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.

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.

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.

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.

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.

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.

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.

A cross-sectional study of the impact of school neighbourhood on children obesity and body composition.

Schools' neighbourhoods provide an important environmental context that may influence the risk of obesity among children. The aim of this study was to assess the effect of neighbourhood surrounding schools on obesity and body composition in schoolchildren. Data on 845 children aged 7 to 12 years old from 20 primary schools were considered. Anthropometric measurements and bioelectrical impedance analysis were performed to assess body mass index (BMI) and characterize body composition. Land use characteristics were quantified within a 500-m buffer zone around schools. Mixed-effect models measured the effects of school neighbourhood on obesity and body composition. The results showed a tendency between green urban areas around schools and lower values of BMI and better body composition parameters compared with built areas, being BMI z-scores CDC, and body fat percentage significantly higher in-built than in green urban areas (ß = 0.48, 95% CI 0.05; 0.90, and ß = 2.56, 95% CI 0.39; 4.73, respectively).Conclusion: Our findings suggest that the school neighbourhood has an effect on BMI and body fat percentage in schoolchildren. These results may contribute to the creation of healthier cities and help reduce health expenses by focusing on prevention programmes towards the expansion of green spaces. What is Known: • Living in greener areas has been associated with healthy weight outcomes and to the lower impact of obesogenic urban environments. • The school environment may be especially important for youth health outcomes. What is New: • Neighbourhoods around schools may affect child health, specifically the development of obesity. • The presence of urban green areas around school may promote a framework of lifestyle or behaviours conducive to achieving a healthy weight.

Human volatilome analysis using eNose to assess uncontrolled asthma in a clinical setting.

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.

The influence of species richness in primary school surroundings on children lung function and allergic disease development.

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.

The inflammatory potential of diet impacts the association between air pollution and childhood asthma.

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.

Exposure to indoor endocrine-disrupting chemicals and childhood asthma and obesity.

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.

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.

Indoor fungal diversity in primary schools may differently influence allergic sensitization and asthma in children.

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.

Indoor air risk factors for schoolchildren's health in Portuguese homes: Results from a case-control survey.

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 for d-limonene. For both groups, most VOC were present at low concentrations (median < 5 µg/m(3)) 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.