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BACKGROUND: Changes in land use and climate change have been reported to reduce biodiversity of both the environment and human microbiota. These reductions in biodiversity may lead to inadequate and unbalanced stimulation of immunoregulatory circuits and, ultimately, to clinical diseases, such as asthma and allergies. OBJECTIVE: We summarized available empirical evidence on the role of inner (gut, skin, and airways) and outer (air, soil, natural waters, plants, and animals) layers of biodiversity in the development of asthma, wheezing, and allergic sensitization. METHODS: We conducted a systematic search in SciVerse Scopus, PubMed MEDLINE, and Web of Science up to 5 March 2024 to identify relevant human studies assessing the relationships between inner and outer layers of biodiversity and the risk of asthma, wheezing, or allergic sensitization. The protocol was registered in PROSPERO (CRD42022381725). RESULTS: A total of 2,419 studies were screened and, after exclusions and a full-text review of 447 studies, 82 studies were included in the comprehensive, final review. Twenty-nine studies reported a protective effect of outer layer biodiversity in the development of asthma, wheezing, or allergic sensitization. There were also 16 studies suggesting an effect of outer layer biodiversity on increasing asthma, wheezing, or allergic sensitization. However, there was no clear evidence on the role of inner layer biodiversity in the development of asthma, wheezing, and allergic sensitization (13 studies reported a protective effect and 15 reported evidence of an increased risk). CONCLUSIONS: Based on the reviewed literature, a future systematic review could focus more specifically on outer layer biodiversity and asthma. It is unlikely that association with inner layer biodiversity would have enough evidence for systematic review. Based on this comprehensive review, there is a need for population-based longitudinal studies to identify critical periods of exposure in the life course into adulthood and to better understand mechanisms linking environmental exposures and changes in microbiome composition, diversity, and/or function to development of asthma and allergic sensitization. [ABSTRACT FROM AUTHOR]

There seems to exist an intricate relationship between airway inflammation, body mass index (BMI), and diet. The intake of specific foods or food groups has been suggested to suppress the oxidative stress and inflammatory processes that characterize airway inflammation, but little is known about dietary patterns and their complex interplay with BMI and airway inflammation. Therefore, this cross-sectional study aimed to explore the association between adherence to the Mediterranean diet (MD), a characteristic European diet, and levels of airway inflammation in school-aged children, taking into account their BMI. This cross-sectional analysis comprised 660 children: 49.1% females, 7–12 years old. Adherence to the MD was assessed through the alternate Mediterranean score (aMED). Higher scores represent a healthier diet (0–8). Airway inflammation was assessed measuring exhaled fractional nitric oxide (eNO). Two categories of BMI were considered: non-overweight/non-obese (p < 85th) and overweight/obese (p ≥ 85th). The associations between diet and airway inflammation were estimated using logistic regression models. Higher scores of the aMED were associated with decreased odds of having eNO ≥ 35 ppb, but only in non-overweight/non-obese children (OR = 0.77; 95% CI, 0.61–0.97). For overweight/obese children, the previous association was not significant (OR = 1.57, 95% CI, 0.88–2.79). Our findings suggest that adherence to the MD is associated with lower levels of airway inflammation among non-overweight/non-obese children. [ABSTRACT FROM AUTHOR]

Asthma is a chronic respiratory disease that impacts millions of people worldwide. Recent studies suggest that diet may play a role in asthma pathophysiology. Several dietary factors have been recognized as potential contributors to the development and severity of asthma for its inflammatory and oxidative effects. Some food groups such as fruits and vegetables, whole grains, and healthy fats appear to exert positive effects on asthma disease. On the other hand, a high consumption of dietary salt, saturated fats, and trans-fat seems to have the opposite effect. Nonetheless, as foods are not consumed separately, more research is warranted on the topic of dietary patterns. The mechanisms underlying these associations are not yet fully understood, but it is thought that diet can modulate both the immune system and inflammation, two key factors in asthma development and exacerbation. The purpose of this review is to examine how common food groups and dietary patterns are associated with asthma. In general, this research demonstrated that fruits and vegetables, fiber, healthy fats, and dietary patterns considered of high quality appear to be beneficial to asthma disease. Nonetheless, additional research is needed to better understand the interrelation between diet and asthma, and to determine the most effective dietary interventions for asthma prevention and management. Currently, there is no established dietary pattern for asthma management and prevention, and the nuances of certain food groups in relation to this disease require further investigation. [ABSTRACT FROM AUTHOR]

