| 1. |
- Tedner, Sandra G, et al.
(författare)
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Depression or anxiety in adult twins is associated with asthma diagnosis but not with offspring asthma
- 2017
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear. Objective: To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins, and secondly the association between parental depression or anxiety and offspring asthma in children of twins. Methods: In total, 24,685 adult twins aged 20-47 years were interviewed or completed a web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), Major Depression and Generalized Anxiety Disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding we performed a co-twin analysis using disease-discordant twin pairs. Results: We found an association between asthma and CES-D, major depression and GAD, e.g. adjusted OR for major depression and register-based asthma 1.56(1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding. Conclusions: We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins.
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| 2. |
- Almqvist, Catarina, et al.
(författare)
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The impact of birth mode of delivery on childhood asthma and allergic diseases : a sibling study
- 2012
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Ingår i: Clinical and experimental allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caesarean section (CS) has been reported to increase the risk of asthma in offspring. This may be due to that infants delivered by CS are unexposed to vaginal flora, according to the ‘hygiene hypothesis’. Objective: Our aim was to investigate if CS increases risk of childhood asthma, and if the risk increase remains after adjustment for familial confounding using sibling design. Methods: A register-based cohort study with 87 500 Swedish sibling pairs was undertaken. Asthma outcome variables were collected from national health registers as diagnosis or asthma medication (ICD-10 J45-J46; ATC code R03) during the 10th or 13th year of life (year of follow-up). Mode of delivery and confounders were retrieved from the Medical Birth Register. The data were analysed both as a cohort and with sibling control analysis which adjusts for unmeasured familial confounding. Results: In the cohort analyses, there was an increased risk of asthma medication and asthma diagnosis during year of follow-up in children born with CS (adjusted ORs, 95% CI 1.13, 1.04–1.24 and 1.10, 1.03–1.18 respectively). When separating between emergency and elective CS the effect on asthma medication remained for emergency CS, but not for elective CS, while both groups had significant effects on asthma diagnosis compared with vaginal delivery. In sibling control analyses, the effect of elective CS on asthma disappeared, while similar but non-significant ORs of medication were obtained for emergency CS. Conclusions and Clinical Relevance: An increased risk of asthma medication in the group born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora. A more probable explanation should be sought in the indications for emergency CS.
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| 3. |
- Tedner, Sandra G, et al.
(författare)
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Fetal growth and risk of childhood asthma and allergic disease
- 2012
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods: PubMed-search on pre-defined terms and cross-references. Results: Several studies have shown a correlation between low birth weight and/or gesta- tional age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subse- quent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that dis- eases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.
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| 4. |
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| 5. |
- Almqvist, Catarina, et al.
(författare)
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Season of birth, childhood asthma and allergy in a nationwide cohort : Mediation through lower respiratory infections
- 2020
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley. - 0954-7894 .- 1365-2222. ; 50:2, s. 222-230
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.ObjectiveWe aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or allergic rhinoconjunctivitis in a population‐based setting, and the mediating effect of lower respiratory infections.MethodsTwo population‐based cohorts were identified from the nationwide Swedish Medical Birth, Patient and Prescribed Drug Registers. The association between birth month/season and asthma/wheeze incidence was analysed using Cox proportional regression in the younger cohort born 2005‐2010 (n = 582 494) and asthma/allergic rhinoconjunctivitis prevalence during the 7th year of life using log‐binomial models in the older cohort born 2001‐2004 (n = 367 583). Interactions were formally tested. Mediation analyses to address the effect of lower respiratory infections were performed in the older cohort using the R package “medflex.”ResultsChildren born during fall and winter had an increased risk of asthma/wheeze after 2 years of age in the younger cohort: hazard ratio 1.24 (95% confidence interval, CI 1.17, 1.33) for winter and risk of prevalent asthma during their 7th year of life in the older cohort; prevalence ratio (PR) 1.12 (95% CI 1.08, 1.16) for winter. These estimates were partly mediated by lower respiratory infections; the indirect effect for winter compared with summer was PR 1.03 (95% CI 1.03, 1.04). The association was similar for allergic rhinoconjunctivitis in the 7th year of life, but not mediated by respiratory infections.ConclusionWe found that the association between season of birth and risk of childhood asthma/wheeze, but not allergic rhinoconjunctivitis, is partly mediated through lower respiratory infections.Clinical relevanceThis has important implications for patient care, such as asthma management programmes to notify timing of seasonality for viral respiratory tract infections.
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| 6. |
- Brew, Bronwyn K., et al.
