| 1. |
- Brew, Bronwyn K., et al.
(author)
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Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms
- 2022
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In: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047
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Research review (peer-reviewed)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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| 2. |
- Caffrey Osvald, Emma
(author)
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Appeasing the wheezing : determinants and outcomes of respiratory disease in childhood
- 2024
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to study the determinants and outcomes asthma and cystic fibrosis in childhood by using study populations of persons born in Sweden and data from a clinical cohort and national health and demographic registers and a quality register. In Paper I and Paper II we explored determinants of respiratory disease. In Paper I we studied if there was association between maternal asthma, allergic asthma, and lung function during pregnancy and childhood asthma and growth using a clinical cohort of mothers and their children born from 2012 to 2017, retrieved from the MAESTRO (Maternal Asthma Events, Stress and Offspring) and MAESTRO-Child studies. Results showed that higher lung function values in the mother was associated with a lowered risk of childhood asthma. Further, there was no statistically significant association between maternal asthma/maternal allergic asthma/lung function during pregnancy and childhood growth. In Paper II we studied the relationship between parental socioeconomic status (SES, education and income) measured at birth and at five years and childhood asthma using data from national registers and a cohort born from 2001 to 2013. We found that parental education and income at birth was associated with childhood asthma with onset under one year of age and that only parental education at birth was associated with an increased risk of childhood asthma with onset over one year of age. When this was studied in a cousin-comparison we found that the association between parental education persisted, implying that confounding by shared factors in the family do not fully account for the association between SES and asthma Finally low parental SES measured at five years was associated with an increased risk of asthma at five years. In Paper III and Paper IV, we explored the outcomes of respiratory disease. In Paper III we investigated the association between asthma and all-cause mortality in children and young adults born from 1986 to 2012 using data from national registers. Asthma was associated with an increase in all-cause mortality and the highest mortality rate was for children aged five to 15 years with asthma. The estimates remained increased when this association between asthma and all- cause mortality was studied in a sub-group analysis of children born from 2000. Further, the estimates differed depending on if the person also had a life-limiting condition, but not on parental SES at birth. In Paper IV we studied the association between parental SES (measured at birth and at five years) and severe disease, lung function and growth in persons with cystic fibrosis born 1973 to 2019 using a cohort from the Swedish Cystic Fibrosis Register and data from the Swedish Cystic Fibrosis Register and national registers We found some evidence that parental SES measured at birth and at five years was associated with severe disease and increased lung function decline, however there was no statistically significant relationship between low parental SES and growth decline. In conclusion factors associated with respiratory disease in childhood include maternal asthma, maternal lung function and parental SES. Asthma is associated with all-cause mortality, where comorbidity but not parental SES play an import role.
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| 3. |
- Caffrey Osvald, Emma, et al.
(author)
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Asthma and all-cause mortality in children and young adults : a population-based study
- 2020
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In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 75:12, s. 1040-1046
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Journal article (peer-reviewed)abstract
- BACKGROUND: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES).METHODS: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model.RESULTS: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83).CONCLUSION: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.
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| 4. |
- Caffrey Osvald, Emma, et al.
(author)
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Parental socioeconomic status and asthma in children : using a population-based cohort and family design
- 2022
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In: Clinical and Experimental Allergy. - : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 52:1, s. 94-103
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Journal article (peer-reviewed)abstract
- BACKGROUND: The observed association between the parental socioeconomic status (SES, measured as education/income) and asthma or wheezing in offspring may be explained by confounding of unmeasured factors (shared genes and family environment). We aimed to study the association between parental SES and asthma/wheeze using cousin-comparison.METHOD: Data was collected on individuals born in Sweden 2001-2013. Parental SES (education and income) was gathered from Statistics Sweden. Asthma/wheeze was identified using national health registers. The association between parental SES at birth and incident asthma/wheeze was estimated using Cox regression also comparing differently exposed cousins. The association between parental SES at five years and current asthma was estimated using logistic regression.RESULTS: Included were 955 371 individuals. Mothers with compulsory school only (lowest education group) compared to those with further education (highest education group) was associated with incident asthma/wheeze below one year of age HRadj=1.45(1.38-1.52) and over one year of age HRadj=1.17(1.13-1.20). The corresponding estimates for the lowest income group were HRadj=1.61(1.54-1.69) and HRadj=0.94(0.92-0.97) respectively. In maternal cousin-comparisons, the associations for asthma/wheeze over one year of age was HRadj=1.21(1.05-1.40) for compulsory school only and HRadj=0.94 (0.84-1.07) for the lowest income group. The ORadj for current asthma at five years was 1.05(1.00-1.11) for mother's compulsory school only and 0.98(0.94-1.02) for mother's lowest income group. Results for estimates were similar for father's SES.CONCLUSION: We confirm an association between low parental SES (measured as education) and asthma/wheeze. Cousin-comparison suggests that this association is not wholly due to confounding of unknown familial factors, therefore supporting a causal relationship. The relationship between parental income and asthma/wheeze is less clear. This study is important for understanding risk factors for asthma/wheeze and for future prevention strategies. Further research is warranted to investigate the possible mechanisms for association between parental education and asthma/wheeze.
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| 5. |
- Lundholm, Cecilia, et al.
