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  • 1
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    Online Resource
    Lifelines COVID-19 cohort: investigating COVID-19 infection and its health and societal impacts in a Dutch population-based cohort
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 3 ( 2021-03), p. e044474-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 3 ( 2021-03), p. e044474-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-044474
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 2
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    A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis
    BMJ ; 2016
    In:  Thorax Vol. 71, No. 4 ( 2016-04), p. 312-322
    Details
    In: Thorax, BMJ, Vol. 71, No. 4 ( 2016-04), p. 312-322
    Type of Medium: Online Resource
    ISSN: 0040-6376 , 1468-3296
    URL: Article
    DOI: 10.1136/thoraxjnl-2015-206958
    Language: English
    Publisher: BMJ
    Publication Date: 2016
    detail.hit.zdb_id: 1481491-2
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  • 3
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    Influence of age on real-life effects of doxycycline for acute exacerbations among COPD outpatients: a population-based cohort study
    BMJ ; 2020
    In:  BMJ Open Respiratory Research Vol. 7, No. 1 ( 2020-02), p. e000535-
    Details
    In: BMJ Open Respiratory Research, BMJ, Vol. 7, No. 1 ( 2020-02), p. e000535-
    Abstract: Although bacteria contribute significantly to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), the added value of antibiotics remains controversial, especially in outpatient settings. Age may affect antibiotic effectiveness, but real-world evidence is lacking. We aimed to assess the influence of age on the effectiveness of doxycycline for AECOPD. Methods A retrospective cohort study among outpatients with the first recorded AECOPD treated with oral corticosteroids was conducted using a large pharmacy dispensing database. The primary outcome was treatment failure within 15–31 days after treatment start. Secondary outcome was time to second exacerbation. All analyses were stratified by age groups. Results We identified 6300 outpatients with the first AECOPD. 2261 (36%) received doxycycline and 4039 (64%) did not receive any antibiotic (reference group). Overall, there was no difference in treatment failure (adjusted OR: 0.97, 95% CI: 0.84 to 1.12) between two groups. Similarly, no difference in treatment failure was observed in younger groups. However, in patients with advanced age (≥75 years), treatment failure was significantly reduced by doxycycline compared with reference (16% vs 20%, adjusted OR: 0.77, 95% CI: 0.62 to 0.97). Overall, median time to second exacerbation was 169 days (95% CI: 158 to 182 days) in doxycycline group compared with 180 days (95% CI: 169 to 191 days) in reference group (adjusted HR: 1.06, 95% CI: 0.99 to 1.12). Although in older patients there was a trend within 3 months towards longer time of next exacerbation by doxycycline, it did not achieve statistical significance. Conclusions Our findings showed short-term treatment benefit of doxycycline added to oral corticosteroids for chronic obstructive pulmonary disease patients with advanced age. This value remains unclear for persons aged under 75 years in current primary care. Long-term preventive benefits of doxycycline for the next exacerbation were not observed, irrespective of age.
    Type of Medium: Online Resource
    ISSN: 2052-4439
    URL: Article
    DOI: 10.1136/bmjresp-2019-000535
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2736454-9
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  • 4
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    Neuropsychiatric safety of varenicline in the general and COPD population with and without psychiatric disorders: a retrospective cohort study in a real-world setting
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 5 ( 2021-05), p. e042417-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 5 ( 2021-05), p. e042417-
    Abstract: To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD) population with and without psychiatric disorders compared with nicotine replacement therapy (NRT) to strengthen the knowledge of varenicline safety. Design A retrospective cohort study. Setting Prescription database IADB.nl, the Netherlands. Participants New users of varenicline or NRT among general (≥18 years) and COPD (≥40 years) population. Psychiatric subcohort was defined as people prescribed psychotropic medications (≥2) within 6 months before the index date. Outcome measures The incidence of NPAEs including depression, anxiety and insomnia, defined by new or naive prescriptions of related medications in IADB.nl within 24 weeks after the first treatment initiation of varenicline or NRT. Results For the general population in non-psychiatric cohort, the incidence of total NPAEs in varenicline (4480) and NRT (1970) groups was 10.5% and 12.6%, respectively (adjusted OR (aOR) 0.85, 95% CI 0.72 to 1.00). For the general population in psychiatric cohort, the incidence of total NPAEs was much higher, 75.3% and 78.5% for varenicline (1427) and NRT (1200) groups, respectively (aOR 0.82, 95% CI 0.68 to 0.99). For the COPD population (1598), there were no differences in the incidence of NPAEs between comparison groups in both the psychiatric cohort (aOR 0.97, 95% CI 0.66 to 1.44) and non-psychiatric cohort (aOR 0.81, 95% CI 0.54 to 1.20). Results from subgroup or sensitivity analyses also did not reveal increased risks of NPAEs but showed decreased risk of some subgroup NPAEs associated with varenicline. Conclusions In contrast to the concerns of a possible increased risk of NPAEs among varenicline users, we found a relative decreased risk of total NPAEs in varenicline users of the general population in psychiatric or non-psychiatric cohorts compared with NRT and no difference for NPAEs between varenicline and NRT users in smaller population with COPD.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-042417
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 5
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    Maternal occupational exposure to solvents and gastroschisis in offspring - National Birth Defects Prevention Study 1997–2011
    BMJ ; 2020
    In:  Occupational and Environmental Medicine Vol. 77, No. 3 ( 2020-03), p. 172-178
    Details
    In: Occupational and Environmental Medicine, BMJ, Vol. 77, No. 3 ( 2020-03), p. 172-178
    Abstract: The aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring. Methods We used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk. Results Among 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age. Conclusion Our study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis.
