Transition of Adolescents With Severe Asthma From Pediatric to Adult Care in Spain: The STAR Consensus.

OBJECTIVES: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care. METHODS: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement. RESULTS: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments. CONCLUSION: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient.

Eosinophil-derived exosomes contribute to asthma remodelling by activating structural lung cells.

BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesized that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals. All experiments were performed with eosinophil-derived exosomes from healthy and asthmatic subjects. Epithelial damage was evaluated using primary small airway epithelial cell lines through 2 types of apoptosis assays, that is, flow cytometry and TUNEL assay with confocal microscopy. Additionally, the epithelial repair was analysed by performing wound healing assays with epithelial cells. Functional studies such as proliferation and inhibition-proliferation assays were carried out in primary bronchial smooth muscle cell lines. Also, gene expression analysis of pro-inflammatory molecules was evaluated by real-time PCR on epithelial and muscle cells. Lastly, protein expression of epithelial and muscle cell signalling factors was estimated by Western blot. RESULTS: Asthmatic eosinophil-derived exosomes induced an increase in epithelial cell apoptosis at 24 hour and 48 hour, impeding wound closure. In addition, muscle cell proliferation was increased at 72 hours after exosome addition and was linked with higher phosphorylation of ERK1/2. We also found higher expression of several genes when both cell types were cultured in the presence of exosomes from asthmatics: CCR3 and VEGFA in muscle cells, and CCL26, TNF and POSTN in epithelial cells. Healthy eosinophil-derived exosomes did not exert any effect over these cell types. CONCLUSIONS AND CLINICAL RELEVANCE: Eosinophil-derived exosomes from asthmatic patients participate actively in the development of the pathological features of asthma via structural lung cells.

Changes in exhaled nitric oxide after inhalation challenge with occupational agents.

BACKGROUND AND OBJECTIVE: The use of fractional exhaled nitric oxide (FeNO) concentration has been proposed as a surrogate marker for monitoring airway response to specific inhalation challenge (SIC). We investigated the usefulness of FeNO measurements for monitoring airway response to SIC with occupational agents. Materialandmethods: Workers with suspected occupational asthma were recruited to undergo SIC with occupational agents and subsequently FeNO testing at baseline and 24 hours. RESULTS: Sixty-eight patients were evaluated, 45 of whom had a positive SIC. SIC-positive patients showed a significant increase in FeNO 24 hours postchallenge, with an increase ratio of 1.25 (95% CI, 1.05-1.48; P=.01); no increase was seen in patients with a negative SIC (P=.08). The predictive capacity of variations in FeNO showed that for each unit increase in FeNO, the probability of a positive SIC rose by 4%. A baseline FeNO value of 25 ppb predicted a positive SIC with 60% sensitivity and 80% specificity. The increase in %FeNO cutoff point providing maximal sensitivity and specificity for predicting a positive SIC was 41% (sensitivity 50%, specificity 95%). CONCLUSIONS: We demonstrated that asthmatic reactions induced by occupational agents during SICs are associated with a consistent increase in FeNO. However, the predictive diagnostic capacity of FeNO measurements is low. While FeNO may aid in the interpretation of SIC in some cases, it cannot be used as a general surrogate marker to predict or to assess SICs with occupational agents.

Recombinant lipid transfer protein Tri a 14: a novel heat and proteolytic resistant tool for the diagnosis of baker's asthma.

