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  • 1. Accordini, Simone
    et al.
    Calciano, Lucia
    Johannessen, Ane
    Portas, Laura
    Benediktsdóttir, Bryndis
    Bertelsen, Randi Jacobsen
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Carsin, Anne-Elie
    Dharmage, Shyamali C.
    Dratva, Julia
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gomez Real, Francisco
    Heinrich, Joachim
    Holloway, John W.
    Holm, Mathias
    Janson, Christer
    Jögi, Rain
    Leynaert, Bénédicte
    Malinovschi, Andrei
    Marcon, Alessandro
    Martínez-Moratalla Rovira, Jesús
    Raherison, Chantal
    Sánchez-Ramos, José Luis
    Schlünssen, Vivi
    Bono, Roberto
    Corsico, Angelo G.
    Demoly, Pascal
    Dorado Arenas, Sandra
    Nowak, Dennis
    Pin, Isabelle
    Weyler, Joost
    Jarvis, Deborah
    Svanes, Cecilie
    A three-generation study on the association of tobacco smoking with asthma2018In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 47, no 4, p. 1106-1117Article in journal (Refereed)
    Abstract [en]

    Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma.

    Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines.

    Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55).

    Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.

  • 2.
    Al-Tamprouri, Chaifa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Barman, Malin
    Hesselmar, Bill
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandin, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cat and dog ownership during/after the first year of life and risk for sensitization and reported allergy symptoms at age 132019In: Immunity, Inflammation and Disease, E-ISSN 2050-4527Article in journal (Refereed)
    Abstract [en]

    Background: Avoidance of pets as a strategy for preventing atopic diseases has been questioned. This study aimed to identify the risk of sensitization and allergic symptoms at age 13 in relation to dog‐ and cat‐keeping during and after the first year of life.

    Methods: The study included all children born at Östersund Hospital in Northern Sweden between February 1996 and January 1997 (n = 1231). At inclusion, parents were asked to answer questionnaires about lifestyle, including cat‐ and dog‐keeping. Dog allergy, cat allergy, hay fever, and asthma were diagnosed based on parental reported allergic symptoms at 13 years of age (n = 834). The risks of sensitization or allergy in relation to dog‐ and cat‐keeping during and after the first year of life were analyzed with logistic regression. To adjust for reverse causation, all subjects that had reported avoidance of pets due to allergic symptoms of the child or allergy in the family (n = 177) were excluded.

    Results: Dog‐ or cat‐keeping during the first year of life reduced the risk of sensitization to dog or cat allergens, respectively, and to birch and to at least one of the 10 allergens tested. Cat‐keeping, both during and after the first year of life, reduced the risk of cat allergy and hay fever. Having a dog at home during the first year of life reduced the risk of dog and cat allergy, whereas dog‐keeping after the first year of life did not affect allergic symptoms.

    Conclusions: Cat ownership, either during or after the first year of life, may be a strategy for preventing the development of cat allergy and hay fever later in life. Dog ownership reduced the risk of sensitization to dog and birch allergen, and also the risk of cat and dog allergy, but had no effect on hay fever.

  • 3.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Allergic diseases: Health in Sweden2012In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 40, no 9 Suppl, p. 268-274Article in journal (Refereed)
  • 4.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Research and Development, Västernorrland County Council and Sundsvalls sjukhus, Sundsvall.
    Ekéus, Cecilia
    Lowe, Adrian J
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Murdoch Childrens Research Institute and Centre for MEGA Epidemiology , School of Population Health, The University of Melbourne, Melbourne, Australia.
    Hjern, Anders
    Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication: a national cohort study2013In: Allergy, Asthma & Clinical Immunology, ISSN 1710-1484, E-ISSN 1710-1492, Vol. 9, no 1, p. 14-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies. METHODS: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors. RESULTS: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses. CONCLUSIONS: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.

  • 5.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Public Health and Research, Sundsvall Hospital, Sundsvall, Sweden.
    Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies.2009In: Environmental health : a global access science source, ISSN 1476-069X, Vol. 8, no 17, p. 1-11Article in journal (Refereed)
    Abstract [en]

