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1.
Environ Int ; 157: 106792, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34388675

RESUMO

BACKGROUND: Particulate matter (PM) air pollution exposure has been linked to lung function in adolescents, but little is known about the relevance of specific PM components and ultrafine particles (UFP). OBJECTIVES: To investigate the associations of long-term exposure to PM elemental composition and UFP with lung function at age 16 years. METHODS: For 706 participants of a prospective Dutch birth cohort, we assessed associations of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 with average exposure to eight elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc) in PM2.5 and PM10, as well as UFP during the preceding years (age 13-16 years) estimated by land-use regression models. After assessing associations for each pollutant individually using linear regression models with adjustment for potential confounders, independence of associations with different pollutants was assessed in two-pollutant models with PM mass and NO2, for which associations with lung function have been reported previously. RESULTS: We observed that for most PM elemental components higher exposure was associated with lower FEV1, especially PM10 sulfur [e.g. adjusted difference -2.23% (95% confidence interval (CI) -3.70 to -0.74%) per interquartile range (IQR) increase in PM10 sulfur]. The association with PM10 sulfur remained after adjusting for PM10 mass. Negative associations of exposure to UFP with both FEV1 and FVC were observed [-1.06% (95% CI: -2.08 to -0.03%) and -0.65% (95% CI: -1.53 to 0.23%), respectively per IQR increase in UFP], but did not persist in two-pollutant models with NO2 or PM2.5. CONCLUSIONS: Long-term exposure to sulfur in PM10 may result in lower FEV1 at age 16. There is no evidence for an independent effect of UFP exposure.

2.
PLoS One ; 16(8): e0255402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34379666

RESUMO

Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID-19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, large-effect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak.


Assuntos
COVID-19/patologia , Predisposição Genética para Doença , Área Sob a Curva , COVID-19/genética , COVID-19/virologia , Estudos Transversais , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Curva ROC , SARS-CoV-2/isolamento & purificação
3.
Artigo em Inglês | MEDLINE | ID: mdl-34435396

RESUMO

BACKGROUND: It is of major importance to diagnose food allergy accurately. Current guidelines support the use of oral food challenges to do so. The double-blind placebo-controlled food challenge (DBPCFC) has been regarded as the 'gold standard' for decades. However, DBPCFCs are costly, and time- and resource-intensive procedures. Structural implementation of less demanding open food challenges will only find support if research demonstrates that their outcome is comparable to DBPCFC, yet this has been proven difficult to investigate. METHODS: We performed a literature review to investigate the diagnostic accuracy of oral food challenges and interviewed 19 parents of children with proven or suspected food allergy about the design of a trial to study this. RESULTS: An overview of the dilemma of diagnosing food allergy using oral food challenges, and the methodological issues and parents' opinions to study this. No comparative studies have been performed using the latest guidelines on oral food challenges. CONCLUSIONS: There is an urgent need to investigate the diagnostic accuracy of different oral food challenge protocols. We present the rationale and design of the ALDORADO trial (ALlergy Diagnosed by Open oR DOuble-blind food challenge) that has been set up to investigate whether the outcome of the open food challenge is comparable to DBPCFC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34215566

RESUMO

OBJECTIVES: Previous studies on the association between psychosocial work factors and blood pressure mainly focused on specific occupations or populations and had limited sample sizes. We, therefore, investigated the associations between psychosocial work factors and blood pressure in a large general working population in the Netherlands. METHODS: We included 63 800 employees from the Netherlands, aged 18-65 years, with blood pressure measurements and a reliable job code at baseline. Psychosocial work factors (job strain, effort-reward imbalance (ERI) and emotional demands) in the current job were estimated with three recently developed psychosocial job exposure matrices. To examine the associations, regression analyses adjusted for covariates (age, sex, body mass index, education, monthly income, pack-years, smoking, alcohol consumption and antihypertensive medication (not included for hypertension)) were performed. RESULTS: Higher job strain was associated with higher systolic blood pressure (SBP) (B (regression coefficients) (95% CI) 2.14 (1.23 to 3.06)) and diastolic blood pressure (DBP) (B (95% CI) 1.26 (0.65 to 1.86)) and with higher odds of hypertension (OR (95% CI) 1.43 (1.17 to 1.74)). Higher ERI was associated with higher DBP (B (95% CI) 4.37 (3.05 to 5.68)), but not with SBP or hypertension. Higher emotional demands were associated with lower SBP (B (95% CI) -0.90 (-1.14 to -0.66)) and lower odds of hypertension ((OR) (95% CI) 0.91 (0.87 to 0.96)). CONCLUSIONS: In the general working population, employees in jobs with high job strain and ERI have higher blood pressure compared with employees with low job strain and ERI. Emotional demands at work are inversely associated with blood pressure.

