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.This study has been performed in the framework of the EXALAR 21 project, which was funded by the European Regional Development Fund (FEDER), through the Competitiveness and Internationalization Operational Program, and by national funding from the Foundation for Science and Technology (FCT) under the reference info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/GES-AMB/30193/2017/PT (POCI-01-0145-FEDER-030193, 02/SAICT/2017—Project n° 30193)

Serum biomarkers in elderly asthma

Asthma is a chronic disease of the airways that can affect all ages. It is usually undertreated in the elderly population, resulting in complications and increased severity for the patient. Different phenotypes may imply different treatments and therefore it becomes important to correctly determine which type of asthma the patient is suffering from. Biomarkers of asthma have been clinically studied in order to help discriminate among the different phenotypes of the disease, cytokines being among the most promising. Our main goal was to measure six serum cytokines, including IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNFα, in an elderly population with asthma. The population of this study included 16 elderly patients with allergic asthma, 20 elderly patients with non-allergic asthma, 9 elderly control individuals, as well as 11 young adult control individuals. The serum of the experimental subjects was quantified for the six aforementioned cytokines by flow cytometry, using the Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit (BD Biosciences). The results showed that the measured levels of TNF-α, IL-10 and IL-8 were increased in the non-allergic asthmatics group, although with no statistical significance. IL-6 was significantly increased in the elderly non-allergic asthmatic group, when compared to both control groups and when compared to the young adult controls alone, but no significant differences were found when comparing to the elderly control group separately. IL-1β median levels were shown to be elevated in the young adults control group, but also without a significant statistical difference. IL-12p70 was not detected in any subject. In conclusion, we could not define a pattern of changes in the measured cytokine levels related to phenotype differences or aging, although it is possible to notice a trend for increased levels of severity cytokines (TNF-α, IL-6 and IL-8) in non-allergic asthmatic elderly individuals, suggesting that this phenotype of asthma is indeed more severe than its counterpart. So far, this is the only study that measured the aforementioned serum inflammatory cytokines in an elderly population with asthma.A asma é uma doença crónica das vias aéreas que afeta todas as idades e é incorretamente tratada ou sub-diagnosticada na população idosa, resultando em complicações para o doente e numa diminuição da qualidade de vida. Diferentes fenótipos podem requerer diferentes tratamentos e, portanto, é necessário diagnosticar corretamente qual o tipo de asma de que o doente sofre. Apesar de grande parte do tratamento e pesquisa se concentrarem na asma alérgica, existem várias outras formas da doença que requerem atenção, tal como a asma neutrofílica ou asma não-alérgica, que afeta normalmente os doentes mais velhos. A doença pulmonar obstrutiva crónica (DPOC), também muito comum em idosos, pode prejudicar ainda mais o diagnóstico da asma, devido às semelhanças entre as duas doenças. Biomarcadores da asma estão a ser estudados clinicamente com vista a aumentar o poder discriminativo entre os diferentes fenótipos da doença, estando as citocinas dentro dos mais promissores. Assim sendo, o nosso principal objetivo foi medir seis citocinas, nomeadamente a IL-1β, IL-6, IL-8, IL-10, IL-12p70 e TNF-α, no sangue periférico de uma população de idosos asmáticos. Pretendíamos também usar a citometria de fluxo para quantificar as citocinas, de modo a podermos comparar facilmente os resultados e estabelecer padrões citocínicos. Também tínhamos como objectivo avaliar alterações nos padrões citocínicos relacionadas com a idade, usando um grupo controlo de adultos jovens. Por fim, pretendíamos investigar possíveis alterações nos padrões citocínicos relacionados com cada fenótipo da asma (alérgica ou não-alérgica). A população deste estudo foi constituída por 16 idosos com asma alérgica, 20 idosos com asma não-alérgica, 9 idosos não asmáticos para controlo, assim como 11 adultos jovens não asmáticos para controlo, recrutados através de uma base de dados. Os indivíduos foram inseridos nos respectivos grupos pelos resultados de testes cutâneos, medição da IgE total e específica, e pelas respostas dadas a um questionário. As citocinas previamente referidas foram quantificadas no soro dos indivíduos por citometria de fluxo, usando o Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit (BD Biosciences). Os resultados obtidos mostraram que o TNF-α, a IL-10 e a IL-8 se encontravam elevadas no grupo dos asmáticos não alérgicos, apesar da diferença não ser significativa. A IL-6 encontrava-se significativamente elevada no grupo dos idosos com asma não-alérgica, quando comparada com ambos os grupos de controlo e quando comparada com o grupo dos adultos jovens individualmente, embora não tenham sido encontradas diferenças significativas quando comparada com o grupo de controlo dos idosos, separadamente. Os níveis de IL-1β encontravam-se elevados no grupo dos adultos jovens, porém sem significado estatístico. A IL8 encontrava-se geralmente mais elevada nos idosos. A IL12p70 não foi detectada em nenhum indivíduo. Concluindo, medimos as citocinas previamente referidas no sangue periférico de uma população idosa, cumprindo assim o nosso objectivo principal. Porém, não foi possível definir um padrão de altercações a nível das citocinas relacionado com diferenças entre os fenótipos ou relacionadas com o envelhecimento, embora tenha sido possível notar uma tendência para um aumento das citocinas ligadas à severidade (TNF-α, IL-6 e IL-8) no grupo dos idosos com asma não-alérgica, o que nos leva a concluir que este fenótipo da asma é, de facto, mais severo, tal como sugere a bibliografia. O principal ponto forte é o facto deste ser o primeiro estudo a medir estas seis citocinas no soro de idosos com asma. Uma limitação deste estudo centra-se no facto dos voluntários terem sido classificados como asmáticos através das respostas a um questionário, não tendo, portanto, nenhuma confirmação clínica da existência da patologia. Isto pode ter levado à inclusão de voluntários nos grupos errados. Para obtenção de melhores resultados os voluntários deveriam ser recrutados após o diagnóstico efetuado por um especialista e submetidos a testes complementares, como por exemplo a espirometria, de modo a garantir a correta inserção dos indivíduos nos grupos. Outros dos marcadores referenciados neste trabalho, como a proteína catiónica dos eosinófilos (ECP) e a YKL-40, também aparentam ter algum potencial para a monitorização e diagnóstico da asma, devendo ser investigados

