Magnus Wickman

Karolinska Institutet | KI

Background Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first‐line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self‐administrable devices, especially in co...

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE‐mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the e...

Background: Understanding differences in sensitization profiles at the molecular allergen level is important for diagnosis, personalised treatment and prevention strategies in allergy. Methods: IgE sensitization profiles were determined in more than 2800 sera from children in 9 population-based cohorts in different geographical regions of Europe...

Background: Whether long-term air pollution exposure has effects on allergic sensitization is controversial. Objective: To investigate associations of air pollution exposure at birth and at the time of later biosampling, with IgE sensitization against common food/inhalant allergens, or specific allergen molecules, in children up to 16 years. Me...

Background: Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD). Methods: This open-la...

Background Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large‐scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. Methods Integrated transcriptomic analysis was conducted in 12...

Background: Grass pollen allergy is one of the most common allergies worldwide. Objective: To evaluate the usefulness of grass pollen allergen molecules for prediction of grass pollen allergy during childhood up to adolescence. Method: Questionnaire data and sera obtained at 4, 8 and 16 years from the population-based BAMSE birth cohort were u...

Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity...

Background Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission’s Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method...

Abstract mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the be...

Background Mobile technology may help to better understand the adherence to treatment MASK‐rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient‐centered ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives To assess the adherence to treatment in allergic rhinitis patie...

Background: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for h...

Background Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology...

Background: Large observational implementation studies are needed to triangulate the findings from randomized control trials (RCTs) as they reflect "real world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real life treatment of allergic rhinitis using mobile technology. Methods: A mob...

Background: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the risk of allergic disease. However, evidence from previous studies is inconclusive, and limited longitudinal data exist using circulating biomarkers of PUFA intake and metabolism. Objective: We aimed to investigate associations between n-3 and n-6 PUFAs at age 8 year...

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology - later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric...

Background: Sensitization in early childhood may precede respiratory allergy in adolescence. Methods: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by qu...

Allergic sensitization is a risk factor for developing IgE-mediated allergic diseases, which are a major cause of chronic illness world-wide. The introduction of allergen molecules to the field of allergy diagnostics has allowed dissecting the IgE response on a molecular level to pinpoint the specific disease-causing allergens. Studying birth cohor...

Background: Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (CHI3L1) and are increased in several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. Objective: To determine (1) whether methylation levels at CHI3L1 CpG sites mediate the...

Computational analysis of multimorbidity between asthma, eczema and rhinitis (excluding GWAS-derived association data). (PDF)

Example of the calculation of the topological overlap for proteins associated to three diseases. (A) Disease A (orange ellipse) is associated to 7 proteins: p1, p2, p3, p4, p5, p6, p7. Disease B (blue ellipse) is associated to 7 proteins: p4, p5, p6, p7, p8, p9, p10. Disease C (purple ellipse) is associated to 5 proteins: p4, p5, p6, p7, p11. Prote...

Number of proteins associated to asthma, eczema and rhinitis. Blue dots indicate the observed fraction of proteins. Orange scatter boxplots indicate random expectation. One asterisk: observed results are significantly larger than random expectation (z-test; P < 0.05). Two asterisks: observed results are significantly larger than random expectation...

Fraction of proteins associated to asthma, eczema and rhinitis (GWAS-derived data excluded). Blue dots indicate the observed fraction of proteins. (A) Orange scatter boxplots indicate random expectation. One asterisk: observed results are significantly larger than random expectation (z-test; P < 0.05). Two asterisks: observed results are significan...

Mean topological overlap between proteins associated to a single disease only. Blue dots indicate the observed mean topological overlap (TO) between proteins uniquely associated to either asthma, eczema or rhinitis. Orange scatter boxplots indicate random expectation. One asterisk: observed results are significantly larger than random expectation (...

Parameters used in the Génie tool. The Génie tool (http://cbdm-01.zdv.uni-mainz.de/~jfontain/cms/) was used to extract gene names present in PubMed abstracts related to a topic of interest, as defined by a PubMed query. (DOC)

Fraction of proteins associated to asthma, eczema and rhinitis. Blue dots indicate the observed fraction of proteins. Orange scatter boxplots indicate fraction of associated proteins for pairs/trios of immune system diseases. One asterisk: observed results are significantly larger than random expectation (empirical distribution test; P < 0.05). Two...