5.
Environ Res ; 201: 111533, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34153335

RESUMO

BACKGROUND: Exposure to fine particulate matter and black carbon is related to cognitive impairment and poor lung function, but less is known about the routes taken by different types of air pollutants to affect cognition. OBJECTIVES: We tested two possible routes of fine particulate matter (PM2.5) and black carbon (BC) in impairing cognition, and evaluated their importance: a direct route over the olfactory nerve or the blood stream, and an indirect route over the lung. METHODS: We used longitudinal observational data for 49,705 people aged 18+ from 2006 to 2015 from the Dutch Lifelines cohort study. By linking current home addresses to air pollution exposure data from ELAPSE in 2010, long-term average exposure to PM2.5 and BC was assessed. Lung function was measured by spirometry and Global Initiative (GLI) z-scores of forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were calculated. Cognitive performance was measured by cognitive processing time (CPT) assessed by the Cogstate Brief Battery. Linear structural equation modeling was performed to test direct/indirect associations. RESULTS: Higher exposure to PM2.5 but not BC was related to higher CPT and slower cognitive processing speed [Total Effect PM2.5: FEV1 model = 8.31 × 10-3 (95% CI: 5.71 × 10-3, 10.91 × 10-3), FVC model = 8.30 × 10-3 (95% CI: 5.69 × 10-3, 10.90 × 10-3)]. The direct association of PM2.5 constituted more than 97% of the total effect. Mediation by lung function was low for PM2.5 with a mediated proportion of 1.32% (FEV1) and 2.05% (FVC), but higher for BC (7.01% and 13.82% respectively). DISCUSSION: Our results emphasise the importance of the lung acting as a mediator in the relationship between both exposure to PM2.5 and BC, and cognitive performance. However, higher exposure to PM2.5 was mainly directly associated with worse cognitive performance, which emphasises the health-relevance of fine particles due to their ability to reach vital organs directly.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34099273

RESUMO

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired.

7.
Environ Int ; 153: 106505, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33872926

RESUMO

RATIONALE: PM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known. OBJECTIVES: We aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells. METHODS: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA). RESULTS: In adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10-8) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM2.5. CONCLUSION: We observed wide-spread DNAm variability associated with average past year PM2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.


Assuntos
Poluição do Ar , Epigenoma , Adolescente , Poluição do Ar/efeitos adversos , Criança , Metilação de DNA , Humanos , Países Baixos , Material Particulado
8.
Pediatr Allergy Immunol ; 32(6): 1238-1254, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33835532

RESUMO

BACKGROUND: It is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper-responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood. METHODS: We searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21-26) and include at least one candidate risk factor. RESULTS: Of the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow-up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non-affected individuals until peak function was attained. CLINICAL IMPLICATIONS AND FUTURE RESEARCH: Deficits in lung function growth develop in early childhood, and children with asthma, BHR and early-life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at-risk subjects and provide treatment aimed at preventing long-term sequelae of lung function.