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.João Cavaleiro Rufo was funded by Fundação para a Ciência e Tecnologia through the Stimulus for Scientific Employment Individual Support (2020.01350.CEECIND). Mariana Farraia was funded by Fundação para a Ciência e Tecnologia through the PhD Grant Number SFRH/BD/145168/2019. This study was funded by FEDER through the Operational Program Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology, and Higher Education) under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2019)

Childhood asthma and land-use characteristics in school and residential neighborhoods: A decision tree learning approach

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 info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/GES-AMB/30193/2017/PT (POCI-01-0145-FEDER-030193, 02/SAICT/2017—Project nº 30193). This study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). G21 was funded by Programa Operacional de Saúde—Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health). Ana Isabel Ribeiro was supported by National Funds through FCT, under the program of “Stimulus of Scientific Employment—Individual Support” within the contract info:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND/02386/2018/CP1538/CT0001/PT. João Cavaleiro Rufo was supported by National Funds through FCT, under the program of “Stimulus of Scientific Employment—Individual Support” within the contract 2020.01350.CEECIND

Cost-effectiveness analysis of grass pollen specific immunotherapy in children with allergic rhinitis compared to the standard of care symptomatic treatment in Portugal

Background. Cost-effectiveness studies evaluating allergen immunothera-py (AIT) in children are scarce. We aim to compare the cost-effectiveness of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) against stan-dard-of-care (SOC) treatment in children with grass pollen allergic rhinitis. Methods. We created a Markov model to compare the three strategies over a 10-year horizon. SOC was the reference to calculate the incremental cost-ef-fectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis were used to assess models’ uncertainty. Results. We obtained an ICER of 12,605€ and 6,318€ for SLIT and SCIT, respectively. In sensitivity analysis, SCIT was more cost-effective than SLIT. Conclusions. AIT is cost-effective in children with grass pollen allergic rhinitis, especially for the subcutaneous route. © 2023 Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri-AAIITO. Published by EDRA SpA. All rights reserved.MF is funded by Fundação para a Ciência e Tecnologia (FCT) through the PhD Grant number SFRH/BD/145168/2019, cofinanced by Programa Operacional Regional do Norte (NORTE2020) through Fundo Social Europeu (FSE). JCR is funded by Fundação para a Ciência e Tecnologia through the Stimulus for Scientific Employment Individual Support (2020.01350.CEECIND)

