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Background: Previous studies which applied machine learning on multiplex component‐resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes. Objective: To investigate whether within different allergen component sensitization clusters, the internal within‐cluster sensitization structure, including the number of c‐sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms. Methods: In a previous analysis in a population‐based birth cohort, by clustering component‐specific (c‐s)IgEs, we derived allergen component clusters from infancy to adolescence. In the current analysis, we defined each subject's within‐cluster sensitization structure which captured the total number of c‐sIgE responses in each cluster and intra‐cluster sensitization patterns. Associations between within‐cluster sensitization patterns and clinical outcomes (asthma and rhinitis) in early‐school age and adolescence were examined using logistic regression and binomial generalized additive models. Results: Intra‐cluster sensitization patterns revealed specific associations with asthma and rhinitis (both contemporaneously and longitudinally) that were previously unseen using binary sensitization to clusters. A more detailed description of the subjects' within‐cluster c‐sIgE responses in terms of the number of positive c‐sIgEs and unique sensitization patterns added new information relevant to allergic diseases, both for diagnostic and prognostic purposes. For example, the increase in the number of within‐cluster positive c‐sIgEs at age 5 years was correlated with the increase in prevalence of asthma at ages 5 and 16 years, with the correlations being stronger in the prediction context (e.g. for the largest 'Broad' component cluster, contemporaneous: r =.28, p =.012; r =.22, p =.043; longitudinal: r =.36, p =.004; r =.27, p =.04). Conclusion: Among sensitized individuals, a more detailed description of within‐cluster c‐sIgE responses in terms of the number of positive c‐sIgE responses and distinct sensitization patterns, adds potentially important information relevant to allergic diseases. [ABSTRACT FROM AUTHOR]

A study published in the journal Clinical & Experimental Allergy investigated the connection between long-term exposure to particulate matter (PM10) in subway environments and the prevalence of asthma in subway workers. The study discovered that there was a link between the concentration of nitrite in exhaled breath condensate (EBC) and atopic sensitization, poly-atopic sensitization, and current asthma. Nitrate levels, on the other hand, were negatively associated with current eczema. The study used a retrospective exposure assessment method and had a high response rate, but it had limitations such as a small sample size and reliance on self-reported data. The study emphasizes the risk of allergic asthma in subway settings and the potential use of noninvasive biomarkers in occupational allergology research. [Extracted from the article]

This article discusses two studies that explore the relationship between DNA methylation and asthma development, as well as prenatal vitamin D levels and childhood asthma. The first study found that DNA methylation in newborns is linked to the development of asthma in adolescence, with specific CpG sites potentially serving as biomarkers for different types of asthma. The second study found that higher levels of vitamin D during pregnancy are associated with a reduced risk of childhood asthma. Both studies emphasize the importance of understanding these factors in the development of asthma and suggest further avenues for research. [Extracted from the article]

Objective: Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta‐analysis to obtain summary estimates of the effectiveness of FeNO‐guided asthma treatment. Design: We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse‐variance random‐effects meta‐analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. Data Sources: The Cochrane Airways Group Trials Register was searched on 9 May 2023. Eligibility Criteria: We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO‐guided treatment versus usual (symptom‐guided) treatment in adult asthma patients. Results: We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO‐guided treatment probably reduces the number of patients having ≥1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = −0.10; 95%CI −0.18 to −0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. Conclusions: FeNO‐guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes. [ABSTRACT FROM AUTHOR]

Eosinophilic asthma distributes in two clusters with patients expressing very different disease severity. Here, we have leveraged our large asthma clinic database to perform an unsupervised cluster analysis among asthmatics displaying a sputum eosinophil >=3% ( I N i = 426). While cluster analysis has been largely applied in asthma research over the last 15 years,[6] to the best of our knowledge, there has been no study that specifically focused on eosinophilic asthma as defined by sputum percentage of eosinophils. [Extracted from the article]

Background: Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood. Objectives: The objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases. Methods: Questions about cough, wheeze and allergic diseases were asked at 1, 1.5, 2, 3, 4, 5, 6 and 10 years of age in the European prospective cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Specific IgE assays were performed at 10 years of age. Questions regarding a cough without a cold were used to build a latent class model of cough over time. Results: Among the 961 children included in the study, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. For asthma, the strongest association was with the early persistent trajectory (ORa = 31.00 [14.03–68.51]), which was inversely associated with farm environment (ORa = 0.39 [0.19–0.77]) and had a high prevalence of cough triggers and unremitting wheeze. Late and early persistent trajectories were also associated with food allergy. Atopic sensitization was only associated with the late persistent trajectory. Conclusion: Late and early persistent coughs without a cold are positively associated with atopic respiratory diseases and food allergy. Children having recurrent cough without a cold with night cough and triggers would benefit from an asthma and allergy assessment. Growing up on a farm is associated with reduced early persistent cough. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown a rise in the prevalence of allergic diseases in India during the last two decades. However, recent evidence from the Global Asthma Network study has observed a decrease in allergic rhinitis, asthma and atopic dermatitis in children. Still, with a population over 1.3 billion, there is a huge burden of allergic rhinitis, asthma and atopic dermatitis, and this is compounded by an unmet demand for trained allergy specialists and poor health service framework. There is wide variation in the prevalence of allergic diseases between different geographical locations in India, and the reasons are unclear at present. This may at least in part be attributable to considerable heterogeneity in aero‐biology, weather, air pollution levels, cultural and religious factors, diet, socioeconomic strata and literacy. At present, factors enhancing risks and those protecting from development of atopy and allergic diseases have not been well delineated, although there is some evidence for the influence of genetic factors alongside cultural and environmental variables such as diet, exposure to tobacco smoke and air pollution and residence in urban areas. This narrative review provides an overview of data from India regarding epidemiology, risk factors and genetics and highlights gaps in evidence as well as areas for future research. [ABSTRACT FROM AUTHOR]

