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This article explores the relationship between skin barrier integrity and type 2 inflammatory diseases. The study found that individuals with allergic rhinitis, food allergy, and eczema had higher levels of transepidermal water loss (TEWL), indicating compromised skin barrier integrity. The study also identified factors such as gender, testicular volume, armpit hair growth, and medical diagnoses that influenced skin barrier function. However, the model only captured a small percentage of the variation in TEWL. The study suggests an association between T2 inflammatory diseases and epithelial barrier disruption, but further research is needed to determine the diagnostic and predictive utility of TEWL in allergic diseases. [Extracted from the article]

ABSTRACT Recognition of obesity as a treatable trait of asthma, impacting its development, clinical presentation and management, is gaining widespread acceptance. Obesity is a significant risk factor and disease modifier for asthma, complicating treatment. Epidemiological evidence highlights that obese asthma correlates with poorer disease control, increased severity and persistence, compromised lung function and reduced quality of life. Various mechanisms contribute to the physiological and clinical complexities observed in individuals with obesity and asthma. These encompass different immune responses, including Type IVb, where T helper 2 cells are pivotal and driven by cytokines like interleukins 4, 5, 9 and 13, and Type IVc, characterised by T helper 17 cells and Type 3 innate lymphoid cells producing interleukin 17, which recruits neutrophils. Additionally, Type V involves immune response dysregulation with significant activation of T helper 1, 2 and 17 responses. Finally, Type VI is recognised as metabolic‐induced immune dysregulation associated with obesity. Body mass index (BMI) stands out as a biomarker of a treatable trait in asthma, readily identifiable and targetable, with significant implications for disease management. There exists a notable gap in treatment options for individuals with obese asthma, where asthma management guidelines lack specificity. For example, there is currently no evidence supporting the use of incretin mimetics to improve asthma outcomes in asthmatic individuals without Type 2 diabetes mellitus (T2DM). In this review, we advocate for integrating BMI into asthma care models by establishing clear target BMI goals, promoting sustainable weight loss via healthy dietary choices and physical activity and implementing regular reassessment and referral as necessary. [ABSTRACT FROM AUTHOR]

Introduction: Component‐resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD. Methods: One thousand one hundred one twenty‐five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics. Results: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82. Conclusions: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models. [ABSTRACT FROM AUTHOR]

Background: The characteristics of allergic sensitization profiles can differ between populations and geographic regions, contributing differently to the association with allergic diseases. Consequently, the sensitization trajectories found in previous studies conducted in Northern Europe may not apply in Southern European countries. Objective: To identify trajectories of allergic sensitization profiles during childhood and evaluate the association with allergic outcomes, using data from a Portuguese birth cohort. Methods: A random sample from Generation XXI was screened for allergic sensitization at 10 years of age. Among 452 allergic sensitized children, 186 were tested with ImmunoCAP™ ISAC multiplex array that detects 112 molecular components, at three follow‐ups (4, 7, and 10 years old). Information on allergic outcomes (asthma, rhinitis, atopic dermatitis) was obtained at the 13‐year‐old follow‐up. Latent class analysis (LCA) was used to identify clusters of participants with similar sensitization profiles. Then, sensitization trajectories were defined based on the most prevalent transitions between clusters over time. Logistic regression was applied to estimate the association between sensitization trajectories and allergic diseases. Results: Five trajectories were proposed: "no/few sensitizations," "early persistent house dust mites (HDM)," "early HDM and persistent/late grass pollen," "late grass pollen," and "late HDM." The "early HDM and persistent/late grass pollen" trajectory was associated with rhinitis and "early persistent HDM" with asthma and rhinitis. Conclusion: Distinct sensitization trajectories pose different risks in the development of allergic diseases. These trajectories present some differences from those in Northern European countries and are important for planning adequate prevention health plans. [ABSTRACT FROM AUTHOR]