Exhaled breath condensate (EBC) analysis is a recently developed, non-invasive method used to identify and quantify biomarkers, mainly those coming from the lower respiratory tract. It seems that diet can influence the airway's inflammation and change the exhaled breath composition. This study aimed to assess the association between diet quality intake and markers in EBC among school-aged children. A cross-sectional analysis included 150 children (48.3% females, aged 7–12 years, mean age: 8.7 ± 0.8 years) from 20 schools across Porto, Portugal. We assessed diet quality through the Healthy Eating Index (HEI)-2015, which was estimated based on a single 24 h food recall questionnaire. EBC samples were collected, and we assessed their ionic content (Na+, K+) and conductivity. The association between diet quality and Na+, K+, Na+/K+ ratio and conductivity was estimated using logistic regression models adjusted for potential confounders. After adjustment, a higher quality diet score increases the odds of higher conductivity values of the EBC (aOR = 1.04, 95%CI 1.00; 1.08). Our findings suggest that a higher diet quality in school-aged children is associated with higher conductivity levels of the EBC. [ABSTRACT FROM AUTHOR]

Keywords: allergic rhinitis; early life; greenspaces; population-based cohort study; season EN allergic rhinitis early life greenspaces population-based cohort study season 1680 1682 3 06/02/23 20230601 NES 230601 The world has experienced considerable growth of urban areas in recent decades, with approximately 54% of the world population living in cities.[1] While this development provides some benefits, unplanned, uncontrolled and rapid urbanization has also been associated with environmental degradation, land changes and loss of green areas.[2] Epidemiological studies on the association between urban greenspaces and development of allergic diseases have provided inconsistent results.[3] This heterogeneity in the effects of greenspaces on the development of allergic rhinitis could be explained by the season of exposure. However, an increase in exposure to NDVI during spring season in early life was associated with an increased risk of allergic rhinitis up to 12 years of age [aHR (95% CI) = 1.726 (1.078; 2.765)] and up to 27 years of age [aHR (95% CI) = 1.703 (1.139; 2.545)]. During the summer, an increase in the exposure to NDVI was associated with a decrease in the risk of allergic rhinitis up to 12 years of age [aHR (95% CI) = 0.754 (0.585; 0.972)] and up to 27 years of age [aHR (95% CI) = 0.801 (0.649; 0.989)]. [Extracted from the article]

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]

Introduction: Whether you benefit from high‐quality urban environments, such as those rich in green and blue spaces, that may offer benefits to allergic and respiratory health depends on where you live and work. Environmental inequality, therefore, results from the unequal distribution of the risks and benefits that stem from interactions with our environment. Methods: Within this perspective, this article reviews the evidence for an association between air pollution caused by industrial activities, traffic, disinfection‐by‐products, and tobacco/e‐cigarettes, and asthma in children. We also discuss the proposed mechanisms by which air pollution increases asthma risk, including environmental epigenetic regulations, oxidative stress, and damage, disrupted barrier integrity, inflammatory pathways, and enhancement of respiratory sensitization to aeroallergens. Results and conclusions: Environmental air pollution is a major determinant of childhood asthma, but the magnitude of effect is not shared equally across the population, regions, and settings where people live, work, and spend their time. Improvement of the exposure assessment, a better understanding of critical exposure time windows, underlying mechanisms, and drivers of heterogeneity may improve the risk estimates. Urban conditions and air quality are not only important features for national and local authorities to shape healthy cities and protect their citizens from environmental and health risks, but they also provide opportunities to mitigate inequalities in the most deprived areas where the environmental burden is highest. Actions to avoid exposure to indoor and outdoor air pollutants should be complementary at different levels—individual, local, and national levels—to take effective measures to protect children who have little or no control over the air they breathe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Regression tree models were used to identity the land-use characteristics in school and residential neighborhoods associated with the prevalence of asthma among children. The mean imputation method was used for residences without information on land-use characteristics, and the missing values are replaced with the mean of the same land-use type for each child's school. Keywords: asthma; children; environment; regression tree models; respiratory disease predictors EN asthma children environment regression tree models respiratory disease predictors 1 4 4 01/05/22 20220101 NES 220101 ACKNOWLEDGEMENTS Authors gratefully acknowledge the Project EXALAR 21 funded by the European Regional Development Fund (FEDER), through the Competitiveness and Internationalization Operational Programme, and by national funding from the Foundation for Science and Technology (FCT) under the scope of the project PTDC/GES-AMB/30193/2017 (POCI-01-0145-FEDER-030193, 02/SAICT/2017 - Project nº 30193). Childhood asthma and land-use characteristics in school and residential neighborhoods: A decision tree learning approach. [Extracted from the article]

