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Objective: To quantify the impact of different air pollutants on respiratory health based on robust estimates based on international data and to summarise the evidence of associations between indoor exposure to those pollutants and respiratory morbidity in the Portuguese population., Results: Several systematic reviews and meta-analyses (MA) at the world level demonstrate the impact of indoor air quality on respiratory health, with indoor particulate matter and gasses exerting a significant effect on the airways. Volatile organic compounds (VOC) have been related to asthma and lung cancer. However, only meta-analyses on biomass use allowed documentation of long-term respiratory effects. While early publications concerning Portuguese-based populations mainly focused on indoor exposure to environmental tobacco smoke, later studies relocated the attention to relevant exposure environments, such as day care buildings, schools, residences and nursing homes. Looking at the pooled effects from the reviewed studies, high levels of carbon dioxide and particulate matter in Portuguese buildings were significantly associated with asthma and wheezing, with VOC and fungi showing a similar effect in some instances., Conclusions: Despite the significant reduction of indoor air pollution effects after the 2008 indoor smoking prohibition in public buildings, studies show that several indoor air parameters are still significantly associated with respiratory health in Portugal. The country shares the worldwide necessity of standardisation of methods and contextual data to increase the reach of epidemiological studies on household air pollution, allowing a weighted evaluation of interventions and policies focused on reducing the associated respiratory morbidity., Competing Interests: Conflicts of interest None., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD., Methods: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics., Results: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82., Conclusions: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

An adequate sodium intake is related to various health benefits. Parallelly, the Mediterranean diet (MD) is a dietary pattern known for its many positive impacts on health. Nonetheless, the association between adherence to the MD and sodium urinary excretion is scarce, even more in children. This study aimed to assess the association between MD adherence and the excretion of sodium, as a proxy of intake. This cross-sectional analysis comprised 295 children (46.8% females, aged 7-11 years, mean age: 8.53 ± 0.73 years) from 20 schools within Porto, Portugal. MD adherence was evaluated utilizing the alternate Mediterranean score (aMED). Higher scores denote a healthier dietary pattern (0-8). Sodium excretion was estimated by 24-h urine collection. The association between adherence to MD and Na excretion was estimated by logistic regression, adjusting for confounders. Children in the higher sodium excretion group had a higher intake of legumes, a higher body mass index and parents with lower education levels compared to children in the lower sodium excretion group. In logistic regression analysis, sodium urinary excretion was not associated with higher MD adherence, even after adjustment for confounders. High MD adherence could not be associated with lower sodium excretion in children.

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.

Background: Asthma is a highly prevalent disease, one of the chronic diseases with the highest economic costs; thus, it imposes a high economic burden on society, the healthcare system, patients, and third-party payers. Contrary to this study, until now, systematic reviews of economic evaluations (EEs) of treatments for severe asthma have not been exclusively focused on biological treatments, and have included a small number of studies and only model-based EEs., Methods: This study systematically reviews EEs of biological therapies for severe asthma published until December 2022 using PRISMA guidelines. The review analyzes the cost-effectiveness of biologicals in comparison to SOC, or SOC plus OCS. The quality of the EEs is assessed using Consensus on Health Economics Checklist extended (CHEC-extended)., Results: Thirty-nine studies were eligible: 15 based on a Markov model, and 19 trial-based; eight adopting societal and NHS perspectives, and seven the payer's perspective. The reviewed EEs addressed cost-effectiveness, cost-utility, and incremental costs and outcomes comparison. Their findings were mainly expressed through ICER-incremental cost-effectiveness ratio (24 studies: 13 concluded that biological were cost-effective) and cost comparison analysis (14 studies: 6 concluded that biological were cost-effective), and were sensitive to a wide variety of factors (e.g. medication cost, treatment response, time horizon, utility benefits, mortality, exacerbation rate, discount rate, etc.)., Conclusions: There has been some ambiguity concerning the EE of biological therapies due to variation in choice of study design and contradictory results. Nevertheless, it can be concluded that biological treatments improve health outcomes, in many contexts at a high cost.

