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Pape, K., Svanes, C., Malinovschi, A., Benediktsdottir, B., Lodge, C., Janson, C., . . . Schlunssen, V. (2019). Agreement of offspring-reported parental smoking status: the RHINESSA generation study. BMC Public Health, 19, Article ID 94.
Open this publication in new window or tab >>Agreement of offspring-reported parental smoking status: the RHINESSA generation study
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2019 (English)In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, article id 94Article in journal (Refereed) Published
Abstract [en]

Background:

With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others.

Aims:

To compare adult's report of their parent's smoking status against parent's own report and examine predictors for discrepant answers.

Methods:

We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [kappa] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement.

Results:

The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81-0.84), specificity was 0.95 (95% CI 0.95-0.96) and a good agreement was observed, kappa = 0.79 (95% CI 0.78-0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60-0.71), a slightly lower specificity, 0.92 (95% CI 0.90-0.95) and a good agreement, kappa = 0.61 (95% CI 0.55-0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21-3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71-4.31]) also predicted disagreement compared to >= 10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09-2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers.

Conclusions:

Adults report their parent's smoking status during their childhood, as well as their mother' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable.

Keywords
Generation study, Validation study, Tobacco smoking, Self-report, Smoking during pregnancy, Parental smoking, Agreement, Sensitivity, Specificity
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-379236 (URN)10.1186/s12889-019-6414-0 (DOI)000459898400003 ()30665381 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareEU, Horizon 2020, 633212
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19Bibliographically approved
Timm, S., Frydenberg, M., Abramson, M. J., Bertelsen, R. J., Braback, L., Benediktsdottir, B., . . . Schlunssen, V. (2019). Asthma and selective migration from farming environments in a three-generation cohort study. European Journal of Epidemiology, 34(6), 601-609
Open this publication in new window or tab >>Asthma and selective migration from farming environments in a three-generation cohort study
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2019 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 34, no 6, p. 601-609Article in journal (Refereed) Published
Abstract [en]

Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

Keywords
Asthma, Farming, Selective migration, ECRHS, RHINE, RHINESSA
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-384058 (URN)10.1007/s10654-019-00491-9 (DOI)000466919800009 ()30729356 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Tsolakis, N., Nordvall, L., Janson, C., Rydell, N., Malinovschi, A. & Alving, K. (2019). Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects. Clinical and Translational Allergy, 9, Article ID 12.
Open this publication in new window or tab >>Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects
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2019 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 12Article in journal (Refereed) Published
Abstract [en]

Background: Asthma with atopy is often characterized by type 2 inflammation but less progress has been made in defining non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control. Objective: Our aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins. Methods: Sex-and age-matched subjects (10-35 years old) were divided into three groups with regard to history of asthma and atopy: non-atopic asthmatics with perceived cow's milk hypersensitivity but with IgE antibodies < 0.35 kU(A)/L (NAA; n = 24), non-atopic controls with IgE < 0.35 kU(A)/L (NAC; n = 24), and atopic asthmatics with IgE >= 0.35 kU(A)/L (AA; n = 29). Serum or plasma were analysed using the multi-allergen tests Phadiatop and fx5 (Immuno-CAP), a multiplex immunoassay comprising 92 inflammation-related proteins (Proseek Inflammation), and an ELISA for human neutrophil lipocalin (S-HNL). Fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, C-reactive protein (CRP), airway responsiveness to methacholine - (PD20), and asthma-related quality of life (mAQLQ) were also measured. Results: NAA had lower FeNO (p < 0.001) and B-Eos count (p < 0.001), but scored worse on mAQLQ (p = 0.045) compared with AA. NAA displayed higher levels of matrix metalloproteinase-1 (MMP-1) compared with both NAC (p = 0.011) and AA (p = 0.001), and lower - PD20 compared with NAC (p < 0.001). In NAA, S-HNL correlated negatively with -PD20 (rho = -0.048, p < 0.05) and CRP correlated negatively with mAQLQ (rho = -0.439, p < 0.05). Conclusion: In a subgroup of non-atopic young asthmatics with perceived cow's milk hypersensitivity we observed poor asthma-related quality of life, airway hyperresponsiveness, and clinically relevant non-type 2 inflammation. MMP-1 was elevated in this group, which deserves further studies.

