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2.
Artigo em Inglês | MEDLINE | ID: mdl-31505189

RESUMO

BACKGROUND: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. OBJECTIVE: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. METHODS: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. RESULTS: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. CONCLUSION: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.

3.
Health Technol Assess ; 23(49): 1-144, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31538569

RESUMO

BACKGROUND: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. OBJECTIVES: To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. DESIGN: A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. SETTING: Sixteen UK fetal medicine centres. PARTICIPANTS: Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. INTERVENTIONS: Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. MAIN OUTCOME MEASURES: Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. RESULTS: The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. CONCLUSIONS: iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27626961. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.

4.
Eur Respir J ; 54(4)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439684

RESUMO

In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.We included 94 742 naturally post-menopausal women from the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, spirometric restriction (FVC

5.
Int J Epidemiol ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270549

RESUMO

BACKGROUND: Although physical activity has many known health benefits, its association with lung function in childhood/adolescence remains unclear. We examined the association of physical-activity trajectories between 11 and 15 years with lung function at 15 years in 2266 adolescents. METHODS: A population-based cohort of 14 305 singleton births alive at 1 year was recruited in the UK population-based Avon Longitudinal Study of Parents and Children cohort. Physical activity (counts/minute and moderate-to-vigorous physical activity) was assessed for 7 days using an accelerometer at 11, 13 and 15 years. We identified sex-specific physical-activity trajectories applying K-means for longitudinal data in children with at least two accelerometer measurements (n = 3584). We then estimated the sex-specific associations of these trajectories with post-bronchodilation lung-function parameters using multivariable linear-regression models (n = 2266, 45% boys). RESULTS: Fewer than 7% of participants met the WHO physical-activity recommendations (i.e. daily average of at least 60 minutes of moderate-to-vigorous physical activity). Boys were substantially more active than girls. In both sexes, we identified three distinct physical-activity trajectories ('low': 39.8% boys, 45.8% girls; 'moderate': 42.9% boys, 41.4% girls; and 'high' physical activity: 17.3% boys, 12.8% girls). Girls in the moderate and high physical-activity trajectories had 0.11 L [95% confidence interval (CI): 0.04-0.19] and 0.15 L (95% CI: 0.03-0.26) higher forced vital capacity than their less-active peers. No association was observed in boys. CONCLUSIONS: Higher childhood physical activity relates to higher lung-function levels in adolescent girls. A better understanding of the mechanisms underlying this association should be pursued.

6.
Eur Respir J ; 54(3)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31221806

RESUMO

Bronchodilator response (BDR) testing is used as a diagnostic method in obstructive airway diseases. The aim of this investigation was to compare different methods for measuring BDR in participants with asthma and chronic obstructive pulmonary disease (COPD) and to study to the extent to which BDR was related to symptom burden and phenotypic characteristics.Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured before and 15 min after 200 µg of salbutamol in 35 628 subjects aged ≥16 years from three large international population studies. The subjects were categorised in three groups: current asthma (n=2833), COPD (n=1146) and no airway disease (n=31 649). Three definitions for flow-related reversibility (increase in FEV1) and three for volume-related reversibility (increase in FVC) were used.The prevalence of bronchodilator reversibility expressed as increase FEV1 ≥12% and 200 mL was 17.3% and 18.4% in participants with asthma and COPD, respectively, while the corresponding prevalence was 5.1% in those with no airway disease. In asthma, bronchodilator reversibility was associated with wheeze (OR 1.36, 95% CI 1.04-1.79), atopy (OR 1.36, 95% CI 1.04-1.79) and higher exhaled nitric oxide fraction, while in COPD neither flow- nor volume-related bronchodilator reversibility was associated with symptom burden, exacerbations or health status after adjusting for pre-bronchodilator FEV1Bronchodilator reversibility was at least as common in participants with COPD as those with asthma. This indicates that measures of reversibility are of limited value for distinguishing asthma from COPD in population studies. However, in asthma, bronchodilator reversibility may be a phenotypic marker.