Taking AD as a systemic disease with skin symptomatology, we have measured systemic levels of IL-19 as a possible marker of skin inflammation, showing an increased plasma IL-19 concentration in children and adolescents with AD, especially moderate to severe, compared with healthy controls. AD, atopic dermatitis; HC, healthy controls; ns, not significant gl IL-19 plasma concentration was positively correlated with SCORAD score in AD individuals ( I r i = .44, I p i < .01) (Figure 1D) even when adjusting for the age of children. Keywords: atopic dermatitis; endotypes; IL-19; phenotypes EN atopic dermatitis endotypes IL-19 phenotypes 109 112 4 01/27/23 20230101 NES 230101 Key messages IL-19 was elevated in the plasma of children with moderate-to-severe AD IL-19 was increased in children <5 y.o. with AD compared with older ones Plasma IL-19 may be a useful marker in age-related atopic dermatitis endophenotyping To the editor, Atopic dermatitis (AD) is one of the most common skin diseases worldwide and is characterized by substantial heterogeneity in the age of onset, clinical manifestation, disease course, severity and concomitant allergic diseases. Plasma concentration of IL-19 differed significantly between AD patients and healthy controls (Figure 1A), and IL-19 was significantly increased in children with moderate-to-severe AD expressed as SCORAD index compared with healthy controls (Figure 1B). [Extracted from the article]

Keywords: atopic dermatitis; mental health; psychodermatology; quality of life EN atopic dermatitis mental health psychodermatology quality of life 113 117 5 01/27/23 20230101 NES 230101 Key messages Stress and Atopic Dermatitis severity significantly predict the quality of life in UK adults There are differences in Atopic Dermatitis severity and depression reported across different ethnicities. Therefore, when comparisons with healthy groups are not needed, measuring QoL in those with AD using an AD-specific QoL tool rather than a generic tool is recommended to help inform AD management. Physical QoL, social QoL, stress and AD severity were significantly associated with AD-specific QoL. AD severity was significantly associated with QoL after controlling for psychological factors, a finding consistent with a recent systematic review.[3] Stress, general physical and social QoL were also significantly associated with AD-specific QoL, after controlling for demographic and clinical variables. [Extracted from the article]

Background: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. Methods: Data were derived from the West Sweden Asthma Study, a population‐based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). Results: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. Conclusion: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization. [ABSTRACT FROM AUTHOR]

The severity of cashew nut allergy was dichotomized into mild to moderate cashew nut allergy (i.e. oFASS-3 grade 1 and 2) versus severe cashew nut allergy (i.e. oFASS-3 grade 3). Patients with a severe cashew nut allergy tended to have higher median IgE levels against both cashew nut extract and Ana o 3 than patients with mild to moderate cashew nut allergy, but this was not statistically significant ( I p i = .43 vs. I p i = .42, respectively; Figure 2). Keywords: Ana o 3; cashew nut allergy; cashew nut extract; diagnostic value; severity EN Ana o 3 cashew nut allergy cashew nut extract diagnostic value severity 880 882 3 08/14/23 20230801 NES 230801 Key messages We undertook a diagnostic test accuracy study in 43 adults with a suspected cashew nut allergy. [Extracted from the article]

IL-5 is associated with asthma severity in both AT-EOS and NA-EOS subjects. Thus, we conclude that asthma severity in both phenotypes (AT-EOS and NA-EOS) is associated with high levels of IL-5. However, we observed that the severity of asthma in both phenotypes (AT-EOS and NA-EOS) is associated with high serum levels of IL-5, but not eotaxin-1. [Extracted from the article]

Keywords: anaphylaxis; carmine; cochineal lice; cross-reactivity; Dermatophagoides pteronyssinus; food hypersensitivity; specific IgE EN anaphylaxis carmine cochineal lice cross-reactivity Dermatophagoides pteronyssinus food hypersensitivity specific IgE 1225 1229 5 10/13/22 20221001 NES 221001 Key messages Cochineal lice sIgE testing is a weak predictor for carmine allergy due to irrelevant cross-reactivity. ONLY IN PRIMARY CARMINE ALLERGY, CARMINIC ACID CAUSES BASOPHIL DEGRANULATION Six patients with cochineal lice sIgE were available for BAT experiments, including COCH1 (Figure 1D-H) and five had a positive BAT for HDM (Figure 1E). Diagnosis of carmine allergy using carminic acid solves interference of house dust mite and crustacean cross-reactivity These experiments supported a carminic acid allergy in patient COCH1, whereas other patients demonstrated clinically irrelevant cross-reactivity due to HDM and/or crustacean sensitization. [Extracted from the article]

Background: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. Objective: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. Methods: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. Results: Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B‐cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. Conclusion: The flow cytometry‐based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma. [ABSTRACT FROM AUTHOR]

