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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: 2019-12-19Bibliographically 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
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: 2019-12-19Bibliographically approved
Kalm-Stephens, P., Nordvall, L., Janson, C., Neuman, Å., Malinovschi, A. & Alving, K. (2019). Elevated exhaled nitric oxide in adolescents relates to incident allergic symptoms: a prospective cohort study. Journal of investigational allergology & clinical immunology, 29(3), 231-238
Open this publication in new window or tab >>Elevated exhaled nitric oxide in adolescents relates to incident allergic symptoms: a prospective cohort study
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2019 (English)In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 29, no 3, p. 231-238Article in journal (Refereed) Published
Abstract [en]

Background: The fraction of exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways and elevated FeNO may precede development of allergic disease. The aim of the present study was to investigate the association between elevated FeNO and the development of allergic symptoms.

Methods: A total of 959 adolescents from a general population answered, together with their parents, a standardized questionnaire, performed lung function and FeNO measurements at a baseline visit. Four years later, 921 of these subjects (96%) completed a to a great extent same version of the baseline questionnaire.

Results: Adolescents with self-reported incident allergic symptoms to cat (n = 50) or dog (n = 33) had higher baseline FeNO (p < 0.001) than subjects without allergic symptoms to cat and dog at either time point (n = 776 and n = 838, respectively). Adolescents with incident allergic symptoms to pollen did not have elevated baseline FeNO. The adjusted odds ratio [aOR (95% confidence interval)] for incident allergic symptoms to cat was 4.2 (2.2, 8.0) times higher if FeNO was > 75th percentile (vs. < 75th percentile) at baseline. This was consistent after exclusion of subjects with reported asthma, wheeze or rhinitis at baseline [aOR (95% CI) 8.6 (3.0, 24.1)].

Conclusion: Elevated FeNO in adolescents related to an increased risk of developing allergic symptoms to cat and dog, but not pollen allergens, within four years.

Place, publisher, year, edition, pages
ESMON Publicidad, 2019
Keywords
Adolescents, Breath test, Epidemiology, Hypersensitivity, Incident, Nitric oxide
National Category
Public Health, Global Health, Social Medicine and Epidemiology Pediatrics Respiratory Medicine and Allergy
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-372786 (URN)10.18176/jiaci.0317 (DOI)000472145600006 ()30183659 (PubMedID)
Funder
AstraZenecaÅke Wiberg FoundationSwedish Foundation for Strategic Research , RB13-0196Swedish Heart Lung Foundation, 20150609; 20160618Swedish Asthma and Allergy Association, F2016-0045
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-08-05Bibliographically approved
Perotin, J.-M., Schofield, J. P. R., Wilson, S. J., Ward, J., Brandsma, J., Strazzeri, F., . . . Gozzard, N. (2019). Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux [Letter to the editor]. European Respiratory Journal, 53(6), Article ID 1900453.
Open this publication in new window or tab >>Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux
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2019 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 53, no 6, article id 1900453Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-390336 (URN)10.1183/13993003.00453-2019 (DOI)000474194800028 ()31023846 (PubMedID)
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Mogensen, I., Alving, K., Dahlen, S.-E., James, A., Forsberg, B., Ono, J., . . . Malinovschi, A. (2019). Fixed airflow obstruction relates to eosinophil activation in asthmatics. Clinical and Experimental Allergy, 49(2), 155-162
Open this publication in new window or tab >>Fixed airflow obstruction relates to eosinophil activation in asthmatics
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 2, p. 155-162Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO.

OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.

METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).

RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO.

CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

National Category
Medical and Health Sciences Immunology in the medical area
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-372784 (URN)10.1111/cea.13302 (DOI)000457469600003 ()30365193 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilVårdal FoundationStockholm County CouncilSwedish Asthma and Allergy AssociationSwedish Foundation for Strategic Research
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-03-08Bibliographically approved
Schofield, J. P. R., Burg, D., Nicholas, B., Strazzeri, F., Brandsma, J., Staykova, D., . . . Wecksell, P.-A. (2019). Stratification of asthma phenotypes by airway proteomic signatures. Journal of Allergy and Clinical Immunology, 144(1), 70-82
Open this publication in new window or tab >>Stratification of asthma phenotypes by airway proteomic signatures
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2019 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 1, p. 70-82Article in journal (Refereed) Published
Abstract [en]

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Asthma, proteomics, biomarkers, eosinophils, neutrophils
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-390913 (URN)10.1016/j.jaci.2019.03.013 (DOI)000473432800011 ()30928653 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, FP7/2007-2013
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-08-16Bibliographically approved
Diamant, Z., Vijverberg, S., Alving, K., Bakirtas, A., Bjermer, L., Custovic, A., . . . Seys, S. F. (2019). Toward clinically applicable biomarkers for asthma: An EAACI position paper. Allergy. European Journal of Allergy and Clinical Immunology, 74(10), 1835-1851
Open this publication in new window or tab >>Toward clinically applicable biomarkers for asthma: An EAACI position paper
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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 10, p. 1835-1851Article in journal (Refereed) Published
Abstract [en]

Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.

Keywords
endotype, eosinophil, FeNO, IgE, phenotype
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-397414 (URN)10.1111/all.13806 (DOI)000493013400002 ()30953574 (PubMedID)
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-11-20Bibliographically approved
Kalm-Stephens, P., Nordvall, L., Janson, C., Malinovschi, A. & Alving, K. (2018). Airway responsiveness and inflammatory markers in non-asthmatic adolescents with elevated FeNO. Paper presented at 28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE. European Respiratory Journal, 52
Open this publication in new window or tab >>Airway responsiveness and inflammatory markers in non-asthmatic adolescents with elevated FeNO
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2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal, Meeting abstract (Other academic) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-376266 (URN)10.1183/13993003.congress-2018.PA1309 (DOI)000455567101505 ()
Conference
28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE
Note

Supplement: 62

Meeting Abstract: PA1309

Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Tsolakis, N., Malinovschi, A., Janson, C. & Alving, K. (2018). Biomarker-assisted characterisation of non-type 2 disease in young asthmatics. Paper presented at 28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE. European Respiratory Journal, 52
Open this publication in new window or tab >>Biomarker-assisted characterisation of non-type 2 disease in young asthmatics
2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2018
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-375821 (URN)10.1183/13993003.congress-2018.PA5061 (DOI)000455567107006 ()
Conference
28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE
Note

Kjell Alving felaktigt angiven som Kjell Alvin i artikeln

Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-0784-0443

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