Long-term exposure to outdoor air pollution and asthma in low-and middle-income countries: A systematic review protocol

Background Several epidemiological studies have examined the risk of asthma and respiratory diseases in association with long-term exposure to outdoor air pollution. However, little is known regarding the adverse effects of long-term exposure to outdoor air pollution on the development of these outcomes in low- and middle-income countries (LMICs). Our study aims to investigate the association between long-term exposure to outdoor air pollution and asthma and respiratory diseases in LMICs through a systematic review with meta-analysis. Methods This systematic review and meta-analysis will follow the PRISMA (Preferred Reporting for Systematic Reviews and Meta-Analyses) checklist and flowchart guidelines. The inclusion criteria that will be used in our study are 1) Original research articles with full text in English; 2) Studies including adult humans; 3) Studies with long-term air pollution assessment in LMICs, air pollutants including nitrogen oxide (NO2), sulfur oxide (SO2), particulate matter (PM2.5 and PM10), carbon monoxide (CO) and ozone (O3); 4) cohort and cross-sectional studies; 5) Studies reporting associations between air pollution and asthma and respiratory symptoms. A comprehensive search strategy will be used to identify studies published up till August 2022 and indexed in Embase, Medline, and Web of Science. Three reviewers will independently screen records retrieved from the database searches. Where there are enough studies with similar exposure and outcomes, we will calculate, and report pooled effect estimates using meta-analysis. Systematic review registration PROSPERO CRD42022311326. Discussion Findings from the health effects of long-term exposure to outdoor air pollution may be of importance for policymakers. This review will also identify any gaps in the current literature on this topic in LMICs and provide direction for future research.publishedVersio

Body Fluid Identification in Samples Collected after Intimate and Social Contact: A Comparison of Two mRNA Profiling Methods and the Additional Information Gained by cSNP Genotypes

The ability to associate a contributor with a specific body fluid in a crime stain can aid casework investigation. The detection of body fluids combined with DNA analyses may supply essential information, but as the two tests are independent, they may not be associated. Recently, the analysis of coding region SNPs (cSNPs) within the RNA transcript has been proven to be a promising method to face this challenge. In this study, we performed targeted RNA sequencing of 158 samples (boxershorts, fingernail swabs and penile swabs) collected from 12 couples at different time points post-intimate contact and after non-intimate contact, using the Ion S5™ System and BFID-cSNP-6F assay. The aim of the study was to compare the performance of the MPS and CE methods in the detection of mRNA markers, and to associate body fluids with contributors by their cSNP genotypes. The results of the study show a lower success rate in the detection of vaginal mucosa by the MPS compared to the CE method. However, the additional information obtained with the cSNP genotypes could successfully associate body fluids with contributors in most cases

CT-defined emphysema in COPD patients and risk for change in desaturation status in 6-min walk test

Under embargo until: 2022-07-23Background Emphysema and exercise induced desaturation (EID) are both related to poorer COPD prognosis. More knowledge of associations between emphysema and desaturation is needed for more efficient disease management. Research question Is emphysema a risk factor for both new and repeated desaturation, and is emphysema of more or less importance than other known risk factors? Methods 283 COPD patients completed a 6-min walk test (6MWT) at baseline and one year later in the Bergen COPD cohort study 2006–2011. Degree of emphysema was assessed as percent of low attenuation areas (%LAA) under −950 Hounsfield units using high-resolution computed tomography at baseline. We performed multinomial logistic regression analysis, receiver operating curves (ROC) and area under the curve (AUC) estimations. Dominance analysis was used to rank emphysema and risk factors in terms of importance. Results A one percent increase in %LAA increases the relative risk (RR) of new desaturation by 10 % (RR 1.1 (95%CI 1.1, 1.2)) and for repeated desaturation by 20 % (RR 1.2 (95%CI 1.1, 1.3)). Compared with other important desaturation risk factors, %LAA ranked as number one in the dominance analysis, accounting for 50 % and 37 % of the predicted variance for new and repeated desaturators, respectively. FEV1% predicted accounted for 9 % and 24 %, and resting SpO2 accounted for 22 % and 21 % for new and repeated desaturation. Conclusion Emphysema increases the risk of developing and repeatedly experiencing EID. Emphysema seems to be a more important risk factor for desaturation than FEV1% predicted and resting saturation.acceptedVersio

Seventy years of asthma in Italy: age, period and cohort effects on incidence and remission of self-reported asthma from 1940 to 2010

Background: It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma. Objective: To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010. Methods: The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20–84 and born between 1925–1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models. Results: The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1–4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease. Conclusions: After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study

Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers’ smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11–54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006–0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR)  < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers’ smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers’ exposures might persistently modify their future offspring’s epigenome.publishedVersio

Associations of preconception exposure to air pollution and greenness with offspring asthma and hay fever

We investigated if greenness and air pollution exposure in parents’ childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O3) (µg/m3) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0-18 years old and offspring 0-10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM2.5 and PM10 exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32-3.78, OR 2.27, 95%CI 1.36-3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11-0.87). Hay fever risk increased for offspring of fathers with medium O3 exposure (OR 4.15, 95%CI 1.28-13.50) and mothers with high PM10 exposure (OR 2.66, 95%CI 1.19-5.91). The effect of maternal PM10 exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring’s own exposures. Paternal O3 exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring

Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels

Equation 6. Quadratic logistic function approximating the function mu(B)(with age in years). Equation 1. Proportion of women who have regular menstruation for each number of reported menstruations in the last year(with period = number of periods per year, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months" and z = number of women answering "No, my periods have stopped", e.g. x(11) = number of women reporting regular menstruation among those who report 11 menstruations in the last 12 months). Equation 5. Biquadratic exponential function mu(A)depending of the number of periods. Equation 3. Age modification by smoking and oophorectomy. Equation 2. Proportion of women whose menstruations have already stopped, for each reported year of age(with age = age in years, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months", z = number of women answering "No, my periods have stopped", e.g. x(40) = number of women reporting regular menstruations among those who are 40 years old). Equation 7. Final formula to calculate the reproductive ageing score (RAS)(with period being the number of periods per year and age as the age in years, modified according to smoking status and oophorectomy). Objective Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause;categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Methods Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17 beta-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). Results The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. Conclusions: The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials. Equation 4. The reproductive ageing score as an aggregation function of mu(A)and mu(B)

Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms : Results from a Nordic longitudinal population survey

Publisher Copyright: © 2023 The AuthorsAim: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive. Methods: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: “never”; “former”; “incident”; “persistent”. Incident respiratory symptoms were analyzed among participants without respective symptom at baseline. Results: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21–1.72)), nGER (2.18 (1.60–2.98)) and in those with both snoring and nGER (2.59 (1.83–3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15–1.82)), nGER (1.99 (1.35–2.93)) and in those with both snoring and nGER (1.72 (1.06–2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring. Conclusion: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms.Peer reviewe

The CRCbiome study : a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Peer reviewe