Introduction: Gastro‐oesophageal reflux disease (GERD) is the most common non‐allergic comorbidity in adults with asthma; however, comorbidity with other atopic diseases such as eczema and hay fever is unclear. The objective was to assess the comorbidity of GERD with asthma and atopic diseases and to investigate possible mechanisms, including genetic and/or affective factors. Methods: A co‐twin control study harnessing 46 583 adult twins. Questionnaires on health status were linked to national patient and prescribed drug register data. Analyses tested associations of comorbidity between multiple definitions of atopic diseases (self‐report and register‐based) with GERD. Comparisons were made between unpaired, monozygotic (MZ) and dizygotic (DZ) twins to assess genetic liability. Affective traits (depression, anxiety and neuroticism) were added to models as possible explanatory factors. Results: The risk of GERD in those with asthma was OR (odds ratio) 1.52 (95% CI 1.38, 1.68), hay fever OR 1.22 (95%CI 1.12, 1.34) and eczema OR 1.23 (95%CI 1.10, 1.38). Adjusting for affective traits completely attenuated the comorbidity associations for hay fever and eczema with GERD, and partly for asthma with GERD. Co‐twin control associations attenuated suggesting a shared cause for both GERD and atopic diseases. For example, all twins adjOR 1.32 (95%CI 1.00, 1.74), 0.97 (95% CI 0.76–1.23) and 1.11 (95%CI 0.85–1.45) for self‐report asthma, hay fever and eczema with GERD respectively. Conclusions: GERD is a common comorbidity in adults with asthma, hay fever and/or eczema. We found evidence for shared mechanisms suggesting common underlying causes that may involve affective traits requiring further investigation. [ABSTRACT FROM AUTHOR]

Keywords: asthma; clinical immunology; eosinophils; innate immunity; pneumology EN asthma clinical immunology eosinophils innate immunity pneumology 792 796 5 06/01/22 20220601 NES 220601 Key messages The eosinophil gradient algorithm from ISAR is successfully replicated in the WATCH cohort of difficult asthma. Similar ISAR eosinophil phenotype distributions were observed in the subset ( I n i = 130) of WATCH patients with paired sputum analysis: 107 (82.3%) patients were classified as Grade 3 (Table 2). [Extracted from the article]

Aldehydes, asthma, biomarkers, children, oxidative stress, exhaled breath condensate, nitric oxide metabolites FeNO values increased during exacerbation while EBC NO SB 2 sb /NO SB 3 sb levels did not change.8 So, another explanation may be that in asthmatic subjects, the oxidative stress may be persistent and perhaps follow the inflammatory peak that increases FeNO. Keywords: aldehydes; asthma; biomarkers; children; exhaled breath condensate; nitric oxide metabolites; oxidative stress EN aldehydes asthma biomarkers children exhaled breath condensate nitric oxide metabolites oxidative stress 561 564 4 04/04/22 20220401 NES 220401 Key messages The role of aldehydes and oxides of nitrogen profiles in exhaled breath condensate in asthmatic children is still unclear. We found that both increased NOx and decreased 4-HNE in EBC may enable to distinguish children with asthma and with atopic asthma. [Extracted from the article]

Rationale: Rhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations. Objectives: To characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus‐16 infection. Methods: Moderately‐severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus‐16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting. Measurements and Main Results: Numbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons. Conclusions: Reduced numbers of anti‐viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients. [ABSTRACT FROM AUTHOR]

Keywords: asthma; epithelial cells; IL-17A; paediatrics EN asthma epithelial cells IL-17A paediatrics 569 573 5 04/04/22 20220401 NES 220401 To the Editor, Although asthma is often associated with cytokines typically produced by Th2 cells, the "T2 paradigm" is unable to explain the full spectrum of asthma severity; indeed, "severe" asthmatics often display inflammatory profiles consistent with mixed T2/T17 inflammation.1 Using a mouse model of asthma, we have shown that while severe asthma-like disease is associated with expansion of both Th2 and Th17 cells, increased production of Th17-associated cytokines are accompanied by increased measures of IL-17A-induced cellular activation (intracellular signalling, IL-17A-induced gene expression) in lung structural cells.2 These findings suggest that intrinsic differences in IL-17A responsiveness may contribute to the development of more severe asthma independently of changes in IL-17A production. The goals of the current study were to identify clinical factors associated with IL-17A responsiveness in children with asthma, and determine if IL-17A responsiveness differs in nasal epithelial cells from children with mild, moderate and severe asthma. To our knowledge, this represents the first attempt to determine if nasal epithelial cell responsiveness to IL-17A is associated with asthma-relevant clinical parameters, or asthma severity. However, our results demonstrate that increased IL-17A-induced CXCL1 production is comparable in children with different asthma severities, suggesting that increased epithelial cell responsiveness to IL-17A may be a general marker of asthma pathogenesis and not a marker of severe asthma as proposed by Andersson et al. [Extracted from the article]

Hence, although marked eosinophilia has been associated with the presence of severe asthma and although a sub-phenotype of severely eosinophilic asthma has been described,5 our study shows that a sub-phenotype of less severe asthma with increased sputum eosinophils exists as well. A key finding of the present analysis is that more than one-third of all subjects with EA had very mild asthma and nearly half of very mild asthma patients had EA. Eosinophilic airway inflammation can be observed in patients from all asthma severities. In addition, when stratifying subjects based on degrees of airway eosinophilia and looking at those with very high sputum eosinophils count, we observed that a considerable percentage of EA patients with corticosteroid-naïve asthma had sputum eosinophils >10%. [Extracted from the article]

Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL‐4, IL‐5, IL‐13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2‐targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field. [ABSTRACT FROM AUTHOR]