(författare)
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Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms
- 2022
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047
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Forskningsöversikt (refereegranskat)abstract
- It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
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| 7. |
- Flanigan, Catherine, et al.
(författare)
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Prenatal maternal psychosocial stress and offspring’s asthma and allergic disease : a systematic review and meta-analysis
- 2018
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary-axis (HPA), leading to Th2-biased cell differentiation in the fetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. METHODS: We searched 11 electronic databases from 1960 to 2016, search the grey literature, and contacted experts in the field. Type of stress indicator included mood disorders, anxiety, exposure to violence, bereavement and socio-economic problems occurring during pregnancy, both objectively or subjectively measured. We included all possible asthma and IgE-mediated allergy outcomes. We conducted random-effects meta-analyses to synthesize the data. RESULTS: We identified 9,779 papers of which 30 studies (enrolling >6 million participants) satisfied inclusion criteria. The quality of 25 studies was moderate, four were strong, and one was weak. Maternal exposure to any type of stressors was associated with an increased risk of offspring atopic eczema/dermatitis (OR 1.34, 95%CI 1.22-1.47), allergic rhinitis (OR 1.30, 95%CI 1.04-1.62), wheeze (OR 1.34, 95%CI 1.16-1.54) and asthma (OR 1.15, 95%CI 1.04-1.27). Exposure to anxiety and depression had strongest effect compared to other stressors. Exposure during the third trimester had the greatest impact compared to first and second trimesters. The increased risk was stronger for early-onset and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%CI 1.10-1.48) or a spouse (HR 1.40, 95%CI 1.03-1.90) increased the risk of offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress was associated with increased risk, albeit modestly, of asthma and allergy in the offspring. The pronounced risk during the third trimester may represent cumulative stress exposure throughout pregnancy rather than trimester-specific effect. Our findings may represent a causal effect or a result of inherent biases in studies, particularly residual confounding.
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| 8. |
- Holmberg, K., et al.
(författare)
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Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study
- 2015
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley. - 0954-7894 .- 1365-2222. ; 45:5, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAsthma and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear. ObjectiveOur aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma-ADHD relationship. MethodsData on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12years on 20072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association. ResultsAsthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for 4 asthma attacks in the last 12months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak. Conclusions and Clinical RelevanceChildhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co-existing disorders.
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| 9. |
- Rejnö, Gustaf, et al.
(författare)
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Maternal asthma and early fetal growth : the MAESTRO study
- 2021
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0954-7894 .- 1365-2222.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several maternal conditions can affect fetal growth, and asthma during pregnancy is known to be associated with lower birth weight and shorter gestational age. Objective: In a new Swedish cohort study on maternal asthma exposure and stress during pregnancy (MAESTRO), we have assessed if there is evidence of early fetal growth restriction in asthmatic women or if a growth restriction might come later during pregnancy. Methods: We recruited women from eight antenatal clinics in Stockholm, Sweden. Questionnaires on background factors, asthma status and stress were assessed during pregnancy. The participants were asked to consent to collection of medical records including ultrasound measures during pregnancy, and linkage to national health registers. In women with and without asthma, we studied reduced or increased growth by comparing the second-trimester ultrasound with first-trimester estimation. We defined reduced growth as estimated days below the 10th percentile and increased growth as days above the 90th percentile. At birth, the weight and length of the newborn and the gestational age was compared between women with and without asthma. Results: We enrolled 1693 participants in early pregnancy and collected data on deliveries and ultrasound scans in 1580 pregnancies, of which 18% of the mothers had asthma. No statistically significant reduced or increased growth between different measurement points were found when women with and without asthma were compared; adjusted odds ratios for reduced growth between first and second trimester 1.11 95% CI (0.63–1.95) and increased growth 1.09 95% CI (0.68–1.77). Conclusion and clinical relevance: In conclusion, we could not find evidence sup- porting an influence of maternal asthma on early fetal growth in the present cohort. Although the relatively small sample size, which may enhance the risk of a type II error, it is concluded that a potential difference is likely to be very small.
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| 10. |
- Ullemar, Vilhelmina, et al.
(författare)
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Twins' risk of childhood asthma mediated by gestational age and birthweight
- 2016
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Ingår i: Clinical and Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0954-7894. ; 45:8, s. 1328-1336
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children born with low gestational age (GA) or low birth weight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW, and have been hypothesized to comprise a high risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. Objective: To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. Methods: The study population consisted of two cohorts including all children born in Sweden from January 1st 1993 to June 1st 2001 (n=756,363 singletons, n=22,478 twins) and July 1st 2005 to December 31st 2009 (n=456,239 singletons, n=12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birth weight. Results: In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Conclusions: Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding.
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