1. |
- Almqvist, Linnea, 1987-
(författare)
-
Asthma epidemiology : prognosis of asthma with onset in childhood and in adulthood
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: to update the knowledge on the epidemiology of asthma with onset in childhood and adulthood as well as examine the importance of risk factors in early childhood and clinical characteristics on the incidence and prognosis of asthma.Methods: The thesis is based on the epidemiological research program Obstructive Lung Disease in Northern Sweden (OLIN) studies. Pediatric cohort: recruited in 1996 (age 8y, n=3430, 97% of invited) and followed annually by questionnaire about asthma, allergy and risk factors until 19y and a postal questionnaire at 28y. Clinical examinations included skin prick tests (SPT at 8, 12 and 19y) and spirometry (19y). Adult cohort: 309 adults (age 20–60y) with asthma onset in the last 12 months were recruited 1995-99 and re-examined in 2012-14 (n=205). Structured interviews, spirometry and SPT were performed at recruitment and follow-up and bronchial hyperreactivity (BHR) at recruitment.Results: The asthma incidence rate was 10-13/1000/year in childhood and adolescence and 6/1000/year in young adulthood. Several risk factors in early life were associated with asthma onset in childhood, adolescence and young adulthood, e.g. family history of asthma, <3 months breastfeeding, rhinoconjunctivitis and positive SPT at 8y, while low birthweight, maternal smoking during pregnancy, severe respiratory infections and eczema were associated with onset in childhood and adolescence. Among those with asthma at 8y, 62% still had asthma at 28y and this was associated with positive SPT, rhinoconjunctivitis, severe respiratory infection in childhood, and bronchial hyperreactivity (BHR) in adolescence. Coexistence of asthma, rhinitis and eczema increased by age, especially among those with a positive SPT. However, having all three conditions was uncommon. In the 15y follow-up adult onset asthma, 89% had persistent asthma. Better lung function at recruitment and less severe BHR was associated with remission. Remission rate of adult onset asthma was <1% per year.Conclusion: The incidence of asthma was high during childhood and adolescence and then decreased in young adulthood. Factors in early life that were associated with incident asthma during childhood were still associated with the incidence in adult age. Among those with asthma onset by 8 years, 62%, still had asthma as young adults. The coexistence of asthma, rhinitis and eczema varied from 8 to 28y without following a specific pattern, only a small proportion reported having all three conditions. Remission of adult onset asthma was rare.
|
|
2. |
- Vogt, Hartmut
(författare)
-
Early life factors and the long-term development of asthma
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
|
|
3. |
- Furuhjelm, Catrin
(författare)
-
Can fish oil in pregnancy and lactation alter maternal and infant immunological responses and prevent allergy in the offspring?
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: A connection has been proposed between the increase of allergic disease and the altered composition of fatty acids in the diet in the westernised world. Less oily fish and more vegetable oil are consumed today compared to 50-100 years ago. Programming of the immune responses takes place very early in life and environmental factors, such as fish in the diet, have been suggested to protect from infant allergy.Aim: The general aim of this thesis was to assess the effects of maternal dietary supplementation with ω-3 long chain polyunsaturated fatty acids (LCPUFA), i.e. fish oil, in pregnancy and lactation on the development of allergic symptoms and sensitisation in the infants as well as some immunological markers in mothers and infants.Subjects and methods: This thesis is based on the results from a prospective double-blind placebo-controlled multi-centre trial comprising 145 families. Pregnant women, at risk of having an allergic infant, were recruited at the antenatal clinics and randomised to daily supplementation with 1.6 g eicosapentaenoic acid (EPA, C20:5ω-3) and 1.1 g docosahexaenoic acid (DHA, C22:6ω-3) or placebo, starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Phospholipid fatty acids in maternal and infant plasma were analysed to assess compliance. Maternal prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokines along with infant vaccine induced responses and chemokines were analysed with ELISA and Luminex techniques. Clinical outcomes were allergic disease and positive skin prick test/detectable circulating IgE antibodies to common allergens.Results: Phospholipid proportions of ω-3 LCPUFA increased significantly in the ω-3 supplemented women and their infants. Lipopolysaccharide-induced PGE2 secretion from whole blood culture supernatants decreased in a majority of the ω-3-supplemented mothers (p<0.01). The decrease in PGE2 production was more pronounced among non-atopic than atopic mothers. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE associated eczema and IgE mediated food allergy was though reduced in the ω-3 group during the first two years (OR=0.2 and 0.3 compared to placebo, p<0.05 for both). The cumulative incidence of any IgE associated disease during the first two years of life was 13% in the ω-3 supplemented group compared to 30% in the placebo group (p=0.01, OR 0.3, p<0.05). This effect was most evident in infants of non-allergic mothers. Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05), in a dose dependent manner. In addition, no allergic symptoms as compared to multiple allergic symptoms in the infants, regardless of sensitisation, were related to higher maternal and infant ω-3 LCPUFA status (p<0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CC-chemokine ligand 17 (CCL17)/ CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p<0.05). Furthermore in non-allergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p<0.05), as well as increased IgG titres to diphtheria (p=0.01) and tetanus (p=0.05) toxins.Conclusions: A decreased cumulative incidence of IgE associated disease in the infants was found after maternal ω-3 LCPUFA supplementation as well as a reverse dose response relationship between maternal ω-3 LCPUFA status and infant IgE associated disease. Higher plasma proportions of DHA and EPA in were also associated to less severe allergic disease. A tendency towards strengthened Th1 associated response after maternal ω-3 LCPUFA supplementation was indicated in the analysis of maternal and infant immunological markers. These effects, as well as the clinical outcomes, were more pronounced in non-allergic individuals, suggesting gene-by-environment interactions.
|
|