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Background and Objective Methods Results Conclusion Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non‐pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1–3 treatment according to the Global Initiative for Asthma (GINA).Twenty‐eight thousand five hundred eighty‐four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index‐date). The database was linked to other national registers to obtain information on prescribed drugs 2‐years pre‐index and exacerbations 1‐year post‐index. Asthma treatment was classified into step 1–3 or 4–5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function.GINA step 1–3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1–3). In adjusted analyses, UCA 1–3 was associated with female sex (OR 1.34, 95% CI 1.27–1.41), older age (1.00, 1.00–1.00), primary education (1.30, 1.20–1.40) and secondary education (1.19, 1.12–1.26), and TTs such as smoking (1.25, 1.15–1.36), obesity (1.23, 1.15–1.32), cardiovascular disease (1.12, 1.06–1.20) and depression/anxiety (1.13, 1.06–1.21). Furthermore, UCA 1–3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74–2.09) and asthma hospitalization (2.55, 2.17–3.00), respectively, also when adjusted for treatment step 4–5.Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations. [ABSTRACT FROM AUTHOR]

Aim: This study explored whether early- life factors, such as rhinovirus- induced wheeze and allergic sensitisation, were related to asthma at 11 years of age. Methods: We focused on 107 children aged 6-48 months, who attended the paediatric emergency department at Astrid Lindgren's Children's Hospital in Stockholm, Sweden, with acute wheeze in 2008-2012. They also attended follow- up visits at 11 years of age and were compared with 46 age-matched healthy controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with logistic regression. Results: We found that 62.6% of the acute wheeze cases had asthma at 11 years of age. Rhinoviruses at inclusion were the only common airway viruses associated with an increased asthma risk (OR 2.4, 95% CI 1.02-5.6). Other increased risks were parental heredity for asthma and/or allergies (adjusted OR 3.4, 95% CI 1.1-9.9) and allergic sensitisation at 2 years of age (adjusted OR 3.0, 95% CI 1.02-8.7). The highest prevalence of asthma was when children had both rhinovirus- induced wheeze at inclusion and allergic sensitisation at 7 years of age. Conclusion: Our findings highlight the importance of hereditary factors and allergic sensitisation on the development of asthma and suggest that rhinoviruses are associated with asthma development in predisposed children. [ABSTRACT FROM AUTHOR]

Background: IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome. Methods: We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA. Results: IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV. Conclusion: The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals. [ABSTRACT FROM AUTHOR]

Background: Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. Methods: From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF/tE) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2/h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma‐like symptoms (≥3 episodes of bronchial obstruction) between age 2–3 years as well as a history of doctor‐diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). Results: Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). Conclusion: Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years. [ABSTRACT FROM AUTHOR]

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45–7.98, p =.38), 2.87 (95% CI: 1.38–5.95, p <.05), and 3.38 (95% CI: 1.72–6.64, p <.05) for cutoff values in the <300, 300–449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease in children with an increasing prevalence. Its development is caused by genetic and environmental factors and allergic sensitization is a known trigger. Dog allergens affect up to 30% of all children and dog dander‐sensitized children show increased expression of cystatin‐1 (CST1) and eotaxin‐3 (CCL26) in nasal epithelium. The aim of our study was to investigate the functional mechanism of CST1 and CCL26 in the alveolar basal epithelial cell line A549. Methods: A549 cells were transfected with individual overexpression vectors for CST1 and CCL26 and RNA sequencing was performed to examine the transcriptomics. edgeR was used to identify differentially expressed genes (= DEG, |log2FC | ≥ 2, FDR < 0.01). The protein expression levels of A549 cells overexpressing CST1 and CCL26 were analyzed using the Target 96 inflammation panel from OLINK (antibody‐mediated proximity extension–based assay; OLINK Proteomics). Differentially expressed proteins were considered with a |log2FC| ≥ 1, p <.05. Results: The overexpression of CST1 resulted in a total of 27 DEG (1 upregulated and 26 downregulated) and the overexpression of CCL26 in a total of 137 DEG (0 upregulated and 137 downregulated). The gene ontology enrichment analysis showed a significant downregulation of type I and III interferon signaling pathway genes as well as interferon‐stimulated genes. At the protein level, overexpression of CST1 induced a significantly increased expression of CCL3, whereas CCL26 overexpression led to increased expression of HGF, and a decrease of CXCL11, CCL20, CCL3 and CXCL10. Conclusion: Our results indicate that an overexpression of CST1 and CCL26 cause a downregulation of interferon related genes and inflammatory proteins. It might cause a higher disease susceptibility, mainly for allergic asthma, as CCL26 is an agonist for CCR‐3‐carrying cells, such as eosinophils and Th2 lymphocytes, mostly active in allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood. Objective: Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters. Method: We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW‐R, n = 113/145) and 101 healthy controls (HC) aged 6–48 months in the GEWAC cohort using the antibody‐mediated proximity extension‐based assay (Olink Proteomics, Uppsala). Results: Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL‐10, IL‐6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF‐β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL‐10, TNF‐β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW‐R and HC for three (IL‐10, SIRT2 and FGF21) of the 10 proteins. Conclusion: Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma. [ABSTRACT FROM AUTHOR]

