The Influence of Obesity in the Autonomic Nervous System Activity in School-Aged Children in Northern Portugal: A Cross-Sectional Study.

INTRODUCTION: Obesity is one of the most prevalent chronic diseases in childhood, being an important public health issue. Excessive weight has been associated with autonomic dysfunction but the evidence in children is scarce. Therefore, the aim of this study was to assess the effect of overweight and obesity on the autonomic nervous system activity, in children. MATERIAL AND METHODS: Data from a cross-sectional study of 1602 children, aged 7 to 12 years, was used and 858 children were included in the analysis. Body mass index was calculated and classified according to criteria of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF). Body composition was characterized by bioelectrical impedance. Linear regression models were used to determine the association between body mass index, body composition and the autonomic nervous system activity, assessed by pupillometry. RESULTS: Average dilation velocity was higher among children with obesity, according to the CDC and percentage of body fat criteria (ß = 0.053, 95% CI = 0.005 to 0.101 and ß = 0.063, 95% CI = 0.016 to 0.109, respectively). The same trend was observed for WHO and IOTF criteria (ß = 0.045, 95% CI = -0.001 to 0.091, and ß = 0.055, 95% CI = -0.001 to 0.111, respectively). CDC and WHO body mass index z-scores were also positively associated with the values of average dilation velocity (rs = 0.030, p = 0.048; and rs = 0.027, p = 0.042, respectively). CONCLUSION: Our findings suggest an association between body mass and changes in the autonomic activity, Moreover, this study provides proof of concept for interventions targeting the prevention/treatment of obesity in children that may offer some benefit in re-establishing the balance of the autonomic nervous system, and subsequently preventing the consequences associated with the autonomic nervous system dysfunction.

Diet Quality and Exhaled Breath Condensate Markers in a Sample of School-Aged Children.

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.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Green and blue spaces and lung function in the Generation XXI cohort: a life-course approach.

BACKGROUND: Exposure to natural environments may affect respiratory health. This study examined the association of exposure to green and blue spaces with lung function in children, and assessed the mediation effect of air pollution and physical activity. METHODS: The study used data from the Generation XXI, a population-based birth cohort from the Porto Metropolitan Area (Portugal). Residential Normalised Difference Vegetation Index (NDVI) at different buffers (100, 250 and 500 m), the accessibility to urban green spaces (UGS) within 400 and 800 m and the minimum distance to the nearest UGS and to the nearest blue spaces were assessed at birth, 4, 7 and 10 years of age. Three life-course measures were calculated: averaged exposure, early-life exposure (birth) and exposure trend over time (change in exposure). Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and forced expiratory flow between 25% and 75% of FVC (FEF25-75%) at 10 years were used as outcomes. To assess associations, linear regression models and path analysis were used. RESULTS: This study included 3278 children. The adjusted models showed that increasing the NDVI exposure over time within 100 m of the child's residence was associated with higher values of FEV1 (L) and FEF25-75% (L·s-1) (ß 0.01, 95% CI 0.0002-0.03 and ß 0.02, 95% CI 0.001-0.05, respectively). No significant associations were observed for the remaining measures of exposure, and no mediation effect was found for pollution or physical activity. CONCLUSION: Increasing exposure to greenness at close proximity from residences was associated with improved lung function. While the mechanism remains unknown, this study brings evidence that city greening may improve children's respiratory health.

Environmental inequality: Air pollution and asthma in children.

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.

Cost-effectiveness analysis of house dust mite allergen immunotherapy in children with allergic asthma.

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.

Allergen immunotherapy for asthma prevention: A systematic review and meta-analysis of randomized and non-randomized controlled studies.

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.

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 Land Use Mix and Respiratory Symptoms and Asthma in Children from the Generation XXI Birth Cohort.

