Understanding uncontrolled severe allergic asthma by integration of omic and clinical data.

BACKGROUND: Asthma is a complex, multifactorial disease often linked with sensitization to house dust mites (HDM). There is a subset of patients that does not respond to available treatments, who present a higher number of exacerbations and a worse quality of life. To understand the mechanisms of poor asthma control and disease severity, we aim to elucidate the metabolic and immunologic routes underlying this specific phenotype and the associated clinical features. METHODS: Eighty-seven patients with a clinical history of asthma were recruited and stratified in 4 groups according to their response to treatment: corticosteroid-controlled (ICS), immunotherapy-controlled (IT), biologicals-controlled (BIO) or uncontrolled (UC). Serum samples were analysed by metabolomics and proteomics; and classifiers were built using machine-learning algorithms. RESULTS: Metabolomic analysis showed that ICS and UC groups cluster separately from one another and display the highest number of significantly different metabolites among all comparisons. Metabolite identification and pathway enrichment analysis highlighted increased levels of lysophospholipids related to inflammatory pathways in the UC patients. Likewise, 8 proteins were either upregulated (CCL13, ARG1, IL15 and TNFRSF12A) or downregulated (sCD4, CCL19 and IFNγ) in UC patients compared to ICS, suggesting a significant activation of T cells in these patients. Finally, the machine-learning model built including metabolomic and clinical data was able to classify the patients with an 87.5% accuracy. CONCLUSIONS: UC patients display a unique fingerprint characterized by inflammatory-related metabolites and proteins, suggesting a pro-inflammatory environment. Moreover, the integration of clinical and experimental data led to a deeper understanding of the mechanisms underlying UC phenotype.

[What needs do experts and future Physical Activity and Sport professionals perceive to promote healthy aging? Professionals and students' views]. / ¿Qué necesidades perciben los expertos y los futuros profesionales de la Actividad Física y del Deporte para promover un envejecimiento saludable? Visión de profesionales y estudiantes.

INTRODUCTION: Physical activity acts as an adjuvant in the treatment of numerous diseases and in the promotion of healthy aging. Increasing longevity entails an increase in the demand for professionals who prescribe physical activity, specifically physiotherapists and physical-activity educators. OBJECTIVES: The main objective of this study was to explore the perceptions of a group of third- and fourth-year Physiotherapy students (n=9) and Sport Sciences students (n=5), and experts who work with older adults (n=3) about their knowledge of the older adult population and healthy aging. The secondary objectives were to: (a) explore what knowledge future professionals need about physical activity programming and about physical activity programs aimed at maintaining and improving health among older adults; (b) explore what would be the best methodology to acquire such knowledge; and (c) explore whether a relationship is perceived between knowledge about the older adult population and motivation to work with this population group. METHODS: Two discussion groups with students and three interviews with experts were conducted. Discussion groups and interviews were transcribed verbatim and analyzed through a reflexive thematic analysis, following the steps described by Braun and Clarke (2021). RESULTS: Three themes were identified from the discussion groups: (1) conception and ideas about older adults, (2) skills and knowledge perceived as important, and (3) proposals for motivational intervention addressed to the older population. Four themes were identified from the interviews with experts: (1) characteristics of the future professional, (2) physical activity programs for older people: the recipe for success, (3) the role of enjoyment as key to success, and (4) barriers/obstacles along the path. CONCLUSION: Students of both degrees and experts believe that more practical training opportunities are needed, to enable students to interact with the older population and get to know their needs, motivations, and barriers, to increase physical activity levels in this population group.

Boosting enjoyment and social inclusion to increase physical activity and reduce sedentary behaviour among older adults: protocol for a feasibility study to test the JOIN4JOY approach in five European countries.

INTRODUCTION: Programmes for older people aimed at increasing physical activity (PA) and reducing sedentary behaviour (SB) traditionally focus on achieving functional and health improvements. Focusing on enjoyment and social inclusion could strengthen adherence and help reach older people with social disadvantages. The aim of this study is to assess the feasibility and acceptability of the Join4Joy approach in PA programmes and its assessment tools. METHODS AND ANALYSIS: A multicentric, pragmatic, pre-post feasibility study using mixed methods will be conducted. The intervention will consist of a PA programme boosting enjoyment and social inclusion, grounded on a co-creation process. Trainers will offer twelve, 1-hour weekly sessions of structured, supervised, group-based PA. Participants will be encouraged to increase activity in daily living. 144 older people will be recruited from the community and nursing homes in Spain, Denmark, Italy, Germany, and France. Additionally, participants and trainers will be invited to join virtual communities of practice to share their experiences across settings and countries. Qualitative procedures will be used to explore the acceptability of the design via interviews and focus groups with participants and trainers. Quantitative methods will be used to assess uptake, adherence, retention, reach, satisfaction, enjoyment (PACES questionnaire), physical function (e.g., Short Physical Performance Battery), quality of life (EQ-5D-5L scale), perceived improvement (Patient Global Impression of Improvement scale-I), activities of daily living (Barthel index) and SB and PA patterns (IPAQ and accelerometry). The degree and type of participation in virtual communities of practice will also be assessed. SPSS software will be used for the analysis of quantitative variables. Qualitative data will be analysed using reflective thematic analysis following Braun and Clarke (2006). ETHICS AND DISSEMINATION: A favourable report by the Research Ethics Committee of UVic-UCC (282/2023) was obtained on 26 June 26th, 2023. Participation and withdrawal will be voluntary. Participants' (or their legal guardians', when necessary) written permission will be required. Results of the study will be disseminated through publication of scientific articles, presentations at sport and health-related professional conferences and congresses, as well as through social media and via the Join4Joy website. STUDY REGISTRATION: ClinicalTrials.gov, NCT06100835.

No association between genetic ancestry and susceptibility to asthma or atopy in Canary Islanders.

Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005 ≤ p value ≤ 0.042; 0.221 ≤ q value ≤ 0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility.

Comprehensive Study of Patients' Compliance with Sublingual Immunotherapy in House Dust Mite Perennial Allergic Rhinitis.

INTRODUCTION: Allergen immunotherapy is a long-term treatment that has been associated with patient adherence issues. The aim of the study was to increase the knowledge on compliance of patients allergic to house dust mites, receiving sublingual immunotherapy (SLIT). METHODS: A retrospective observational study was performed in 53 Spanish allergy units. We enrolled patients undergoing the SLIT treatment for house dust mites including a scheduled control visit 12 months after initiating the therapy. We conducted a comprehensive assessment of compliance using three methods. In the first step, an allergist evaluated the patients according to the results of an interview and the existing medical records. The subjects taking more than 80% of the overall prescription were defined as compliant. The remaining noncompliant patients were divided into groups taking less than 25%, 25-50%, and 50-80% of the prescribed SLIT. In the second stage, we conducted the Morisky-Green test. Finally, the noncompliant patients were asked to fill a self-report assessment form. Data were stratified into age groups. The potential factors affecting compliance were also investigated. RESULTS: Overall, 380 subjects participated in the study. The compliance rate was 79.7%, and the treatment discontinuation rate was 22.5%, while 66.8% of patients were adherent (both compliant and continuing with the treatment). The results showed that children were the most compliant and adolescents the least compliant (86.6% and 60.9%, respectively). The main reason for noncompliance was "forgetting some doses" in 31.0% of the children, 48.0% of the adolescents, and 53.2% of the adults. Compliance was associated with the following factors: age, number of annual control visits, and reduction in symptomatic medication. CONCLUSION: Our results showed that two out of three patients with house dust mite-induced allergic rhinitis adhered to the SLIT treatment. Multidisciplinary and integral solutions are needed to improve the compliance, with special attention paid to adolescents. FUNDING: Stallergenes Greer Spain.

Ion mobility spectrometry versus classical physico-chemical analysis for assessing the shelf life of extra virgin olive oil according to container type and storage conditions.

An experimental study was conducted to assess the stability of a single-variety (Arbequina) extra virgin olive oil (EVOO) as a function of container type and storage conditions over a period of 11 months. EVOO quality was assessed by using ion mobility spectrometry (IMS), which provides increased simplicity, expeditiousness, and relative economy. The results were compared with the ones obtained by using the official method based on classical physico-chemical analysis. Bag-in-box, metal, dark glass, clear glass, and polyethylene terephthalate containers holding EVOO were opened on a periodic basis for sampling to simulate domestic use; in parallel, other containers were kept closed until analysis to simulate the storage conditions on market shelves. The results of the physico-chemical and instrumental analyses led to similar conclusions. Thus, samples packaged in bag-in-box containers preserved oil quality for 11 months, better than other container types. The HS-GC-IMS results confirm that 2-heptenal and 1-penten-3-one are two accurate markers of EVOO quality.

Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects.

BACKGROUND: Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R. CONCLUSIONS/SIGNIFICANCE: Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.

[Bladder leiomyosarcoma. Partial cystectomy and adjuvant treatment]. / Leiomiosarcoma de vejiga: cistectomía parcial y tratamiento complementario.

OBJECTIVE: We report a new case of bladder leiomyosarcoma in an old patient. METHODS: We present the case of a 75-year-old man with bladder leiomyosarcoma treated by partial surgery followed by adjuvant treatment. RESULTS: Partial surgery of the primary tumor followed by concomitant chemoradiotherapy was the approach for this patient. Nowadays, patient is free of tumor and living without any problems. CONCLUSIONS: Bladder leiomyosarcoma is an uncommon tumor (only about 1% of all bladder cancers) treated basically with radical surgery. Nowadays, partial surgery is a usual approach in other tumors and there is a trend toward less aggressive surgery with preservation of function (such as head and neck cancer, bladder cancer).

Differential allergen sensitization patterns in chestnut allergy with or without associated latex-fruit syndrome.

BACKGROUND: Chestnut allergy has been almost exclusively considered in the context of the latex-fruit syndrome. Chestnut allergens not linked to latex hypersensitivity have not been studied. OBJECTIVE: We sought to explore whether differences in sensitization patterns between chestnut allergy with or without associated latex-fruit syndrome can be detected. METHODS: Twelve patients sensitized to chestnut but not to latex and 3 control patients with latex-chestnut allergy were analyzed. A major chestnut allergen was purified and characterized. IgE immunoblotting, specific IgE determination, and skin prick tests with 5 isolated allergens involved in food allergy or latex-fruit syndrome were also performed. RESULTS: A major 9-kd allergen was detected in chestnut extract, isolated, and identified as lipid transfer protein (LTP) Cas s 8. Specific IgE to this allergen was found in 91% (by means of IgE immunoblotting) and 58% (by means of ELISA) of sera from patients with chestnut but not latex allergy. Moreover, 66% of these patients had positive skin prick test responses to Cas s 8. Additionally, allergenic LTPs from peach fruit and Artemisia vulgaris pollen were also reactive. In contrast, avocado class I chitinase and latex hevein, allergens associated with the latex-fruit syndrome, showed no reaction. The opposite situation was exhibited by patients with latex-chestnut allergy. CONCLUSIONS: Patients with chestnut allergy with or without associated latex hypersensitivity present different patterns of major allergens (LTPs and class I chitinases, respectively). CLINICAL IMPLICATIONS: LTPs and class I chitinases can be used as diagnostic tools in patients with chestnut allergy to predict whether an associated latex sensitization and a risk of potential cross-reactivity with other plant foods and pollens exist.

Cabbage lipid transfer protein Bra o 3 is a major allergen responsible for cross-reactivity between plant foods and pollens.

BACKGROUND: Food IgE-mediated allergy to members of the Brassicaceae family has been increasingly reported. OBJECTIVE: To characterize cabbage-Brassica oleracea var capitata-allergy and its major allergens. METHODS: A prospective study was performed, recruiting 17 patients allergic to cabbage, and control subjects. Skin prick tests and double-blind placebo-controlled food challenges were performed. A major allergen was isolated from cabbage by RP-HPLC and characterized by N-terminal amino acid sequencing and matrix-assisted laser desorption/ionization mass spectrometry analysis. Specific IgE determinations, IgE immunoblots, and CAP-inhibition assays were also performed. RESULTS: Skin prick test and specific IgE were positive to cabbage in all patients. Five of them referred anaphylactic reactions when eating cabbage, and in another 5 patients, cabbage allergy was further confirmed by double-blind placebo-controlled food challenge. Most of them showed associated sensitizations to mugwort pollen, mustard, and peach. A 9-kd cabbage IgE-binding protein, Bra o 3, was identified as a lipid transfer protein (LTP) with 50% of identity to peach LTP Pru p 3. Skin prick test with Bra o 3 showed positive results in 12 of 14 cases (86%). On CAP inhibition assays, Bra o 3 managed to inhibit significantly the IgE binding to cabbage, mugwort pollen, and peach. Both Bra o 3 and Pru p 3 were recognized by IgE from the patients' sera. CONCLUSION: Bra o 3, a cabbage LTP, is a major allergen in this food, cross-reacting with mugwort pollen and with other plant foods, such as peach. CLINICAL IMPLICATIONS: Cabbage IgE-mediated allergy is a potentially severe condition that can present with other plant food and pollen allergies.