    The aim of this review was to assess the evidence from recent prospective studies that long-term traffic pollution could contribute to the development of asthma-like symptoms and allergic sensitization in children. We have reviewed cohort studies published since 2002 and found in PubMed in Oct 2008. In all, 13 papers based on data from 9 cohorts have evaluated the relationship between traffic exposure and respiratory health. All surveys reported associations with at least some of the studied respiratory symptoms. The outcome varied, however, according to the age of the child. Nevertheless, the consistency in the results indicates that traffic exhaust contributes to the development of respiratory symptoms in healthy children. Potential effects of traffic exhaust on the development of allergic sensitization were only assessed in the four European birth cohorts. Long-term exposure to outdoor air pollutants had no association with sensitization in ten-year-old schoolchildren in Norway. In contrast, German, Dutch and Swedish preschool children had an increased risk of sensitization related to traffic exhaust despite fairly similar levels of outdoor air pollution as in Norway. Traffic-related effects on sensitization could be restricted to individuals with a specific genetic polymorphism. Assessment of gene-environment interactions on sensitization has so far only been carried out in a subgroup of the Swedish birth cohort. Further genetic association studies are required and may identify individuals vulnerable to adverse effects from traffic-related pollutants. Future studies should also evaluate effects of traffic exhaust on the development and long term outcome of different phenotypes of asthma and wheezing symptoms.

  • 6.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lowe, Adrian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hjern, Anders
    Elective cesarean section and childhood asthma2013In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 209, no 5, p. 496-496Article in journal (Refereed)
  • 7.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lowe, Adrian J
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Australia. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia..
    Lodge, Caroline J
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Australia. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia..
    Dharmage, Shyamali C
    Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Australia. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia..
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Childhood asthma and smoking exposures before conception - a three-generational cohort study.2018In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 29, no 4, p. 361-368Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some human and animal studies have recently shown that maternal grandmother's smoking during pregnancy increases the risk of asthma in the grandchildren. We have investigated whether sex of the exposed parent and/or grandchild modifies the association between grandmaternal smoking and grandchild asthma.

    METHODS: We formed a cohort study based on linkage of national registries with prospectively collected data over three generations. Smoking habits in early pregnancy were registered since 1982 and purchases of prescribed medication since 2005. In all, 10329 children born since 2005 had information on maternal and grandmaternal smoking on both sides and were followed from birth up to 6 years of age. Ages when medication was purchased were used to classify the cohort into never, early transient (0-3 years), early persistent (0-3 and 4-6 years) and late-onset (4-6 years) phenotypes of childhood asthma.

    RESULTS: Maternal grandmother's smoking was associated with an increased odds of early persistent asthma after adjustment for maternal smoking and other confounders (odds ratio 1.29, 95% confidence interval 1.10-1.51). Grandchild sex did not modify the association. Paternal grandmother's smoking was not associated with any of the asthma phenotypes.

    CONCLUSION: Maternal but not paternal exposure to nicotine before conception was related to an increased risk of early persistent childhood asthma, but not other asthma phenotypes. Our findings are possibly consistent with a sex specific mode of epigenetic transfer. 

  • 8.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Grandmaternal smoking during pregnancy and asthma in grandchildren2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 2, article id 624Article in journal (Refereed)
  • 9.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Vogt, H.
    Hjern, A.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 10. Dratva, Julia
    et al.
    Bertelsen, Randi
    Janson, Christer
    Johannessen, Ane
    Benediktsdóttir, Bryndis
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Dharmage, Shyamali C
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gislason, Thorarinn
    Jarvis, Debbie
    Jogi, Rain
    Lindberg, Eva
    Norback, Dan
    Omenaas, Ernst
    Skorge, Trude D
    Sigsgaard, Torben
    Toren, Kjell
    Waatevik, Marie
    Wieslander, Gundula
    Schlünssen, Vivi
    Svanes, Cecilie
    Real, Francisco Gomez
    Validation of self-reported figural drawing scales against anthropometric measurements in adults2016In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 19, no 11, p. 1944-1951Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys.

    DESIGN: Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model.

    SETTING: Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since.

    SUBJECTS: Individuals aged 38-66 years with complete data for BMI (n 1580) and waist circumference (n 1017).

    RESULTS: Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25·0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI.

    CONCLUSIONS: Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible.

  • 11.
    Forsberg, Bertil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Keune, Hans
    Kobernus, Mike
    Krayer von Krauss, Martin
    Yang, Aileen
    Bartonova, Alena
    An expert assessment on climate change and health: with a European focus on lungs and allergies2012In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 11, no Supplement 1, p. S4-Article in journal (Refereed)
    Abstract [en]

    Background

    For almost 20 years, the Intergovernmental Panel on Climate Change has been assessing the potential health risks associated with climate change; with increasingly convincing evidence that climate change presents existing impacts on human health. In industrialized countries climate change may further affect public health and in particular respiratory health, through existing health stressors, including, anticipated increased number of deaths and acute morbidity due to heat waves; increased frequency of cardiopulmonary events due to higher concentrations of air pollutants; and altered spatial and temporal distribution of allergens and some infectious disease vectors. Additionally exposure to moulds and contaminants from water damaged buildings may increase.