Multimorbidity-associated genes obtained via the Génie data mining tool. Columns are as follows: Query: PubMed query used; Rank: position (rank) of the gene (ordered by ascending FDR); GeneID: gene name; n: number of PubMed abstracts manually associated to the gene; n_pos: number of PubMed abstracts that Génie has selected at P < 0.01; FDR: False D...

Complete list of all proteins associated to asthma, eczema and rhinitis (GWAS-derived data excluded). Gene names are provided as common (HGNC) gene names and protein names as UniProt accessions. (XLS)

Functional similarity between asthma, eczema and rhinitis (GWAS-derived data excluded). Numerical values show how similar is the use of a cellular pathway by pairs of trios of diseases. Similarity = 1 means that the diseases affect the pathway in exactly the same way. Similarity = 0 is represented by blank cells. Dark blue cells: similarity is sign...

Complete list of predicted disease-associated proteins. Gene names are provided as common gene names and protein names as UniProt accessions. NetZcore prediction scores are shown as z-scores. Proteins are ranked according to their average z-score for all diseases. Empty cell: the protein was not predicted to be associated with the disease with z-sc...

Extended methods. (PDF)

Example of the calculation of the topological overlap for proteins associated to two diseases. (A) Disease A (orange ellipse) is associated to 6 proteins: p1, p2, p3, p4, p5, p6. Disease B (blue ellipse) is associated to 6 proteins: p4, p5, p6, p7, p8, p9. Three proteins are common to both diseases (p4, p5, p6; shown in the intersection of both dis...

Mean topological overlap for proteins associated to asthma, eczema and rhinitis (GWAS-derived data excluded). (A) Blue dots indicate the observed mean topological overlap (TO) for proteins common to combinations of asthma, eczema and rhinitis. Orange scatter boxplots indicate random expectation. (B) Blue dots indicate the observed mean TO for prote...

Random pairs and trios of immune system diseases. Tab-delimited text file. Diseases were extracted from the CTD database (see Methods in the main paper). (GZ)

Source of disease-protein associations. OMIM: On-line Mendelian Inheritance in Man; CTD: Comparative Toxicogenomics Database; EV84: Ensembl Variation 84. (PDF)

Diseases in the immune system diseases category in CTD database. Disease-associated proteins (provided as UniProt accessions), are separated by a semicolon. The network column indicates whether the disease has at least one associated protein present in then FIN (1) or not (0). (XLS)

Parameters used in the Génie tool (predicted genes excluded). The Génie tool was used to extract gene names present in PubMed abstracts related to a topic of interest, as defined by a PubMed query. Unlike S4 Table, this table does not exclude the terms predicted nor prediction, and includes the terms predictive or predictor. (DOC)

Statistical association between predicted multimorbidity-associated proteins and literature predictions. Literature predictions were automatically extracted from PubMed abstracts using the Génie data mining tool. The terms used to query PubMed database were those shown in S4 Table minus the word “comorbidity”. Statistical association was calculated...

Functional Interaction Network. This network was generated by combining data from the HIPPIE, Reactome and InnateDB databases (see Methods in the main paper). (GZ)

Pathways in BioCarta database. Pathway-associated proteins (provided as UniProt accessions) and interactions between pathway-associated proteins are separated by a semicolon. (XLS)

Complete list of all proteins associated to asthma, eczema and rhinitis. Gene names are provided as common (HGNC) gene names and protein names as UniProt accessions. (XLS)

Fraction of edges associated to asthma, eczema and rhinitis. Mean random expectation in shown between parenthesis. The fraction of common edges was calculated using the Jaccard index (see Methods in the main paper). The fraction of common edges is statistically larger than random expectation in all four cases (p-value < 0.01). The fraction of uniqu...

Complete list of predicted disease-associated proteins (GWAS-derived data excluded). Gene names are provided as common gene names and protein names as UniProt accessions. NetZcore prediction scores are shown as z-scores. Proteins are ranked according to their average z-score for all diseases. Empty cell: the protein was not predicted to be associat...

Background Allergic rhinitis affects 10 to 40% of the population. It reduces quality of life, school and work performance, and is a frequent reason for office visits in general practice. Medical costs are large but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated sinc...

