Ambient air pollution, lifestyle, and genetic predisposition on all-cause and cause-specific mortality: A prospective cohort study.

BACKGROUND: Although it is widely acknowledged that long-term exposure to ambient air pollution is closely related to the risk of mortality, there were inconsistencies in terms of cause-specific mortality and it is still unknown whether lifestyle and genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study involved 461,112 participants from the UK Biobank. The land-use regression model was used to estimate the concentrations of particulate matter (PM2.5, PMcoarse, PM10), and nitrogen oxides (NO2 and NOx). The association between air pollution and mortality was evaluated using Cox proportional hazard models. Furthermore, a lifestyle score incorporated with smoking status, physical activity, alcohol consumption, and diet behaviors, and polygenic risk score using 12 genetic variants, were developed to assess the modifying effect of air pollution on mortality outcomes. RESULTS: During a median follow-up of 14.0 years, 33,903 deaths were recorded, including 17,083 (2835; 14,248), 6970, 2429, and 1287 deaths due to cancer (lung cancer, non-lung cancer), cardiovascular disease (CVD), respiratory and digestive disease, respectively. Each interquartile range (IQR) increase in PM2.5, NO2 and NOx was associated with 7 %, 6 % and 5 % higher risk of all-cause mortality, respectively. Specifically, for cause-specific mortality, each IQR increase in PM2.5, NO2 and NOx was also linked to mortality due to cancer (lung cancer and non-lung cancer), CVD, respiratory and digestive disease. Furthermore, additive and multiplicative interactions were identified between high ambient air pollution and unhealthy lifestyle on mortality. In addition, associations between air pollution and mortality were modified by lifestyle behaviors. CONCLUSION: Long-term exposure to air pollutants increased the risk of all-cause and cause-specific mortality, which was modified by lifestyle behaviors. In addition, we also revealed a synergistically detrimental effect between air pollution and an unhealthy lifestyle, suggesting the significance of joint air pollution management and adherence to a healthy lifestyle on public health.

Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients.

BACKGROUND: Several characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk. RESEARCH QUESTION: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types? STUDY DESIGN AND METHODS: A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further. RESULTS: A total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma, in populations with high genetic risk and more detrimental behaviors. INTERPRETATION: Early age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of lung adenocarcinoma, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among female individuals.

Association of telomere length with risk of lung cancer: A large prospective cohort study from the UK Biobank.

OBJECTIVES: Leukocyte telomere length (LTL) is associated with a wide variety of diseases, including cancer. However, findings regarding the association between LTL and the risk for lung cancer have been inconclusive and inconsistent across previous observational studies. METHODS: This prospective cohort study included data from 425,146 participants 37-73 years of age housed in the UK Biobank. Quantitative polymerase chain reaction (qPCR) was used to measure LTL in baseline DNA samples. A multivariate Cox proportional hazards model was used to evaluate the relationship between LTL and the risk for lung cancer. RESULTS: An increase in LTL per interquartile range (IQR) was associated with a 9% increase in the risk for lung cancer (hazard ratio [HR] 1.09 [95% confidence interval (CI) 1.03-1.16]). Participants in the highest LTL quintile exhibited an approximately 25% elevated risk for developing lung cancer (HR 1.25 [95% CI 1.09-1.45]) compared with those in the lowest quintile. The relationship between per IQR increase in LTL and elevated risk for lung cancer was greater in the histological subtype of adenocarcinoma (HR 1.30 [95% CI 1.18-1.43]), female sex (HR 1.16 [95% CI 1.06-1.26]), non-smokers (HR 1.45 [95% CI 1.23-1.71]), and individuals with high genetic risk for lung cancer (HR 1.18 [95% CI 1.03-1.34]), respectively. Surprisingly, a per IQR increase in LTL was associated with increased risks for both lung adenocarcinoma (HR 1.56 [95% CI 1.24-1.96]) and squamous cell carcinoma (HR 2.01 [95% CI 1.13-3.56]) in never smokers. CONCLUSIONS: Longer LTL was associated with an elevated risk for lung cancer, particularly for adenocarcinoma and squamous cell carcinoma in never smokers. The results suggest the potential of telomeres as non-invasive biomarkers for the early screening of lung cancer, particularly in non-smokers, who are typically overlooked.

Vitamin D status, sleep patterns, genetic susceptibility, and the risk of incident adult-onset asthma: a large prospective cohort study.