Background: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. Methods: A cross‐sectional analysis of exhaled breath condensates from 613 children, aged 7–12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post‐deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. Results: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [β = −0.09 (−0.15, −0.02)] and PM 2.5 concentration [β = −0.16 (−0.32, −0.01)], and in the alkaline group by relative humidity [β = 0.07 (0.02, 0.13)] and concentration of endotoxins [β = −0.06 (−0.1, −0.01)]. Conclusion: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children. [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]

The collection and analysis of settled dust samples from indoor environments has become one of several environmental sampling methods used to assess bioburden indoors. The aim of the study was to characterize the bioburden in vacuumed settled dust from 10 Primary Health Care Centers by culture based and molecular methods. Results for bacterial load ranged from 1 to 12 CFU.g−1 of dust and Gram-negative bacteria ranged between 1 to 344 CFU.g−1 of dust. Fungal load ranged from 0 CFU.g−1 of dust to uncountable. Aspergillus section Fumigati was detected in 4 sampling sites where culture base-methods could not identify this section. Mucorales (Rhizopus sp.) was observed on 1 mg/L voriconazole. Three out of 10 settled dust samples were contaminated by mycotoxins. Settled dust sampling coupled with air sampling in a routine way might provide useful information about bioburden exposure. [ABSTRACT FROM AUTHOR]

The number of microbiome-related studies has notably increased the availability of data on human microbiome composition and function. These studies provide the essential material to deeply explore host-microbiome associations and their relation to the development and progression of various complex diseases. Improved data-analytical tools are needed to exploit all information from these biological datasets, taking into account the peculiarities of microbiome data, i.e., compositional, heterogeneous and sparse nature of these datasets. The possibility of predicting host-phenotypes based on taxonomy-informed feature selection to establish an association between microbiome and predict disease states is beneficial for personalized medicine. In this regard, machine learning (ML) provides new insights into the development of models that can be used to predict outputs, such as classification and prediction in microbiology, infer host phenotypes to predict diseases and use microbial communities to stratify patients by their characterization of state-specific microbial signatures. Here we review the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on the application of ML in microbiome studies related to association and clinical use for diagnostics, prognostics, and therapeutics. Although the data presented here is more related to the bacterial community, many algorithms could be applied in general, regardless of the feature type. This literature and software review covering this broad topic is aligned with the scoping review methodology. The manual identification of data sources has been complemented with: (1) automated publication search through digital libraries of the three major publishers using natural language processing (NLP) Toolkit, and (2) an automated identification of relevant software repositories on GitHub and ranking of the related research papers relying on learning to rank approach. [ABSTRACT FROM AUTHOR]