It is unclear whether intranasal corticosteroids reduce patient-reported disease severity in non-allergic rhinitis patients compared with placebo when measured at up to 3 months. No distinction between different pheno- and endotypes could be made, although a few studies only included a specific phenotype such as pregnancy rhinitis, vasomotor rhinitis, rhinitis medicamentosa or senile rhinitis. Keywords: ENT (rhinitis, sinusitis, nasal polyps...); epithelium; prevention; quality-of-life; rhinitis EN ENT (rhinitis, sinusitis, nasal polyps...) epithelium prevention quality-of-life rhinitis 836 838 3 07/11/22 20220701 NES 220701 Key Messages Non-allergic rhinitis is a group of conditions with similar symptoms but different pathophysiology. [Extracted from the article]

Keywords: asthma; atopic dermatitis; pharmacogenomics; pharmacology; rhinitis EN asthma atopic dermatitis pharmacogenomics pharmacology rhinitis 1089 1092 4 08/03/21 20210801 NES 210801 Key Messages We explored associations between genotype and prescriptions for allergic conditions in the BREATHE cohort. Asthma, atopic dermatitis, pharmacogenomics, pharmacology, rhinitis Of the 927 participants included in the study, 493 (53.2%) reported having eczema, 397 (42.8%) reported having rhinitis, 230 (24.8%) reported having rhinitis and eczema, and 267 (28.8%) reported having neither eczema nor rhinitis. We decided to perform rhinitis-related analysis in the entire sample due to discrepant reporting in the data and add a sensitivity analysis, analysing only children and young adults that reported having rhinitis (see Supplementary Material for more details on the methodology). [Extracted from the article]

Keywords: anaphylaxis; food allergy; IgE; paediatrics EN anaphylaxis food allergy IgE paediatrics 364 368 5 02/24/21 20210201 NES 210201 To the Editor: Food-induced allergic reactions are diagnosed through corroboration of a suggestive clinical history with appropriate confirmatory tests. We did not compare changes in sIgE in food-induced anaphylaxis versus drug- or venom-induced anaphylaxis. In conclusion, our study shows that following anaphylaxis, sIgE levels to culprit food allergens increase, while sIgE levels to unrelated tolerated foods do not change substantially. Further studies with a larger sample size and additional time-points before and after anaphylaxis are needed to better assess the temporal trends of sIgE levels and characterize its role in diagnosing the cause of anaphylaxis. [Extracted from the article]

During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma and currently, five monoclonal antibodies have been approved. Although these therapeutic agents have been formulated to target specific asthma endotypes, it is often difficult for the treating physician to identify which patient is the best candidate for each one of these specific treatments especially in the clinical scenario of a patient in whom clinical characteristics overlap between different endotypes, allowing the selection of more than one biologic agent. As no head‐to‐head comparisons between these biologics have been attempted, there is no evidence on the superiority of one biologic agent over the other. Furthermore, a physician's first therapeutic decision, no matter how carefully has been made, may often result in suboptimal clinical response and drug discontinuation, indicating the need for switching to a different biologic. In this short review, we discuss the available evidence regarding the switching between biologics in patients with severe asthma and we propose a simple algorithm on switching possibilities in case that the physicians' initial choice is proven not to be the best. [ABSTRACT FROM AUTHOR]

Resolvin D1 and miR-146a are independent distinctive parameters in children with moderate and severe asthma To the Editor, To date, a large number of mediators and biomarkers have been detected in childhood asthma, with a potential role in monitoring the disease course. Resolvin D1 and miR-146a levels, along with eosinophil and neutrophil counts and FEV SB 1 sb /FVC, were significantly different in MA and SA (Table S1). Resolvin D1 had the highest ability to characterize MA and SA; miR-146a, eosinophil and neutrophil counts and FEV SB 1 sb /FVC had a fair ability too (VIP >= 1, Figure 1). [Extracted from the article]

Background: Long‐term trajectories of asthma with fixed airflow obstruction (FAO) may reveal links to inflammatory endotypes. Objective: We investigated whether measures of asthma control and airway inflammation and remodelling differed by long‐term FAO status in moderate‐to‐severe asthma. Methods: Adults enrolled in the Difficult Asthma Study assessed initially using serial Asthma Control Questionnaire (ACQ), exacerbation history, spirometry and sputum cytology over 12 months, as well as endoscopic bronchial biopsy with airway smooth muscle (ASM) quantification, were revaluated three or more years later with questionnaires and spirometry. FAO was defined as a persistent post‐bronchodilator forced expired volume in one second (FEV1)‐to‐forced vital capacity ratio below 0.70. Results: Sixty‐two participants (mean ± SD age 48 ± 11 years; 50% female; 75% atopic; asthma duration 24 ± 14 years) returned for follow‐up assessment (median interval 7.9 years; IQR: 5.4‐8.8 years). Compared to participants without FAO (n = 28), those with FAO at baseline and long‐term follow‐up (n = 18) had higher baseline sputum neutrophil content and ASM, and a higher exacerbation frequency that persisted at long‐term follow‐up. Sputum eosinophils, ACQ and long‐term FEV1 decline did not differ. Participants with incident FAO at long‐term follow‐up (n = 16) had higher baseline exacerbation frequency, sputum eosinophil content, higher ACQ scores and greater decline in FEV1, whereas baseline ASM was similar to those without FAO. Conclusion: In moderate‐to‐severe asthma, long‐term FAO is characterized by neutrophilic sputum inflammation and airway remodelling, but FEV1 decline is similar to those without FAO. Long‐term incident FAO is preceded by higher exacerbation frequency, higher sputum eosinophil content and significant FEV1 decline. [ABSTRACT FROM AUTHOR]