Place, publisher, year, edition, pages
BMC, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-380493 (URN)10.1186/s13601-019-0250-2 (DOI)000460910600001 ()30834110 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Heart Lung FoundationSwedish Asthma and Allergy Association
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Salomonsson, M., Malinovschi, A., Kalm-Stephens, P., Dahlin, J. S., Janson, C., Alving, K. & Hallgren, J. (2019). Circulating mast cell progenitors correlate with reduced lung function in allergic asthma. Clinical and Experimental Allergy, 49(6), 874-882
Open this publication in new window or tab >>Circulating mast cell progenitors correlate with reduced lung function in allergic asthma
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 874-882Article in journal (Refereed) Published
Abstract [en]

Background

Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings.

Objectives

To explore the possible association between the frequency of mast cell progenitors in the blood circulation and allergic asthma, we assessed the relation of this recently identified cell population with asthma outcomes and inflammatory mediators in allergic asthmatic patients and controls.

Methods

Blood samples were obtained, and spirometry was performed on 38 well‐controlled allergic asthmatic patients and 29 controls. The frequency of blood mast cell progenitors, total serum IgE and 180 inflammation‐ and immune‐related plasma proteins were quantified.

Results

Allergic asthmatic patients and controls had a similar mean frequency of blood mast cell progenitors, but the frequency was higher in allergic asthmatic patients with reduced FEV1 and PEF (% of predicted) as well as in women. The level of fibroblast growth factor 21 (FGF‐21) correlated positively with the frequency of mast cell progenitors, independent of age and gender, and negatively with lung function. The expression of FcεRI on mast cell progenitors was higher in allergic asthmatic patients and correlated positively with the level of total IgE in the controls but not in the asthmatic patients.

Conclusion

Elevated levels of circulating mast cell progenitors are related to reduced lung function, female gender and high levels of FGF‐21 in young adults with allergic asthma.

Keywords
allergic asthma, asthma, lung function, mast cell progenitors, mast cells
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-379233 (URN)10.1111/cea.13388 (DOI)000475694600015 ()30892731 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20150379Swedish Asthma and Allergy Association, F2016-0045VinnovaSwedish Research Council, 2014-03293Swedish Research Council, 2016-00803Swedish Foundation for Strategic Research , RB13-0196Swedish Heart Lung Foundation, 20160618
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-09-20Bibliographically approved
Sundh, J., Bornefalk, H., Sköld, M., Janson, C., Blomberg, A., Sandberg, J., . . . Ekström, M. (2019). Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease.. BMJ Open Resp Res
Open this publication in new window or tab >>Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease.
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2019 (English)In: BMJ Open Resp ResArticle in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-394302 (URN)10.1136/ bmjresp-2019-000418 (DOI)
Available from: 2019-10-07 Created: 2019-10-07 Last updated: 2019-10-07
Amaral, R., Pereira, A. M., Jacinto, T., Malinovschi, A., Janson, C., Alving, K. & Fonseca, J. A. (2019). Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability. Clinical and Translational Allergy, 9, Article ID 17.
Open this publication in new window or tab >>Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability
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2019 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 17Article in journal (Refereed) Published
Abstract [en]

Background

Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one.

Aim

To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012.

Methods

Adults (18years) with current asthma from the NHANES were included (n=1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: <40 and 40years old.

Results

Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p>0.05). Class A <40years (n=285; 75%) and Class A 40years (n=462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B <40years (n=94; 25%) and Class B 40years (n=170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes.

Conclusion

Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.

Keywords
Asthma, Phenotypes, Population-based study, Unsupervised analysis
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-380449 (URN)10.1186/s13601-019-0258-7 (DOI)000461351800001 ()
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Wang, J., Pindus, M., Janson, C., Sigsgaard, T., Kim, J.-L., Holm, M., . . . Norbäck, D. (2019). Dampness, mould, onset and remission of adult respiratory symptoms, asthma and rhinitis. European Respiratory Journal, 53(5), Article ID 1801921.
Open this publication in new window or tab >>Dampness, mould, onset and remission of adult respiratory symptoms, asthma and rhinitis
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2019 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 53, no 5, article id 1801921Article in journal (Refereed) Published
Abstract [en]

Study question: Is dampness and indoor mould associated with onset and remission of respiratory symptoms, asthma and rhinitis among adults?

Materials and methods: Associations between dampness, mould and mould odour at home and at work and respiratory health were investigated in a cohort of 11 506 adults from Iceland, Norway, Sweden, Denmark and Estonia. They answered a questionnaire at baseline and 10 years later, with questions on respiratory health, home and work environment.