Background: Cost‐effectiveness studies evaluating allergen immunotherapy (AIT) in children are limited but needed to drive clinical and policy‐making decisions such as reimbursement of new interventions. In this study, we compared the cost effectiveness of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) tablets to the standard of care (SOC) treatment in children with house dust mite‐driven (HDM) allergic asthma. Methods: We developed a hypothetical Markov model based on the Global Initiative for Asthma (GINA) severity steps to compare the three strategies over a 10‐year horizon divided by cycles of 6 months. SOC was used as a reference to calculate the incremental cost‐effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were used to assess models' uncertainty. Other scenarios were evaluated to strengthen the presentation of results. Results: The ICER for SCIT and SLIT tablets was 1281€ and 7717€, respectively. The cost‐effectiveness threshold for Portugal was 18,482.80€; both treatment approaches were below this limit. The major contributors to these results were the AIT effects on reducing moderate and severe exacerbations and asthma controller medication. In the sensitivity analysis, SCIT revealed a higher probability of cost‐effectiveness than SLIT. When including allergic rhinitis as comorbidity, ICER values reduced markedly, especially for SCIT intervention. Conclusions: AIT was cost effective in children with HDM‐driven allergic asthma, especially when given by the subcutaneous route. The high probability of cost effectiveness, especially for SCIT, may drive future policy decisions and AIT‐prescribing habits. AIT adherence greatly influenced the results highlighting the value of implementing strategies to promote adherence rates. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is a disease‐modifying treatment for IgE‐mediated diseases. Randomized controlled trials (RCTs) support AIT's potential role in asthma prevention but evidence from non‐randomized studies of interventions (NRSI) and longitudinal observational studies has been poorly addressed. Therefore, we aimed to conduct a systematic review and meta‐analysis to assess clinical data from all study types to evaluate quantitatively the preventive role of AIT in asthma onset. Methods: We search three databases. Studies were screened, selected and evaluated for quality using risk‐of‐bias (ROB) tools. Data were descriptively summarized and meta‐analysed using random effects. We performed a sensitivity, influence and subgroup analyses. Publication bias and heterogeneity were assessed. Results: From the 4549 identified studies, 24 (12 RCTs and 12 NRSI) were included in the qualitative synthesis and 18 underwent meta‐analysis. One study was at low ROB, seven had moderate ROB, and 15 were proven of high ROB. Random‐effects analysis showed a significant decrease in the risk of developing asthma following AIT by 25% (RR, 95% CI: 0.75, 0.64–0.88). This effect was not significant in the sensitivity analysis. Publication bias raised concerns, together with the moderate heterogeneity between studies (I2 = 58%). Subgroup analysis showed a remarkable preventive effect of AIT in children (RR, 95% CI: 0.71, 0.53–0.96), when completing 3 years of therapy (RR, 95% CI: 0.64, 0.47–0.88), and in mono‐sensitized patients (RR, 95% CI: 0.49, 0.39–0.61). Conclusions: Our findings support a possible preventive effect of AIT in asthma onset and suggest an enhanced effect when administered in children, mono‐sensitized, and for at least 3 years, independently of allergen type. [ABSTRACT FROM AUTHOR]

Background: A diet rich in fruits and vegetables has been suggested to counteract the oxidative stress and inflammation that characterize asthma. We aimed to assess the association between vegetable and fruit diversity consumption and asthma and its related outcomes in school‐aged children. Methods: Participants included 647 children (49% females, aged 7‐12 years) recruited from 20 public schools across the city of Porto, in Portugal. Vegetable intake and fruit intake were ascertained using a single self‐reported 24‐hour recall questionnaire. A diversity score was built taking into account the different number of individual vegetables and fruits consumed and categorized into two groups based on the total reported median consumption, which was rounded to the nearest whole number (≤3 and >3, for vegetables; and ≤1 and >1, for fruits). A questionnaire was used to enquire about self‐reported medical diagnosis of asthma and respiratory symptoms. Airway inflammation was assessed measuring exhaled fractional nitric oxide concentration (eNO) and was categorized into two groups (<35 and ≥35 ppb). The association between fruit and vegetable diversity and respiratory outcomes was examined using logistic regression models, adjusting for confounders. Results: A higher vegetable diversity consumption per day was negatively associated with having self‐reported asthma (OR = 0.67; 95% CI 0.47, 0.95), while having a vegetable diversity consumption superior to 3 items per day was negatively associated with levels of eNO ≥ 35 ppb (OR = 0.38; 95% CI 0.16, 0.88) and breathing difficulties (OR = 0.39; 95% CI 0.16, 0.97). Conclusion: Eating a greater variety of vegetables was associated with a lower chance of airway inflammation and prevalence of self‐reported asthma in school children. [ABSTRACT FROM AUTHOR]