Land use mix (LUM) in the neighbourhoods has been associated with healthier lifestyles. However, less is known about the association between LUM and health outcomes, namely during childhood. The objective of this study was to evaluate the association between different LUM indexes for Porto Metropolitan Area and asthma and respiratory symptoms in children. A cross-sectional analysis was performed involving 6260 children enrolled in Generation XXI. Land use around the child's residence was assessed with the Portuguese official map of land cover using a GIS. Generalized linear mixed-effects models were fitted to estimate the association between LUM and respiratory symptoms and asthma at 7 years of age. Adjusted associations were quantified using odds ratio (OR) and 95% confidence interval (95% CI). After adjustment, LUM was associated with a lower odds of wheezing in the last 12 months [OR (95% CI) = 0.37 (0.15; 0.93) using Shannon's Evenness Index within 500 m; and OR = 0.93 (0.89; 0.98) using the number of different land use types within 250 m]. Living in neighbourhoods with high LUM has a protective effect on current wheezing symptoms. Our results highlight the association between LUM and respiratory symptoms among children, suggesting that public health considerations should be incorporated in land use decision-making.

Diagnosis of pathological conditions through electronic nose analysis of urine samples: a systematic review and meta-analysis.

Currently available urinalysis methods are often applied for screening and monitoring of several pathologies. However, traditionally analyzed biomarkers in urinalysis still lack sensitivity and specificity to accurately diagnose some diseases. Several studies have proposed the use of electronic noses (eNoses) for the analysis of volatile organic compounds in urine samples that may, directly or indirectly, correlate with certain pathologies. Hence, the aim of this study was to perform a systematic review and meta-analysis of studies concerning the use of portable electronic noses for diagnosis or monitoring of pathologies through analysis of urine samples. A systematic review of the literature was held according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-four articles met the inclusion criteria and were included in the analysis. The results of the revised studies showed that there are various volatile organic compound profiles, identified through eNose analysis, that may be applied for diagnosis or monitoring of several diseases, such as diabetes, urinary tract infection, inflammatory bowel disease, and kidney disease. A meta-analysis was conducted taking into consideration the data of 10 of the initial 24 articles. The pooled sensitivity, specificity, and diagnostic odds ratio were 84% (95% CI, 0.72-0.92), 85% (95% CI, 0.75-0.91), and 24.17 (95% CI: 7.85-74.41), respectively. The area under the receiver operating characteristic curve was 0.897. These results suggest that eNose technology has adequate diagnostic accuracy for several pathologies and could be a promising screening tool for clinical settings. However, more studies are needed to reduce heterogeneity between results.

Exhaled breath condensate pH determinants in school-aged children: A population-based study.

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 [ß = -0.09 (-0.15, -0.02)] and PM 2.5 concentration [ß = -0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [ß = 0.07 (0.02, 0.13)] and concentration of endotoxins [ß = -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.

The Influence of Eating at Home on Dietary Diversity and Airway Inflammation in Portuguese School-Aged Children.

Considering the negative impact of a lack of dietary diversity on children's nutritional status, we aimed to describe dietary variety according to eating at home frequency and assessed its association with respiratory outcomes in school-aged children. This cross-sectional study included 590 children (49% girls) aged 7 to 12 years from 20 public schools located in city of Porto, Portugal. Daily frequency of eating at home groups were calculated and dietary diversity was calculated using a 10-food group score from a 24 h recall questionnaire. Spirometry and exhaled nitric oxide levels (eNO; <35 and ≥35 ppb) were assessed. The comparison of diet diversity according to the groups was performed by ANOVA and ANCOVA. The association between dietary diversity and respiratory outcomes was examined using regression models. In multivariate analysis, children in the highest group of eating at home episodes (≥4 occasions) obtained the lowest dietary diversity mean score, while the lowest group (<2) had the highest mean score (p-value 0.026). After adjustment for confounders, higher diet diversity (≥5 food groups) significantly decreased the odds of having an eNO ≥35. Diet diversity might decrease the chance of airway inflammation among children. However, having more eating episodes at home could be a barrier to a more diverse diet.