    Methods

    We undertook an expert elicitation amongst European researchers engaged in environmental medicine or respiratory health. All experts were actively publishing researchers on lung disease and air pollution, climate and health or a closely related research. We conducted an online questionnaire on proposed causal diagrams and determined levels of confidence that climate change will have an impact on a series of stressors. In a workshop following the online questionnaire, half of the experts further discussed the results and reasons for differences in assessments of the state of knowledge on exposures and health effects.

    Results

    Out of 16 experts, 100% expressed high to very high confidence that climate change would increase the frequency of heat waves. At least half expressed high or very high confidence that climate change would increase levels of pollen (50%), particulate matter (PM2.5) (55%), and ozone (70%). While clarity is needed around the impacts of increased exposures to health impacts of some stressors, including ozone and particulate matter levels, it was noted that definitive knowledge is not a prerequisite for policy action. Information to the public, preventive measures, monitoring and warning systems were among the most commonly mentioned preventative actions.

    Conclusions

    This group of experts identifies clear health risks associated with climate change, and express opinions about these risks even while they do not necessarily regard themselves as covering all areas of expertise. Since some changes in exposure have already been observed, the consensus is that there is already a scientific basis for preventative action, and that the associated adaptation and mitigation policies should also be evidence based.

  • 12. Koplin, J.
    et al.
    Svanes, C.
    Dharmage, S.
    Schlunssen, V
    Gislason, T.
    Holm, M.
    Bråback, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Janson, C.
    Real, Gomez F.
    Father's smoking and welding prior to conception and asthma risk in his children: a multi-generational analysis of the respiratory health in northern Europe study2015In: Respirology (Carlton South. Print), ISSN 1323-7799, E-ISSN 1440-1843, Vol. 20, p. 42-42Article in journal (Other academic)
  • 13. Kuiper, Ingrid N.
    et al.
    Svanes, Cecilie
    Benediktsdottir, Bryndis
    Bertelsen, Randi J.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Dharmage, Shyamali C.
    Holm, Mathias
    Janson, Christer
    Jögi, Rain
    Malinovschi, Andrei
    Matheson, Melanie
    Martinez Moratalla, Jesús
    Gómez Real, Francisco
    Luis Sánchez-Ramos, José
    Schlünssen, Vivi
    Timm, Signe
    Johannessen, Ane
    Agreement in reporting of asthma by parents or offspring - the RHINESSA generation study2018In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 18, article id 122Article in journal (Refereed)
    Abstract [en]

    Background: Self-report questionnaires are commonly used in epidemiology, but may be susceptible to misclassification, especially if answers are given on behalf of others, e.g. children or parents. The aim was to determine agreement and analyse predictors of disagreement in parents' reports of offspring asthma, and in offspring reports of parents' asthma. Methods: In the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, 6752 offspring (age range 18-51 years) and their parents (age range 39-66 years) reported their own and each other's asthma status. Agreement between asthma reports from offspring and parents was determined by calculating sensitivity, specificity, positive and negative predictive value and Cohen's kappa. The participants' own answers regarding themselves were defined as the gold standard. To investigate predictors for disagreement logistic regression analyses were performed to obtain odds ratios (OR) with 95% confidence intervals (CI) for sex, smoking status, education, comorbidity and severity of asthma. Results: Agreement was good for parental report of offspring early onset asthma (< 10 years, Cohen's kappa 0.72) and moderate for offspring later onset asthma (Cohen's kappa 0.46). Specificity was 0.99 for both, and sensitivity was 0.68 and 0.36, respectively. For offspring report of maternal and paternal asthma the agreement was good (Cohen's kappa 0.69 and 0.68), specificity was 0.96 and 0.97, and sensitivity was 0.72 and 0.68, respectively. The positive predictive value (PPV) was lowest for offspring report of maternal asthma (0.75), and highest for parents' report of early onset asthma in the offspring (0.83). The negative predictive value (NPV) was high for all four groups (0.94-0.97). In multivariate analyses current smokers (OR = 1.46 [95% CI 1.05, 2.02]) and fathers (OR = 1.31 [95% CI 1. 08, 1.59]) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting parental asthma incorrectly (OR = 1.60 [95% CI 1.21, 2.11]), both under- and over reporting. Conclusions: Asthma reports across generations show moderate to good agreement, making information from other generations a useful tool in the absence of direct reports.

  • 14.
    Lodge, Caroline J.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Vic., Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Vic., Australia.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lowe, Adrian J.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Vic., Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Melbourne, Vic., Australia.
    Dharmage, S. C.
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Grandmaternal smoking increases asthma risk in grandchildren: a nationwide Swedish cohort2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 2, p. 167-174Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing interest in exposures prior to conception as possible risk factors for offspring asthma. Although partially supported by evidence from limited human studies, current evidence is inconsistent, and based on recall of exposure status.