Background: A lower exposure to the natural environment has been hypothesized to adversely affect the human microbiome and its immunomodulatory capacity. However, the underlying effects of this hypothesis are still not understood. We aimed to evaluate the effect of early‐life exposure to greenness and species richness on the development of allergic diseases and asthma in children. Methods: A longitudinal study was conducted comprising 1050 children from a population‐based birth cohort recruited in Portugal. Residential normalized difference vegetation index (NDVI) and species richness index (SRI) were assessed at baseline to estimate their association with allergic diseases and asthma at the ages of 4 and 7. Results: Significant predisposing associations were observed between the exposure to species richness at baseline and the onset of asthma and wheezing at the age of 7. Children living in neighbourhoods surrounded by high levels of SRI were at a significantly higher risk developing allergic sensitization(OR [95% CI] = 2.00 [1.04:3.86] at age 4; 2.35 [1.20:4.63] at age 7). Living surrounded by greener environments was significantly associated with a lower prevalence of asthma and rhinitis at the age of 7(0.41 [0.18:0.97] and 0.37 [0.15:0.93], respectively). Conclusions: Living in close proximity to a greener environment at birth has a protective effect on the development of allergic diseases and asthma at the age of 7. Conversely, living in neighbourhoods with a high number of fauna species appears to be associated with a higher risk for allergy, asthma and wheezing. [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: Primary schools represent important environments for biodiversity exposure and thus may play a crucial role on early‐life immunomodulation, protecting against allergic sensitization. The aim of this study was to understand how the exposure to different levels of species richness surrounding urban primary schools may influence the development of allergic diseases and asthma in children. Methods: A species richness index (SRI), evaluating habitat diversity in terms of amphibians, birds, reptiles, and small mammals, was estimated and attributed to 20 primary schools in the city of Porto, Portugal. The SRI was measured considering a 100 m straight‐line buffer around the schools. Children who attended the participating schools were invited to participate in the study, performed spirometry with bronchodilation and skin‐prick tests, and had their parents fill a questionnaire concerning allergy and asthma symptoms, as well as demographic and socioeconomic data. Asthma was defined according to three distinct criteria. Results: The study results showed significant and positive associations between the exposure to species richness in schools and the forced expiratory volume at the first second (FEV1) and forced vital capacity (FVC) parameters both before and after bronchodilation, independently of the asthma and atopic status. Fully adjusted models revealed that a unitary increment in the SRI was associated with an average increase of approximately 2 and 3 mL in FEV1 and FVC, respectively. Conclusion: Species richness in school surroundings may impact lung function development in children. However, this increase in lung function was not associated with any clinically relevant protective effect on allergy and asthma development. [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]

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. [ABSTRACT FROM AUTHOR]

Background: The definitions of childhood asthma differ among epidemiological studies. We aimed to compare the diagnostic accuracy and agreement of previous asthma definitions and to evaluate questionnaire‐driven asthma definition patterns. Methods: Data on 808 participants aged 7‐12 years from 20 schools were analyzed. Asthma definitions based on symptoms assessed by questionnaire, parent‐reported medical asthma diagnosis, current use of asthma medication, airway reversibility after bronchodilatation, and increased (≥35 ppb) levels of exhaled nitric oxide (eNO) were compared with a gold standard (medical diagnosis of asthma with asthma symptoms in the past 12 months and/or airway reversibility). Concordance was assessed by Cohen's kappa. Data‐driven analysis was applied to the questionnaire, and six scores were determined "asthma," "rhinitis," "cough," "non‐specific respiratory symptoms," "treated asthma," and "uncontrolled asthma." Tree decisions were built using these scores. Results: Definitions of asthma based on respiratory symptoms, airway reversibility, and parent‐reported medical diagnosis had a low sensitivity but high specificity. Agreement between reported and objective measures was poor. Parent‐reported medical asthma diagnosis, but not reversibility or eNO, was able to predict questionnaire‐driven symptom patterns. Decision trees indicated that those with recent non‐specific respiratory symptoms had a higher probability of positive bronchodilation. Conclusion: A standardized operational definition of asthma should include a composite score based on reported asthma medical diagnosis, symptoms, and lung function. [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]

Background: Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. Methods: A total of 858 children enrolled a cross sectional survey. Spirometry and airway reversibility to beta-2 agonist, skin-prick-tests and exhaled nitric oxide measurements were performed. Pupillometry was used to evaluate autonomic nervous function. Children were classified as current swimmers (CS), past swimmers (PS) and non-swimmers (NS), according to the amount of swimming practice. Results: Current swimmers group had significantly lower maximum and average pupil constriction velocities when compared to both PS and NS groups (3.8 and 5.1 vs 3.9 and 5.3 vs 4.0 and 5.4 mm/s, p = 0.03 and p = 0.01, respectively). Moreover, affinity to the beta-2 agonist and levels of exhaled nitric oxide were significantly higher in CS when compared to NS (70 vs 60 mL and 12 vs 10 ppb, p<0.01 and p = 0.03, respectively). A non-significant trend for a higher risk of asthma, atopic eczema and allergic rhinitis was found with more years of swimming practice, particularly in atopic individuals (β = 1.12, 1.40 and 1.31, respectively). After case-case analysis, it was possible to observe that results were not influenced by the inclusion of individuals with asthma. Conclusions: Concluding, swimming pool attendance appears to be associated with autonomic changes and increased baseline airway smooth muscle constriction even in children without asthma. [ABSTRACT FROM AUTHOR]