Summary: Background: Adult‐onset asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases caused by complex gene‐environment interactions. A functional single nucleotide polymorphism of cadherin‐related family member 3 (CDHR3), known as a receptor of rhinovirus‐C, is associated with childhood‐onset asthma especially in atopic individuals. Objective: Here, we identified risk factors for adult‐onset asthma and COPD, focusing on the impact of the CDHR3 variant in atopic individuals. Methods: We conducted a longitudinal, retrospective, observational cohort study of 1523 healthy adults with baseline examinations at Tsukuba Medical Center Hospital in 2008 and retrospectively identified new‐onset, physician‐diagnosed asthma or COPD from 2009 to 2018. We assessed risk factors by the Cox regression analysis. The impact of CDHR3 variant rs6967330 was also examined in individuals with pre‐existing atopy. Results: Over 10 study years, 103 people developed airway diseases (79 asthma and 24 COPD; 52 females, average onset‐age 55 years old, range 38‐80). Higher body mass index (BMI) and lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio were significant risk factors (BMI: HR 1.072 [95% CI 1.005‐1.14], P =.034; FEV1/FVC ratio: HR 1.091 [1.044‐1.14], P =.00011). Restriction to atopic individuals saw the A allele at rs6967330 and lower FEV1/FVC ratio to associate with adult‐onset disease (A allele: HR 2.89 [1.57‐5.20], P =.00062; FEV1/FVC ratio: HR 1.10 [1.04‐1.17], P =.0010). Conclusion and clinical relevance: Genetic susceptibility to rhinovirus‐C infection in atopic individuals is a risk factor for chronic airway diseases even in later life. [ABSTRACT FROM AUTHOR]

Background: Anti‐interleukin‐5 (IL‐5) monoclonal antibodies can be used as add‐on biological therapies in allergic and non‐allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real‐life investigations are lacking. Objective: Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non‐allergic subjects with severe eosinophilic asthma. Methods: Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups. Results: After one year of add‐on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV1), blood eosinophil numbers, annual rate of disease exacerbations, and daily intake of oral corticosteroids (OCS). In particular, FEV1 enhanced from 1640 mL (1110‐2275) to 1920 mL (1525‐2615), blood eosinophil count dropped from 711.0 cells/μL (500.0‐1022) to 90.00 cells/μL (50.00‐117.5), the annual rate of asthma exacerbations decreased from 3.000 (2.000‐6.000) to 0.000 (0.000‐1.000), and the daily prednisone intake fell from 6.250 mg (0.000‐25.00) to 0.000 mg (0.000‐0.000). After one year of mepolizumab treatment, the improvements in clinical, functional, and haematological parameters were quite similar in patient subgroups characterized by skin prick test (SPT) negativity or positivity, respectively. A significant correlation was observed between serum IgE levels and OCS intake decrease (r = −0.2257; P <.05). Conclusion and Clinical Relevance: Hence, our real‐life data suggest that mepolizumab can represent a valid add‐on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization. [ABSTRACT FROM AUTHOR]

To the Editor, In asthma, sensitization to fungal, perennial or seasonal allergens increases the risk of uncontrolled symptoms, exacerbations and poor disease outcomes.[1] In severe asthma, typically 20%-29% of patients show sensitization to >=1 fungal allergen, with I Aspergillus i being one of the most common.[2], [3], [4] These patients have worse lung function, increased risk of oral corticosteroid use, hospitalization and a greater degree of airflow obstruction than patients non-sensitized to fungal allergens.[3], [4], [5] Severe eosinophilic asthma is characterized by frequent exacerbations and elevated eosinophil counts. Overall, 51/576 (9%) patients were sensitized to fungal allergens only, 167/576 (29%) to perennial/seasonal allergens only and 131/576 (23%) to both fungal and perennial/seasonal allergens; 198/576 (34%) patients were not sensitized to allergens. In patients with fungal and perennial/seasonal allergen or only perennial/seasonal allergen sensitization, mepolizumab reduced exacerbation frequency, with a trend for improved HRQoL and disease control, as measured by SGRQ and ACQ-5 score, respectively, vs placebo. [Extracted from the article]

Background: Treatment of drinking water may decrease microbial exposure. Objective: To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases. Methods: We recruited 1,110 schoolchildren aged 6‐16 years between 2011 and 2013 in Požega‐Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life). Results: Cumulative bacterial load in drinking water was higher (median [IQR]: 6390 [4190‐9550] vs 0 [0‐0]; P <.0001), and lifetime prevalence of allergic diseases was significantly lower among children with individual supply (5.5% vs 2.3%, P =.01; 14.4% vs 6.7%, P <.001; 25.2% vs 15.1%, P <.001; asthma, atopic dermatitis [AD] and rhinitis, respectively). Compared with the reference group (Urban/Public), there was a significant reduction in the risk of ever asthma, AD and rhinitis amongst rural children with individual supply: OR [95% CI]: 0.14 [0.03,0.67], P =.013; 0.20 [0.09,0.43], P <.001; 0.17 [0.10,0.32], P <.001. Protection was also observed in the Rural/Public group, but the effect was consistently highest among Rural/Individual children. In the quantitative analysis, the risk of allergic diseases decreased significantly with increasing bacterial load in drinking water in the first year of life (0.79 [0.70,0.88], P <.001; 0.90 [0.83,0.99], P =.025; 0.80 [0.74,0.86], P <.001; current wheeze, AD and rhinitis). Conclusions and Clinical Relevance: High commensal bacterial content in drinking water may protect against allergic diseases. [ABSTRACT FROM AUTHOR]