Background: The characteristics of allergic sensitization profiles can differ between populations and geographic regions, contributing differently to the association with allergic diseases. Consequently, the sensitization trajectories found in previous studies conducted in Northern Europe may not apply in Southern European countries., Objective: To identify trajectories of allergic sensitization profiles during childhood and evaluate the association with allergic outcomes, using data from a Portuguese birth cohort., Methods: A random sample from Generation XXI was screened for allergic sensitization at 10 years of age. Among 452 allergic sensitized children, 186 were tested with ImmunoCAP ™ ISAC multiplex array that detects 112 molecular components, at three follow-ups (4, 7, and 10 years old). Information on allergic outcomes (asthma, rhinitis, atopic dermatitis) was obtained at the 13-year-old follow-up. Latent class analysis (LCA) was used to identify clusters of participants with similar sensitization profiles. Then, sensitization trajectories were defined based on the most prevalent transitions between clusters over time. Logistic regression was applied to estimate the association between sensitization trajectories and allergic diseases., Results: Five trajectories were proposed: "no/few sensitizations," "early persistent house dust mites (HDM)," "early HDM and persistent/late grass pollen," "late grass pollen," and "late HDM." The "early HDM and persistent/late grass pollen" trajectory was associated with rhinitis and "early persistent HDM" with asthma and rhinitis., Conclusion: Distinct sensitization trajectories pose different risks in the development of allergic diseases. These trajectories present some differences from those in Northern European countries and are important for planning adequate prevention health plans., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Evidence about the impact of vegetable and fruit diversity consumption on the autonomic nervous system (ANS) functioning is scarce. In this cross-sectional study (513 participants, 49.9% girls aged 7 to 12 years), we evaluated the association between vegetable and fruit diversity consumption and the ANS in school-aged children. Dietary intake was collected using a single 24-h recall questionnaire. Fruit and vegetable diversity consumption was estimated by summing up all the different individual vegetables and fruits consumed in one day. Pupillometry was used to assess pupillary light response, which evaluated the ANS activity. Adjusted linear regressions estimated the association between vegetable and fruit diversity consumption with pupillary light response measures. There was a positive and significant association between vegetable diversity consumption and the average dilation velocity, a measure related to the sympathetic nervous system activity (β-coefficient = 0.03, 95%CI: 0.002; 0.07). Our findings show that vegetable diversity consumption is associated with the ANS response, a possible early link between diet and health in school-aged children.

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.

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., Competing Interests: The authors have declared that no competing interests exist.

Differing body mass classifications challenge the strength of the epidemiological evidence suggesting asthma and obesity are linked. The relationship between asthma and overweight in children depends on the body mass definitions adopted. http://bit.ly/2lSxhC5., Competing Interests: Conflict of interest: F. de Castro Mendes has nothing to disclose. Conflict of interest: I. Paciência has nothing to disclose. Conflict of interest: J. Cavaleiro Rufo has nothing to disclose. Conflict of interest: D. Silva has nothing to disclose. Conflict of interest: P. Cunha has nothing to disclose. Conflict of interest: M. Farraia has nothing to disclose. Conflict of interest: L. Delgado has nothing to disclose. Conflict of interest: P. Moreira has nothing to disclose. Conflict of interest: A. Moreira has nothing to disclose., (Copyright ©ERS 2019.)

Children are in contact with local environments, which may affect respiratory symptoms and allergic sensitization. We aimed to assess the effect of the environment and the walkability surrounding schools on lung function, airway inflammation and autonomic nervous system activity. Data on 701 children from 20 primary schools were analysed. Lung function, airway inflammation and pH from exhaled breath condensate were measured. Pupillometry was performed to evaluate autonomic activity. Land use composition and walkability index were quantified within a 500 m buffer zone around schools. The proportion of effects explained by the school environment was measured by mixed-effect models. We found that green school areas tended to be associated with higher lung volumes (FVC, FEV1 and FEF25-75%) compared with built areas. FVC was significantly lower in-built than in green areas. After adjustment, the school environment explained 23%, 34% and 99.9% of the school effect on FVC, FEV1, and FEF25-75%, respectively. The walkability of school neighbourhoods was negatively associated with both pupil constriction amplitude and redilatation time, explaining -16% to 18% of parasympathetic and 8% to 29% of sympathetic activity. Our findings suggest that the environment surrounding schools has an effect on the lung function of its students. This effect may be partially mediated by the autonomic nervous system.