9.
Blood Adv ; 5(8): 2115-2122, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33877299

RESUMO

Clonal hematopoiesis (CH), characterized by a fraction of peripheral blood cells carrying an acquired genetic variant, emerges with age. Although in general CH is associated with increased mortality and morbidity, no higher risk of death was observed for individuals ≥80 years. Here, we investigated CH in 621 individuals aged ≥80 years from the population-based LifeLines cohort. Sensitive error-corrected sequencing of 27 driver genes at a variant allele frequency ≥1% revealed CH in the majority (62%) of individuals, independent of gender. The observed mutational spectrum was dominated by DNMT3A and TET2 variants, which frequently (29%) displayed multiple mutations per gene. In line with previous results in individuals ≥80 years, the overall presence of CH did not associate with a higher risk of death (hazard ratio, 0.91; 95% confidence interval, 0.70-1.18; P = .48). Being able to assess the causes of death, we observed no difference between individuals with or without CH, except for deaths related to hematological malignancies. Interestingly, comparison of mutational spectra confined to DNMT3A and TET2 vs spectra containing other mutated genes, showed a higher risk of death when mutations other than DNMT3A or TET2 were present (hazard ratio, 1.48; 95% confidence interval, 1.06-2.08; P = .025). Surprisingly, no association of CH with cardiovascular morbidity was found, irrespective of clone size. Further, CH associated with chronic obstructive pulmonary disease. Data on estimated exposure to DNA damaging toxicities (ie, smoking, a history of cancer [as a proxy for previous genotoxic therapy], and job-related pesticide exposure) showed an association with spliceosome and ASXL1 variants, but not with DNMT3A and TET2 variants.


Assuntos
Neoplasias Hematológicas , Hematopoese , Hematopoiese Clonal , Hematopoese/genética , Humanos , Mutação , Prevalência
10.
Thorax ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653936

RESUMO

OBJECTIVES: To date, only a few studies have investigated the associations between occupational exposures and respiratory outcomes longitudinally in the general population. We investigated the associations between occupational exposures and the development of respiratory symptoms and airway obstruction in the Lifelines Cohort Study. METHODS: We included 35 739 occupationally active subjects with data on chronic cough, chronic phlegm, chronic bronchitis or airway obstruction at baseline and approximately 4.5 years follow-up. Exposures to biological dust, mineral dust, gases/fumes, pesticides, solvents and metals in the current job at baseline were estimated with the ALOHA+job-exposure matrix (JEM). Airway obstruction was defined as FEV1/FVC below the lower limit of normal. Logistic regression analysis adjusted for baseline covariates was used to investigate the associations. RESULTS: At follow-up, 1888 (6.0%), 1495 (4.7%), 710 (2.5%) and 508 (4.5%) subjects had developed chronic cough, chronic phlegm, chronic bronchitis and airway obstruction, respectively. High exposure to biological dust was associated with a higher odds to develop chronic cough and chronic bronchitis. High exposure to pesticides was associated with a higher odds for the development of all respiratory symptoms and airway obstruction. In the multiple exposures analyses, only the association between pesticides exposure and respiratory symptoms remained. CONCLUSIONS: Subjects exposed to high pesticides had a higher odds to develop respiratory symptoms on average 4.5 years later. Control measures should be taken to reduce pesticides exposure among the working population to prevent respiratory symptoms and airway obstruction.

11.
Pediatr Pulmonol ; 56(7): 1896-1905, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33751861

RESUMO

BACKGROUND: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms. METHODS: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA). RESULTS: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10-7 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05. CONCLUSIONS: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.

12.
BMJ Open ; 11(3): e044474, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33737436

RESUMO

PURPOSE: The Lifelines COVID-19 cohort was set up to assess the psychological and societal impacts of the COVID-19 pandemic and investigate potential risk factors for COVID-19 within the Lifelines prospective population cohort. PARTICIPANTS: Participants were recruited from the 140 000 eligible participants of Lifelines and the Lifelines NEXT birth cohort, who are all residents of the three northern provinces of the Netherlands. Participants filled out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March 2020, and the cohort consists of everyone who filled in at least one questionnaire in the first 8 weeks of the project. FINDINGS TO DATE: >71 000 unique participants responded to the questionnaires at least once during the first 8 weeks, with >22 000 participants responding to seven questionnaires. Compiled questionnaire results are continuously updated and shared with the public through the Corona Barometer website. Early results included a clear signal that younger people living alone were experiencing greater levels of loneliness due to lockdown, and subsequent results showed the easing of anxiety as lockdown was eased in June 2020. FUTURE PLANS: Questionnaires were sent on a (bi)weekly basis starting in March 2020 and on a monthly basis starting July 2020, with plans for new questionnaire rounds to continue through 2020 and early 2021. Questionnaire frequency can be increased again for subsequent waves of infections. Cohort data will be used to address how the COVID-19 pandemic developed in the northern provinces of the Netherlands, which environmental and genetic risk factors predict disease susceptibility and severity and the psychological and societal impacts of the crisis. Cohort data are linked to the extensive health, lifestyle and sociodemographic data held for these participants by Lifelines, a 30-year project that started in 2006, and to data about participants held in national databases.