Background Childhood exposure to microbiologic agents may influence the development of allergic and respiratory diseases. Apart from home, children spend most of their time at school, which represents an environment of significant exposure to indoor air microbes. Therefore, we aimed to assess how the prevalence of allergic sensitization and asthma in schoolchildren is affected by microbiologic exposure within classrooms. Methods Spirometry with bronchodilation, exhaled nitric oxide measurements and skin-prick tests data were retrieved from 858 children aged 8-10 years attending 71 classrooms in 20 primary schools. Air samples were collected in all classrooms using a single-stage microbiologic air impactor through agar plates. Gram-negative endotoxins were collected using flow control pumps and analysed by limulus amebocyte lysate assay. Diversity scores were established as the number of different fungal species found in each classroom. Results Classrooms with increased diversity scores showed a significantly lower prevalence of children with atopic sensitization, but not asthma. The risk of sensitization increased with increasing endotoxin exposure in classrooms. Similarly, significantly higher concentrations of Penicillium spp were found in classrooms with a higher number of children with atopic sensitization. Conclusions Although no causal relationships could be established, exposure to higher fungal diversity was protective against allergic sensitization but this was not seen for asthma. In contrast, higher exposure to Gram-negative endotoxins and Penicillium spp in primary school′s classrooms was associated with increasing odds of allergic sensitization in children. [ABSTRACT FROM AUTHOR]

Considering the time spent in enclosed spaces, indoor air pollutants are of major interest because of its possible impact on health. However, to date, few studies have analysed the air concentrations of a large set of indoor pollutants of respiratory health relevance in dwellings, particularly in Portugal. This study aimed to measure the concentrations of air pollutants that are present in residential buildings and to investigate whether some clustering pattern of indoor air pollutants exists in the dwellings of children with (case group) and without asthma (control group). Measurements were taken in 30 and 38 dwellings of asthmatic and non-asthmatic schoolchildren, respectively, located in the city of Porto, Portugal, during the cold season (October 2012-April 2013), to assess the concentrations of 12 volatile organic compounds (VOC), aldehydes, PM, PM, bacteria and fungi. Toluene, d-limonene, formaldehyde, PM, bacteria and fungi are widely present in dwellings, sometimes in relatively high concentrations in reference to WHO guideline values. Moreover, concentrations of CO exceeding 1000 ppm were often encountered, indicating that 70 % of all dwellings had poor ventilation (<4 L/s person). While exposures to common dwelling indoor pollutants are similar for schoolchildren with and without asthma, except for d-limonene levels, the identification and control of VOC and PM sources is important and prudent, especially for vulnerable individuals. [ABSTRACT FROM AUTHOR]

Allergic diseases have been on the rise in many countries over the past few decades and indoor exposure may be a possible cause. An overall investigation of children’s health status and residential indoor air pollutants known or suspected to affect respiratory health was conducted in the homes of primary schoolchildren during winter in Porto, Portugal. In a case-control study (30 case children with asthma and 38 controls) and over a 1-wk monitoring period, air sample collection was conducted in children’s bedrooms for the analysis of 12 volatile organic compounds (VOC), aldehydes, particulate matter (PM)2.5, PM10, bacteria, and fungi. Home exposures to indoor pollutants are similar for children with and without asthma, except ford-limonene. For both groups, most VOC were present at low concentrations (median < 5 µg/m3) and below the respective World Health Organization (WHO) guidelines. Concentrations of PM2.5, PM10, and bacteria were frequently higher than WHO/reference values (80, 25, and 60% of all studied dwellings, respectively). Concentrations of carbon dioxide (CO2) exceeding 1000 ppm were encountered in 60% of the homes. Although this study does not provide evidence of causative factors for asthmatic status, the postulation that poor indoor air quality in homes heightens the risk of allergic symptoms development among children is conceivable. [ABSTRACT FROM AUTHOR]