7.
Eur Respir J ; 54(1)2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31248951

RESUMO

Occupational exposures are important, preventable causes of chronic obstructive pulmonary disease (COPD). Identification of COPD high-risk jobs is key to focus preventive strategies, but a definitive job-list is unavailable.We addressed this issue by evaluating the association of lifetime job-histories and lung function data in the population-based UK Biobank cohort, whose unprecedented sample size allowed analyses restricted to never-smokers to rule out the most important confounder, tobacco smoking. COPD was spirometrically defined as forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. Lifetime job-histories were collected via OSCAR (Occupations Self-Coding Automatic Recording), a new validated online tool that automatically codes jobs into the UK Standard Occupational Classification v.2000. Prevalence ratios for COPD by employment duration in each job compared to lifetime office workers were estimated using robust Poisson regression adjusted for age, sex, centre and smoking. Only associations confirmed among never-smokers and never-asthmatics were considered reliable.From the 116 375 participants with complete job-histories, 94 551 had acceptable/repeatable spirometry data and smoking information and were included in the analysis. Six occupations showed an increased COPD risk among never-smokers and never-asthmatics; most of these also with positive exposure-response trends. Interesting new findings included sculptors, gardeners and warehouse workers.COPD patients, especially never-smokers, should be asked about their job-history for better disease management. Focussed preventive strategies in COPD high-risk jobs are warranted.

8.
Int J Chron Obstruct Pulmon Dis ; 14: 1063-1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213788

RESUMO

Background: Inhaled corticosteroid (ICS)-containing medications slow rate of decline of FEV1. Blood eosinophil (EOS) levels are associated with the degree of exacerbation reduction with ICS. Purpose: We investigated whether FEV1 decline differs between patients with and without ICS, stratified by blood EOS level. Patients and methods: The UK Clinical Practice Research Datalink (primary care records) and Hospital Episode Statistics (hospital records) were used to identify COPD patients aged 35 years or older, who were current or ex-smokers with ≥2 FEV1 measurements ≥6 months apart. Prevalent ICS use and the nearest EOS count to start of follow-up were identified. Patients were classified at baseline as higher stratum EOS (≥150 cell/µL) on ICS; higher stratum EOS not on ICS; lower stratum EOS (<150 cells/µL) on ICS; and lower stratum EOS not on ICS. In addition, an incident ICS cohort was used to investigate the rate of FEV1 change by EOS and incident ICS use. Mixed-effects linear regression was used to compare rates of FEV1 change in mL/year. Results: A total of 26,675 COPD patients met our inclusion criteria (median age 69, 46% female). The median duration of follow up was 4.2 years. The rate of FEV1 change in prevalent ICS users was slower than non-ICS users (-12.6 mL/year vs -21.1 mL/year; P =0.001). The rate of FEV1 change was not significantly different when stratified by EOS level. The rate of FEV1 change in incident ICS users increased (+4.2 mL/year) vs -21.2 mL/year loss in non-ICS users; P<0.001. In patients with high EOS, incident ICS patients showed an increase in FEV1 (+12 mL/year) compared to non-ICS users whose FEV1 decreased (-20.8 mL/year); P<0.001. No statistical difference was seen in low EOS patients. Incident ICS use is associated with an improvement in FEV1 change, however, over time this association is lost. Conclusion: Regardless of blood EOS level, prevalent ICS use is associated with slower rates of FEV1 decline in COPD.

9.
Eur Respir J ; 54(1)2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31073081

RESUMO

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute ß-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.

10.
Indoor Air ; 29(4): 670-679, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30963644

RESUMO

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.

11.
Clin Exp Allergy ; 49(7): 969-979, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30934155

RESUMO

INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. OBJECTIVE: To identify determinants of FE NO in men and women without lung diseases. METHOD: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. RESULTS: Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P < 0.001) and 5% higher FE NO levels in women (P = 0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, P < 0.001 for both. CONCLUSION AND CLINICAL RELEVANCE: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex.

12.
Pediatr Allergy Immunol ; 30(6): 589-597, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30968967

RESUMO

What are the implications of a lower than expected forced expiratory volume in one second (FEV1) in childhood on respiratory health later in adulthood? Lung function is known to track with age, and there is evidence from recent epidemiologic studies that impaired lung function early in life is associated with later chronic airflow limitation, or even chronic obstructive pulmonary disease, COPD. This risk seems particularly strong in subjects with persistent and severe forms of childhood asthma. Can we translate findings from longitudinal cohort studies to individual risk predictions and preventive guidelines in our pediatric care? In this review, we discuss the clinical implementations of recent epidemiological respiratory studies and the importance of preserved lung health across the life course. Also, we evaluate available clinical tools, primarily lung function measures, and profiles of risk factors, including biomarkers, that may help identifying children at risk of chronic airway disease in adulthood. We conclude that translating population level results to the individual patient in the pediatric care setting is not straight forward, and that there is a need for studies specifically designed to evaluate performance of prediction of risk profiles for long-term sequelae of childhood asthma and lung function impairment.