Background: Eczema (atopic dermatitis) is associated with an increased risk of having IgE antibodies. IgE sensitization may occur through an impaired skin barrier. Filaggrin (FLG) mutation is associated with eczema, and possibly also with IgE sensitization. Objective: To explore the longitudinal relation between preschool eczema and/or FLG mutat...

Background: Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more biologically and clinically relevant. Objective: W...

Background: Dietary antioxidant intake has been hypothesized to influence the development of allergic diseases, however, few prospective studies have investigated this association. Objective: Our aim was to study the association between total antioxidant capacity (TAC) of the diet at age 8 years and the subsequent development of asthma, rhinitis...

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels b...

IgE signatures to peanut allergen measured in early childhood allow predicting the likelihood of peanut allergy in adolescence. Peanut symptoms and Ara h 2 IgE >2.0 ISU-E at 4 years predict peanut allergy in adolescence.

Google Trends (GT) searches trends of specific queries in Google and reflects the real-life epidemiology of allergic rhinitis. We compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from January 1, 2011 to December 20, 2016. The aim was to assess whether the same terms could be used t...

Allergy is an immediate hypersensitivity reaction caused by a skewed immune response lacking tolerance. Immunoglobulin E-mediated immune responses are directed against antigens, which are usually environmental protein-containing allergens that normally are not harmful to the human body. Certain antigens seem to be more likely to become an allergen....

Background Risk factors for persistence of food-related symptoms (FRS) and food allergy (FA) from early life to adolescence are incompletely understood. The aim of this study was to identify risk factors for FRS and FA in adolescence amongst children with FRS or FA in the first four years of life (early life). Methods In children enrolled in a Swe...

Definition of food-induced anaphylaxis at 16 years, based on criteria from the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network. *Based on Reference 32. †Excludes information on blood pressure, heart rate or oxygen saturation, as these data were not collected in the BAMSE study. (DOCX)

Definitions of baseline characteristics, infant feeding, early life allergy multimorbidity and Immunoglobulin E (IgE) activity. (DOCX)

Distribution of baseline characteristics and infant feeding of the entire cohort and the study population. *Parent.report of doctor-diagnosis of asthma and/or hayfever in combination with allergy to furred pets by either or both parents at time of enrolment. †Mother reporting smoking 1+ cigarettes per day during pregnancy. Bold text denotes statist...

Children with early life food-related symptoms (FRS) or food allergy (FA) and for whom IgE-reactivity data at 4 years were available in relation to food IgE reactivity-associated FRS or FA to 16 years. (DOCX)

Background: Information about severe reactions to foods in adolescence is limited. Objective: To describe reactions to foods, including anaphylaxis, with regard to incidence, characteristics and associated risks, among 16-year-olds (adolescents) in a large, population-based birth cohort. Methods: Parent-reported questionnaire data from ages 2-...

Background: The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. Objective: We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. Methods: A cross-sectional anal...

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from...

The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information...

Table of contents A1 Role of fibrocytes in allergic rhinitis Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet A2 Patterns of aeroallergens sensitization in Northern Alberta Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis A3 Addressing acceptable risk for adolescents with Food-Induced Anap...

Background and objective: Knowledge regarding lung function after moderately preterm birth is limited. We therefore investigated lung function at early school age and adolescence among children born moderately preterm. Methods: Data were used from the Swedish prospective birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Sto...

The objective was to evaluate the efficacy of MP-AzeFlu (Dymista(®) ) versus fluticasone propionate (FP), (both 1 spray/nostril bid), in children with allergic rhinitis (AR). MP-AzeFlu combines azelastine hydrochloride, FP and a novel formulation in a single spray. Children were randomized in a 3:1 ratio to MP-AzeFlu or FP in this open-label, 3-mon...

The selection of pharmacotherapy for patients with allergic rhinitis depends on several factors, including age, prominent symptoms, symptom severity, control of allergic rhinitis, patient preferences and cost. Allergen exposure and resulting symptoms vary and treatment adjustment is required. Clinical decision support systems (CDSS) may be benefici...

MeDALL Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 20 (10) -2015 proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy(.) MeDALL linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: precisely...

Background: This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. Methods: A total...

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most like...

Background: Several authors have reported on allergic reactions that resulted in presentation to the emergency department. However, studies of the secular trend of hospitalisations for paediatric allergic reactions, including anaphylaxis, are scarce. The aim of this study was to describe the secular trends of hospitalisations for allergic reaction...