Results: Baseline water damage, floor dampness, mould and mould odour at home were associated with onset of respiratory symptoms and asthma (OR 1.23-2.24). Dampness at home during follow-up was associated with onset of respiratory symptoms, asthma and rhinitis (OR 1.21-1.52). Dampness at work during follow-up was associated with onset of respiratory symptoms, asthma and rhinitis (OR 1.31-1.50). Combined dampness at home and at work increased the risk of onset of respiratory symptoms and rhinitis. Dampness and mould at home and at work decreased remission of respiratory symptoms and rhinitis.

The answer to the question: Dampness and mould at home and at work can increase onset of respiratory symptoms, asthma and rhinitis, and decrease remission.

Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-387961 (URN)10.1183/13993003.01921-2018 (DOI)000470244000010 ()30880288 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Heart Lung FoundationVårdal FoundationThe Research Council of Norway
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
Boudier, A., Chanoine, S., Accordini, S., Anto, J. M., Basagana, X., Bousquet, J., . . . Siroux, V. (2019). Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later. Allergy. European Journal of Allergy and Clinical Immunology, 74(5), 953-963
Open this publication in new window or tab >>Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later
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2019 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, no 5, p. 953-963Article in journal (Refereed) Published
Abstract [en]

BackgroundResearch based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long-term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20years earlier. MethodsThe study relied on two cohorts of adults with asthma with 20-year follow-up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1) at follow-up and the course of FEV(1)between sevencluster-based asthma phenotypes identified20years earlier. ResultsThe analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow-up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1% predicted varied from 0.6 (-3.5 to 4.6) to -9.9 (-14.2 to -5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters. ConclusionOur findings show that the long-term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
asthma, clustering, follow-up, lung function, phenotypes
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-389830 (URN)10.1111/all.13697 (DOI)000471282600007 ()30548629 (PubMedID)
Available from: 2019-07-29 Created: 2019-07-29 Last updated: 2019-07-29Bibliographically approved
Nerpin, E., Olivieri, M., Gislason, T., Olin, A. C., Nielsen, R., Johannessen, A., . . . Malinovschi, A. (2019). Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III. Clinical and Experimental Allergy, 49(7), 969-979
Open this publication in new window or tab >>Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 7, p. 969-979Article in journal (Refereed) Published
Abstract [en]

Introduction

The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex.

Objective

To identify determinants of FENO in men and women without lung diseases. Method Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease.

Results

Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FENO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = FENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P < 0.001) and 5% higher FENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FENO levels compared with non-sensitized subjects 26% and 29%, P Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex.

Keywords
fractional exhaled nitric oxide, healthy population, IgE sensitization, smoking
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-390981 (URN)10.1111/cea.13394 (DOI)000474610200004 ()30934155 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Heart Lung FoundationSwedish Asthma and Allergy Association
Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved
Heddini, A., Sundh, J., Ekström, M. & Janson, C. (2019). Effectiveness trials: critical data to help understand how respiratory medicines really work?. European Clinical Respiratory Journal, 6(1), Article ID 1565804.
Open this publication in new window or tab >>Effectiveness trials: critical data to help understand how respiratory medicines really work?
2019 (English)In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 6, no 1, article id 1565804Article, review/survey (Refereed) Published
Abstract [en]

Most of the information about the benefits, safety aspects, and cost effectiveness of pharmacological treatment in the respiratory field has been obtained from traditional efficacy studies, such as randomised controlled trials (RCT). The highly controlled environment of an RCT does not always reflect everyday practice. The collection, analysis, and application of effectiveness data to generate Real World Evidence (RWE) through pragmatic trials or observational studies therefore has the potential to improve decision making by regulators, payers, and clinicians. Despite calls for more RWE, effectiveness data are not widely used in decision making in the respiratory field. Recent advances in data capture, curation, and storage combined with new analytical tools have now made it feasible for effectiveness data to become routine sources of evidence to supplement traditional efficacy data. In this paper, we will examine some of the current data gaps, diverse types of effectiveness data, look at proposed frameworks for the positioning of effectiveness data, as well as provide examples from therapeutic areas. We will give examples of both previous effectiveness studies and studies that are ongoing within the respiratory field. Effectiveness data hold the potential to address several evidentiary gaps related to the effectiveness, safety, and value of treatments in patients with respiratory diseases.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Effectiveness, real-world evidence, pragmatic trials, evidence-base, efficacy RCT, levels of evidence, respiratory disease, asthma, COPD, co-morbidity
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-377497 (URN)10.1080/20018525.2019.1565804 (DOI)000457088000001 ()30728925 (PubMedID)
Available from: 2019-02-22 Created: 2019-02-22 Last updated: 2019-02-22Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5093-6980

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