Background: Cleaning is associated with an increased risk of asthma symptoms, but few studies have measured functional characteristics of airway disease in cleaners. Aims: To assess and characterize respiratory symptoms and lung function in professional cleaners, and determine potential risk factors for adverse respiratory outcomes. Methods: Symptoms, pre‐/post‐bronchodilator lung function, atopy, and cleaning exposures were assessed in 425 cleaners and 281 reference workers in Wellington, New Zealand between 2008 and 2010. Results: Cleaners had an increased risk of current asthma (past 12 months), defined as: woken by shortness of breath, asthma attack, or asthma medication (OR = 1.83, 95% CI = 1.18‐2.85). Despite this, they had similar rates of current wheezing (OR = 0.93, 95% CI = 0.65‐1.32) and were less likely to have a doctor diagnosis of asthma ever (OR = 0.62, 95% CI = 0.42‐0.92). Cleaners overall had lower lung function (FEV1, FVC; P <.05). Asthma in cleaners was associated with less atopy (OR = 0.35, 95% CI = 0.13‐0.90), fewer wheezing attacks (OR = 0.40, 95% CI = 0.17‐0.97; >3 vs ≤3 times/year), and reduced bronchodilator response (6% vs 9% mean FEV1‐%‐predicted change, P <.05) compared to asthma in reference workers. Cleaning of cafes/restaurants/kitchens and using upholstery sprays or liquid multi‐use cleaner was associated with symptoms, whilst several exposures were also associated with lung function deficits (P <.05). Conclusions and Clinical Relevance: Cleaners are at risk of some asthma‐associated symptoms and reduced lung function. However, as it was not strongly associated with wheeze and atopy, and airway obstruction was less reversible, asthma in some cleaners may represent a distinct phenotype. [ABSTRACT FROM AUTHOR]

Background: Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro‐ or anti‐inflammatory manner depending on their glycosylation status. Objective: Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. Methods: Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn‐297 IgG glycosylation was analysed in maternal and offspring serum. Results: When mothers and offspring were sensitized to the same allergen (OVA‐OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS‐OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro‐inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn‐297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. Conclusions and Clinical Relevance: We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro‐inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors. Objective: We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort. Methods: A total of 588 individuals with moderate‐severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC112® and Allergy Explorer‐ALEX® microarray analysis. Results: The olive tree pollen β‐1,3‐glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper‐reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross‐reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross‐reactive carbohydrate determinants (CCDs) IgE was found in about one‐third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient‐reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity. Conclusion and Clinical Relevance: Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore this relationship in the first year following severe exacerbation in our previously cited cohort of school-aged children.[7] We also compared asthma characteristics recorded at baseline and asthma outcomes at 1 year. At 1-year visit, patients were classified into three groups according to asthma outcomes: (a) good responders: no exacerbation during follow-up and well-controlled asthma according to GINA guidelines; (b) partial responders: no more than one severe exacerbation during follow-up and/or partly controlled asthma; (c) poor responders: >=2 severe exacerbations during follow-up and/or uncontrolled asthma. We also observed that control and lung function evaluated 8 weeks after an asthma exacerbation might be predictive of future asthma outcomes. The influence of asthma control on the severity of virus-induced asthma exacerbations. [Extracted from the article]

Asthma is a chronic, recurrent and incurable allergy‐related respiratory disease characterized by inflammation, bronchial hyperresponsiveness and narrowing of the airways. Extracellular vesicles (EVs) are a universal feature of cellular function and can be detected in different bodily fluids. Recent evidence has shown the possibility of using EVs in understanding the pathogenesis of asthma, including their potential as diagnostic and therapeutic tools. Studies have reported that EVs released from key cells involved in asthma can induce priming and activation of other asthma‐associated cells. A literature review was conducted on all current research regarding the role and function of EVs in the pathogenesis of asthma via the PRISMA statement method. An electronic search was performed using EMBASE and PubMed through to November 2018. The EMBASE search returned 76 papers, while the PubMed search returned 211 papers. Following duplicate removal, titles and abstracts were screened for eligibility with a total of 34 studies included in the final qualitative analysis. The review found evidence of association between the presence of EVs and physiological changes characteristic of asthma, suggesting that EVs are involved in the pathogenesis, with the weight of evidence presently favouring deleterious effects of EVs in asthma. Numerous studies highlighted differences in exosomal contents between EVs of healthy and asthmatic individuals, which could be employed as potential diagnostic markers. In some circumstances, EVs were also found to be suppressive to disease, but more often promote inflammation and airway remodelling. In conclusion, EVs hold immense potential in understanding the pathophysiology of asthma, and as diagnostic and therapeutic markers. While more research is needed for definitive conclusions and their application in medical practice, the literature presented in this review should encourage further research and discovery within the field of EVs and asthma. [ABSTRACT FROM AUTHOR]