Assuntos
COVID-19/psicologia , Pandemias , Adulto , Ansiedade , Controle de Doenças Transmissíveis , Feminino , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
13.
Thorax ; 76(5): 441-447, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33542091

RESUMO

BACKGROUND/OBJECTIVE: Limited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three-generation design. METHODS: 37 291 participants (25 747 adults and 11 544 children) were included from the Lifelines study, a prospective longitudinal three generation cohort study in The Netherlands. Spirometry was available in 69.5% and 61.1% of the included adults and children. Logistic and linear regression were used to analyse the association between grandmaternal smoking during pregnancy and (1) asthma, (2) early childhood asthma (ie, onset before 6 years) and (3) lung function level. Maternal and paternal grandmaternal smoking were studied separately and the analyses were stratified by adult/child and by gender. The analyses were adjusted for gender, current smoking, birth variables and socioeconomic status. RESULTS: In the adult population, maternal grandmaternal smoking during pregnancy was associated with a higher risk for asthma (OR (95% CI): 1.38 (1.06 to 1.79)), early childhood asthma (1.49 (95% CI 1.06 to 2.11)) and a lower FEV1/FVC% predicted (B (95% CI): -1.04 (-1.91 to -0.16) in men. These findings were not observed in a separate analysis of children that participated in this study. There was also no significant association between paternal grandmaternal smoking and asthma/lung function. CONCLUSION: Maternal grandmaternal smoking during pregnancy is associated with higher asthma risk and lower lung function in male grandchildren and a reverse effect in male grandchildren of subsequent generations. Our study highlights the deep-rooted effects of tobacco smoking across generations.


Assuntos
Asma/epidemiologia , Avós , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Gravidez , Estudos Prospectivos , Testes de Função Respiratória , Inquéritos e Questionários
14.
J Pediatr ; 233: 198-205.e2, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33548259

RESUMO

OBJECTIVES: To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma. STUDY DESIGN: Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental well-being and perceived general health using generalized estimating equations. RESULTS: At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages. CONCLUSIONS: The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.


Assuntos
Asma/epidemiologia , Nível de Saúde , Saúde Mental , Adolescente , Animais , Criança , Estudos de Coortes , Humanos , Ácaros , Países Baixos/epidemiologia , Índice de Gravidade de Doença , Adulto Jovem
15.
Clin Exp Allergy ; 51(4): 556-563, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33386641

RESUMO

BACKGROUND AND OBJECTIVE: Some children with asthma have low lung growth, putting them at increased risk for COPD later in life. However, it is currently not clear who will experience this adverse growth pattern. We therefore investigated the predictive role of blood eosinophils as a type 2 inflammation marker in lung growth, focusing on the presence and severity of asthma. METHODS: We investigated blood eosinophils and lung function growth (percentage of predicted values) using linear mixed models in children and adolescents from two longitudinal cohorts. One cohort was hospital-based and consisted of asthmatic children at their first outpatient clinic visit after referral by the general practitioner (n = 133, mean age 9.8), while the second was a general population-based birth cohort (PIAMA, asthma n = 52 and non-asthma n = 433, mean age 8.1). The hospital-based cohort had not been treated with inhaled corticosteroids (ICS) before referral. RESULTS: Subjects in the hospital-based asthma cohort had more severe asthma compared with the asthmatic subjects in the population-based cohort, defined by lower lung function levels and a higher prevalence of bronchial hyper-responsiveness. In the asthma cohort, higher blood eosinophil numbers were associated with less growth in FEV1 (estimated change in lung function per 1 unit increase in ln blood eosinophils (B): -0.66%/year (95% confidence interval (CI): -1.11 to -0.20, p < .01)) and FVC (B: -0.40%/year (95% CI: -0.75 to -0.05), p = .025)) during follow-up in adolescence (min 7, max 17 years). These associations were not observed in the general population-based birth cohort, regardless of asthma status during follow-up (age 8-16). CONCLUSIONS AND CLINICAL RELEVANCE: Blood eosinophil counts in children with asthma not treated with ICS at referral were predictive of lower growth in FEV1 and FVC during follow-up in adolescence. Our findings indicate that this association is dependent on the degree of asthma severity. Future studies should address whether anti-eosinophilic treatments preserve lung function growth in children with asthma.

