Diagnosis, management and therapeutic options for eosinophilic esophagitis.

PURPOSE OF REVIEW: Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. RECENT FINDINGS: Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features. SUMMARY: In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Epidemiology of the relationship between allergic bronchopulmonary aspergillosis and asthma.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis (ABPA) can complicate the natural history of asthmatic patients, especially the more severe ones, worsening disease control and increasing the need for therapies, steroids in particular, and medical care. The aim of the present review is to summarize the latest epidemiological data related to the relationship between asthma and ABPA and to offer a summary of the most recent strategies that could potentially facilitate in the identification of ABPA in asthmatic patients. RECENT FINDINGS: In the last years, great efforts have been made by researchers worldwide to provide reliable epidemiological data on fungal sensitization and ABPA, especially in severe asthma patients both in adult and pediatric population. Data differ depending on the geographical area and population studied, but pooled data show a concerning 11% of severe asthma patients having ABPA and one out of four asthmatic patients being sensitized to fungi, Aspergillus fumigatus in particular. SUMMARY: Reliable epidemiological data and advances in the diagnostic procedures can facilitate the detection of ABPA among asthmatic patients, improving the management of a still under-recognized and challenging condition.

Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance.

Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. According to the available real-life evidence mepolizumab 300 mg and 100 mg, licensed for severe eosinophilic asthma, are comparable in terms of drug efficacy. However, the clinical rationale for selecting one dose or the other has not been explored. We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3-6-12 months follow-up. Overall, 11 patients were enrolled (females 4-36%) with a median age of 62 years (IQR 55.0-72.0). At 3-month visit both prednisone daily dose and BEC significantly decreased from baseline, whilst a substantial improvement of Brief fatigue inventory score (BFI) was not recorded before the 6 months assessment. More than 70% of patients completely stopped prednisone at 12-months follow-up, without any flare in terms of BEC and BFI. No adverse event was registered. Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.

Hidden Comorbidities in Asthma: A Perspective for a Personalized Approach.

Bronchial asthma is the most frequent inflammatory non-communicable condition affecting the airways worldwide. It is commonly associated with concomitant conditions, which substantially contribute to its burden, whether they involve the lung or other districts. The present review aims at providing an overview of the recent acquisitions in terms of asthma concomitant systemic conditions, besides the commonly known respiratory comorbidities. The most recent research has highlighted a number of pathobiological interactions between asthma and other organs in the view of a shared immunological background underling different diseases. A bi-univocal relationship between asthma and common conditions, including cardiovascular, metabolic or neurodegenerative diseases, as well as rare disorders such as sickle cell disease, α1-Antitrypsin deficiency and immunologic conditions with hyper-eosinophilia, should be considered and explored, in terms of diagnostic work-up and long-term assessment of asthma patients. The relevance of that acquisition is of utmost importance in the management of asthma patients and paves the way to a new approach in the light of a personalized medicine perspective, besides targeted therapies.

Benralizumab Efficacy in Late Non-Responders to Mepolizumab and Variables Associated with Occurrence of Switching: A Real-Word Perspective.

Overlapping eligibility to different biologics for severe asthma is still challenging, especially when addressing the same target. We aimed to characterize severe eosinophilic asthma patients according to their maintained or reduced response to mepolizumab over time and to explore baseline variables significantly associated with the occurrence of switching to benralizumab. We performed a multicentre retrospective observational study evaluating OCS reduction, exacerbation rate, lung function, exhaled nitric oxide levels (FeNO), Asthma control test (ACT), and blood eosinophil concentrations at baseline and before and after switching occurrence among 43 female and 25 male patients with severe asthma aged 23 to 84 years. Younger age, higher OCS daily dose and lower blood eosinophils at baseline were associated with a significantly higher risk (odds) for switching occurrence. All the patients showed an optimal response to mepolizumab, up to six months. The need for switching, according to the above-mentioned criterion, occurred for 30 out of 68 patients after a median time of 21 months (Q1-Q3: 12-24) from mepolizumab initiation. At the follow-up time-point after the switch (median time: 31 months, Q-Q3: 22-35), all the outcomes substantially improved and no cases of poor clinical response to benralizumab were detected. Although the small sample size and the retrospective design represent major limitations, to our knowledge, our study provides the first real-word focus on clinical variables potentially predicting a better response to anti IL-5r in patients fully eligible for both mepolizumab and benralizumab and suggests that in late non responder patients to mepolizumab, more robustly targeting the IL-5 axis may be effective.

Diagnosis and Management of Allergic Rhinitis in Asthmatic Children.

Allergic rhinitis (AR) is a common upper airways inflammatory condition especially in paediatric population; its burden potentially impacts on quality of life, quality of sleep and daily performance, which can be difficult to perceive but not less relevant in the middle-long term. The present review aims to provide an updated overview on AR epidemiology, diagnosis and with a special focus on its connections with bronchial asthma. In fact, when considering asthmatic pediatric population, AR is probably the most important risk factor for asthma onset and the most impactful extra-bronchial determinant of asthma control. Under this perspective, allergen immunotherapy (AIT) should always be considered in the light of a precision medicine approach. In fact, AIT does represent a unique opportunity to specifically interfere with AR immunological background, improve both AR and bronchial asthma control and prevent allergic disease evolution. Verifying the patient's eligibility to that option should be considered as a priority for every physician managing children suffering from AR, especially when associated with bronchial asthma.

Biologics for eosinophilic granulomatosis with polyangiitis.

PURPOSE OF REVIEW: The link between severe asthma and eosinophilic granulomatosis with polyangiitis (EGPA) in terms of pathophysiological background, clinical manifestations and disease evolution has leaded to investigate the relevance of anti T2 monoclonal antibodies licensed for severe asthma patients as a treatment option for EGPA. The present review aimed to provide un update on EGPA pathophysiology and to critically summarize the most robust evidence coming from trials and real-life setting on the use of anti T2 biologics in EGPA patients. RECENT FINDINGS: Mepolizumab, an anti-interleukin-5 monoclonal antibody, is the only biologic drug targeting eosinophilic inflammation currently approved for EGPA treatment at the dose of 300 mg/4 weeks. Its use is restricted by the American College of Rheumatology guidelines to specific diseases phases and severity grades. However the most appropriate mepolizumab positioning and dose is still under investigation in the real life practice, which is providing an increasing amount of evidence confirming its efficacy, alone or in combination with other options in different disease stages. The relevance of other monoclonal antibodies interfering with T2 inflammation, including omalizumab and benralizumab, is under investigation but the evidence is still scarce. SUMMARY: Taking into account the suboptimal medium-long term safety profile of conventional EGPA treatments, the opportunity of selectively targeting eosinophilic inflammation certainly represents a revolutionary approach. However, further real-word evidence is required to effectively position the new treatments in the light of the disease complexity, including different immunological drivers, and individual variability.

Current Take on Systemic Sclerosis Patients' Vaccination Recommendations.

Systemic sclerosis (SSc) is a rare autoimmune inflammatory rheumatic disease. The prevalence of SSc ranges from 7 to 700 cases per million worldwide. Due to multiple organ involvement and constant inflammatory state, this group of patients presents an increased risk of infectious diseases. This paper aimed to gather the up-to-date evidence on vaccination strategies for patients with SSc and to be a useful tool for the prevention and management of infectious diseases. The authors conducted a scoping review in which each paragraph presents data on a specific vaccine's safety, immunogenicity, and efficacy. The work deals with the following topics: SARS-CoV-2, seasonal influenza, S. pneumoniae, HAV, HBV, HZV, N. meningitidis, H. influenzae, HPV, and diphtheria-tetanus-pertussis.