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Introduction: The clinical assessment of mobility, and walking specifically, is still mainly based on functional tests that lack ecological validity. Thanks to inermeasurement units (IMUs), gait analysis is shifting to unsupervised monitoring in naturalistic and unconstrained settings. However, the extraction of clinically relevant gait parameters from IMU data often depends on heuristics-based algorithms that rely on empirically determined thresholds. These were mainly validated on small cohorts in supervised settings. Methods: Here, a deep learning (DL) algorithm was developed and validated for gait event detection in a heterogeneous population of dierent mobilitylimiting disease cohorts and a cohort of healthy adults. Participants wore pressure insoles and IMUs on both feet for 2.5 h in their habitual environment. The raw accelerometer and gyroscope data from both feet were used as input to a deep convolutional neural network, while reference timings for gait events were based on the combined IMU and pressure insoles data. Results and discussion: The results showed a high-detection performance for initial contacts (ICs) (recall: 98%, precision: 96%) and final contacts (FCs) (recall: 99%, precision: 94%) and a maximum median time error of −0.02 s for ICs and 0.03 s for FCs. Subsequently derived temporal gait parameters were in good agreement with a pressure insoles-based reference with a maximum mean dierence of 0.07, −0.07, and <0.01 s for stance, swing, and stride time, respectively. Thus, the DL algorithm is considered successful in detecting gait events in ecologically valid environments across dierent mobility-limiting diseases. [ABSTRACT FROM AUTHOR]

Background: The study of impact of lockdowns on individual health-related behaviors has produced divergent results.Purpose: To identify patterns of change in multiple health-related behaviors analyzed as a whole, and their individual determinants.Methods: Between March and August 2020, we collected data on smoking, alcohol, physical activity, weight, and sleep in a population-based cohort from Catalonia who had available pre-pandemic data. We performed multiple correspondence and cluster analyses to identify patterns of change in health-related behaviors and built multivariable multinomial logistic regressions to identify determinants of behavioral change.Results: In 10,032 participants (59% female, mean (SD) age 55 (8) years), 8,606 individuals (86%) modified their behavior during the lockdown. We identified five patterns of behavioral change that were heterogeneous and directed both towards worsening and improvement in diverse combinations. Patterns ranged from "global worsening" (2,063 participants, 21%) characterized by increases in smoking, alcohol consumption, and weight, and decreases in physical activity levels and sleep time, to "improvement" (2,548 participants, 25%) characterized by increases in physical activity levels, decreases in weight and alcohol consumption, and both increases and decreases in sleep time. Being female, of older age, teleworking, having a higher education level, assuming caregiving responsibilities, and being more exposed to pandemic news were associated with changing behavior (all p < .05), but did not discriminate between favorable or unfavorable changes.Conclusions: Most of the population experienced changes in health-related behavior during lockdowns. Determinants of behavior modification were not explicitly associated with the direction of changes but allowed the identification of older, teleworking, and highly educated women who assumed caregiving responsibilities at home as susceptible population groups more vulnerable to lockdowns. [ABSTRACT FROM AUTHOR]

The article offers several studies that have assessed various protein panels in asthma with most using airway-derived samples, recruiting clinic-based cohorts and focuses on cytokines and chemokines. Topics include examines there is a lack of large-scale population-based studies that examine multiple circulating proteins for association with asthma in children.