Background: The prevalence and severity of asthma, particularly the most common (atopic) form of the disease, increase amongst females but not males after puberty, and asthma activity also changes throughout the menstrual cycle and during pregnancy. The contribution of female sex hormones to asthma pathogenesis is incompletely understood. Objective: To obtain insight into the role of oestrogen (E2) in experimental atopic asthma, and guide future research on sex‐related variations in atopic asthma susceptibility/intensity in humans. Methods: We utilized an experimental model comprising rat strains expressing dichotomous Th2‐high vs Th2‐low immunophenotypes exemplified by eosinophilia, mirroring differences between human atopics/non‐atopics. We compared the efficiency of Th2‐associated immunoinflammatory mechanisms, which differed markedly between the two strains, and between sexes in the Th2‐high strain, and determined the effects of E2 administration on these differences. Results: Unique to the Th2‐high strain, eosinophil: neutrophil ratios in the airways at baseline and following sensitization/aeroallergen challenge were logfold higher in females relative to males, and this was reflected by higher baseline blood eosinophil numbers in females. Pretreatment of Th2‐high males with E2 abrogated this sex difference by selectively boosting Th2‐associated genes in the airways and eosinophilia, but was without corresponding effect in the Th2‐low strain. In contrast, parallel E2 effects on myeloid and lymphoid cell populations were relatively modest. Conclusions and Clinical Relevance: E2 acts to amplify the eosinophilic component of pre‐existing Th2‐high immunophenotype, possibly acting at the level of the common eosinophil/neutrophil precursor in bone marrow to preferentially drive eosinophil differentiation. Constitutive granulocyte profiles in which the balance between eosinophils and neutrophils is skewed towards eosinophils have been identified in independent cohort studies as markers of asthma risk, and these findings suggest that more detailed studies on the role of E2 in this context, and in relation to asthma pathogenesis in post‐pubertal females in particular, appear warranted. [ABSTRACT FROM AUTHOR]

Asthma, a complex, chronic disease characterized by airway inflammation, hyperresponsiveness and remodelling, affects over 300 million people worldwide. While the disease is typically associated with exaggerated allergen‐induced type 2 immune responses, these responses are strongly influenced by environmental exposures that stimulate innate immune pathways capable of promoting or protecting from asthma. The dual role played by innate immunity in asthma pathogenesis offers multiple opportunities for both research and clinical interventions and is the subject of this review. [ABSTRACT FROM AUTHOR]

Background: The role of pubertal BMI change in adult‐onset concomitant asthma and allergic rhinitis is unknown. Objective: We investigated the association of childhood and young adult BMI, and pubertal BMI changes with adult‐onset asthma, allergic rhinitis, and concomitant asthma and rhinitis in Swedish men. Methods: The BMI Epidemiology Study in Gothenburg, Sweden, comprised of height and weight measures taken from school health records (6.5‐9.5 years) and during military conscription (17.5‐22 years) for all men born 1945‐1961 (n = 37 652). Age‐adjusted childhood BMI centred at 8 years and young adult BMI at 20 years were linked to high quality data on asthma and allergic rhinitis diagnoses from the Swedish National Patient Register. Findings: High BMI (4th quartile vs the two median quartiles) at 8 years was associated with increased risk of concomitant asthma and allergic rhinitis (HR 1.45; 95% CI 1.00‐2.11). Overweight (HR 1.45; 95% CI 1.12‐1.89) and obesity (HR 1.95; 95% CI 1.08‐3.54) at 20 years were associated with increased risk of asthma without concomitant allergic rhinitis as main or auxiliary diagnosis. Pubertal BMI change showed a non‐linear association, so that both low (1st quartile vs the two median quartiles) and high pubertal BMI changes were associated with increased risk of asthma (low: HR 1.36; 95% CI 1.11‐1.68; high: HR 1.32; 95% CI 1.07‐1.63) and asthma without concomitant allergic rhinitis (low: HR 1.33; 95% CI 1.04‐1.69; high: HR 1.36; 95% CI 1.07‐1.74) as a main diagnosis. Conclusions and Clinical Relevance: Both low and high pubertal BMI changes are predictors of adult‐onset asthma in men, particularly asthma without concomitant allergic rhinitis. Primary prevention of adult‐onset asthma requires monitoring of changes in BMI during puberty. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3‐like 1 (CHI3L1), also known as breast regression protein 39 (BRP‐39) in mice and human homologue YKL‐40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive. Objective: The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD. Results: We investigated YKL‐40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild‐type (WT) and BRP‐39 null mutant (BRP‐39−/−) mice. YKL‐40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP‐39 were higher in OVA‐sensitized WT mice than in control mice. OVA‐sensitized BRP‐39−/− mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA‐sensitized WT mice. Induction of BRP‐39 was dominant in dermal macrophages. BRP‐39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL‐40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP‐39 deficiency attenuated dysregulation of skin barrier and tight junction genes. Conclusions and Clinical Relevance: These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether prolonged treatment with omalizumab influences development or progression of solid epithelial cancer in patients with atopic asthma or chronic idiopathic urticaria. Design: Systematic review and meta‐analysis of intervention and observational studies. Randomized controlled trials were assessed for risk of bias using the Cochrane Risk of Bias tool, comparative observational studies were assessed using the Newcastle‐Ottawa Scale, and non‐comparative observational studies were assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. Data sources: We searched MEDLINE, EMBASE, Cochrane Library and grey literature for eligible studies to November 2017. All searches were updated in January 2019. Eligibility criteria for included studies: Randomized, quasi‐randomized, controlled clinical trials and observational studies were included if they involved patients ≥ 12 years with moderate‐to‐severe persistent asthma or chronic idiopathic urticaria treated with omalizumab for ≥ 40 weeks. Eligible comparators included standard of care, placebo, cromoglycate or no treatment. Results: One hundred and sixty seven unique studies were eligible for inclusion; however, only twelve (7.2%, n = 11 758) reported any outcome of interest, none of which involved patients with urticaria. 195 cancer events were reported. We found no statistically significant increase in the odds of study‐emergent solid epithelial cancer in patients randomized to long‐term treatment with omalizumab compared to standard of care (Peto OR: 0.65, 95% CI: 0.11, 3.74, I2 = 41%). Less than one per cent of participants of non‐comparative observational studies (n = 2350) were diagnosed with a solid epithelial tumour (meta‐proportion: 0.86% [95% CI: 0.24, 1.86%, I2 = 56%]). In the only comparative observational study reporting on cancer, the proportion of study‐emergent solid epithelial tumour events was nearly identical in both study groups (omalizumab: 2.3%, standard of care: 2.2%). Conclusions: There is insufficient evidence to determine whether long‐term treatment with omalizumab influences development or progression of solid epithelial cancer in these patient populations. PROSPERO registration # CRD 42018082211. [ABSTRACT FROM AUTHOR]