    OBJECTIVE: We aimed to investigate grandmaternal smoking during pregnancy and the risk of asthma in grandchildren using prospectively collected population-based data.

    METHODS: Information on grandmaternal and maternal smoking during pregnancy and grandchild use of asthma medications was collected from national Swedish registries. Associations between grandmaternal smoking during pregnancy (10-12 weeks), and asthma medication use in grandchildren were investigated using generalized estimating equations. Ages at which asthma medications were prescribed classified childhood asthma into never, early transient (0-3years), late onset (3-6 years) and early persistent (0-3 and 3-6 years) phenotypes.

    RESULTS: From 1982 to 1986, 44,583 grandmothers gave birth to 46,197 mothers, who gave birth to 66,271 grandchildren (born 1996-2010). Children aged 1-6 years had an increased asthma risk if their grandmothers had smoked during pregnancy, with a higher risk for more exposure (10+ cigs/day; adjusted OR 1·23; 1·17, 1·30). Maternal smoking did not modify this relationship.

    CONCLUSIONS & CLINICAL RELEVANCE: Children had an increased risk of asthma in the first six years of life if their grandmothers smoked during early pregnancy, independent of maternal smoking. Importantly this exhibited a dose-response relationship and was associated with a persistent childhood asthma phenotype. These findings support possible epigenetic transmission of risk from environmental exposures in previous generations. 

  • 15.
    Lowe, Adrian
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Braback, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ekeus, Cecilia
    Hjern, Anders
    Fosberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    The association between maternal obesity and childhood asthma - an analysis based on swedish sib-pairs2011In: Internal Medicine Journal - Special Issue: 22nd Australasian Society of Clinical Immunology and Allergy (ASCIA) Annual Scientific Meeting, Sydney Convention & Exhibition Centre, Darling Harbour, NSW, 7 - 9 September 2011, Carlton, Vic.: Blackwell Science , 2011, Vol. 41, no Suppl. 4, p. 11-11Conference paper (Refereed)
    Abstract [en]

    Background: The prevalence of both asthma and obesity have increased inwesternised countries over recent decades. It has been proposed that maternalobesity during pregnancy may induce a pro-infl ammatory intrauterineenvironment, which may increase the child’s risk of asthma and allergicdisease. Sib-pair analysis is a powerful technique for assessing the possibilitythat an exposure is causal for an outcome.

    Methods: The study population comprised all children born between 1998and 2005 in Stockholm (n = 99,830 born to 43,103 separate mothers)registered on the Swedish Medical Birth Registry. Maternal BMI was typicallymeasured typically at 8–10 weeks post conception. Use of asthma medications(either inhaled corticosteroids or montelukast) was recorded inthe Swedish Prescription Registry between July 2005 and February 2011. Conditional logistic regression models were used to assess the effect ofchanging maternal BMI on asthma medication use within sibling pairsmatched for age. Adjustment was made for maternal smoking during pregnancy,pregnancy complications, the child’s gender and other potentialconfounders.

    Results: There were 4,311 children with siblings with discordant asthmamedication use between 5 and 9 years of age. There was a trend for childrenborn to obese mothers (30–34.9 kg/m2) to have an elevated risk (aOR = 1.53,95% CI = 0.88–2.65) of asthma medication use when compared to theirmatched sibs. Children born to very obese mothers (BMI > 35 kg/m2) hada much greater risk of asthma than their siblings (aOR = 4.45, 95%CI = 1.79–11.05).

    Conclusion: Maternal early pregnancy obesity is associated with increasedrisk of asthma in the child. These associations are unlikely to be due to sharedgenetic or other familial risk factors for obesity and asthma, as the reportedassociations are based on a sib-pair analysis. Maternal obesity, or changes inlifestyle factors that lead to it, appear to cause an increase risk of childhoodasthma.

  • 16.
    Lowe, Adrian
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ekeus, Cecilia
    Hjern, Anders
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Maternal obesity during pregnancy as a risk for early-life asthma2011In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 128, no 5, p. 1107-1109Article in journal (Refereed)
  • 17.
    Lowe, Adrian J
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ekeus, Cecilia
    Karolinska Institute, Stockholm, Sweden.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rajaleid, Kristiina
    Karolinska Institute, Stockholm, Sweden.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hjern, Anders
    National Board of Health and Welfare and Karolinska Institutet, Stockholm, Sweden.
    Impact of Maternal Obesity on Inhaled Corticosteroid Use in Childhood: A Registry Based Analysis of First Born Children and a Sibling Pair Analysis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e67368-Article in journal (Refereed)
    Abstract [en]

    Background: It has been proposed that maternal obesity during pregnancy may increase the risk that the child developsallergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought toassess if this association may be due to confounding by genetic or environmental risk factors that are common to maternalobesity and childhood asthma, using a sibling pair analysis.