Precision medicine is a medical model aiming to deliver customised healthcare - with medical decisions, practices, and/or products tailored to the individual patient informed but not directed by guidelines. Allergen immunotherapy has unique immunological rationale, since the approach is tailored to the specific IgE spectrum of an individual and mod...

Background: Sensitization to individual cat and dog allergen molecules can contribute differently to development of allergy to these animals. Objective: We sought to investigate the association between sensitization patterns to cat and dog allergen molecules during childhood and symptoms to these furry animals up to age 16 years. Methods: Data...

Background: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the...

Background Eczema, asthma, and rhinitis affect a large proportion of children, but their prevalence varies with age. IgE antibodies are also common in the pediatric population. However, the links between IgE, disease, and trajectories are unclear. Objective To better understand the links between sensitization and disease, we studied IgE sensitizati...

Background: The relation between secondhand tobacco smoke (SHS) exposure and the development of allergic sensitization in children is unclear. The aim of this study was to determine whether maternal smoking during pregnancy and postnatal SHS exposure contributes to the development of allergic sensitization in children and adolescents up to 16 year...

Background: Asthma in combination with rhinitis and eczema has been suggested to be associated with worse lung function than isolated asthma. Aim: To examine associations between asthma with and without rhinitis, eczema, allergic sensitization and; (1) spirometry, and (2) small airway involvement measured by impulse oscillometry (IOS). Methods: In...

Allergic diseases and asthma are increasing in prevalence globally. They can start early in life and many persist. It is important to prevent, detect and control these diseases early on and throughout life, so as to promote active and healthy ageing. The translational activities of MeDALL (Mechanisms of the Development of Allergy; EU FP7) are of gr...

Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of...

Rhinitis is one of the most common diseases in childhood. Fish, polyunsaturated fatty acid (PUFA), and vitamin D intakes have been hypothesized to affect the risk of allergic disease; however, it is unclear whether these are linked to the development of rhinitis. We sought to assess potential associations between consumption of fish, dietary n-3 an...

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and above all patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel Netw...

Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust have raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is an important exposure route of FRs, especially in children and can be hazardous for...

Allergic response to pollen is increasing world-wide, leading to high medical and social costs. However, the effect of pollen exposure on lung function has rarely been investigated. Over 1800 children in the Swedish birth cohort BAMSE were lung-function and IgE tested when 8 and 16 year old. Daily concentrations for 9 pollen types together with mea...

Asthma, rhinitis, and eczema often co-occur in children but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis, and eczema using unsupervised statistical techniques. We included 17,209 children at 4 years and 14,585 at 8 years from seven European-population-based birt...

Allergic diseases (asthma, rhinitis and atopic dermatitis) are complex. They are associated with allergen-specific IgE and non-allergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a qu...

Diagnosing peanut allergy properly is important and can be achieved by combining clinical history with various diagnostic methods such as IgE-antibody (IgE-ab) measurements, skin-prick test, basophil allergen threshold sensitivity (CD-sens) and food challenge. We aimed to evaluate CD-sens to peanut, Ara h 8 and Gly m 4 in relation to an oral peanut...

Exposure to indoor allergens during early life may play a role in the development of the immune system and inception of asthma. To describe the house dust mite (HDM) allergen concentrations in bedroom dust during early life and to evaluate its associations with HDM sensitization, wheezing and asthma, from birth to school age, in 5 geographically sp...

Allergic sensitization is frequently present in asthma and rhinitis, but the role of specific immunoglobulin E (s-IgE) is not always clear. Multiple s-IgE analyses may provide insight into this relationship, thus a micro-array-chip was developed within the EU-funded MeDALL project. The main objective was to evaluate the performance of the MeDALL-ch...

Background In Africa peanuts are frequently consumed but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut sensitized but asymptomatic patients from central Africa compared to peanut allergic and peanut sensitized but asymptomatic patients from Sweden.Methods Sera from allergic pati...

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective no...

Component-resolved diagnosis might improve the prediction of future allergy in young children. We sought to investigate the association between IgE reactivity to the pathogenesis-related class 10 (PR-10) protein family and allergic rhinitis to birch pollen (ARbp) from early childhood up to age 16 years. Questionnaire data and sera obtained at 4, 8,...