Highlights: The SINPHONIE guidelines were successful in reducing PM 2.5 and PM 10 in schools.The schools failed to reduce the levels of other IAQ pollutants.No significant changes were observed in the prevalence of atopy., Background: The onset and exacerbation of allergic diseases and asthma have been associated with poor indoor air quality (IAQ) inside classrooms., Objective: The aim was to investigate how IAQ changed in primary schools after applying indoor air quality recommendations, and to explore how these changes influenced allergic sensitization on children., Methods: Total volatile organic compounds, PM 2.5 , PM 10 , CO 2 , CO, temperature and relative humidity in the indoor and outdoor air of 20 primary schools were measured in 2010-2012. The school staff received instructions on how to improve IAQ in accordance with the dedicated guidelines. Atopy status was assessed in children attending the participating classrooms by skin prick tests and exhaled nitric oxide. A follow-up sampling campaign was performed in 2014-2015 in the same schools., Results: Indoor PM 2.5 and PM 10 concentrations were approximately 40% lower in the follow-up measurements ( p < 0.05). There were no significant differences regarding outdoor PM concentrations. Nevertheless, PM levels from the follow-up campaign still exceeded the reference value established by Portuguese legislation. Moreover, there were no significant differences in atopic prevalence and FENO values between the campaigns., Conclusion: These findings suggest that adoption of the recommendations based on the SINPHONIE guidelines was particularly successful in reducing PM 2.5 and PM 10 in primary schools of Porto. Nevertheless, the schools failed to reduce the levels of other IAQ pollutants, as well as the prevalence of atopic disease., Competing Interests: The authors declare no conflicts of interest., (Copyright 2016 PBJ-Associação Porto Biomedical/Porto Biomedical Society.)

We aimed to assess the value and classification rate of exhaled volatile organic compounds (VOCs) in asthma diagnosis. A PRISMA-oriented systematic search for published studies regarding exhaled VOCs in asthma diagnosis was conducted based on predefined criteria. Studies presenting sensitivity and specificity values for the test were included in the meta-analysis. Pooled diagnosis odds ratios (DOR), area under the curve (AUC) and positive and negative likelihood ratios (LR) for exhaled VOC profiles were calculated; and publication bias, threshold effect and heterogeneity were estimated. Eighteen studies were selected for the qualitative analysis and six met the criteria for inclusion in the quantitative analysis. Mean (95% CI) pooled DOR, positive and negative LR were 49.3 (15.9-153.3), 5.86 (3.07-11.21) and 0.16 (0.10-0.26), respectively. The AUC value was 0.94. Only three of the 18 reviewed studies performed an external validation of the model using a different data set. The results from the revised studies suggest that exhaled VOCs are promising biomarkers for asthma diagnosis and that several compounds, mainly alkanes, may be significantly associated with asthma inflammation. However, there are still various constraints associated with standardization and externally validated studies are needed to introduce exhaled VOC profiling in a clinical scenario., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction and Objectives: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP., Material and Methods: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls., Results: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P <0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP., Conclusion: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

Children spend a large part of their time at schools, which might be reflected as chronic exposure. Ultrafine particles (UFP) are generally associated with a more severe toxicity compared to fine and coarse particles, due to their ability to penetrate cell membranes. In addition, children tend to be more susceptible to UFP-mediated toxicity compared to adults, due to various factors including undeveloped immune and respiratory systems and inhalation rates. Thus, the purpose of this study was to determine indoor UFP number concentrations in Portuguese primary schools. Ultrafine particles were sampled between January and March 2014 in 10 public primary schools (35 classrooms) located in Porto, Portugal. Overall, the average indoor UFP number concentrations were not significantly different from outdoor concentrations (8.69 × 10(3) vs. 9.25 × 10(3) pt/cm(3), respectively; considering 6.5 h of indoor occupancy). Classrooms with distinct characteristics showed different trends of indoor UFP concentrations. The levels of carbon dioxide were negatively correlated with indoor UFP concentrations. Occupational density was significantly and positively correlated with UFP concentrations. Although the obtained results need to be interpreted with caution since there are no guidelines for UFP levels, special attention needs to be given to source control strategies in order to reduce major particle emissions and ensure good indoor air quality.