    Methods: The study population comprised a Swedish national cohort of term children born between 1992 and 2008 tonative Swedish parents. Maternal body mass index (BMI) was measured at 8–10 weeks gestation. Unconditional logisticregression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid(ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysiswas performed, taking into account shared genetic and environmental risk factors.

    Results: Maternal over-weight and obesity were associated with increased risk that the child would require ICS (forBMI$35 kg/m2, aOR = 1.30, 95%CI = 1.10–1.52 compared with normal weight mothers) in children aged 6–12 years. Similareffects were seen in younger children, but in children aged 13–16 years, maternal obesity (BMI$30) was related to increasedrisk of ICS use in girls (aOR = 1.28, 95%CI = 1.07–1.53) but not boys (OR = 1.05, 95%CI = 0.87–1.26). The sib-pair analysis,which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failedto find any evidence that increasing maternal weight was related to increased risk of ICS use.

    Conclusion: Maternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, butonly in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statisticalpower, or the effects of maternal BMI may be due to shared genetic or environmental risk factors.

  • 18.
    Lowe, Adrian J
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Murdoch Children’s Research Institute; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne.
    Olsson, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Research and Development, Västernorrland County Council.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Pollen exposure in pregnancy and infancy and risk of asthma hospitalisation: a register based cohort study2012In: Allergy, Asthma & Clinical Immunology, ISSN 1710-1484, E-ISSN 1710-1492, Vol. 8, no 1, article id 17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A seasonal effect of month of birth and risk of allergic disease has been suggested by numerous studies. Few studies have directly measured pollen exposures at different points during pregnancy and in early life, and assessed their effects on risk of respiratory disease outcomes.

    METHODS: Pollen exposure was calculated for the first and last 12 weeks of pregnancy and the first 12 weeks of infancy for all children conceived by women residing in Stockholm, Sweden, between 1988 and 1995. Hospital admission data for respiratory conditions in the first year of life was also collected.

    RESULTS: Out of 110,381 children, 940 had been hospitalised for asthma by 12-months of age. Pollen levels showed both marked seasonal variations and between year differences. Exposure to high levels of pollen in the last 12 weeks of pregnancy was associated with an increased risk of asthma hospitalisation (aOR = 1.35, 95% CI = 1.07-1.71 for highest quartile versus remaining infants). Exposure to high levels of pollen in the first three months of life was associated with a reduced risk (aOR = 0.76, 95% CI = 0.59-0.98) but only in children of heavy smoking mothers.

    CONCLUSIONS: High levels of pollen exposure during late pregnancy were somewhat unexpectedly associated with an elevated risk of hospitalisation for asthma within the first year of life.

  • 19. Lowe, Adrian J
    et al.
    Williamson, Elizabeth
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lodge, Caroline J
    Dharmage, Shyamali C
    The mediating effect of microbial colonization on the effect of cesarean section delivery2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 584-585Article in journal (Refereed)
  • 20. Olofsson, Niclas
    et al.
    Lindqvist, Kent
    Gillander Gådin, Katja
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Research and Development, Västernorrland County Council, Sundsvall, Sweden.
    Danielsson, Ingela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Department of Research and Development, Västernorrland County Council, Sundsvall, Sweden .
    Physical and psychological symptoms and learning difficulties in children of women exposed and non-exposed to violence: a population-based study2011In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 56, no 1, p. 89-96Article in journal (Refereed)
    Abstract [en]

    Objectives: To analyse the association between violence against mothers and the health of their children as reported by the mothers. Methods: The data originate from a multistage sampling health-questionnaire survey, distributed to a representative sample of women in Sweden. The health of 283 children (aged 0-18 years), as reported by women who had been exposed to violence at home or outside home during the past 12 months, was compared with that of 4,664 children of non-exposed mothers. Results: Odds ratios regarding most registered physical symptoms showed that children of violence-exposed mothers had a significant higher risk of ill health than children of non-exposed mothers. Regarding psychological symptoms and learning difficulties, the odds were raised for girls for most symptoms, but not for boys. A twofold increase in health-care utilisation and an overall general increase in the risk of pharmaceutical consumption were shown for both girls and boys of exposed mothers. Conclusions: This population-based study shows an increased risk of poorer health amongst boys and girls aged 0-18 years, as reported by mothers exposed to violence.