16.
Occup Environ Med ; 78(2): 82-85, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32769140

RESUMO

INTRODUCTION: Inflammatory biomarkers are associated with negative health outcomes. In this study, we investigated the associations between airborne occupational exposures and levels and changes in inflammatory biomarkers. METHODS: We included 79 604 adults at baseline from the Lifelines cohort of which 48 403 (60.8%) subjects were followed for a median of 4.5 years. Airborne occupational exposures at the current or last-held job at baseline were estimated with the occupational asthma-specific job-exposure matrix. Both in cross-sectional and longitudinal analyses, we used linear regression models (adjusted for age, sex, education, monthly income, body mass index, smoking, pack-years, asthma and anti-inflammatory medication) to investigate the associations between airborne occupational exposures (allergens, reactive chemicals, pesticides and micro-organisms) and inflammatory biomarkers (C reactive protein (CRP), eosinophils and neutrophils). RESULTS: In the cross-sectional analyses, exposure to allergens, reactive chemicals and micro-organisms was associated with a lower (Log) CRP level (B(95% CI)=-0.05 (-0.08 to -0.02),-0.05(-0.08 to -0.02) and -0.09(-0.16 to -0.02), respectively). Likewise, exposure to allergens, reactive chemicals, pesticides and micro-organisms was associated with a lower (log) neutrophils count (-0.01 (-0.02 to -0.01), -0.01 (-0.02 to -0.01),-0.02 (-0.04 to -0.01) and -0.02(-0.03 to -0.01), respectively). No association between airborne occupational exposures and eosinophils count was found. In the longitudinal analyses, no association between airborne occupational exposures and changes in inflammatory biomarkers was found. CONCLUSIONS: At baseline, airborne occupational exposures are inversely associated with inflammation; no effect of occupational exposures on inflammation was found at follow-up. In the future studies, details of occupational exposures, such as duration of exposures and cumulative exposures, need to be included to investigate the airborne occupational exposures and inflammatory biomarkers.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Asma Ocupacional/etiologia , Biomarcadores/sangue , Exposição Ocupacional/efeitos adversos , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários
17.
Ann Am Thorac Soc ; 18(1): 60-67, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795190

RESUMO

Rationale: The association between airborne occupational exposures and lung function level is inconsistent in the general population. Moreover, little is known about the association between occupational exposures and annual lung function decline.Objectives: We investigated the association between occupational exposures and lung function level and annual lung function decline in the population-based Lifelines cohort study.Methods: We included 55,631 adults with baseline spirometry and reliable job code-13,759 of these subjects were aged ≥30 years and underwent spirometry again after 4.5 years of follow-up. Occupational exposures in the current or last-held job at baseline were estimated with the ALOHA+ job-exposure matrix. Linear regression analyses adjusted for covariates were used to test the association between each occupational exposure-biological dust, mineral dust, gases and fumes, pesticides, solvents, and metals-and lung function level and annual lung function decline. Interactions were used to test effect modification by sex or smoking.Results: Exposures to biological dust, mineral dust, gases and fumes, insecticides, fungicides, and aromatic solvents were associated with a lower lung function level at baseline. The effects were larger in males and smokers compared with females and nonsmokers, respectively. However, no association between occupational exposures and the rate of annual lung function decline was found between baseline and follow-up.Conclusions: In this study, airborne occupational exposures are associated with lower lung function level but not with a faster lung function decline. These negative effects are more pronounced among males and smokers.