13.
Int J Hyg Environ Health ; 222(3): 364-386, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876873

RESUMO

BACKGROUND: Rapid population growth and urbanisation around the world has led to increasing waste generation rates. Composting of organic waste in large-scale facilities is part of a growing trend in the UK, and elsewhere, to better manage and re-use the organic waste. However, composting inevitably generates bioaerosols, which have been associated with human health effects. In 2015, we reported that there was some, albeit limited, qualitative evidence linking bioaerosol emissions from composting facilities to poor respiratory health in nearby residents. However, the limited evidence precluded any quantitative assessment. Since then, the number of operational industrial-scale composting facilities in England has increased by 9% - nearly twice the growth from 2012 to 2014. At the same time, rapid urbanisation has led to expansion of city borders with more people living near large composting facilities and exposed to bioaerosol pollution. It is essential that regulatory authorities have access to the most up to date and accurate information. OBJECTIVE: In this update of a systematic review published in 2015, we review and summarise the evidence from more recent studies that have assessed bioaerosol exposures within and near composting facilities and their associated health effects in both community and occupational health settings. Specifically, we wanted to find out if new evidence has emerged since the previous review to strengthen and confirm its conclusions. MATERIAL AND METHODS: Two electronic databases (Medline and Embase) and bibliographies were searched for studies reporting on health outcomes and/or exposure to bioaerosols from composting facilities published between 1 January 2014 and 15 June 2018. Identification of relevant articles and data extraction was undertaken and studies were assessed for risk of bias. RESULTS: 23 studies met the inclusion criteria (15 exposure studies, 4 health studies, 4 health and exposure studies (one of which used an exposure proxy)). The majority of studies were conducted in occupational settings, and over short time periods. Some progress has been made in the characterisation of bioaerosol emissions from these composting facilities, with the application of molecular-based methods. Whilst the latest health studies do not rely solely on subjective self-reported measures of health status but include more objective health measures, these studies were almost exclusively carried out in compost workers and were characterised by profound methodological limitations. Only one community health study was identified and used a proxy measure of bioaerosol exposure. CONCLUSIONS: Although this review identified an additional 23 studies since the earlier review, the conclusions remain largely unchanged. Given the absence of any consistent evidence on the toxicity of bioaerosols from composting facilities, there is insufficient evidence to provide a quantitative comment on the risk to nearby residents from exposure to compost bioaerosols. To improve risk assessment and to best advise on risk management, it is important to ensure that the research recommendations outlined in this review are addressed.

14.
PLoS One ; 14(2): e0211976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730998

RESUMO

BACKGROUND: Smoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010. METHODS: Data on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe). RESULTS: Overall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/year) compared to the other regions (range: 26.5-32.7 per 1,000/year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later. CONCLUSIONS: Our findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later life.

15.
Neuroradiology ; 61(5): 603-611, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30796469

RESUMO

PURPOSE: To refine methods that assess structural brain abnormalities and calculate intracranial volumes in fetuses with congenital heart diseases (CHD) using in utero MR (iuMR) imaging. Our secondary objective was to assess the prevalence of brain abnormalities in this high-risk cohort and compare the brain volumes with normative values. METHODS: We performed iuMR on 16 pregnant women carrying a fetus with CHD and gestational age ≥ 28-week gestation and no brain abnormality on ultrasonography. All cases had fetal echocardiography by a pediatric cardiologist. Structural brain abnormalities on iuMR were recorded. Intracranial volumes were made from 3D FIESTA acquisitions following manual segmentation and the use of 3D Slicer software and were compared with normal fetuses. Z scores were calculated, and regression analyses were performed to look for differences between the normal and CHD fetuses. RESULTS: Successful 2D and 3D volume imaging was obtained in all 16 cases within a 30-min scan. Despite normal ultrasonography, 5/16 fetuses (31%) had structural brain abnormalities detected by iuMR (3 with ventriculomegaly, 2 with vermian hypoplasia). Brain volume, extra-axial volume, and total intracranial volume were statistically significantly reduced, while ventricular volumes were increased in the CHD cohort. CONCLUSION: We have shown that it is possible to perform detailed 2D and 3D studies using iuMR that allow thorough investigation of all intracranial compartments in fetuses with CHD in a clinically appropriate scan time. Those fetuses have a high risk of structural brain abnormalities and smaller brain volumes even when brain ultrasonography is normal.


Assuntos
Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Cardiopatias Congênitas/complicações , Imagem por Ressonância Magnética/métodos , Adulto , Estudos de Casos e Controles , Ecocardiografia , Estudos de Viabilidade , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Interpretação de Imagem Assistida por Computador , Imagem Tridimensional , Tamanho do Órgão , Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos , Software
16.
Artigo em Inglês | MEDLINE | ID: mdl-30791383

RESUMO

A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-κB signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.