Background: Analyses of exhaled volatile organic compounds (VOCs) have shown promising results when distinguishing individuals with asthma. Currently, there are no biomarkers for uncontrolled asthma. Therefore, we aimed to assess, in a real‐life clinical setting, the ability of the exhaled VOC analysis, using an electronic nose (eNose), to identify individuals with uncontrolled asthma. Methods: A cross‐sectional study was conducted, and breath samples from 199 participants (130 females, aged 6‐78, 66% with asthma) were analysed using an eNose. A multivariate unsupervised cluster analysis, using the resistance data from 32 sensors, could distinguish three clusters of VOC patterns in the training and testing groups. Comparisons between the clusters were performed using the one‐way ANOVA, Kruskal‐Wallis and chi‐squared tests. Results: In the training set (n = 121), three different clusters covering asthma, lung function, symptoms in the previous 4 weeks and age were identified. The pairwise comparisons showed significant differences with respect to chest tightness during exercise, dyspnoea and gender. These findings were confirmed in the testing set (n = 78) where the training model identified three clusters. The participants who reported fewer respiratory symptoms (dyspnoea and night‐time awakenings) were grouped into one cluster, while the others comprised participants who showed similar poor control over symptoms with the distribution of the individuals with asthma being significantly different between them. Conclusions: In a clinical setting, the analysis of the exhaled VOC profiles using an eNose could be used as a fast and noninvasive complementary assessment tool for the detection of uncontrolled asthma symptoms. [ABSTRACT FROM AUTHOR]

Background: Inhalation of fine particulate matter (PM) can cause systematic inflammation and oxidative stress, which may further aggravate the development and progression of asthma. Although nutritional intake of fatty acids and antioxidants may attenuate some effects of fine PM, the role of the inflammatory potential of diet has not been addressed. Therefore, we aimed to investigate possible modulatory effects of dietary inflammatory potential on the association between indoor air pollution and childhood asthma–related outcomes. Methods: In a sample of 501 children (48.1% females, aged 7‐12 years) from 20 public schools located in Porto, Portugal, we evaluated airway reversibility, exhaled nitric oxide levels, atopy, and current respiratory symptoms. Dietary inflammatory index was calculated based on information collected through a reported 24‐hour recall questionnaire, and participants were categorized as having an anti‐inflammatory or pro‐inflammatory diet. Concentrations of indoor PM2.5 and PM10 were measured to assess indoor air quality. Generalized linear mixed models were used to investigate the proportion of effects explained by the exposure to PM2.5 and PM10. Results: After adjustment, the exposure effect of PM2.5 and PM10 levels on children with asthma was higher for those having a pro‐inflammatory diet (OR = 1.44, 95% CI: 1.01‐2.21; and OR = 1.29, 95% CI: 1.03‐1.68, respectively) compared to those having an anti‐inflammatory diet. Conclusion: These findings suggest that the quality of diet might affect the association between indoor pollution and asthma in children, highlighting the relevance of children's diet as a potential protective factor to pollutant exposure in childhood asthma. [ABSTRACT FROM AUTHOR]