18.
J Allergy Clin Immunol ; 147(2): 713-722, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32926877

RESUMO

BACKGROUND: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE: Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. METHODS: A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 µm, less than 10 µm, and between 2.5 and 10 µm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021). RESULTS: Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-µg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-µg/m3 increase in exposure). CONCLUSION: Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.

19.
Cancer Cytopathol ; 129(4): 304-317, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33108706

RESUMO

BACKGROUND: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) is used to determine which patients with non-small cell lung cancer (NSCLC) may benefit most from immunotherapy. Therapeutic management of many patients with NSCLC is based on cytology instead of histology. In this study, concordance of PD-L1 immunostaining between cytology cell blocks and their histologic counterparts was analyzed. Furthermore, the effect of various fixatives and fixation times on PD-L1 immunoreactivity was studied. METHODS: Paired histologic and cytologic samples from 67 patients with NSCLC were collected by performing fine-needle aspiration on pneumonectomy/lobectomy specimens. Formalin-fixed, agar-based or CytoLyt/PreservCyt-fixed Cellient cell blocks were prepared. Sections from cell blocks and tissue blocks were stained with SP263 (standardized assay) and 22C3 (laboratory-developed test) antibodies. PD-L1 scores were compared between histology and cytology. In addition, immunostaining was compared between PD-L1-expressing human cell lines fixed in various fixatives at increasing increments in fixation duration. RESULTS: Agar cell blocks and tissue blocks showed substantial agreement (κ = 0.70 and κ = 0.67, respectively), whereas fair-to-moderate agreement was found between Cellient cell blocks and histology (κ = 0.28 and κ = 0.49, respectively). Cell lines fixed in various alcohol-based fixatives showed less PD-L1 immunoreactivity compared with those fixed in formalin. In contrast to SP263, additional formalin fixation after alcohol fixation resulted in preserved staining intensity using the 22C3 laboratory-developed test and the 22C3 pharmDx assay. CONCLUSIONS: Performing PD-L1 staining on cytologic specimens fixed in alcohol-based fixatives could result in false-negative immunostaining results, whereas fixation in formalin leads to higher and more histology-concordant PD-L1 immunostaining. The deleterious effect of alcohol fixation could be reversed to some degree by postfixation in formalin.

20.
J Allergy Clin Immunol ; 147(1): 144-157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32442646

RESUMO

BACKGROUND: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevated in sputum and bronchial biopsies of patients with asthma. The functional consequences of IL33 asthma SNPs remain unknown. OBJECTIVE: This study sought to determine whether IL33 SNPs associate with asthma-related phenotypes and with IL33 expression in lung or bronchial epithelium. This study investigated the effect of increased IL33 expression on human bronchial epithelial cell (HBEC) function. METHODS: Association between IL33 SNPs (Chr9: 5,815,786-6,657,983) and asthma phenotypes (Lifelines/DAG [Dutch Asthma GWAS]/GASP [Genetics of Asthma Severity & Phenotypes] cohorts) and between SNPs and expression (lung tissue, bronchial brushes, HBECs) was done using regression modeling. Lentiviral overexpression was used to study IL33 effects on HBECs. RESULTS: We found that 161 SNPs spanning the IL33 region associated with 1 or more asthma phenotypes after correction for multiple testing. We report a main independent signal tagged by rs992969 associating with blood eosinophil levels, asthma, and eosinophilic asthma. A second, independent signal tagged by rs4008366 presented modest association with eosinophilic asthma. Neither signal associated with FEV1, FEV1/forced vital capacity, atopy, and age of asthma onset. The 2 IL33 signals are expression quantitative loci in bronchial brushes and cultured HBECs, but not in lung tissue. IL33 overexpression in vitro resulted in reduced viability and reactive oxygen species-capturing of HBECs, without influencing epithelial cell count, metabolic activity, or barrier function. CONCLUSIONS: We identify IL33 as an epithelial susceptibility gene for eosinophilia and asthma, provide mechanistic insight, and implicate targeting of the IL33 pathway specifically in eosinophilic asthma.

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