  • 21.
    Olsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Traffic pollution exposure at home during pregnancy and infancy and childhood asthma medicationManuscript (preprint) (Other academic)
  • 22.
    Oudin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Oudin Åström, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Air pollution and dispensed medications for asthma, and possible effect modifiers related to mental health and socio-economy: a longitudinal cohort study of Swedish children and adolescents2017In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 14, no 11, article id 1392Article in journal (Refereed)
    Abstract [en]

    It has been suggested that children that are exposed to a stressful environment at home have an increased susceptibility for air pollution-related asthma. The aim here was to investigate the association between air pollution exposure and asthma, and effect modification by mental health and by socio-economic status (as markers of a stressful environment). All individuals under 18 years of age in four Swedish counties during 2007 to 2010 (1.2 million people) were included. The outcome was defined as dispensing at least two asthma medications during follow up. We linked data on NO₂ from an empirical land use regression to data from national registers on outcome and potential confounders. Data was analyzed with logistic regression. There was an odds ratio (OR) of 1.02 (95% Confidence Interval (CI: 1.01-1.03) for asthma associated with a 10 µg·m(-3) increase in NO₂. The association only seemed to be present in areas where NO₂ was higher than 15 µg·m(-3) with an OR of 1.09 (95% CI: 1.07-1.12), and the association seemed stronger in children with parents with a high education, OR = 1.05 (95% CI: 1.02-1.09) and OR = 1.04 (95% CI: 1.01-1.07) in children to mothers and father with a high education, respectively. The association did not seem to depend on medication history of psychiatric disorders. There was weak evidence for the association between air pollution and asthma to be stronger in neighborhoods with higher education levels. In conclusion, air pollution was associated with dispensed asthma medications, especially in areas with comparatively higher levels of air pollution, and in children to parents with high education. We did not observe support for our hypothesis that stressors linked to socio-economy or mental health problems would increase susceptibility to the effects of air pollution on the development of asthma.

  • 23.
    Oudin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Oudin Åström, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Strömgren, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Association between neighbourhood air pollution concentrations and dispensed medication for psychiatric disorders in a large longitudinal cohort of Swedish children and adolescents2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 6, article id e010004Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations between exposure to air pollution and child and adolescent mental health.

    DESIGN: Observational study.

    SETTING: Swedish National Register data on dispensed medications for a broad range of psychiatric disorders, including sedative medications, sleeping pills and antipsychotic medications, together with socioeconomic and demographic data and a national land use regression model for air pollution concentrations for NO2, PM10 and PM2.5.

    PARTICIPANTS: The entire population under 18 years of age in 4 major counties. We excluded cohort members whose parents had dispensed a medication in the same medication group since the start date of the register. The cohort size was 552 221.

    MAIN OUTCOME MEASURES: Cox proportional hazards models to estimate HRs and their 95% CIs for the outcomes, adjusted for individual-level and group-level characteristics.

    RESULTS: The average length of follow-up was 3.5 years, with an average number of events per 1000 cohort members of ∼21. The mean annual level of NO2 was 9.8 µg/m(3). Children and adolescents living in areas with higher air pollution concentrations were more likely to have a dispensed medication for a psychiatric disorder during follow-up (HR=1.09, 95% CI 1.06 to 1.12, associated with a 10 µg/m(3) increase in NO2). The association with NO2 was clearly present in 3 out of 4 counties in the study area; however, no statistically significant heterogeneity was detected.

    CONCLUSION: There may be a link between exposure to air pollution and dispensed medications for certain psychiatric disorders in children and adolescents even at the relatively low levels of air pollution in the study regions. The findings should be corroborated by others.

  • 24. Pape, Kathrine
    et al.
    Svanes, Cecilie
    Malinovschi, Andrei
    Benediktsdottir, Bryndis
    Lodge, Caroline
    Janson, Christer
    Moratalla, Jesus
    Sánchez-Ramos, José Luis
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Holm, Mathias
    Jögi, Rain
    Jacobsen Bertelsen, Randi
    Sigsgaard, Torben
    Johannessen, Ane
    Schlünssen, Vivi
    Agreement of offspring-reported parental smoking status: the RHINESSA generation study2019In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, article id 94Article in journal (Refereed)
    Abstract [en]

    Background: With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others.

    Aims: To compare adult's report of their parent’s smoking status against parent's own report and examine predictors for discrepant answers.

    Methods: We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [κ] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement.

    Results: The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81–0.84), specificity was 0.95 (95% CI 0.95–0.96) and a good agreement was observed, κ = 0.79 (95% CI 0.78–0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60–0.71), a slightly lower specificity, 0.92 (95% CI 0.90–0.95) and a good agreement, κ = 0.61 (95% CI 0.55–0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21–3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71–4.31]) also predicted disagreement compared to ≥10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09–2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers.