The association between fungi exposure and hypersensitivity pneumonitis: a systematic review.

A systematic review of published studies focused on the association between hypersensitivity pneumonitis (HP) and fungi exposure was conducted on PubMed, following PRISMA guidelines for systematic reviews. A total of 14 studies met the inclusion criteria but only 6 of these studies were eligible, as the remaining 8 represented case reports that were separately included for further discussion. HP is an interstitial lung disease (ILD) characterized by a hypersensitization response to inhalable antigens and represents 1.5% to 12% of all ILD in the European population. Several fungi species that populate the indoor environment have been associated with the incidence of HP upon cumulative exposure, with Penicillium spp and Aspergillus spp being the fungi species most frequently associated with the onset of disease. Although some studies have shown that avoiding exposure to causative HP fungi tends to improve patients' symptoms, other studies were unable to identify the source of sensitization. More microbial exposure studies are needed to properly estimate the risk of HP development in the built environment.

Neighbourhood green and blue spaces and allergic sensitization in children: A longitudinal study based on repeated measures from the Generation XXI cohort.

Evidence on the effect of natural environments on atopy in children is limited and inconsistent, disregarding the time-varying and cumulative exposures throughout the life course. To assess critical periods of exposure as well as the effect of longitudinal trajectories of exposure to green and blue spaces on the development of allergic sensitization in children at the age of 10 years. A longitudinal study was conducted involving 730 children enrolled in Generation XXI, a population-based birth cohort from the Porto Metropolitan Area (Portugal). Food and aeroallergens sensitization were evaluated at 10 years of age using Phadiatop Infant, Phadiatop fx1 and fx22 ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden). Residential Normalized Difference Vegetation Index (NDVI) and distance to the nearest blue space (sea, river) were assessed using a Geographic Information System. Latent class linear mixed models were fitted to determine longitudinal trajectories of exposure. Associations were estimated using Cox proportional hazards regression models and expressed using hazard ratios (HR) and 95% confidence intervals (95% CI). Residing in neighbourhoods surrounded by more vegetation at 10 years, as well as lifetime exposure to a trajectory of higher levels of NDVI, were associated with a lower risk of allergic sensitization [HR (95% CI) = 0.095 (0.011, 0.823) and HR (95% CI) = 0.539 (0.301, 0.965), respectively]. Our findings support a role for both longitudinal, but particularly late-childhood, exposure to green spaces, in the prevention of allergic sensitization in children.

Higher diversity of vegetable consumption is associated with less airway inflammation and prevalence of asthma in school-aged children.

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.

Effects of Exercise on the Skin Epithelial Barrier of Young Elite Athletes-Swimming Comparatively to Non-Water Sports Training Session.

The benefits of swimming have been extensively assessed. However, swimming pools contain chlorine and other irritating chemicals that may induce contact dermatitis. To evaluate the effect of a swimming training session on transepidermal water loss (TWEL) in swimmers compared to football players, elite swimmers and football players were invited to participate (58 athletes) in the study, where TEWL was measured before, immediately after, and 30 min after a 2 h training session. The probe was held on the dorsum of the hand, volar forearm, and on the antecubital flexure for 1 min. The volar forearm, antecubital flexure, and hand dorsum showed a significant increase in TEWL in swimmers in both measurements after training compared to baseline (p < 0.001). In football players, an increase in TEWL was observed on the hands' dorsum between baseline and after training measurements. The variations on TEWL levels before and immediately after the training session were higher among swimmers on the volar forearm (p = 0.002) and antecubital flexure (p = 0.019). Our findings support the effect of the training environment-swimming pool versus outdoor sports-on the skin barrier function, with an increase of transepidermal water loss immediately after exercise. Exposure to a swimming pool environment in a 2 h training session may lead to changes in skin barrier function.

The neighbourhood natural environment is associated with asthma in children: A birth cohort study.

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.