Assuntos
Asma/genética , Índice de Massa Corporal , Metilação de DNA , Inflamação/metabolismo , Adulto , Animais , Estudos de Coortes , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , NF-kappa B/metabolismo , Obesidade/complicações , PPAR gama/metabolismo
17.
Respir Res ; 20(1): 33, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764884

RESUMO

BACKGROUND: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. METHODS: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. RESULTS: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (ß: - 49 ml; 95%-CI: -132, 35 for FEV1 and ß: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. CONCLUSION: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.


Assuntos
Nível de Saúde , Sistema Respiratório/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Asma/epidemiologia , Asma/etiologia , Bronquite Crônica/epidemiologia , Bronquite Crônica/etiologia , Dispneia/epidemiologia , Dispneia/etiologia , Europa (Continente)/epidemiologia , União Europeia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Incidência , Prevalência , Testes de Função Respiratória , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/etiologia , Fatores Socioeconômicos , Poluição por Fumaça de Tabaco/estatística & dados numéricos
18.
Occup Environ Med ; 76(4): 222-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30700596

RESUMO

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

19.
Am J Respir Crit Care Med ; 200(1): 75-83, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30630337

RESUMO

Rationale: Body composition changes throughout life may explain the inconsistent associations reported between body mass index and lung function in children. Objectives: To assess the associations of body weight and composition trajectories from 7 to 15 years with lung function at 15 years and lung function growth between 8 and 15 years. Methods: Sex-specific body mass index, lean body mass index, and fat mass index trajectories were developed using Group-Based Trajectory Modeling on data collected at least twice between 7 and 15 years from 6,964 children (49% boys) in the UK Avon Longitudinal Study of Parents and Children birth cohort. Associations of these trajectories with post-bronchodilation lung function parameters at 15 years and with lung function growth rates from 8 to 15 years were assessed using multivariable linear regression models, stratified by sex, in a subgroup with lung function data (n = 3,575). Measurements and Main Results: For all body mass measures we identified parallel trajectories that increased with age. There was no consistent evidence of an association between the body mass index trajectories and lung function measures. Higher lean body mass index trajectories were associated with higher levels and growth rates of FVC, FEV1, and forced expiratory flow, midexpiratory phase in both sexes (e.g., boys in the highest lean body mass index trajectory had on average a 0.62 L [95% confidence interval, 0.44-0.79; P trend < 0.0001] higher FVC at 15 yr than boys in the lowest trajectory). Increasing fat mass index trajectories were associated with lower levels and growth rates of FEV1 and forced expiratory flow, midexpiratory phase only in boys and lower levels of FEV1/FVC in both sexes. Conclusions: Higher lean body mass during childhood and adolescence is consistently associated with higher lung function at 15 years in both sexes, whereas higher fat mass is associated with lower levels of only some lung function parameters.

20.
Eur Radiol ; 29(7): 3488-3495, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30683990

RESUMO

PURPOSE: To describe the normal linear measurements of the skull (bi-parietal diameter and occipito-frontal diameter) and intracranial volumes (ventricular volume, brain parenchymal volume, extra-axial volume and total intra-cranial volume) in normal fetuses. MATERIALS AND METHODS: We recruited pregnant women from low-risk pregnancies whose fetuses had normal ultrasound and in utero MR studies. All volunteers had in utero MR imaging on the same 1.5T MR scanner with a protocol consisting of routine and 3D steady-state volume imaging of the fetal brain. Linear measurements of the skull were made using the volume imaging. The 3D volume imaging also was manually segmented to delineate the intracranial compartments described above to determine quantitative values for each. RESULTS: Two hundred normal fetuses were studied with gestational ages between 18 and 37 weeks. The linear skull measurements made on in utero MR imaging closely correlate with published data from ultrasonography. The intracranial volume data is presented as graphs and as tabular summaries of 3rd, 10th, 50th, 90th and 97th centiles. CONCLUSION: It is now possible to measure the volumes of the intracranial compartments in individual fetuses using ultrafast in utero MR techniques. KEY POINTS: • There are limitations in using the skull size of the fetus to comment on the state of the fetal brain. • Volumes for the intracranial compartments are presented, based on in utero MR imaging of the fetal brain between 18 and 37 weeks gestational age. • Those normative values can be used to assess fetuses with known or suspected structural brain abnormalities and may assist the differential diagnosis provided by visual assessment of routine iuMR studies.


Assuntos
Encéfalo/diagnóstico por imagem , Feto/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imagem Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos , Encéfalo/embriologia , Feminino , Idade Gestacional , Humanos , Tamanho do Órgão , Gravidez , Estudos Prospectivos , Valores de Referência
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