Vitamin D receptor genetic variant associated with asthma in Swedish school-children Keywords: asthma; genetic variants; longitudinal; preschool wheeze; VDBP; VDR; vitamin D EN asthma genetic variants longitudinal preschool wheeze VDBP VDR vitamin D 1045 1049 5 10/09/23 20231001 NES 231001 Key messages Rs11568820, a genetic variant in Vitamin D Receptor ( I VDR i ) is associated with preschool wheeze. Vitamin D insufficiency at preschool age tended to be more common in cases with asthma at 7 years (42.6%, I N i = 23/54) compared to those without asthma (19%, I N i = 4/21, I p i = .056, Figure 2A). Box plots for the number of days and asthma episodes in cases with asthma at 7 years across three genotypes for VDR-rs2228570 (AG; N = 33, AA; N = 4, GG; N = 16) (C, D). [Extracted from the article]

For doses up to 24 mg peanut protein, a mix of peanut and oat flour is used (4.6% peanut protein). The peanut baseline challenge starts with 0.3 mg peanut protein and continues stepwise up to 250 mg peanut protein (Table 1). Keywords: food allergy; peanut allergy; oral immunotherapy; treatment EN food allergy peanut allergy oral immunotherapy treatment 594 597 4 05/10/23 20230501 NES 230501 Key messages This is a study protocol for a trial of low-dose, slow up-dosing peanut oral immunotherapy. [Extracted from the article]

Background: Long‐time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. Methods: The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. Results: The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA/L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE‐ab to peanut extract (median 1,4, range 0.7–2.6 kUA/L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA/L) between 8 and 24 years of age, of whom three had an IgE‐ab level between 0.1–0.12 kUA/L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation‐related systemic proteins. Conclusion: Sensitization to peanut extract after 4 years of age is mainly induced by birch cross‐sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation. [ABSTRACT FROM AUTHOR]

Background: Sensitization to dog is an important risk factor for asthma in children, but the clinical relevance of IgE to available dog‐ and furry animal allergen molecules is uncertain. Methods: Spirometry, methacholine challenge, fraction of exhaled nitric oxide, nasal challenge with dog extract and questionnaires were performed in 59 dog‐sensitized children (age 10–18 years). Serum IgE to dog‐, cat‐, horse extracts and the allergen molecules Can f 1–6, Fel d 1, Fel d 2, Fel d 4 and Equ c 1 were evaluated. Results: Median numbers of positive IgE results to furry animal allergen molecules among children without asthma was 3, with asthma 5.5 and with troublesome asthma 9 (asthma vs. no asthma; p = 0.039; troublesome asthma vs. no asthma; p = 0.009). The odds ratio for asthma if sensitized to any lipocalin was 7.2 (95% confidence Interval: 1.44–35.9). Children with troublesome asthma had higher IgE levels to the lipocalins Can f 2, Can f 4 and Can f 6 compared to the rest of the study population (44 vs. 4.1 kUA/L, p = 0.015; 5.8 vs. 0.9 kUA/L, p = 0.018 and 1.3 vs. 0.7 kUA/L, p = 0.03 respectively). Furthermore, a positive nasal challenge was more common among children with troublesome asthma (83% vs. 36%, p = 0.036). Conclusions: Polysensitization to furry animal allergens and lipocalins is associated with asthma in dog‐sensitized children. Children with troublesome asthma have higher IgE levels to several dog lipocalins than other dog sensitized children. Key message: Polysensitization to furry animal allergens and high IgE levels to the dog lipocalins Can f 2, Can f 4 and Can f 6 is associated with asthma severity in dog dander sensitized children. Molecular allergy diagnostics may thus help the clinicians to evaluate the impact of allergic sensitization on asthma morbidity. [ABSTRACT FROM AUTHOR]