Introduction: Vitamin D has been known to be associated with asthma, particularly in children, while the evidence among adults is limited and inconclusive. This study aimed to investigate the association between serum, vitamin D concentrations, and the incidence of adult-onset asthma and also the modified effect caused by sleep patterns and genetic risks. Methods: A prospective cohort study with 307,872 participants aged between 37 and 73 years was conducted based on the UK Biobank, with a median follow-up of 12 years. The Cox proportional hazard model was applied to evaluate the association between vitamin D status and incident adult-onset asthma, and the modified effect was investigated by conducting stratified analysis according to sleep pattern score and genetic risk score, and subgroup analyses were performed by sex, age, BMI, and smoking status as well. Results: Individuals with optimal vitamin D concentration were associated with 11.1% reduced risk of incident asthma compared to those participants with deficient vitamin D (HR = 0.889; 95% CI: 0.820-0.964; p = 0.005). Moreover, stratification analysis demonstrated that the protective effect of vitamin D on asthma risk was modified by sleep patterns or genetic susceptibility, with the strongest protective effect being observed in the subpopulation with a moderate sleep pattern (HR = 0.883; 95% CI: 0.797-0.977; p = 0.016) and a moderate genetic risk (HR = 0.817; 95% CI: 0.711-0.938; p = 0.004). In subgroup analyses, the protective effect of optimal vitamin D levels was only significant among men, individuals younger than 60 years of age, overweight individuals, and current or previous smokers. Conclusion: Increased serum vitamin D levels were associated with a lower risk of incident adult-onset asthma, and this association was modified by sleep patterns and genetic predisposition to some extent.

Clinical characteristics and prognosis of patient with leptospirosis: A multicenter retrospective analysis in south of China.

Purpose: Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. However, there is currently no consensual definition or diagnostic criteria for severe and different forms of leptospirosis. Therefore, more insight on clinical manifestations, risk factors, and outcomes of leptospirosis is warranted. The identification of leptospirosis with distinct clinical manifestations and prognosis in our population. Methods: Multiple correspondence analysis and hierarchical classification on principal components were presented to identify different clinical types of leptospirosis. The outcomes were clinical phenotypes, laboratory and imaging findings, and prognosis. Results: The 95 enrolled patients had median values of 54.0 years (39.0-65.0) for age, 9.0 (7.0-14.0) for total hospital stay lengths, of whom 86.3% was male and 40.0% was transferred to ICU. Three clinical types were distinguished: mild leptospirosis (n=43, 45.3%) with less organ dysfunction and shorter hospital stays; respiratory leptospirosis (n=28, 29.5%) with hemoptysis, and respiratory and circulatory failure; and hepato-renal leptospirosis (n=24, 25.3%) with worst liver and kidney dysfunction. Total hospital mortality was 15.8% and was associated with dyspnea and high levels of neutrophil counts. Conclusions: The identification of leptospirosis with distinct clinical manifestations and prognosis in our population may assist clinicians to distinguish leptospirosis-like disease. Moreover, dyspnea and neutrophil count were found to be independent risk factors for severe leptospirosis progression.

Vitamin D status and asthma, lung function, and hospitalization among British adults.

Background: Vitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear. Objective: To investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults. Methods: Multivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37-73 years old from the UK Biobank. Results: Compared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio (aOR) = 0.936; 95% CI: 0.911-0.962; p < 0.001] and 9.8% (aOR = 0. 0.902; 95% CI: 0.877-0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (ß = 1.328 ml, 95% CI = 0.575-2.080), FVC (ß = 2.018 ml, 95% CI = 1.127-2.908), and FEV1/FVC (ß = 0.006%, 95% CI = 0.002-0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3-19.9% higher odds of current wheeze than insufficient categories (aOR = 0.907; 95% CI: 0.861-0.957; p < 0.001) and optimal categories (aOR = 0.801; 95% CI: 0.759-0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant. Conclusion: Vitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.

Clinical Characteristics, Laboratory Findings, and Prognosis in Patients With Talaromyces marneffei Infection Across Various Immune Statuses.

Objective: Talaromyces marneffei (TM) is an opportunistic fungus that is predominantly prevalent among patients who are HIV-positive in South-East Asia. However, few studies focused on the clinical features, laboratory findings, and prognosis across varying immune states. Methods: A total of 54 patients with TM infection in Xiangya Hospital of Central South University from January 1, 2006 to October 31, 2021 were retrospectively analyzed. Clinical profiles were compared across the different immune statuses by HIV-positive (HIV group, n = 18), HIV negative but with immunocompromised conditions (Non-HIV with IC Group, n = 11), and immunocompetent patients (n = 25). Results: All the patients were diagnosed by pathogen culture or by metagenomic next-generation sequencing (mNGS). The median age was 50, and patients with HIV were much younger compared to the other two groups. The most common symptom at presentation was fever (79.6%), followed by cough (70.4%), weight loss (61.1%), and expectoration (53.7%). The patients with HIV were more likely to develop into a subtype of disseminated TM affecting multiple organs including lymph node, liver, skin, and spleen, thus, resulting in higher hospital mortality compared to the other two groups. Patients without HIV but with immunocompromised conditions presented similar hospital mortality rates compared to immunocompetent patients, while experiencing longer days of hospitalization to recover from the diseases. Additionally, in this study, the pathogen culture easily confirmed the patients with HIV. However, mNGS presented as a promising tool to confirm TM infection in those suspicious patients without HIV. Conclusions: In summary, patients with HIV were more likely to develop into disseminated TM, resulting in higher mortality compared to those patients without HIV. Additionally, mNGS presented as an important supplementary tool to confirm TM infection in patients without HIV, particularly in those with immunocompromised diseases.