    Conclusions: Adults report their parent's smoking status during their childhood, as well as their mothers' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable.

  • 25.
    Sandin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Annus, T
    Björkstén, B
    Nilsson, L
    Riikjärv, M-A
    van Hage-Hamsten, M
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Prevalence of self-reported food allergy and IgE antibodies to food allergens in Swedish and Estonian schoolchildren.2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 3, p. 399-403Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries. DESIGN AND SETTING: As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Ostersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children. SUBJECTS: Children aged 10-11 y. RESULTS: The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Ostersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5). CONCLUSION: Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries.

  • 26.
    Sandin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Björkstén, Bengt
    Böttcher, Malin
    Jenmalm, Maria
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    High salivary secretory IgA antibody levels are associated with less late-onset wheezing in IgE-sensitized infants2011In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 22, no 5, p. 477-481Article in journal (Refereed)
    Abstract [en]

    Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late-onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late-onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.

  • 27.
    Sandin, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Norin, Elisabeth
    Björkstén, Bengt
    Faecal short chain fatty acid pattern and allergy in early childhood2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 5, p. 823-827Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate whether functional changes of the gut flora over time were related to sensitization and allergic symptoms at four years of age.

    Methods: The levels of short chain fatty acids (SCFAs) in faecal samples at one (n = 139) and four (n = 53) years of age were related to the development of positive skin prick tests (SPT) and allergic symptoms during the first four years of life.

    Results: Faecal acetic (p < 0.01) and propionic (p < 0.01) acids decreased from one to four years of age, while valeric acid (p < 0.001) increased. Low levels of i-butyric (p = 0.01), i-valeric (p = 0.03) and valeric acids (p = 0.02) at one year were associated with questionnaire-reported symptoms of food allergy at four years. Positive SPTs and allergic symptoms at four years were associated with low faecal levels of i-butyric, i-valeric and valeric acids. At one year of age, infants with, as compared to without older siblings had higher median levels of valeric acid.

    Conclusion: A slow functional maturation of the gut microflora, as measured by faecal levels of SCFAs is associated with allergy both at one and four years. The findings lend further support to an association between allergy and the development of microbial diversity.

  • 28. Svanes, Cecilie
    et al.
    Koplin, Jennifer
    Skulstad, Svein Magne
    Johannessen, Ane
    Bertelsen, Randi Jakobsen
    Benediktsdottir, Byndis
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elie Carsin, Anne
    Dharmage, Shyamali
    Dratva, Julia
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gislason, Thorarinn
    Heinrich, Joachim
    Holm, Mathias
    Janson, Christer
    Jarvis, Deborah
    Jögi, Rain
    Krauss-Etschmann, Susanne
    Lindberg, Eva
    Macsali, Ferenc
    Malinovschi, Andrei
    Modig, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Centre for International Health, University of Bergen, Norway.
    Norbäck, Dan
    Omenaas, Ernst
    Waatevik Saure, Eirunn
    Sigsgaard, Torben
    Skorge, Trude Duelien
    Svanes, Øistein
    Torén, Kjell
    Torres, Carl
    Schlünssen, Vivi
    Gomez Real, Francisco
    Father's environment before conception and asthma risk in his children: a multi-generation analysis of the respiratory health in northern Europe study2017In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 49, no 1, p. 235-245Article in journal (Refereed)
    Abstract [en]

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

  • 29.
    Thorén, Annelie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Werner, Bo
    Lundholm, Cecilia
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    A rapid growth rate in early childhood is a risk factor for becoming overweight in late adolescence.2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 11Article in journal (Refereed)
    Abstract [en]

    AIM: We evaluated whether body mass index (BMI) and rapid growth in early life were associated with an increased risk of becoming overweight at 16 and 18 years of age.

    METHODS: The study population comprised all children born in Sweden on the 15th of each month in 1981. Individuals born on the 5th, 10th and 20th of every month were added for counties with low population densities. Information on weight and height was collected from birth up to 18 years of age for 98.6% of the 3537 children identified.

    RESULTS: Weight at 12 months of age was associated with being overweight at both 16 and 18 years of age. Rapid weight gain from birth to 12 months was associated with higher odds for being overweight later in life, and the weight gain between 18 months and four years of age was the strongest risk factor for being overweight in late adolescence in both sexes. There was no association between a birthweight of <2500 g or >4500 g and being overweight at 16 or 18 years of age.

    CONCLUSION: Fast growth during early childhood was associated with an increased risk of being overweight later in life, emphasising the importance of early prevention.

