| 1. |
- Ovadia, C., et al.
(författare)
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Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis
- 2021
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 mu mol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67.8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0.7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0.6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1.04, 95% CI 0.35-3.07; p=0.95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0.29, 95% CI 0.04-2.42; p=0.25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1.28, 95% CI 0.86-1.91; p=0.22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0.60, 0.39-0.91; p=0.016). Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Copyright (C) 2021 The Authors(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 2. |
- Lassmann-Klee, P. G., et al.
(författare)
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Parallel gradients in F-ENO and in the prevalences of asthma and atopy in adult general populations of Sweden, Finland and Estonia - A Nordic EpiLung study
- 2020
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases. We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and dOrebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997-2003. The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO >= 25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29-6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02-5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04-6.02), Narva OR 2.45 (1.05-6.19), dOrebro OR 3.38 (1.59-8.09), and Stockholm OR 5.54 (2.18-14.79). There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FEND level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.
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| 3. |
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| 4. |
- Pallasaho, P., et al.
(författare)
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Allergic rhinoconjunctivitis doubles the risk for incident asthma : Results from a population study in Helsinki, Finland
- 2011
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Ingår i: Respiratory Medicine. - London : Baillière Tindall. - 0954-6111 .- 1532-3064. ; 105:10, s. 1449-1456
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the incidence of allergic rhinoconjunctivitis and asthma, and to assess allergic rhinoconjunctivitis as a risk factor for incident asthma, we performed a 11-year follow-up postal survey. Methods: The original study population was a random population sample of 8000 inhabitants of Helsinki aged 20-69 years in 1996. Participants in the first postal questionnaire survey, 6062 subjects, were invited to this follow-up study, and provided 4302 (78%) answers out of 5484 traced subjects in 2007. Results: Cumulative incidence of asthma from 1996 to 2007 was 4.0% corresponding to an annual incidence rate of 3.7/1000/year. After exclusion of those with asthma medication or physician-diagnosed chronic bronchitis or COPD at baseline in 1996, the cumulative incidence decreased to 3.5% (incidence rate 3.2/1000/year), and further to 2.7% (2.5/1000/year) when also those reporting recurrent wheeze or shortness of breath during the last year in 1996 were omitted from the population at risk. Remission of asthma occurred in 43 subjects and was 16.9% over 11 years. Cumulative 11-year incidence of allergic rhinoconjunctivitis was 16.9% corresponding to 16.8/1000/year, and cumulative remission was 18.1%. Incidence of allergic rhinoconjunctivitis was significantly lower among those who had lived in the countryside or on a farm during the first 5 years of life, but this was not true for asthma. In multivariate analysis, farm living during the first 5 years of life was protective for the development of allergic rhinoconjunctivitis, OR 0.75 (95%Cl 0.57-0.99). Allergic rhinoconjunctivitis was a significant independent risk factor for incident asthma, OR 2.15 (95%Cl 1.54-3.02). In the cohort, the prevalence of rhinoconjunctivitis increased from 38.0% in 1996 to 40.9% in 2007, physician-diagnosed asthma from 6.8% to 9.4%, while current smoking decreased from 31.3% to 23.3%. Conclusion: Incidence of allergic rhinoconjunctivitis was higher than in earlier studies, while asthma incidence remained on similar level, both being significantly higher in women. Allergic rhinoconjunctivitis doubled the risk for incident asthma.
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| 5. |
- Juusela, M., et al.
(författare)
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Dose-dependent association of smoking and bronchial hyperresponsiveness
- 2013
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 42:6, s. 1503-1512
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to study the association of smoking habits and environmental tobacco smoke (ETS) exposure with bronchial hyperresponsiveness (BHR). A random sample of 292 adults was examined using a structured interview, spirometry, skin prick tests, exhaled nitric oxide fraction (FeNO) and bronchial histamine challenge. A large majority of subjects with BHR were smokers or ex-smokers. Starting to smoke before 20 years of age was significantly associated with BHR, as was current smoking, quantity of smoking and ETS exposure. The severity of BHR increased significantly with increasing pack-years of exposure (p<0.001). Current smokers with decreased lung function were at a particularly high risk of BHR. Impaired forced expiratory volume in 1 s and mean maximal expiratory flow were independent determinants for more severe BHR, regardless of age. In multivariate analysis, smoking remained an independent determinant for BHR after adjustment for impaired lung function and other covariates: >= 15 pack-years yielded an odds ratio of 3.00 (95% CI 1.33-6.76) for BHR. The association between BHR and FeNO was dependent on smoking habits. The results indicate that smoking is a significant risk factor for BHR, with a dose-dependent pattern, and that the severity of BHR increases with pack-years. The findings strongly suggest assessment of smoking habits in subjects with BHR.
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