Background: Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age. Methods: At 3 months of age, 1,994 infants from the population‐based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m2/h), and allergen‐specific IgE levels <0.1 kUA/L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, and cat) allergen by a skin prick test wheal diameter ≥2 mm larger than negative control. Results: Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n = 177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93–6.04), 2.09 (95% CI 1.51–2.90) and 3.67 (95% CI 2.58–5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity. Conclusion: Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age. [ABSTRACT FROM AUTHOR]

Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on the type of food and mechanism, and it is not always easy to disentangle different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is immunoglobulin E (IgE)–mediated food allergy (prevalence 5–10%). Symptoms vary from mild itching, stomach pain, and rash to severe anaphylaxis. The definition of IgE‐mediated food allergy is allergic symptoms combined with specific IgE‐antibodies, and therefore only IgE‐antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children, and fish and shellfish in adults. In young children, milk/egg allergy has a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non‐IgE‐mediated food allergy, for example, eosinophilic esophagitis, celiac disease, food protein‐induced enterocolitis syndrome, and hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibilities of treating food hypersensitivity, such as through oral immunotherapy. The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

We thank all FASTX patients for their participation and the research staff at Forskningscentrum, Södersjukhuset. All participants then underwent an open peanut challenge (pOIT start), before starting peanut OIT (pOIT) in combination with continued omalizumab treatment. The x-axis shows the gene ratio of the overlapping genes of our gene list with the pathway gene set. [Extracted from the article]

Background: Tree nut allergy may cause anaphylaxis. There are limited population‐based studies on prevalence and early‐life risk factors. Methods: We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population‐based cohort study and assessed early‐life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early‐life risk factors. Results: Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non‐mild symptoms). Sixty‐three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15–33.6), eczema (ORadj 2.53 95% CI 1.21–5.32) and asthma (ORadj 5.59 95% CI 2.35–13.3)) at pre‐school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. Conclusions: In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease. [ABSTRACT FROM AUTHOR]

Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3‐month infants with available serum. Sensitization was defined as s‐IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1‐3, omega‐5‐gliadin were performed in food extract s‐IgE‐positive children. Maternal sensitization was defined as s‐IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18‐week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s‐IgE‐levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s‐IgE to ovomucoid, casein, Ara h 1‐3 and/or omega‐5‐gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s‐IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants' sensitization. [ABSTRACT FROM AUTHOR]

Background: Asthma‐like symptoms in preschool children, such as wheezing and dyspnea, are common time‐ and resource‐consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma. Methods: The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Results: We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%. Conclusion: Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non‐asthmatic preschool wheeze. [ABSTRACT FROM AUTHOR]

To the editor, Diagnosis of dog allergy in children relies mainly on clinical history and the presence of IgE antibodies (IgE) against dog dander. There were too few positive BAT responses for the minor allergens Can f 3 (n = 5), Can f 4 (n = 8), and Can f 6 (n = 5) to allow further analysis. Int Arch Allergy Immunol. 2013; 161 (1): 87 - 90. 4 Dahlen B, Nopp A, Johansson SG, Eduards M, Skedinger M, Adedoyin J. Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma. [Extracted from the article]

Preschool wheezing diagnosis and management-Survey of physicians' and caregivers' perspective The most frequent response (50.7%) points out response to treatment, while allergy tests were also very popular, having been chosen by 34.1%. This is the first survey exploring physicians' views on preschool wheeze, showing that wheezing itself and its association with future asthma remain a substantial challenge for most physicians. Furthermore, this study does not include a completely random sample of physicians, due to methodology used (email and social network), so only physicians familiar with the technology were able to participate. [Extracted from the article]

Current data indicate that the "bronchiolitis" diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor. Respiratory syncytial virus‐induced bronchiolitis and rhinovirus‐induced first wheezing episode are the main clusters of severe bronchiolitis in less than 2‐year‐old children. It is important to distinguish these overlapping patient groups since they differ clinically, pathophysiologically, and genetically and are likely to respond to different treatments. The first episode of severe bronchiolitis appears to be a critical event and an opportunity for designing secondary prevention strategies for asthma. [ABSTRACT FROM AUTHOR]

