Cristina Boccabella

Introduction: Antibiotics are frequently prescribed in preschool wheezing episodes and acute asthma exacerbations (AAEs), even though antibiotics are not recommended as standard AAE treatment. Objective: To systematically present relevant literature about the clinical effects of antibiotics for AAE and conclude with recommendations. Methods: Systematic search was conducted in Medline ALL, Embase, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Primary outcomes included AAE duration and length of hospital stay, while secondary outcomes incorporated AAE severity, treatment failure, AAE recurrence risk, spirometry, health costs, and adverse events. Selection Criteria: Randomised controlled trials and cohort studies were included if they investigated the clinical effect of antibiotics in AAE compared to placebo/standard care. Results: Fifteen studies were included. Evidence for clinical effects of antibiotics in AAE treatment is scarce. Macrolides seem to shorten AAE duration in children; for adults, there is a lack of data. Antibiotics were associated with a longer hospital admission in retrospective observational studies, without evidence in randomised trials. Procalcitonin‐guided treatment led to a reduction of antibiotic prescriptions without adverse outcomes. Conclusion: Limited evidence is available that macrolides shorten AAE duration in preschool wheezers. For other age groups, there is no clear evidence of beneficial effects of antibiotics.

Mepolizumab represents an effective strategy for severe eosinophilic asthma. Small airways disease (SAD) defines a peculiar asthma phenotype related to worse disease control. Limited and indirect findings are currently available on the effect of mepolizumab on SAD. Objectives: We investigated the impact of mepolizumab on SAD assessed through impulse oscillometry (IOS) and spirometry. As secondary outcomes, we tested the correlation between SAD and clinical, functional and inflammatory parameters. Methods: This is a prospective cohort study including severe eosinophilic asthmatics eligible for mepolizumab performed between 2021 and 2023. IOS (R5–R20) and spirometry (FEF25-75%, TLC%, RV/TLC%) parameters were assessed at baseline and over 1 year of mepolizumab. Other functional (FEV1%), clinical (ACT, number of asthma exacerbations/previous year, use of OCS) and inflammatory data (BEC and FeNO) were concomitantly collected for correlations. Results: A total of 18 patients (mean age 61.1 ± 12.0 y; 10 (55.5%) female) were included. Longitudinal data from 16 patients showed that R5–R20 significantly improved after 12-months treatment (p: 0.03), as well as FEF25-75% (p: 0.04) and TLC% (0.04). FEV1% and ACT showed a concomitant improvement (p: 0.03 and p: p: p: 0.048) and ACT at T12 (r: −0.59 p: 0.02). Conclusions: Twelve months treatment with mepolizumab improved R5–R20, suggesting its additional role as a targeted treatment for distal lung regions. This improvement also correlated with a clinically relevant amelioration of asthma symptoms.

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long‐acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long‐acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals. In addition to bronchodilation, LAMA also exert anti‐inflammatory and anti‐fibrotic effects by inhibiting muscarinic receptors present in neutrophils, macrophages, fibroblasts and airway smooth muscle cells. Thus, besides bronchodilation, LAMA might provide additional therapeutic effects, thereby supporting an endotype‐driven approach to asthma management. The Position Paper, developed by the Asthma Section of the European Academy of Allergy and Clinical Immunology, discusses the main cholinergic pathways in the lung, reviews the findings of significant clinical trials and real‐life studies on LAMA use in asthma, examines the placement of these drugs in asthma clinical guidelines, and considers the potential for personalised medicine with LAMA in both adult and paediatric asthma patients.

Background/Objectives: Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor (IL-5Rα), leading to the rapid depletion of blood eosinophils. RCTs have demonstrated efficacy in patients with severe eosinophilic asthma (SEA). The aim of this study was to assess the efficacy of benralizumab on sinonasal outcomes in a real-life setting in patients with SEA and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We included 25 patients (mean age: 57.47 years, range: 35–77, F/M = 12:13) who were prescribed 30 mg benralizumab every month for the first three administrations and then every 2 months. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test-22 (SNOT-22) and nasal polyp score (NPS) over a 24-month treatment period. Secondary endpoints included measuring the effects on nasal obstruction and impaired sense of smell. Results: The mean NPS score decreased significantly from 5.11 ± 1.84 at baseline to 2.37 ± 1.96 at 24 months. The mean SNOT-22 decreased from 57 ± 15.30 at baseline to 26 ± 16.73 at 24 months. The SSIT-16 mean score improved with an increase in olfactory performance from 5.23 ± 2.58 at baseline to 7 ± 3.65 at 24 months. Moreover, 8/25 patients (32%) required rescue treatment with systemic steroids and 2 patients required endoscopic sinus surgery. Conclusions: While the improvement may not seem optimal at 12 months, a progressive enhancement was noted during the second year of treatment. Despite our data showing an improvement in quality of life and a reduction in the size of nasal polyps, no significant improvement in olfactory sensitivity was observed. In addition, in several patients, rescue treatments were required to maintain control of nasal and sinus symptoms. A careful risk–benefit assessment is therefore needed when deciding to continue treatment, weighing the potential for further improvement against the risks of complications. Such decisions should always be made in the context of a multidisciplinary team.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID‐19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face‐to‐face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Bronchial hyperreactivity (BHR), also defined as airway hyperreactivity (AHR), is still nowadays one of the noteworthy pathophysiological elements defining asthma