Background: We previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C‐reactive protein (CRP) at 15 years partially mediate this association. Methods: We included 2263 children from the UK Avon Longitudinal Study of Parents and Children population‐based cohort (ALSPAC). Four fat mass index (FMI) trajectories ("low," "medium‐low," "medium‐high," "high") from 9 to 15 years were previously identified using Group‐Based Trajectory Modeling. Data on CRP, glucose, insulin, and post‐bronchodilator FEV1/FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment‐estimated insulin resistance index (HOMA‐IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA‐IR and CRP. Results: Compared to children in the "low" FMI trajectory, children in the "medium‐high" and "high" FMI trajectories had lower FEV1/FVC at 15 years. The percentage of the total effect explained by HOMA‐IR was 19.8% [−114.1 to 170.0] and 20.4% [1.6 to 69.0] for the "medium‐high" and "high" trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP. Conclusion: The association between mid‐childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight. Methods: The study included 2536 mother‐neonate pairs of a Spanish birth cohort (2004–2006, INMA project). The exposures were questionnaire‐based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40 weeks of gestation. Results: In women sleeping for <7 h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7 g (P = 0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P > 0.05). However, increasing sleep duration for the group of mothers who slept for more than 9 h/day decreased birth weight score by 39.2 g per additional hour (P = 0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression‐anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy. Conclusion: The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U‐shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight. We found an inverse U‐shaped association between maternal sleep duration before and during pregnancy and neonate birth weight, using data from a large cohort study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. OBJECTIVE: We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (N[O.sub.2]) exposure and birth weight. METHODS: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. RESULTS: Pooled estimates indicated that a 10-µg/[m.sup.3] increment in average N[O.sub.2] exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: -9.3, -0.3%) and a 48-g decrease (95% CI: -87, -9 g) in birth weight. However, the association with birth weight was significant for INMA (-66 g; 95% CI: -111, -23 g) but not for ENVIRONAGE (-20 g; 95% CI: -101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal N[O.sub.2] and birth weight was mediated by changes in placental mtDNA content. CONCLUSION: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight. http://dx.doi.org/10.1289/ehp.1408981, Introduction In recent years, traffic-related air pollution has been considered an important risk factor for adverse reproductive health effects. Prenatal exposure to nitrogen dioxide (N[O.sub.2]) has been associated with low [...]

Abstract Background Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant exposures on cough. Methods Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model. Results Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10-6) and usual cough (9-SNP haplotype: p-global = 4.5 × 10-6). Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p < 0.05). Four polymorphisms in TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p < 0.05). Conclusions TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.

Abstract Background Increased use of prostate specific antigen (PSA) has been associated with increased prostate cancer incidence. Ireland is estimated to have one of the highest prostate cancer incidences in Europe and has no national guidelines for prostate cancer screening. GPs have a pivotal role in influencing PSA testing, therefore, our aim was to describe GP testing practices and to identify factors influencing these. Methods A postal survey, including questions on clinical practice and experience, knowledge and demographics was distributed to all GPs (n = 3,683). The main outcomes were (i) PSA testing asymptomatic men and (ii) "inappropriate" PSA testing, defined as testing asymptomatic men aged < 50 or > 75 years. Factors associated with these outcomes were identified using logistic regression. Results 1,625 GPs responded (response rate corrected for eligibility = 53%). Most respondents (79%) would PSA test asymptomatic men. Of these, 34% and 51% would test asymptomatic men < 50 and > 75 years, respectively. In multivariate analyses, GPs were more likely to test asymptomatic men if they were ≥ 50 years, in practice ≥ 10 years, female or less knowledgeable about PSA efficacy. Male GPs who would have a PSA test themselves were > 8-times more likely to PSA test asymptomatic men than GPs who would not have a test. GPs who had an asymptomatic patient diagnosed with prostate cancer following PSA testing, were > 3-times more likely to test asymptomatic men. Practice-related factors positively associated with testing included: running 'well man' clinics, performing occupational health checks and performing other tests routinely with PSA. Factors positively associated with 'inappropriate' testing included; being male and willing to have a PSA test, having worked/trained in the UK and supporting annual PSA testing. 91% of respondents supported the development of national PSA testing guidelines. Conclusion Our findings suggest that widespread PSA testing of asymptomatic men in primary care is primarily due to a combination of clinical experience, poor knowledge and the support of doctors for PSA testing, as evidenced by the willingness of male doctors to have a PSA test. There is an urgent need for education and support for GPs concerning prostate cancer screening, starting with the implementation of national guidelines.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace. [ABSTRACT FROM AUTHOR]

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n  = 2,757, aged 39–67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n  = 2,610, aged 36–82 years) first in 2000–2002 and again approximately 10 years later (2010–2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2–3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years. [ABSTRACT FROM AUTHOR]

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991–1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999–2003, and ECRHS III in 2010–2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21–95) for forced expiratory volume in one second and 83 mL (36–130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS).Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations.Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline.Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life. [ABSTRACT FROM AUTHOR]

Objective: Regular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity. Methods: Cross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28–56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task—minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40–67 years-old). Adjusted cross-sectional mixed linear regression models and the “mediate” package in “R” were used to assess the presence of mediation. Results: Despite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity). Conclusions: In a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood. [ABSTRACT FROM AUTHOR]

