Obesity and Asthma: Implementing a Treatable Trait Care Model.

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.

Sensitization trajectories to multiple allergen components in a population-based birth-cohort.

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.

Component-resolved diagnosis in childhood and prediction of asthma in early adolescence: A birth cohort study.

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.

Exhaled breath condensate volatilome allows sensitive diagnosis of persistent asthma.

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.

Dietary Acid Load Modulation of Asthma-Related miRNAs in the Exhaled Breath Condensate of Children.

Individual nutrients and bioactive compounds have been implicated in the expression of microRNAs (miRNAs), which are related to inflammation and asthma. However, evidence about the impact of diet is scarce. Therefore, we aimed to assess the association between dietary acid load and asthma-related miRNA in the exhaled breath condensate (EBC) of school-aged children. This cross-sectional analysis included 150 participants aged 7 to 12 years (52% girls) from a nested case-control study, which randomly selected 186 children attending 71 classrooms from 20 public schools located in city of Porto, Portugal. Dietary data were collected by one 24 h-recall questionnaire. Dietary acid load was assessed using the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Based on previous studies, eleven asthma-related miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. PRAL, NEAP and miRNAs were categorized as high or low according to the median. Logistic regression models were performed to assess the association between dietary acid load scores and miRNAs. Children in high dietary acid load groups (PRAL ≥ 14.43 and NEAP ≥ 55.79 mEq/day) have significantly increased odds of having high miR-133a-3p levels. In conclusion, higher dietary acid loads possibly modulate asthma-related miRNAs of school-aged children.

Association between Elevated Iodine Intake and IQ among School Children in Portugal.

The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven's Colored Progressive Matrices) were dichotomized to <50 ("below-average" IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food's tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO's criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11−2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.

Development and validation of exhaled breath condensate microRNAs to identify and endotype asthma in children.

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment.