[Recommendations for Reducing the Environmental Impact of Inhalers in Portugal: Consensus Document]. / Recomendações para a Redução do Impacto Ambiental dos Inaladores em Portugal: Documento de Consenso.

This consensus document addresses the reduction of the environmental impact of inhalers in Portugal. It was prepared by the Portuguese Council for Health and the Environment and the societies representing the specialties that account for these drugs' largest volume of prescriptions, namely the Portuguese Society of Pulmonology, the Portuguese Society of Allergology and Clinical Immunology, the Portuguese Society of Pediatrics, the Portuguese Society of Internal Medicine, the Portuguese Association of General and Family Medicine and also a patient association, the Respira Association. The document acknowledges the significant impact of pressurized metered-dose inhalers on greenhouse gas emissions and highlights the need to transition to more sustainable alternatives. The carbon footprint of pressurized metered-dose inhalers and dry powder inhalers in Portugal was calculated, and the level of awareness among prescribing physicians on this topic was also estimated. Finally, recommendations were developed to accelerate the reduction of the ecological footprint of inhalers.

Este documento de consenso aborda a redução do impacto ambiental dos inaladores em Portugal. Foi elaborado pelo Conselho Português para a Saúde e Ambiente e pelas sociedades que representam as especialidades com maior volume de prescrição destes medicamentos, nomeadamente a Sociedade Portuguesa de Pneumologia, a Sociedade Portuguesa de Alergologia e Imunologia Clínica, a Sociedade Portuguesa de Pediatria, a Sociedade Portuguesa de Medicina Interna e a Associação Portuguesa de Medicina Geral e Familiar em conjunto com uma associação de doentes, a Associação Respira. Reconhece-se o impacto significativo dos inaladores pressurizados doseáveis nas emissões de gases com efeito de estufa e a necessidade de transição para alternativas mais sustentáveis. Calculou-se a pegada de carbono dos inaladores pressurizados doseáveis e dos inaladores de pó seco em Portugal e estimou-se o nível de literacia dos médicos prescritores relativamente a este tema. Finalmente, foram elaboradas recomendações com o objetivo de acelerar a redução da pegada ecológica dos inaladores.

From the grapevine to the glass: A wine metabolomics tale by FT-ICR-MS.

Wine is one of the most consumed beverages around the world. Its unique characteristics arise from numerous processes, from the selection of grapevine varieties and grapes, the effect of the terroir and geographical origin, through the biochemical process of fermentation by microorganisms, until its aging. All molecules found in wine define its chemical fingerprint and can be used to tell the story of its origin, production, authenticity and quality. Wine's chemical composition can be characterized using an untargeted metabolomics approach based on extreme resolution mass spectrometry. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is currently the most powerful analytical technique to analyse such complex sample, providing the most comprehensive analysis of the chemical fingerprint of wine.

Regional, sex, and age inequities in asthma hospital admissions in Spain and Portugal.

BACKGROUND: Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma-related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. METHODS: We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female-to-male ratio in asthma hospital admissions per age group, considering the female-to-male ratio in the overall population. RESULTS: Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher-than-average rate of asthma-related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged <65 years were 2.3 times more likely than in men of the same age, hospitalisations in women aged ≥65 years were 3.5 times higher than in men aged ≥65 years. CONCLUSION: This study suggests that marked regional inequities in asthma hospital admissions exist in Spain and Portugal. Additionally, women are particularly at risk of hospitalisation due to asthma, and such risk increases with age.

Impact of Different Treatment Regimens and Timeframes in the Plasmatic Metabolic Profiling of Patients with Lung Adenocarcinoma.

In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) has suffered a variety of alterations. Chemotherapy (CTX), immunotherapy (IT) and tyrosine kinase inhibitors (TKI) have shown remarkable results. However, not all patients with NSCLC respond to these drug treatments or receive durable benefits. In this framework, metabolomics has been applied to improve the diagnosis, treatment, and prognosis of lung cancer and particularly lung adenocarcinoma (AdC). In our study, metabolomics was used to analyze plasma samples from 18 patients with AdC treated with CTX or IT via 1H-NMR spectroscopy. Relevant clinical information was gathered, and several biochemical parameters were also evaluated throughout the treatments. During the follow-up of patients undergoing CTX or IT, imaging control is recommended in order to assess the effectiveness of the therapy. This evaluation is usually performed every three treatments. Based on this procedure, all the samples were collected before the beginning of the treatment and after three and six treatments. The identified and quantified metabolites in the analyzed plasma samples were the following: isoleucine, valine, alanine, acetate, lactate, glucose, tyrosine, and formate. Multivariate/univariate statistical analyses were performed. Our data are in accordance with previous published results, suggesting that the plasma glucose levels of patients under CTX become higher throughout the course of treatment, which we hypothesize could be related to the tumor response to the therapy. It was also found that alanine levels become lower during treatment with CTX regimens, a fact that could be associated with frailty. NMR spectra of long responders' profiles also showed similar results. Based on the results of the study, metabolomics can represent a potential option for future studies, in order to facilitate patient selection and the monitoring of therapy efficacy in treated patients with AdC. Further studies are needed to improve the prospective identification of predictive markers, particularly glucose and alanine levels, as well as confer guidance to NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Cultivation of Melilotus officinalis as a source of bioactive compounds in association with soil recovery practices.

Introduction: Melilotus officinalis is a Leguminosae with relevant applications in medicine and soil recovery. This study reports the application of Melilotus officinalis plants in soil recovery and as a source of bioactive compounds. Methods: Plants were cultivated in semiarid soil under four different fertilizer treatments, urban waste compost at 10 t/ha and 20 t/ha, inorganic fertilizer and a control (no fertilizer). Agronomic properties of soil (pH, EC, soil respiration, C content, macro- and microelements) were analyzed before and after treatment. Also, germination, biomass, element contents, and physiological response were evaluated. Metabolite composition of plants was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Results and discussion: Results showed a significant enhancement of the soil microbial activity in planted soils amended with compost, though there were no other clear effects on the soil physicochemical and chemical characteristics during the short experimental period. An improvement in M. officinalis germination and growth was observed in soils with compost amendment. Metabolite composition of plants was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Principal Component and Agglomerative Hierarchical Clustering models suggest that there is a clear separation of the metabolome of four groups of plants grown under different soil treatments. The five most important discriminative metabolites (annotated) were oleamide, palmitic acid, stearic acid, 3-hydroxy-cis-5-octenoylcarnitine, and 6-hydroxynon-7- enoylcarnitine. This study provides information on how the metabolome of Melilotus might be altered by fertilizer application in poor soil regions. These metabolome changes might have repercussions for the application of this plant in medicine and pharmacology. The results support the profitability of Melilotus officinalis cultivation for bioactive compounds production in association with soil recovery practices.

Lung Cancer Screening: Low-Dose Thoracic Computed Tomography Performed in a High-Risk Portuguese Population.

INTRODUCTION: The Urgeiriça mines were once the main uranium producer in Portugal. The aim of this study was to estimate the benefit of low-dose chest computed tomography (LDCT) for lung cancer screening in former miners that were considered as being at high-risk. METHODS: A subgroup of former miners of the Uranium National Company exposed to uranium and with a smoking load greater than 20 pack-years, agreed to perform a LDCT. The Fleischner Society Guidelines were used to classify the nodules and establish follow-up. RESULTS: Initially, 265 former employees of the Uranium National Company were included. The mean time of employment was 15 (0 - 45) years. The non-smokers represented 50.9% and 30.2% were ever smokers; the remaining chose not to respond. One diagnosis of lung cancer was initially made. In the second phase, a subgroup of 66 former miner underwent a LDCT, 37 of whom presented pulmonary nodules. Most computed tomography (CT) scans revealed one single nodule (n = 13) and the mean size was 5 (1 - 16) mm. A suspicious 16 mm spiculated nodule was evaluated with PET/CT, and percutaneous and surgical biopsies, ultimately revealing a benign lesion. CONCLUSION: The data highlights the importance of lung cancer screening in high-risk populations. This was, to the best of our knowledge, the first study performed in Portugal and can act as a bridge towards a wider implementation in the country.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

A Multimethodological Approach for the Chemical Characterization of Edible Insects: The Case Study of Acheta domesticus.

Acheta domesticus (house cricket) has been recently introduced into the official European list of novel foods, representing an alternative and sustainable food source. Up to now, the chemical characterization of this edible insect has been focused only on specific classes of compounds. Here, three production batches of an A. domesticus powder were investigated by means of a multimethodological approach based on NMR, FT-ICR MS, and GC-MS methodologies. The applied analytical protocol, proposed for the first time in the study of an edible insect, allowed us to identify and quantify compounds not previously reported in crickets. In particular, methyl-branched hydrocarbons, previously identified in other insects, together with other compounds such as citrulline, formate, γ-terpinene, p-cymene, α-thujene, ß-thujene, and 4-carene were detected. Amino acids, organic acids, and fatty acids were also identified and quantified. The improved knowledge of the chemical profile of this novel food opens new horizons both for the use of crickets as a food ingredient and for the use of extracts for the production of new formulations. In order to achieve this objective, studies regarding safety, biological activity, bioaccessibility, and bioavailability are needed as future perspectives in this field.

Important steps towards a big change for lung health: a joint approach by the European Respiratory Society, the European Society of Radiology and their partners to facilitate implementation of the European Union's new recommendations on lung cancer screening.

Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening. https://bit.ly/3J4O0Jb.

Addressing influenza's underestimated burden - Iberian experts call to action.

Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza's impact.

Diagnosis of Fibrotic Hypersensitivity Pneumonitis: Is There a Role for Biomarkers?

Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available.

A multiple criteria approach for building a pandemic impact assessment composite indicator: The case of COVID-19 in Portugal.

The COVID-19 pandemic has caused major damage and disruption to social, economic, and health systems (among others). In addition, it has posed unprecedented challenges to public health and policy/decision-makers who have been responsible for designing and implementing measures to mitigate its strong negative impact. The Portuguese health authorities have used decision analysis techniques to assess the impact of the pandemic and implemented measures for counties, regions, or across the entire country. These decision tools have been subject to some criticism and many stakeholders requested novel approaches. In particular, those which considered the dynamic changes in the pandemic's behaviour due to new virus variants and vaccines. A multidisciplinary team formed by researchers from the COVID-19 Committee of Instituto Superior Técnico at the University of Lisbon (CCIST analyst team) and physicians from the Crisis Office of the Portuguese Medical Association (GCOM expert team) collaborated to create a new tool to help politicians and decision-makers to fight the pandemic. This paper presents the main steps that led to the building of a pandemic impact assessment composite indicator applied to the specific case of COVID-19 in Portugal. A multiple criteria approach based on an additive multi-attribute value theory aggregation model was used to build the pandemic assessment composite indicator. The parameters of the additive model were devised based on an interactive socio-technical and co-constructive process between the CCIST and GCOM team members. The deck of cards method was the adopted technical tool to assist in the assessment the value functions as well as in the assessment of the criteria weights. The final tool was presented at a press conference and had a powerful impact on the Portuguese media and on the main health decision-making stakeholders in the country. In this paper, a completed mathematical and graphical description of this tool is presented.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

FT-ICR-MS-based metabolomics: A deep dive into plant metabolism.

Metabolomics involves the identification and quantification of metabolites to unravel the chemical footprints behind cellular regulatory processes and to decipher metabolic networks, opening new insights to understand the correlation between genes and metabolites. In plants, it is estimated the existence of hundreds of thousands of metabolites and the majority is still unknown. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is a powerful analytical technique to tackle such challenges. The resolving power and sensitivity of this ultrahigh mass accuracy mass analyzer is such that a complex mixture, such as plant extracts, can be analyzed and thousands of metabolite signals can be detected simultaneously and distinguished based on the naturally abundant elemental isotopes. In this review, FT-ICR-MS-based plant metabolomics studies are described, emphasizing FT-ICR-MS increasing applications in plant science through targeted and untargeted approaches, allowing for a better understanding of plant development, responses to biotic and abiotic stresses, and the discovery of new natural nutraceutical compounds. Improved metabolite extraction protocols compatible with FT-ICR-MS, metabolite analysis methods and metabolite identification platforms are also explored as well as new in silico approaches. Most recent advances in MS imaging are also discussed.

Untargeted Metabolomics Reveals Antidepressant Effects in a Marine Photosynthetic Organism: The Diatom Phaeodactylum tricornutum as a Case Study.

The increased use of antidepressants, along with their increased occurrence in aquatic environments, is of concern for marine organisms. Although these pharmaceutical compounds have been shown to negatively affect marine diatoms, their mode of action in these non-target, single-cell phototrophic organisms is yet unknown. Using a Fourier-transform ion cyclotron-resonance mass spectrometer (FT-ICR-MS) we evaluated the effects of fluoxetine in the metabolomics of the model diatom Phaeodactylum tricornutum, as well as the potential use of the identified metabolites as exposure biomarkers. Diatom growth was severely impaired after fluoxetine exposure, particularly in the highest dose tested, along with a down-regulation of photosynthetic and carbohydrate metabolisms. Notably, several mechanisms that are normally down-regulated by fluoxetine in mammal organisms were also down-regulated in diatoms (e.g., glycerolipid metabolism, phosphatidylinositol signalling pathway, vitamin metabolism, terpenoid backbone biosynthesis and serotonin remobilization metabolism). Additionally, the present work also identified a set of potential biomarkers of fluoxetine exposure that were up-regulated with increasing fluoxetine exposure concentration and are of high metabolic significance following the disclosed mode of action, reinforcing the use of metabolomics approaches in ecotoxicology.

Grapevine leaf MALDI-MS imaging reveals the localisation of a putatively identified sucrose metabolite associated to Plasmopara viticola development.

Despite well-established pathways and metabolites involved in grapevine-Plasmopara viticola interaction, information on the molecules involved in the first moments of pathogen contact with the leaf surface and their specific location is still missing. To understand and localise these molecules, we analysed grapevine leaf discs infected with P. viticola with MSI. Plant material preparation was optimised, and different matrices and solvents were tested. Our data shows that trichomes hamper matrix deposition and the ion signal. Results show that putatively identified sucrose presents a higher accumulation and a non-homogeneous distribution in the infected leaf discs in comparison with the controls. This accumulation was mainly on the veins, leading to the hypothesis that sucrose metabolism is being manipulated by the development structures of P. viticola. Up to our knowledge this is the first time that the localisation of a putatively identified sucrose metabolite was shown to be associated to P. viticola infection sites.

Excess hospitalizations and mortality associated with seasonal influenza in Portugal, 2008-2018.

BACKGROUND: Influenza can have a domino effect, triggering severe conditions and leading to hospitalization or even death. Since influenza testing is not routinely performed, statistical modeling techniques are increasingly being used to estimate annual hospitalizations and deaths associated with influenza, to overcome the known underestimation from registers coded with influenza-specific diagnosis. The aim of this study was to estimate the clinical and economic burden of severe influenza in Portugal. METHODS: The study comprised ten epidemic seasons (2008/09-2017/18) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization incidence, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487-488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480-488, 517.1; ICD-10: J09-J18), respiratory (ICD-9: 460-519; ICD-10: J00-J99), respiratory or cardiovascular (R&C, ICD-9: 390-459, 460-519; ICD-10: I00-I99, J00-J99), and all-cause. Means are reported excluding the H1N1pdm09 pandemic (2009/10). RESULTS: The mean number of hospitalizations coded as due to influenza per season was 1,207, resulting in 11.6 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €3.9 million, of which 78.6% was generated by patients with comorbidities. Mean annual influenza-associated R&C hospitalizations were estimated at 5356 (min: 456; max: 8776), corresponding to 51.5 cases per 100,000 (95% CI: 40.9-62.0) for all age groups and 199.6 (95% CI: 163.9-235.8) for the population aged ≥ 65 years. The mean direct annual cost of the estimated excess R&C hospitalizations was €15.2 million for all age groups and €12.8 million for the population aged ≥ 65 years. Mean annual influenza-associated all-cause deaths per 100,000 people were estimated at 22.7 for all age groups. CONCLUSIONS: The study findings suggest that there is an under-detection of influenza in the Portuguese population. A high burden of severe influenza remains to be addressed, not only in the elderly population but also in younger people.