Background The chitinase-like protein YKL-40 ( CHI3L1) is elevated in the circulation of adults and schoolchildren with chronic severe asthma. It is unknown whether YKL-40 is altered in younger, preschool children with wheeze, acute or chronic. We therefore examined YKL-40 in preschool children during an acute episode of wheeze and during remission, in comparison with healthy controls. Methods Blood was obtained from 128 children (aged 6-44 months) at the emergency department during an acute episode of wheeze, and at two follow-up visits (approximately 3 months and 1 year later), as well as from 100 age-matched healthy controls on one occasion. Plasma YKL-40 levels were examined in relation to CHI3L1 rs4950928 genotype and clinical characteristics including Asthma Predictive Index, medication use, time spent with respiratory symptoms, atopic status, and blood leukocytes. Results Children with wheeze had higher median YKL-40 levels at the acute visit (14.7 (11.5-22.6) ng/ml, p < 0.001) and 3-month follow-up (15.9 (11.5-20.2), p < 0.001) compared to the 1-year follow-up (11.9 (9.5-17.3)). YKL-40 levels in healthy controls (13.6 (11.0-17.0)) tended to be lower than those during acute wheeze (p = 0.07) and 3-month follow-up (p = 0.04), but were no different at the 1-year follow-up. CHI3L1 rs4950928 affected YKL-40 in all subjects, with highest levels present in those with the CC genotype (p < 0.001). Genotype frequency was similar in the two subject groups. YKL-40 levels showed a positive correlation with blood neutrophil counts but no consistent relationships with clinical characteristics of relevance to continuous wheeze. Conclusion YKL-40 levels were elevated during acute wheeze in preschool children, a finding which may be related to current neutrophilic inflammation, but YKL-40 was not associated with characteristics of persistent wheeze in this young cohort. [ABSTRACT FROM AUTHOR]

Background: Assessment of inflammation is becoming a common practice in the clinical work-up of children with persistent asthma. Biomarkers of Th2-mediated inflammation include blood eosinophils (B-Eos), exhaled nitric oxide (FeNO), total serum IgE (S-IgE), and serum periostin. The aim of this study was to investigate the associations between asthma morbidity and increased levels of these biomarkers in pediatric asthma. Methods: School-age children (n = 96) with various manifestations of persistent asthma were included in this nationwide Swedish study. The protocol included the asthma control test, Juniper's quality of life questionnaire (QoL), assessment of pulmonary function, bronchial hyperresponsiveness, height-adjusted FeNO, blood sampling for S-IgE, B-Eos, and periostin, and high-resolution computed tomography (HRCT) of the lungs. Results: Children with both high levels of height-adjusted FeNO and B-Eos were younger (p = 0.001), had more often severe asthma (p = 0.015), were more allergic (p < 0.001), had a reduced asthma control (p = 0.035), reduced QoL (p = 0.035), more exacerbations (p = 0.004), reduced FEV1/FVC (p = 0.001), and increased bronchial hyperresponsiveness (p < 0.001) as well as greater bronchial wall thickening on HRCT (p = 0.022) compared to those with low levels of both biomarkers. Grouping children according to high and low serum periostin levels did not relate to differences in clinical characteristics and biomarkers. Conclusions: Assessment of both local and systemic Th2-mediated inflammation by the analysis of easily attainable biomarkers such as exhaled NO and blood eosinophils has a high predictive value for the identification of children with the highest asthma morbidity. Adjusting FeNO values according to the individual child's height increases the clinical usefulness of this biomarker. [ABSTRACT FROM AUTHOR]

Aim This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections. Methods We recruited 130 children with acute wheeze, aged 6 months to 4 years, from paediatric emergency departments in Stockholm, Sweden, and 101 age-matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25( OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria. Results Vitamin D insufficiency (25(OH)D < 75 nmol/L (30 ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1-6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24 months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history . Conclusion Our findings support the hypothesis that subnormal levels of vitamin D are associated with acute wheeze in young children. [ABSTRACT FROM AUTHOR]

Background Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Methods Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap ( kUA/l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Results Children with severe asthma had lower asthma control (p < 0.001) and FEV1 (p = 0.001) and more bronchial hyper-responsiveness (p = 0.008) in spite of high doses of inhaled steroids (≥800 μg budesonide). Children with severe asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p = 0.027), dog (3.8 vs. 1.2, p = 0.012) and horse (7.4 vs. 0.7, p = 0.014). Sensitization towards Can f 2 (22% vs. 0%, p = 0.009) and Equ c 1 (51% vs. 25%, p = 0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated with asthma control ( r = −0.41, p = 0.04). Conclusion Children with severe allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease. [ABSTRACT FROM AUTHOR]