Background: Conflicting findings from studies evaluating associations of allergic disease with child behaviour require longitudinal studies to resolve. Objective: To estimate the magnitude of associations of atopic dermatitis (AD) in infancy, and symptoms of asthma and AD at 6.5 years, with child behaviour at 6.5 years. Methods: Secondary cohort analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT). PROBIT enrolled 17 046 infants at birth and followed them up at 6.5 years (n = 13 889). Study paediatricians collected data on infantile AD at repeated follow‐up examinations during the first year of life. At 6.5 years, paediatricians performed skin prick tests and parents reported asthma and AD symptoms during the prior year. In addition, parents and teachers completed the Strength and Difficulties Questionnaire, which includes scales on hyperactivity/inattention, emotional problems, conduct problems, peer problems and prosocial behaviours. Results: Physician‐diagnosed AD in the first year of life was not associated with increased risk for behavioural problems at 6.5 years. Emotional problems at 6.5 years were more common among children with AD symptoms (OR: 2.24, 95% CI: 1.62‐3.12) and asthma symptoms (OR: 1.45; 95% CI: 1.07‐1.96) during the past year at 6.5 years and ORs for children with symptoms of more severe AD and asthma were also higher. AD in the past year was also associated with probable hyperactivity/inattention disorder at 6.5 years (OR: 2.05; 95% CI: 1.09‐3.84). Other subscales of the SDQ were not related to asthma or AD symptoms during the past year. Conclusions and clinical relevance: Children with AD symptoms were at higher risk for concomitant hyperactivity/inattention and emotional disorder, and children with asthma symptoms were at higher risk of having concomitant emotional problems. However, AD during infancy did not predict childhood behaviours. [ABSTRACT FROM AUTHOR]

Background: Human milk (HM) transforming growth factor beta (TGF‐β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF‐β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF‐β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF‐β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF‐β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF‐β2 on eczema. Meta‐analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF‐β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF‐β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF‐β in combination with other HM immune markers, microbiome and oligosaccharides are required. [ABSTRACT FROM AUTHOR]

Background: Allergy to German cockroach (CR) is common in urban environments and is an important allergen in children with asthma. Objective: We hypothesize that the evolution of allergic sensitization and clinical disease is associated with distinct patterns of allergen‐specific T cell reactivity. To test this hypothesis, a subset of high‐risk inner‐city children participating in the URECA (Urban Environment and Childhood Asthma) birth cohort were selected to evaluate CR‐specific T cell reactivity from three distinct groups based on acquisition of aeroallergen sensitivity from ages 2 to 10: low atopy with minimal to no sensitivity (n = 26), early‐onset allergic sensitization (n = 25) and late‐onset allergic sensitization (n = 25). Methods: Using pools of previously identified CR‐derived T cell epitopes, we characterized the allergen‐specific T cell response in these 76 subjects from blood samples obtained at age 10. CR‐specific production of IL‐5, IFNγ and IL‐10 was measured by ELISPOT following two‐week in vitro culture with CR extract. Results: T cell responses were significantly higher in the early‐onset atopy group compared to low atopy (P = 0.01), and a trend for higher cytokine production in the late onset compared to the low atopy cohort was also observed (P = 0.06). T cell responses were similar between early‐ and late‐onset cohorts. Furthermore, a comparison of T cell reactivity between asthmatic and non‐asthmatic individuals revealed significantly higher cytokine production in asthmatics compared to non‐asthmatics (P = 0.02) within both the CR‐allergic and non‐allergic cohorts. Conclusions and clinical relevance: In conclusion, the present study reports that higher T cell reactivity is associated with allergen sensitization and asthma. Interestingly, no significant difference in T cell reactivity was observed in allergic children with early‐onset versus late‐onset atopy. [ABSTRACT FROM AUTHOR]

Background: The "atopic march" has been considered a linear progression starting with eczema and culminating with development of asthma. Not all asthma cases, however, are preceded by eczema, and not all children with eczema go on to develop asthma. Objective: The aim of this study was to explore the impact of allergic sensitization patterns on the association between early eczema and later childhood asthma. Given the numerous reported associations of the ciliary gene KIF3A with the atopic march, we also examined the impact of KIF3A risk allele rs12186803 on our analyses. Methods: We studied 505 participants in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective birth cohort, with longitudinal eczema and asthma outcomes as well as prospective data regarding timing of sensitization to foods and aeroallergens. KIF3A genotypes were available on all children. Results: Two high‐risk groups were identified: one with and one without early eczema. The high‐risk group with early eczema was more likely to be sensitized to food allergens, while the group without early eczema was more likely to be polysensitized to aeroallergens. The KIF3A rs12186803 risk allele interacted with food sensitization to increase asthma risk in children with eczema (P = 0.02). In children without eczema, asthma was associated with the interaction between rs12186803 and aeroallergen sensitization (P = 0.007). Conclusions & Clinical Relevance: KIF3A interacted differentially with sensitization pattern to increase the risk of asthma in two high‐risk groups of children with and without early eczema. Given the reported role of KIF3A in epithelial cell functioning, the results add evidence to the hypothesis that an impaired epithelial barrier is a key aspect in the development of allergic disease. [ABSTRACT FROM AUTHOR]