Background: Eosinophilic esophagitis (EoE) is a recently defined chronic immune-mediated disease of atopic etiology with esophageal dysfunction and mucosal eosinophilic infiltrate. Among esophageal high-resolution manometry (HRM) parameters, intrabolus pressure (IBP) has shown the possibility to distinguish patients with mucosal inflammation, who benefit from proton pump inhibitors (PPI), from those with initial fibrosis and lack of response to treatment. In this study, we aimed to identify biomarkers able to identify which group a patient belongs to and obtain an early response. Methods: Combining diagnostic and esophageal function tests, proteomic and histological immunohistochemical analysis we studied 24 patients with EoE to extrapolate a protein profile from biopsies of the middle third of the esophagus analysis. Among them, 20 patients also underwent esophageal HRM. Results: IBP values were found to be significantly different among the controls, responsive and non-responsive patients, in relation to PPI treatment. Proteomic analysis identified 1,445 proteins, 456 shared between the two groups of patients, with 58 proteins identified as differentially expressed (DEPs) between the two groups of patients. Among all identified proteins, we found that, by immunohistochemistry, Gal-3 was overexpressed in patients’ responder to PPI, and with image analysis the difference between the two groups was statistically significant (% positive cells p<0.01, % positive area p<0.005) Conclusions: This study showed the chance of knowing forward the response to PPI therapy, improving patients’ personalized therapy and quality of life.

Although airway remodeling in severe and/or fatal asthma is still considered irreversible, its individual components as a cause of clinical symptoms and/or lung function changes remain largely unknown. While inhaled glucocorticoids have not consistently been shown to affect airway remodeling, biologics targeting specific pathways of airway inflammation have been shown to improve lung function, mucus plugging, and airway structural changes that can exceed those seen with glucocorticoids. This superiority of biologic treatment, which cannot be solely explained by insufficient doses or limited durations of glucocorticoid therapies, needs to be further explored. For this field of research, we propose a novel classification of the potential effects of biologics on airway remodeling into 3 temporal effects: early effects (days to weeks, primarily modulating inflammatory processes), late effects (months to years, predominantly affecting structural changes) and potential preventive effects (outcomes of early treatment with biologics). For the identification of potential preventive effects of biologics, we call for studies exploring the impact of early biological treatment on airway remodeling in patients with moderate-to-severe asthma, which should be accompanied by a long-term evaluation of clinical parameters, biomarkers, treatment burden, and socioeconomic implications.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Background: Several biologics are now available as add-on treatment for severe asthma but, currently there are no universally accepted criteria to measure the response to these therapies. This survey aims to establish consensus criteria to use in practice for the initial evaluation of response to biologics after four months of treatment. Method: Using Delphi methodology, a questionnaire including ten items was developed and validated by a 13-member panel of international experts in asthma. The electronic survey circulated within the INterasma Scientific Network platform, Global Asthma Association membership, contact list of the co-authors, national associations for specialists, and social media. For each item, five answers were proposed graduated from “no importance” to “very high importance” and by a score (A=2 points; B=4 points; C=6 points; D=8 points; E=10 points). The final criteria were selected if the median score for the item was ≥7 and >60% of responses accorded “high importance” and “very high importance”. All selected criteria were validated by the thirteen experts. Results: Four criteria were identified to evaluate the efficacy of biologics in asthma: to reduce daily systemic corticosteroids dose by ≥50% (ideally complete withdrawal); to decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%, (ideally no asthma exacerbation); to have no/minimal side-effects and to obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria are needed to conclude a good response to biologics. Conclusions: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.