Search

Background: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO. Methods: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes—VGDF; solvents; pesticides; metals), adjusting for potential confounders. Results: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04–1.78) for low levels and 1.41 (95%CI: 1.11–1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures. Conclusion: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control. [ABSTRACT FROM AUTHOR]

Background: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors. Methods: We performed three analyses: (1) cardio-metabolic health to lung function association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) to compare genetic backgrounds and (3) Mendelian randomisation (MR) analysis to assess the causal effect of cardio-metabolic traits and disease on lung function, and vice versa (bidirectional MR). Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies (N > 82,000). Results: We observed a negative genetic correlation between lung function and cardio-metabolic traits and diseases. In Mendelian Randomisation analysis (MR), we found associations between type 2 diabetes (T2D) instruments and forced vital capacity (FVC) as well as FEV1/FVC. Body mass index (BMI) instruments were associated to all lung function traits and C-reactive protein (CRP) instruments to FVC. These genetic associations provide evidence for a causal effect of cardio-metabolic traits on lung function. Multivariable MR suggested independence of these causal effects from other tested cardio-metabolic traits and diseases. Analysis of lung function specific SNPs revealed a potential causal effect of FEV1/FVC on blood pressure. Conclusions: The present study overcomes many limitations of observational studies by using Mendelian Randomisation. We provide evidence for an independent causal effect of T2D, CRP and BMI on lung function with some of the T2D effect on lung function being attributed to inflammatory mechanisms. Furthermore, this analysis suggests a potential causal effect of FEV1/FVC on blood pressure. Our detailed analysis of the interplay between cardio-metabolic traits and impaired lung function provides the opportunity to improve the quality of existing intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown., Research Question: Is spirometry-defined SAO associated with increased mortality?, Methods: Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV 1 /forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity., Results: A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20)., Interpretation: Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males., Methods and Findings: MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (<12), normal (12-14), or late (>14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10(-5)) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10(-4)), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking., Conclusions: This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: CM and GDS are members of the Editorial Board of PLOS Medicine.