  • 30. Timm, Signe
    et al.
    Frydenberg, Morten
    Abramson, Michael J.
    Bertelsen, Randi J.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Benediktsdottir, Bryndis
    Gislason, Thorarinn
    Holm, Mathias
    Janson, Christer
    Jogi, Rain
    Johannessen, Ane
    Kim, Jeong-Lim
    Malinovschi, Andrei
    Mishra, Gita
    Moratalla, Jesús
    Sigsgaard, Torben
    Svanes, Cecilie
    Schlünssen, Vivi
    Asthma and selective migration from farming environments in a three-generation cohort study2019In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 34, no 6, p. 601-609Article in journal (Refereed)
    Abstract [en]

    Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

  • 31. Timm, Signe
    et al.
    Schlünssen, Vivi
    Benediktsdottir, Bryndis
    Bertelsen, Randi Jacobsen
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Holm, Mathias
    Jogi, Rain
    Malinovschi, Andrei
    Svanes, Cecilie
    Frydenberg, Morten
    Offspring reports on parental place of upbringing: is it valid?2019In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, no 3, p. e16-e18Article in journal (Refereed)
  • 32. Timm, Signe
    et al.
    Svanes, Cecilie
    Janson, Christer
    Sigsgaard, Torben
    Johannessen, Ane
    Gislason, Thorarinn
    Jogi, Rain
    Omenaas, Ernst
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Torén, Kjell
    Holm, Mathias
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Schlünssen, Vivi
    Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe2014In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 6, p. 429-437Article in journal (Refereed)
    Abstract [en]

    Background The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation.

    Objective Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood.

    Methods Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864 subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration.

    Results Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61).

    Conclusion This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.

  • 33. Vogt, Hartmut
    et al.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Kling, Anna-Maria
    Grünewald, Maria
    Nilsson, Lennart
    Pertussis immunization in infancy and adolescent asthma medication.2014In: Pediatrics, ISSN 1098-4275, Vol. 134, no 4, p. 721-728Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Childhood immunization may influence the development of asthma, possibly due to lack of infections or a shift in the T-helper cell type 1/T-helper cell type 2/regulatory T cells balance. We therefore investigated whether pertussis immunization in infancy is associated with asthma medication in adolescence.

    METHODS: After 14 years of no general pertussis vaccination, almost 82 000 Swedish children were immunized for pertussis in a vaccination trial between June 1, 1993, and June 30, 1994. In a follow-up analysis of almost 80 000 children, their data were compared with those of ∼100 000 nonvaccinated children, born during a 5-month period before and a 7-month period after the vaccination trial. Data for the main outcome variable (ie, dispensed prescribed asthma medication for each individual in the cohort during 2008-2010) were obtained from the national prescription database. Multivariate regression models were used to calculate the effect size of vaccination on dispensed asthma medication (odds ratios [OR], 95% confidence intervals [CI]). Approaches similar to intention-to-treat and per-protocol methods were used.

    RESULTS: The prevalence rates of various asthma medications for study patients at 15 years of age differed between 4.6% and 7.0%. The crude ORs for any asthma medication and antiinflammatory treatment in pertussis-vaccinated children after intention-to-treat analysis were 0.97 (95% CI: 0.93-1.00) and 0.94 (95% CI: 0.90-0.98), respectively. Corresponding adjusted ORs were 0.99 (95% CI: 0.95-1.03) and 0.97 (95% CI: 0.92-1.01). Similar ORs were found after per-protocol analysis.

    CONCLUSIONS: Pertussis immunization in infancy does not increase the risk of asthma medication use in adolescents. Our study presents evidence that pertussis immunization in early childhood can be considered safe with respect to long-term development of asthma.

  • 34. Vogt, Hartmut
    et al.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Zetterstrom, Olof
    Zara, Katalin
    Falth-Magnusson, Karin
    Nilsson, Lennart
    Asthma Heredity, Cord Blood IgE and Asthma-Related Symptoms and Medication in Adulthood: A Long-Term Follow-Up in a Swedish Birth Cohort2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e66777-Article in journal (Refereed)
    Abstract [en]

    Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults. A follow-up was carried out in a Swedish birth cohort comprising 1,701 consecutively born children. In all, 1,661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1,227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32-34 years. Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up. In all, 49 out of 60 individuals with dispensed anti-inflammatory asthma medication at 32-34 years of age had not been reported having asthma at previous check-ups of the cohort during childhood. Among those, only 5% with elevated cord blood IgE and 6% with a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication as adults. Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up.

  • 35. Vogt, Hartmut
    et al.
    Lindstrom, Karolina
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hjern, Anders
    Preterm Birth and Inhaled Corticosteroid Use in 6- to 19-Year-Olds: A Swedish National Cohort Study2011In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 127, no 6, p. 1052-1059Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth. METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. CONCLUSION: Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth. Pediatrics 2011; 127:1052-1059

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