YKL-40 is a proposed biomarker of inflammation and remodelling elevated in children with bronchopulmonary dysplasia compared to asthma Keywords: asthma; biomarker; bronchopulmonary dysplasia; YKL-40 EN asthma biomarker bronchopulmonary dysplasia YKL-40 641 642 2 01/23/21 20210201 NES 210201 YKL-40 is a chitinase-like, secreted glycoprotein associated with several respiratory disorders, including asthma and oxidant-induced lung injuries.1 Its biological role remains unclear, but it correlates with markers of airway fibrosis and remodelling in asthma, where it has emerged as a candidate biomarker for non-type 2 inflammation.2 Bronchopulmonary dysplasia (BPD) is a chronic disorder, characterised by underdeveloped, damaged lungs following premature birth and mechanical ventilation, whereas asthma is a chronic inflammatory disease, often associated with atopy and reversibility in children.3 BPD has been associated with more airway fibrosis and non-reversible lung function impairment than asthma. YKL-40 could be useful in distinguishing asthma from BPD and could also indicate the degree of airway dysfunction in BPD. [Extracted from the article]

To cite this article: Konradsen JR, Nordlund B, Nilsson OB, van Hage M, Nopp A, Hedlin G, Grönlund H. High basophil allergen sensitivity (CD-sens) is associated with severe allergic asthma in children. Pediatr Allergy Immunol 2012: 23: 376-384. Abstract Children with problematic severe asthma (PA) have persistent symptoms and/or severe exacerbations despite treatment with several drugs. Classification of asthma severity is currently based on level of treatment and assessment of asthma control, but objective biomarkers of asthma severity are needed. To investigate the clinical relevance of basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in a well-characterized cohort of children with different manifestations of persistent allergic asthma. Cat-allergic children (6-18 yr) with problematic severe asthma (n = 11) according to GINA were compared with eleven age-matched children with controlled, but persistent asthma (CA). The protocol included standardized questionnaires, asthma control test (ACT), spirometry, methacholine challenges, measurement of FENO, IgE, cat IgE and IgG antibodies, and analysis of CD-sens (CD63-expression) by flow cytometry. The 11 cat-allergic children with PA had a significantly lower ACT score (p < 0.001), reduced FEV1 (p = 0.04), and increased numbers of blood eosinophils (p = 0.03) compared with the 11 children with CA. The former exhibited a higher CD-sens to cat (p = 0.02). No significant differences were detected with respect to FENO (p = 0.17), IgE (p = 0.84), cat IgE (p = 0.12), and the major cat-allergen rFel d 1 (p = 0.30). CD-sens significantly correlated with ACT (p = 0.002, r = −0.63) and FENO (p = 0.01, r = 0.55). No significant differences between PA and CA were found regarding IgG antibodies to rFel d 1. Cat-allergic children with problematic severe asthma have higher sensitivity to cat allergen, as measured by CD-sens, compared with children with controlled asthma. This suggests that CD-sens could be used as an additional marker for identifying children with the most severe allergic asthma. [ABSTRACT FROM AUTHOR]

Children with problematic severe asthma (PA) are either difficult to treat because of the presence of aggravating factors or else severely resistant to therapy. We investigated a cohort of school-aged children with PA and compared these children to age-matched peers with controlled persistent asthma (CA). The aims were to characterize features of children suffering from PA and identify children who were severely resistant to therapy. In this cross-sectional, multicenter comparison of children with different manifestations of persistent asthma, PA was defined as insufficient asthma control despite level 4 treatment, according to GINA. The protocol included questionnaires, spirometry, methacholine provocation, measurement of fraction of nitric oxide in exhaled (FENO) and nasal air, blood sampling for inflammatory biomarkers and atopy, and computerized tomography of sinuses and lungs (in the PA group only). Of the 54 children with PA, 61% had therapy-resistant asthma, with the remaining being difficult to treat because of identified aggravating factors. Children with PA more often had parents with asthma (p = 0.003), came from families with a lower socioeconomic status (p = 0.01), were less physically active (p = 0.04), and had more comorbidity with rhinoconjunctivitis (p = 0.01) than did the 39 children with CA. The former also exhibited lower FEV1 values (p = 0.02) and increased bronchial hyper-responsiveness (p = 0.01), but there were no differences in atopy (p = 0.81) or FENO (p = 0.16). A non-invasive protocol, involving a standardized and detailed clinical characterization, revealed distinguishing features of children with PA and enabled the identification of children with therapy-resistant asthma. [ABSTRACT FROM AUTHOR]

First, regarding the definitions of bronchiolitis and wheeze, Manti et al state that bronchiolitis and wheezing are profoundly different clinical entities without overlap and therefore require different diagnostic and therapeutic approaches. 4 Lehtinen P, Ruohola A, Vanto T, Vuorinen T, Ruuskanen O, Jartti T. Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema. [Extracted from the article]