    Type of Medium: Online Resource
    ISSN: 1351-0711 , 1470-7926
    URL: Article
    DOI: 10.1136/oemed-2019-106147
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2020276-3
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  • 6
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    Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study
    BMJ ; 2013
    In:  BMJ Open Vol. 3, No. 2 ( 2013), p. e002178-
    Details
    In: BMJ Open, BMJ, Vol. 3, No. 2 ( 2013), p. e002178-
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2012-002178
    Language: English
    Publisher: BMJ
    Publication Date: 2013
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  • 7
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    Airborne occupational exposures and inflammatory biomarkers in the Lifelines cohort study
    BMJ ; 2021
    In:  Occupational and Environmental Medicine Vol. 78, No. 2 ( 2021-02), p. 82-85
    Details
    In: Occupational and Environmental Medicine, BMJ, Vol. 78, No. 2 ( 2021-02), p. 82-85
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1351-0711 , 1470-7926
    URL: Article
    DOI: 10.1136/oemed-2020-106493
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2020276-3
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  • 8
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    Airborne occupational exposures and the risk of developing respiratory symptoms and airway obstruction in the Lifelines Cohort Study
    BMJ ; 2021
    In:  Thorax Vol. 76, No. 8 ( 2021-08), p. 790-797
    Details
    In: Thorax, BMJ, Vol. 76, No. 8 ( 2021-08), p. 790-797
    Abstract: 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 FEV 1 /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.
    Type of Medium: Online Resource
    ISSN: 0040-6376 , 1468-3296
    URL: Article
    DOI: 10.1136/thoraxjnl-2020-216721
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 9
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    What factors are associated with pre-pregnancy nutritional status? Baseline analysis of the KITE cohort: a prospective study in northern Ethiopia
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 6 ( 2021-06), p. e043484-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 6 ( 2021-06), p. e043484-
    Abstract: To assess a broad range of factors associated with pre-pregnancy nutritional status, a key step towards improving maternal and child health outcomes, in Ethiopia. Design A baseline data analysis of a population-based prospective study. Setting Kilite-Awlaelo Health and Demographic Surveillance Site, eastern zone of Tigray regional state, northern Ethiopia. Participants We used weight measurements of all 17 500 women of reproductive age living in the surveillance site between August 2017 and October 2017 as a baseline. Subsequently, 991 women who became pregnant were included consecutively at an average of 14.8 weeks (SD: 1.9 weeks) of gestation between February 2018 and September 2018. Eligible women were married, aged 18 years or older, with a pre-pregnancy weight measurement performed, and a gestational age ≤20 weeks at inclusion. Outcome measures The outcome measure was pre-pregnancy nutritional status assessed by body mass index (BMI) and mid-upper arm circumference (MUAC). Undernutrition was defined as BMI of 〈 18.5 kg/m 2 and/or MUAC of 〈 21.0 cm. BMI was calculated using weight measured before pregnancy, and MUAC was measured at inclusion. Linear and spline regressions were used to identify factors associated with pre-pregnancy nutritional status as a continuous and Poisson regression with pre-pregnancy undernutrition as a dichotomous variable. Results The mean pre-pregnancy BMI and MUAC were 19.7 kg/m 2 (SD: 2.0 kg/m 2 ) and 22.6 cm (SD: 1.9 cm), respectively. Overall, the prevalence of pre-pregnancy undernutrition was 36.2% based on BMI and/or MUAC. Lower age, not being from a model household, lower values of women empowerment score, food insecurity, lower dietary diversity, regular fasting and low agrobiodiversity showed significant associations with lower BMI and/or MUAC. Conclusion The prevalence of pre-pregnancy undernutrition in our study population was very high. The pre-pregnancy nutritional status could be improved by advancing community awareness on dietary practice and gender equality, empowering females, raising agricultural productivity and strengthening health extension. Such changes require the coordinated efforts of concerned governmental bodies and religious leaders in the Ethiopian setting.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-043484
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 10
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    Occupational exposure to pesticides is associated with differential DNA methylation
    BMJ ; 2018
    In:  Occupational and Environmental Medicine Vol. 75, No. 6 ( 2018-06), p. 427-435
    Details
    In: Occupational and Environmental Medicine, BMJ, Vol. 75, No. 6 ( 2018-06), p. 427-435
    Abstract: Occupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites. Methods 1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on current or last held job). Blood DNA methylation levels were measured using Illumina 450K arrays. Associations between pesticide exposure and 420 938 methylation sites (CpGs) were assessed using robust linear regression adjusted for appropriate confounders. In addition, we performed genome-wide stratified and interaction analyses by gender, smoking and airway obstruction status, and assessed associations between gene expression and methylation for genome-wide significant CpGs (n=2802). Results In total for all analyses, high pesticide exposure was genome-wide significantly (false discovery rate P 〈 0.05) associated with differential DNA methylation of 31 CpGs annotated to 29 genes. Twenty of these CpGs were found in subjects with airway obstruction. Several of the identified genes, for example, RYR1 , ALLC , PTPRN2 , LRRC3B , PAX2 and VTRNA2-1 , are genes previously linked to either pesticide exposure or lung-related diseases. Seven out of 31 CpGs were associated with gene expression levels. Conclusions We show for the first time that occupational exposure to pesticides is genome-wide associated with differential DNA methylation. Further research should reveal whether this differential methylation plays a role in the airway disease pathogenesis induced by pesticides.
    Type of Medium: Online Resource
    ISSN: 1351-0711 , 1470-7926
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/oemed-2017-104787
    DOI: 10.1136/oemed-2017-104787.supp1
    DOI: 10.1136/oemed-2017-104787.supp2
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 2020276-3
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