BACKGROUND: Baker's asthma is an important occupational allergic disease. Wheat lipid transfer protein (LTP) Tri a 14 is a major allergen associated with wheat allergy. No panel of wheat recombinant allergens for component-resolved diagnosis of baker's asthma is currently available. OBJECTIVE: To evaluate the potential role of recombinant Tri a 14 as a novel tool for the diagnosis of baker's asthma, and to test the heat and proteolytic resistance of the wheat LTP allergen. METHODS: A cDNA encoding Tri a 14 was isolated and sequenced, the recombinant allergen produced in Pichia pastoris and purified by chromatographic methods. Physicochemical and immunological comparison of the natural and recombinant forms of Tri a 14 was carried out by N-terminal amino acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry, circular dichroism (CD) analysis, IgE immunodetection, and specific IgE determination and ELISA-inhibition assays using a pool or individual sera from 26 patients with baker's asthma. Thermal denaturation and simulated gastrointestinal digestion of both Tri a 14 forms were checked by spectroscopic and electrophoretic methods, respectively, and biological activity by basophil activation test (BAT). RESULTS: Natural and recombinant Tri a 14 were similarly folded, as indicated by their nearly identical CD spectra and heat denaturation profiles. A high interclass correlation coefficient (0.882) was found between specific IgE levels to both Tri a 14 proteins in individual sera from baker's asthma patients, but a slightly lower IgE-binding potency of rTri a 14 was detected by ELISA-inhibition assays. Natural and recombinant Tri a 14 elicited positive BAT in two and one out of three patients, respectively. Heat denaturation profiles and simulated gastrointestinal digestion assays indicated that Tri a 14 displayed a high heat and digestive proteolytic resistance, comparable to those of peach Pru p 3, the model food allergen of the LTP family. CONCLUSIONS: Recombinant Tri a 14 is a potential tool for baker's asthma diagnosis, based on its physicochemical and immunological similarity with its natural counterpart. Wheat Tri a 14 shows a high thermal stability and resistance to gastrointestinal digestion.

Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis.

BACKGROUND: Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC(4)) and bronchoprotective (prostaglandin E(2); PGE(2)) lipid mediators. METHODS: We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE(2), and LTC(4) were measured by enzyme immunoassays. RESULTS: The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma), IL-2, vascular endothelial growth factor and transforming growth factor beta were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-gamma and tumor necrosis factor alpha (TNF-alpha) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE(2) concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 +/- 612 pg/ml) when compared with asthmatic (7.54 +/- 2.14 pg/ml) and healthy subjects (4 +/- 1.3 pg/ml). CONCLUSION: This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE(2) production in the airways.

Transition of Adolescents With Severe Asthma From Pediatric to Adult Care in Spain: The STAR Consensus

Objective: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care. Methods: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement. Results: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments. Conclusions: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient (AU)

Objetivo: Evaluar el grado de consenso con un panel multidisciplinar de expertos sobre la transición del adolescente con asma grave de los servicios de pediatría a atención de adultos. Métodos: Se elaboró un cuestionario de 61 ítems basado en recomendaciones de transición para otras patologías crónicas, abarcando la planificación de la transición, preparación, transferencia efectiva y seguimiento. Se evaluó el nivel de consenso entre 98 expertos (49 pediatras, 24 alergólogos y 25 neumólogos) mediante un proceso Delphi de dos rondas. El consenso se estableció con un acuerdo ≥70%. Resultados: Cuarenta y dos ítems (70%) alcanzaron consenso. Los panelistas no alcanzaron consenso en el rango de edad para iniciar la transición. El principal objetivo a conseguir durante la transición según los expertos fue que el adolescente gane autonomía en el manejodel asma grave y tratamientos prescritos. Asimismo, alcanzaron acuerdo en la importancia de desarrollar un plan individualizado, promover la autonomía del paciente e identificar los factores clave en el entorno familiar. Los especialistas de adultos deben tener experiencia en asma grave y tratamientos biológicos, así como en el manejo de pacientes adolescentes. Los equipos sanitarios de pediatría y de adultos deben compartir la información clínica, consensuar los criterios para mantener la terapia biológica y realizar una visita conjunta con el paciente antes de la transferencia. Los especialistas de adultos deben realizar un seguimiento estrecho del paciente tras la transferencia para asegurar una correcta técnica inhalatoria, el cumplimiento del tratamiento y la asistencia a las citas sanitarias. Conclusiones: Este documento de consenso proporciona la primera hoja de ruta en España para que los equipos especialistas de pediatría y adultos garanticen aspectos clave del proceso de transición en pacientes adolescentes con asma grave. La aplicación de estas (AU)