods, unbalanced data processing methods, and advanced machine learning methods to enable early identification of COPD risk groups in the smoking population. COPD risk factors in the smoking population were identified using SHAP and PDP, with the goal of providing theoretical support for targeted screening strategies and smoking population self-management strategies.

Screening and early diagnosis of chronic obstructive pulmonary disease: a population study

Background and objectiveAlthough chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD.MethodsWe identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups.ResultsWe collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50–59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading.ConclusionA screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.

Metabolic syndrome, genetic susceptibility, and risk of chronic obstructive pulmonary disease: The UK Biobank Study.

To investigate the effect of metabolic syndrome (MetS), genetic predisposition, and their interactions, on the risk of developing chronic obstructive pulmonary disease (COPD). Cohort analyses included 287 868 participants from the UK Biobank Study. A genetic risk score for COPD was created using 277 single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) for COPD in relation to exposure factors. During 2 658 936 person-years of follow-up, 5877 incident cases of COPD were documented. Compared with participants without MetS, those with MetS had a higher risk of COPD (HR 1.24, 95% CI 1.17-1.32). Compared to participants with low genetic predisposition, those with high genetic predisposition had a 17% increased risk of COPD. In the joint analysis, compared with participants without MetS and low genetic predisposition, the HR for COPD for those with MetS and high genetic predisposition was 1.50 (95% CI 1.36-1.65; P < 0.001). However, no significant interaction between MetS and genetic risk was found. Metabolic syndrome was found to be associated with an increased risk of COPD, regardless of genetic risk. It is crucial to conduct further randomized control trials to determine whether managing MetS and its individual components can potentially reduce the likelihood of developing COPD.

The Synergistic Effect of Dietary Acid Load Levels and Cigarette Smoking Status on the Risk of Chronic Obstructive Pulmonary Disease (COPD) in Healthy, Middle-Aged Korean Men.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with a risk of chronic obstructive pulmonary disease (COPD) in healthy, middle-aged Korean men. Healthy men without diagnosed chronic disease (aged 40-64 years) from the KNHANES-VI (2013-2015) were included in the analysis (n = 774) and were subdivided by smoking status and DAL levels, as estimated using the quartile of net endogenous acid production (NEAP). The current smokers tended to have a higher risk of COPD than the never-smokers before and after adjustment. When divided by the DAL quartile, the Q4 group tended to have a higher risk of COPD than the Q1 group. Additionally, the current smokers with lower (Q2), modest (Q3), and the highest NEAP scores (Q4) showed risks of COPD that were more than fourfold higher than those of the never-smokers with the lowest NEAP scores (Q1). The ex-smokers with higher NEAP scores (Q3 and Q4) showed risks of COPD that were more than fourfold higher than those of the Q1 group. Interestingly, the risk of COPD was also more than sixfold higher in the never-smokers with the highest NEAP scores compared to that in the Q1 group. The NEAP scores and smoking status synergistically increased the risk of COPD in healthy, middle-aged Korean men. This suggests that DAL levels are an important factor in the prevention and management of COPD.

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.

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.

Hypertensive disorders of pregnancy and risk of asthma and chronic obstructive pulmonary disease: a prospective cohort study

Hypertensive disorders of pregnancy (HDPs) have been associated with respiratory dysfunction during pregnancy and postpartum. In this study, we explored the associations between HDPs (gestational hypertension and preeclampsia) and the risk of incident asthma and chronic obstructive pulmonary disease (COPD) during adulthood and the potential mediating role of chronic hypertension. We included parous nurses in the Nurses' Health Study II reporting a pregnancy lasting no less than 6 months. The associations between HDPs and asthma and COPD were estimated using Cox proportional hazards models with adjustment for confounders. We included 73,807 nurses [92.5% (68,246 of 73,807) White] in asthma analyses and 79,843 [92.4% (73,746 of 79,843) White] in COPD analyses, whose mean (SD, range) age, at baseline, were both 34.8 (4.7, 25.0-44.0) years. During 24 years of follow-up, we identified 2663 incident cases of asthma and 537 COPD. Compared with nurses without HDPs, nurses reporting HDPs had an increased HR for incident asthma and COPD of 1.22 (95% CI 1.10-1.36) and 1.39 (95% CI 1.11-1.74), respectively. The risk of asthma was similar when gestational hypertension and preeclampsia were assessed separately [HR=1.25 (95% CI 1.08-1.43) and 1.24 (95% CI 1.11-1.38), respectively]. However, only nurses with preeclampsia had a higher risk of COPD (HR=1.41, 95% CI 1.11-1.78). Mediation analyses estimated that chronic hypertension explained 18.6% (95% CI 8.9-35.0%) and 10.7% (95% CI 2.9-32.4%) of the associations between HDPs and asthma and COPD, respectively. HDPs may serve as useful markers of increased susceptibility to chronic respiratory diseases during adulthood. The National Institutes of Health grants.

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study. The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results. IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria (p = 0.020), genus Allisonella (p = 0.024), genus Coprococcus2 (p = 0.002) and genus Oscillospira (p = 0.018) were protective against COPD. In addition, order Desulfovibrionales (p = 0.011), family Desulfovibrionaceae (p = 0.039), family Peptococcaceae (p = 0.020), family Victivallaceae (p = 0.012) and genus Marvinbryantia (p = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found. According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.