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. © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.Funding text 1: Mariana Farraia is funded by Fundação para a Ciência e Tecnologia through the PhD Grant number SFRH/BD/145168/2019. João Cavaleiro Rufo is funded by Fundação para a Ciência e Tecnologia through the Stimulus for Scientific Employment Individual Support (2020.01350.CEECIND).; Funding text 2: Mariana Farraia is funded by Fundação para a Ciência e Tecnologia through the PhD Grant number SFRH/BD/145168/2019. João Cavaleiro Rufo is funded by Fundação para a Ciência e Tecnologia through the Stimulus for Scientific Employment Individual Support (2020.01350.CEECIND)

Metabolic interactions in asthma

Metabolomics can be used to explore altered metabolic pathways in asthma, giving insights into its pathophysiology. We aimed to review how metabolomics has been used to understand asthma by describing metabolic pathways under research and discussing clinical implications. The search was performed in PubMed, and studies published since 2000 using a metabolomics approach, were included. A total of 32 studies were analysed. Pathways related with cellular energy homeostasis, lipid metabolism and oxidative stress, immune and inflammatory processes and others were altered. Initial studies focused on biomarker discovery. But, metabolomics can be used to evaluate drug effects on specific pathways, to highlight pathways that can further develop in new targeted treatments and to identify differences according to asthma severity and phenotypes.The authors acknowledge funding support by FCT - Fundação para Ciência e Tecnologia, for the project ExPOSE - Establishing protocols to assess occupational exposure to microbiota in clinical settings (02/SAICT/2016, Project no. 23222)

Association between the density and type of trees around urban schools and exhaled nitric oxide levels in school children

Greenspaces in school's neighbourhood represent an important environment to promote healthy development. The aim of this study was to assess the association between the density and type of trees around schools and exhaled Nitric Oxide (NO) levels in schoolchildren. Data on 845 children from 20 primary schools in Porto was analysed. Airway inflammation was assessed by measuring exhaled NO level. The density and type of trees were quantified within a 500 m buffer around schools. Associations were estimated using mixed-effect models. A significant association was observed between non-tree covered areas around schools and exhaled NO levels in schoolchildren (β = - 1.42, 95% CI - 2.84, - 0.001). Our results suggested that the presence of trees in school neighbourhoods may play a role in the biological mechanisms underlying the complex links between environment and airway inflammation.Authors gratefully acknowledge the funding by EXALAR 21 project financed 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 info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/GES-AMB/30193/2017/PT (POCI-01-0145-FEDER-030193, 02/SAICT/2017 - Project nº 30193). This study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2019)

Indoor air quality and atopic sensitization in primary schools: A follow-up study

Background: The onset and exacerbation of allergic diseases and asthma have been associated with poorindoor air quality (IAQ) inside classrooms.Objective: The aim was to investigate how IAQ changed in primary schools after applying indoor air qualityrecommendations, and to explore how these changes influenced allergic sensitization on children.Methods: Total volatile organic compounds, PM2.5, PM10, CO2, CO, temperature and relative humidity inthe indoor and outdoor air of 20 primary schools were measured in 2010–2012. The school staff receivedinstructions on how to improve IAQ in accordance with the SINPHONIE guidelines. Atopy status wasassessed 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 PM2.5and PM10concentrations were approximately 40% lower in the follow-up mea-surements (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 byPortuguese legislation. Moreover, there were no significant differences in atopic prevalence and FENOvalues between the campaigns.Conclusion: These findings suggest that adoption of the recommendations based on the SINPHONIE guide-lines was particularly successful in reducing PM2.5and PM10in primary schools of Porto. Nevertheless,the schools failed to reduce the levels of other IAQ pollutants, as well as the prevalence of atopic disease.This work was financed by the HEBE project (NORTE-01-0145-FEDER-000010), and by Fundação para a Ciência e Tecnologia through the ARIA project (PTDC/DTP-SAP/1522/2012, FCOMP-01-0124-FEDER-028709) and through the scholarships SFRH/BD/108605/2015, SFRH/BD/112269/2015 and SFRH/BPD/105100/2014.info:eu-repo/semantics/publishedVersio