(author)
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Asthma and subsequent school performance at age 15-16 years : A Swedish population-based sibling control study
- 2020
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Asthma may negatively affect children's school performance, such as grades and exam results. Results from previous studies have shown varying results and may have suffered from confounding and other biases. We used a Swedish population-based cohort of 570,595 children with data on asthma (including severity and control) in Grades 7-8 and 9, school performance from Grade 9 (grade point sum, non-eligibility for upper secondary school and national test results) and measured confounders from national registers. We used sibling comparisons to account for unmeasured familial factors. Children with asthma and severe asthma performed slightly better in school than children without asthma when adjusting for measured confounders, but the associations were attenuated in sibling comparisons. In contrast, children with uncontrolled asthma performed slightly worse (e.g. Grade 9: βadj = -9.9; 95% CI -12.8 to -7.0; Cohen's d = 0.16). This association remained for uncontrolled asthma in Grade 9 in sibling comparisons (Grade 9: β = -7.7 points; 95% CI -12.6 to -2.6; Cohen's d = 0.12), but not for Grades 7-8. The attenuation of estimates when controlling for familial factors using sibling comparisons suggests that the differences were due to familial factors, rather than being causal. The remaining associations in sibling comparisons between uncontrolled asthma in Grade 9 and school performance are consistent with a causal association.
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| 6. |
- Osvald, Emma Caffrey, et al.
(author)
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Asthma and all-cause mortality in children and young adults - a Swedish population based study
- 2019
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:Suppl. 63
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Journal article (other academic/artistic)abstract
- Background: Little is known about the relationship between asthma in children and young adults and all-cause mortality. Studies suggest an increased rate of death among adults with asthma. Additionally among children, there is a rising prevalence of life-limiting conditions, defined as conditions with no hope of cure.Aim: To investigate the association between asthma and all-cause mortality in children and young adults aged 1-25 years and to explore if this effect is modified by life-limiting conditions.Method: This register based study includes 2,775,430 individuals born in Sweden between January 1986 and December 2012. Asthma cases, those with life-limiting conditions and other covariates were identified using Swedish national registers. The association between asthma and all-cause mortality was estimated using Cox proportional hazards model. A Cox model with an interaction term between asthma and life-limiting condition was also fitted to assess effect modification.Results: 261,322 asthma cases were identified during the follow-up. The unadjusted all-cause mortality rate for asthma cases was greater than for non-asthma cases with a hazard ratio (HR) of 1.67 (95% CI 1.54-1.83). Adjusting for covariates altered the HR to 1.46 (95% CI 1.33-1.62). Having a life-limiting condition was a significant effect modifier (p=0.002); for patients with a life-limiting condition the HR was 1.86 (95% CI 1.57-2.22) and in patients without a life-limiting condition the HR was 1.33 (95% CI 1.18-1.49).Conclusion: All-cause mortality in children and young adults is higher in those with asthma compared to those without asthma. Life-limiting conditions modify the effect of asthma on all-cause mortality.
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| 7. |
- Rhedin, Samuel, et al.
(author)
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Risk factors for multisystem inflammatory syndrome in children – A population-based cohort study of over 2 million children
- 2022
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In: The Lancet Regional Health - Europe. - : Elsevier BV. - 2666-7762. ; 19
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Journal article (peer-reviewed)abstract
- Background: Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our understanding of the pathogenesis of the condition and better guide targeted public health interventions. The aim of the study was to assess risk factors for MIS-C with the aim to identify vulnerable children. Methods: A register-based cohort study including all children and adolescents <19 years born in Sweden between March 1, 2001- December 31, 2020 was performed. Data on sociodemographic risk factors and comorbidities (sex, age, parental region of birth, parental education, asthma, autoimmune disease, chromosomal anomalies, chronic heart disease, chronic lung disease, obesity, life-limiting condition) were retrieved from national health and population registers. The outcome was MIS-C diagnosis according to the Swedish Pediatric Rheumatology Quality Register during March 1, 2020 – December 8, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis. Incidence rates per 100 000 person-years were calculated assuming a Poisson distribution. Findings: Among 2 117 443 children included in the study, 253 children developed MIS-C, corresponding to an incidence rate of 6·8 (95% CI: 6·0-7·6) per 100 000 person-years. Male sex (HR 1·65, 95% CI: 1·28-2·14), age 5-11 years (adjusted HR 1·44, 95% CI: 1·06-1·95 using children 0-4 years as reference), foreign-born parents (HR 2·53, 95% CI: 1·93-3·34), asthma (aHR 1·49, 95% CI: 1·00-2·20), obesity (aHR 2·15, 95% CI: 1·09-4·25) and life-limiting conditions (aHR 3·10, 95% CI: 1·80-5·33) were associated with MIS-C. Children 16-18 years had a reduced risk for MIS-C (aHR 0·45, 95% CI: 0·24-0·85). Interpretation: We report increased risks for MIS-C in children with male sex, age 5-11 years, foreign-born parents, asthma, obesity, and life-limiting condition. Knowing these risk populations might facilitate identification of children with MIS-C and potentially guide targeted public health interventions. Nevertheless, the absolute risks for MIS-C were very low. Funding: Financial support was provided from the Swedish Research Council (grant no 2018-02640), the Swedish Heart-Lung Foundation (grant no 20210416), the Asthma and Allergy Association, Ake Wiberg foundation, the Samariten Foundation, the Society of Child Care, and Region Stockholm.
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