Objective cough frequency in Idiopathic Pulmonary Fibrosis

Background: Cough is a common presenting symptom in patients with Idiopathic Pulmonary Fibrosis (IPF). This study measured cough rates in IPF patients and investigated the association between cough and measures of health related quality of life and subjective cough assessments. In addition, IPF cough rates were related to measures of physiological disease severity and compared to cough rates in health and other respiratory conditions.Methods: Nineteen IPF patients, mean age 70.8 years ± 8.6, five female (26.3%) were studied. Subjects performed full pulmonary function testing, 24 hour ambulatory cough recordings, completed a cough related quality of life questionnaire (Leicester Cough Questionnaire) and subjectively scored cough severity with a visual analogue scale. Ambulatory cough recordings were manually counted and reported as number of coughs per hour.Results: The 24hr cough rates were high (median 9.4, range 1.5-39.4), with day time rates much higher than night time (median 14.6, range 1.9-56.6 compared to 1.9, range 0-19.2, p = 0.003). Strong correlations were found between objective cough frequency and both the VAS (day r = 0.80, p &lt; 0.001, night r = 0.71, p = 0.001) and LCQ (r = -0.80, p &lt; 0.001), but not with measures of pulmonary function. Cough rates in IPF were higher than healthy subjects (p &lt; 0.001) and asthma patients (p &lt; 0.001) but similar to patients with chronic cough (p = 0.33).Conclusions: This study confirms objectively that cough is a major, very distressing and disabling symptom in IPF patients. The strong correlations between objective cough counts and cough related quality of life measures suggest that in IPF patient's, perception of cough frequency is very accurate.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults

<p>Abstract</p> <p>Background</p> <p>The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies.</p> <p>Methods</p> <p>We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires.</p> <p>Results</p> <p>Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, <it>p </it>= .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, <it>p </it>= .007, respectively). VEG reported significantly lower mean intakes of EPA (<it>p </it>< .001), DHA (<it>p </it>< .001), as well as the omega-6 fatty acid, arachidonic acid (AA; <it>p </it>< .001), and reported higher mean intakes of shorter-chain α-linolenic acid (<it>p </it>< .001) and linoleic acid (<it>p </it>< .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (<it>p </it>< 0.05), DHA (<it>p </it>< 0.05), and AA (<it>p </it>< 0.05), and inversely related to intakes of ALA (<it>p </it>< 0.05), and LA (<it>p </it>< 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood.</p> <p>Conclusions</p> <p>The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.</p

Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. RESULTS: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. CONCLUSIONS: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear

Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer.

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

© 2018 The Author(s). Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants

AbstractBackground: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.Findings: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7–128.3) in men and 122.3 mm Hg (121.0–123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9–79.5) for men and 76.7 mm Hg (75.9–77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4–27.1) in men and 20.1% (17.8–22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.Abstract Background: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7–128.3) in men and 122.3 mm Hg (121.0–123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9–79.5) for men and 76.7 mm Hg (75.9–77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4–27.1) in men and 20.1% (17.8–22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants

Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18.5 kg/m(2) [underweight], 18.5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), = 40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings We used 1698 population-based data sources, with more than 19.2 million adult participants (9.9 million men and 9.3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21.7 kg/m(2) (95% credible interval 21.3-22.1) in 1975 to 24.2 kg/m(2) (24.0-24.4) in 2014 in men, and from 22.1 kg/m(2) (21.7-22.5) in 1975 to 24.4 kg/m(2) (24.2-24.6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21.4 kg/m(2) in central Africa and south Asia to 29.2 kg/m(2) (28.6-29.8) in Polynesia and Micronesia; for women the range was from 21.8 kg/m(2) (21.4-22.3) in south Asia to 32.2 kg/m(2) (31.5-32.8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13.8% (10.5-17.4) to 8.8% (7.4-10.3) in men and from 14.6% (11.6-17.9) to 9.7% (8.3-11.1) in women. South Asia had the highest prevalence of underweight in 2014, 23.4% (17.8-29.2) in men and 24.0% (18.9-29.3) in women. Age-standardised prevalence of obesity increased from 3.2% (2.4-4.1) in 1975 to 10.8% (9.7-12.0) in 2014 in men, and from 6.4% (5.1-7.8) to 14.9% (13.6-16.1) in women. 2.3% (2.0-2.7) of the world's men and 5.0% (4.4-5.6) of women were severely obese (ie, have BMI = 35 kg/m(2)). Globally, prevalence of morbid obesity was 0.64% (0.46-0.86) in men and 1.6% (1.3-1.9) in women. Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia.Wellcome Trust, Grand Challenges Canada