This longitudinal study investigated whether smoking bans influence passive smoking at work and/or at home in the same subjects. Passive smoking at work and/or at home was investigated in random population samples (European Community Respiratory Health Survey) in 1990‐1995, with follow‐up interviews in 1998‐2003 and 2010‐2014. National smoking bans were classified as partial (restricted to public workplaces) or global (extended to private workplaces). Multivariable analysis was accomplished by three‐level logistic regression models, where level‐1, level‐2, and level‐3 units were, respectively, questionnaire responses, subjects, and centers. Passive smoking at work was reported by 31.9% in 1990‐1995, 17.5% in 1998‐2003, and 2.5% in 2010‐2014. Concurrently, passive smoking at home decreased from 28.9% to 18.2% and 8.8%. When controlling for sex, age, education, smoking status, and ECHRS wave, the odds of passive smoking at work was markedly reduced after global smoking bans (OR = 0.45, 95% CI 0.25‐0.81), particularly among non‐smokers, while the protective effect of global smoking bans on passive smoking at home was only detected in non‐smokers. Smoking bans both in public and private workplaces were effective in reducing passive smoking at work in Europe. However, given the inefficacy of smoking bans in current smokers' dwellings, better strategies are needed to avoid smoking indoors. [ABSTRACT FROM AUTHOR]

Background: Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey.Methods: General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework.Findings: 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%.Interpretation: These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD. [ABSTRACT FROM AUTHOR]

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma.Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines.Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55).Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.Funding: European Union (Horizon 2020, GA-633212). [ABSTRACT FROM AUTHOR]

Objective: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort.Methods: FEV1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC.Results: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline.Conclusion: Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline. [ABSTRACT FROM AUTHOR]

Background Currently, the 5-year survival rate for rectal cancer remains at <60%. The identification of potentially modifiable prognostic factors would be of considerable public health importance. A few studies have suggested associations between smoking and survival in rectal cancer; however, the evidence is inconsistent, and most of these studies were relatively small. In a large population-based cohort study, we investigated whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in rectal cancer and whether the association varies by sex, age, or treatment. Methods Rectal cancers (ICD10 C19-20) diagnosed between 1994 and 2012 were abstracted from the National Cancer Registry Ireland and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2012. Multivariable Cox proportional hazards models were used to compare cancer-specific death rates in current smokers, ex-smokers, and never smokers. Subgroup analyses by age at diagnosis, sex, and treatment were conducted. Results A total of 10,794 rectal cancers were diagnosed. At diagnosis, 25% were current smokers, 24% were ex-smokers, and 51% were never smokers. Compared with never smokers, current smokers had a significantly greater rate of death from cancer (multivariable hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.06-1.24), but ex-smokers did not (HR, 1.02; 95% CI, 0.94-1.11). The association was slightly stronger in men (current versus never smokers: HR = 1.13, 95% CI, 1.02-1.24) than females (HR, 1.05; 95% CI, 0.90-1.23), but the test for interaction was not significant ( P = .75). The effect of smoking was not modified by age or receipt of tumor-directed surgery, radiotherapy, or chemotherapy. Conclusions Rectal cancer patients who smoke at diagnosis have a statistically significant increased cancer death rate. Elucidation of the underlying mechanisms is urgently required. Cancer 2017;123:2543-50. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception.Methods: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family.Results: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries.Conclusions: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations. [ABSTRACT FROM AUTHOR]

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1) and FEV 1 /FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV 1 at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (−0.02 (−0.04, 0)) and FEV 1 z-scores (−0.02 (−0.04, −0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV 1 at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV 1 , especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure. [Display omitted] • Gestational phthalates exposure was associated with lower lung function at all ages. • The lung function decline was stronger in younger than in older children. • The reduction in lung function observed at 4 and 7 years was not persistent. • MiBP and MBzP were the key phthalate metabolites driving the lung function reduction. [ABSTRACT FROM AUTHOR]

Summary Background Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV 1 ) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. Methods We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV 1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4–6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. Findings After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV 1 at baseline, we found an inverse association between CC16 concentration and decline in FEV 1 in adults in TESAOD (4·4 mL/year additional FEV 1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV 1 to forced expiratory volume [FEV 1 /FVC] less than 70% plus FEV 1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV 1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (−71 mL, p<0·0001). Interpretation Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. Funding National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme. [ABSTRACT FROM AUTHOR]