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Early life factors and the long-term development of asthma
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Asthma, a huge burden on millions of individuals worldwide, is one of the most important public health issues in many countries. As genetic and   environmental factors interact, asthma may be programmed very early in life, perhaps even in utero.

The aim of this thesis was to assess the impact of gestational age, cord blood immunoglobulin E (IgE), a family history of asthma, migration, and pertussis immunization in early life on the development of asthma in child and adult populations.

As a proxy for asthma disease, dispensed asthma medication was used as the main outcome variable based on data from the Swedish Prescribed Drug  Register. Data from other national registers were used to control for  confounders. Three of our studies were based on national cohorts, and one on a local birth cohort that was initiated in 1974–75.

Gestational age had an inverse dose-response relationship with dispensed asthma medication in 6– to 19-year-olds. Odds ratios for dispensed asthma medication increased with degree of prematurity compared with children born in term. Furthermore, asthma medication was more likely to be dispensed among children and adolescents born early term after 37–38 weeks’ gestation than among those at the same age who were born in term.

Elevated cord blood IgE and a family history of asthma in infancy were associated with a two- to threefold increased likelihood of dispensed asthma medication and self-reported allergen-induced respiratory symptoms at the age of 32–34 years, but the predictive power was poor.

Age at migration had an inverse dose-response relationship with dispensed asthma medication at the age of 6–25 years in adoptees and foreign-born children with foreign-born parents. International adoptees and children born in Sweden to foreign-born parents had three- to fourfold higher rates of asthma medication compared with foreign-born children who were raised by their foreign-born birth parents.

No association was found between pertussis immunization in early infancy and dispensed asthma medication in 15-year-olds. The type of vaccine or vaccine schedule did not affect the outcome.

Fetal life is a vulnerable period. This thesis strengthens the evidence that every week of gestation is important for lung maturation. Cord blood IgE, however, did not predict the risk of asthma in adults. Furthermore, the study of migrating populations demonstrated that environmental changes at any age during childhood may affect the risk of asthma. Another, important public health message from this thesis is that vaccination against pertussis in early childhood can be considered safe with respect to the long-term development of asthma.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. , 92 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1329
Keyword [en]
asthma, birth cohort, national register
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:liu:diva-85159ISBN: 978-91-7519-794-4 (print)OAI: oai:DiVA.org:liu-85159DiVA: diva2:565661
Public defence
2012-12-06, Berzeliussalen, Hälsouniversitet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-11-19 Created: 2012-11-08 Last updated: 2013-05-13Bibliographically approved
List of papers
1. Preterm Birth and Inhaled Corticosteroid Use in 6- to 19-Year-Olds: A Swedish National Cohort Study
Open this publication in new window or tab >>Preterm Birth and Inhaled Corticosteroid Use in 6- to 19-Year-Olds: A Swedish National Cohort Study
2011 (English)In: PEDIATRICS, ISSN 0031-4005, Vol. 127, no 6, 1052-1059 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Academy of Pediatrics; 1999, 2011
Keyword
premature birth, asthma, inhaled corticosteroids, adolescents
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69167 (URN)10.1542/peds.2010-3083 (DOI)000291146100045 ()
Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2012-11-19Bibliographically approved
2. Asthma heredity, cord blood IgE and asthma-related symptoms and medication in adulthood: a long-term follow-up in a Swedish birth cohort
Open this publication in new window or tab >>Asthma heredity, cord blood IgE and asthma-related symptoms and medication in adulthood: a long-term follow-up in a Swedish birth cohort
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, e66777.- p.Article in journal (Refereed) Published
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 1701 consecutively born children. In all, 1661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1227 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.

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.

Keyword
birth cohort, cord blood, family history, prediction, prescription
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-85156 (URN)10.1371/journal.pone.0066777 (DOI)000320846500104 ()
Note

The status of this article was on the day of the defence date Manuscript.

Available from: 2012-11-07 Created: 2012-11-07 Last updated: 2017-12-07Bibliographically approved
3. Migration and asthma medication in international adoptees and immigrant families in Sweden
Open this publication in new window or tab >>Migration and asthma medication in international adoptees and immigrant families in Sweden
2011 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 8, 1108-1115 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2011
Keyword
adoptees; asthma; country of birth; environment; immigration; inhaled corticosteroids
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69780 (URN)10.1111/j.1365-2222.2011.03744.x (DOI)000292700000010 ()
Note

This is the authors’ version of the following article: L. Braback, Hartmut Vogt and A. Hjern, Migration and asthma medication in international adoptees and immigrant families in Sweden, 2011, Clinical and Experimental Allergy, (41), 8, 1108-1115. which has been published in final form at: http://dx.doi.org/10.1111/j.1365-2222.2011.03744.x Copyright: Blackwell Publishing Ltd http://eu.wiley.com/WileyCDA/Brand/id-35.html

Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
4. Pertussis Immunization in Infancy and Adolescent Asthma Medication
Open this publication in new window or tab >>Pertussis Immunization in Infancy and Adolescent Asthma Medication
Show others...
2014 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 134, no 4, 721-728 p.Article in journal (Refereed) Published
Abstract [en]

Context: Lack of infections might contribute to increased risk of asthma among children according to the ‘hygiene hypothesis’. Childhood immunization may play a causal role in the development of asthma.

Objective: To determine whether pertussis immunization in infancy is associated with asthma medication in adolescence.

Design, Settings and Participants: After 14 years of no general pertussis vaccination, almost 80,000 children were immunized for pertussis during a 12-month period in a vaccination trial. They were compared with almost 100,000 non-vaccinated children born during a 6-month period before and after the vaccination trial in a Swedish national cohort study. Information concerning dispensed prescribed asthma medication for each individual in the cohort during 2008–2010 was obtained from the National Prescription database. Multivariable regression models were used to calculate the effect size of vaccination on dispensed asthma medication (Odds ratios and 95% confidence intervals), both in an intent-to-treat model as well as per protocol. The large study size also enabled us to detect very small effects.

Main Outcome Measure: Dispensed prescribed asthma medication at the age of 15 years occurring after pertussis immunization in infancy.

Results: No statistically significant effect of vaccination was found, regardless of vaccination schedule or vaccine type. The prevalence rates of any dispensed anti-inflammatory medication or any asthma medication at 15 years of age were 4.6% and 7.0%, respectively. The crude odds ratios (OR) for any asthma medication and anti-inflammatory treatment in pertussis-vaccinated children after intent-to-treat analysis were 0.97 (95% CI 0.93 – 1.00) and 0.94 (0.90 – 0.98),respectively. Corresponding adjusted ORs were 0.99 (0.95 – 1.03) and 0.97 (0.92 – 1.01),respectively. Similar ORs were found after per-protocol analysis.

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

Place, publisher, year, edition, pages
APP Journals & Periodicals, 2014
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-85157 (URN)10.1542/peds.2014-0723 (DOI)000343140500055 ()
Note

On the day of the defence date the status of this article was Manuscript and the title was Does pertussis in infancy increase the risk of asthma medication in adolescents?.

Available from: 2012-11-07 Created: 2012-11-07 Last updated: 2017-12-07Bibliographically approved

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