Background: Indoor air contaminants may act as endocrine‐disrupting chemicals (EDCs). However, to what extent these contaminants affect health is poorly known. We aimed to assess the association between EDCs exposure and asthma, respiratory symptoms and obesity in schoolchildren. Methods: Data from a cross‐sectional analysis of 815 participants from 20 schools in Porto, Portugal, were analysed. Symptoms were assessed, asthma was defined on lung function, and airway reversibility and body mass index (BMI) were calculated. The concentrations of 13 volatile organic compounds and 2 aldehydes identified as EDCs were measured in 71 classrooms throughout 1 week. Principal component analysis (PCA) was used to assess the effect of co‐exposure. Associations were estimated by regression coefficients using linear and logistic regression models. Results: Increased individual and combined EDCs levels were found in classrooms having more children with asthma and obesity. Higher levels of hexane, styrene, cyclohexanone, butylated hydroxytoluene and 2‐butoxyethanol were associated with obesity, and higher levels of cyclohexanone were associated with increased child BMI. Toluene, o‐xylene, m/p‐xylene and ethylbenzene were significantly associated with nasal obstruction. A positive association was found between PC1 and the risk of obese asthma (OR = 1.43, 95% CI 1.01, 1.98) and between PC2 and overweight (OR = 1.51, 95% CI 1.28, 1.79). PC1 and PC2 were also associated with nasal obstruction, and PC2 was associated with breathing difficulties and lean body mass, although EDCs concentrations were low. Conclusions: Our findings further support the role of EDCs in asthma and obesity development. Moreover, even low levels of indoor exposure may influence the risk of asthma, respiratory symptoms and obesity. [ABSTRACT FROM AUTHOR]

Background: The diagnosis and phenotyping of paediatric asthma are particularly complex due to the lack of currently available sensitive diagnostic tools. This often results in uncertainties associated with inhaled steroid therapy prescription. Therefore, this study aimed to investigate whether volatile organic compounds measured in exhaled breath condensate can be used as biomarkers for asthma diagnosis in the paediatric population. Methods: A total of 64 participants, aged 6‐18 years, were recruited on a random basis during visits to an outpatient allergy clinic and to a juvenile football team training session. Lung function, airway reversibility and skin prick tests were performed. Exhaled breath condensate samples were collected, and breathprints were assessed using an electronic nose. Information on medical diagnosis of asthma, rhinitis and atopic dermatitis was retrieved for each participant. A hierarchical cluster model based on the volatilome profiles was then created. Results: A two‐cluster exhaled volatile organic compound‐based hierarchical model was able to significantly discriminate individuals with asthma from those without the disease (AUC = 0.81 [0.69‐0.93], P < 0.001). Individuals who had persistent asthma and were prescribed corticosteroid therapy by the physician were also significantly distinguished in the model (AUC = 0.81 [0.70‐0.92], P < 0.001). Despite being less specific, the method showed higher overall accuracy, sensitivity and AUC values when compared to spirometry with bronchodilation. Conclusions: Analysis of the exhaled breath condensate volatilome allowed the distinction of paediatric individuals with a medical diagnosis of asthma, identifying those in need of corticosteroid therapy. The developed breathomics model was able to identify individuals with asthma and with persistent asthma with improved performance over spirometry with bronchodilation. The study shows that a breathomics model was able to identify individuals with a medical diagnosis of asthma with high accuracy. Individuals with asthma in need of inhaled corticosteroid therapy were significantly clustered in the model. Breathomics has the potential to assist the physician in the diagnosis of asthma and/or administration of corticosteroid therapy for paediatric patients with asthma. [ABSTRACT FROM AUTHOR]

Keywords: asthma; bronchodilator response; diagnosis; pediatrics; responsiveness cutoffs EN asthma bronchodilator response diagnosis pediatrics responsiveness cutoffs 371 373 3 02/02/21 20210201 NES 210201 To the editor, The term asthma refers to a heterogeneous group of diseases characterized by variable and reversible airflow limitation. Diagnosis of asthma was based on parent-reported prior medical diagnosis, previously demonstrated by our group to be the most accurate measure to predict questionnaire-driven symptom patterns, for this sample.5 We assessed the normal range for BDR of each measure in healthy children, that is, with no previous parent-reported medical diagnosis of asthma. In children, while over-diagnosis is an issue to be tackled, under-diagnosis is still a problem.8 As such, increasing the cutoff to 16% may cause damage to a countless number of children with asthma and the authors do not recommend its use. [Extracted from the article]