Editorial Comment on: „Short-acting β 2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.”Boccabella C. 1, Kalayci O. 2, Eigenmann P. 3Affiliations1Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario “A Gemelli” - IRCCS, University of the Sacred Heart, Rome, Italy2Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey3Pediatric Allergy Unit, Department of Women-Children-Teenagers, University Hospitals of Geneva, Geneva, SwitzerlandAsthma is one of the most common chronic lung diseases with major public health consequences for both children and adults, including high morbidity and even mortality (1). For years, standard asthma treatment for mild asthma has been as needed short acting beta agonist (SABA). Global Initiative for Asthma (GINA) guidelines have questioned this approach suggesting that the use of SABAs should always be accompanied by inhaled corticosteroids (ICSs) (2). Recently, Papi et al. have shown that in adolescents and adults with uncontrolled moderate-to-severe asthma receiving inhaled glucocorticoid-containing maintenance therapies, the risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of albuterol and budesonide than with as-needed use of albuterol alone (3). In children, on the other hand, even though many years ago Martinez et al. have shown that inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children aged 5-18 years with well controlled mild asthma , SABA has remained to be the only reliever option recommended for those under 6 years of age (4).The SABA use IN Asthma (SABINA) program in adults and adolescents with asthma reported that SABA overuse (≥3 canisters/year) is prevalent in Sweden and is associated with poor asthma-related outcomes (5). Melen et al and the SABINA Junior investigators have attempted to investigate the same question in the paediatric population (6). This retrospective cohort study conducted in Sweden, has included patients with physician-diagnosed asthma (aged 0-17 years) in secondary care. Patients have been categorized by the number of SABA canisters collected (dichotomized as 0-2 vs ≥3, based on evidence from studies in adults and adolescents) from pharmacies at baseline and followed up over 12 months (5,7). During the baseline year, SABA overuse (≥3 canisters) has been registered for the majority of the study population, particularly for those aged 0-5 years. A strong correlation between SABA overuse and increased risk of exacerbation episodes has been observed. This result confirms what has been already seen among adult patients, that is strongly connected to the inflammatory nature of asthma disease. SABAs can resolve the immediate bronchospasm but have no anti-inflammatory actions and no effect on the late phase of inflammation. Furthermore, chronic and long-term use of SABAs seems also to contribute to a decreased response to SABA therapy as a reliever (8,9). SABINA investigators have also conducted a post-hoc analysis, stratifying study population based on the presence of atopic comorbidity. Interestingly, increased SABA use has been associated with a higher exacerbation risk also in nonatopic patients with asthma. This may be due to the lack of response to ICSs that is a distinctive aspect of non-atopic population who may in turn resort to the use SABA reliever treatment.There are still several questions that remain unanswered in children mainly due to the difficulties in obtaining data in this specific population. First, recruitment of paediatric patients especially those <6 years old into randomized controlled trials (RCTs) can be a challenge due to ethical issues. In addition, diagnosis of asthma in this age group is often problematic. Despite all the limits of a retrospective study, SABINA study provides extremely useful data in a population where there are hardly any solid data. These results emphasize the need for a better understanding of childhood asthma endotypes and the response to different drugs and disease behaviour over time. Avoiding asthma exacerbations and consequent disease progression should be the principal aim of clinical management in children. This may only be possible by linking the underlying pathophysiology with the clinical response to anti-asthma treatment.References1. Asher MI, Rutter CE, Bissell K, Chiang CY, El Sony A, Ellwood E, et al. Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study. Lancet. 2021;398(10311):1569–80.2. GINA committee. Global Strategy for Asthma Management and Prevention 2022 Update [Internet]. Global Initiative for Asthma. 2022. p. 225. Available from: http://www.ginasthma.org3. Alberto Papi, M.D., Bradley E. Chipps, M.D., Richard Beasley, D.Sc., Reynold A. Panettieri, Jr., M.D., Elliot Israel, M.D., Mark Cooper, M.Sc., Lynn Dunsire, M.Sc., Allison Jeynes-Ellis, M.D., Eva Johnsson, M.D., Robert Rees, Ph.D., Christy Cappelletti, P MD. Albuterol–Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. N Engl J Med [Internet]. 2022 Aug 17;387(7):662–3. Available from: https://doi.org/10.1056/NEJMc22091894. Martinez L, Handel A, Shen Y, Chakraburty S, Quinn FD, Stein CM, et al. detect tuberculosis in child contacts are urgently needed in Sub-Saharan Africa to improve case detection. n. 2018;197(9):2016–9.5. Nwaru BI, Ekström M, Hasvold P, Wiklund F, Telg G, Janson C. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: A nationwide cohort study of the global SABINA programme. Eur Respir J [Internet]. 2020;55(4). Available from: http://dx.doi.org/10.1183/13993003.01872-20196. Melen E., Nwaaru B., Wiklund F., Licht S., Telg G., Maslova E., Valk R.,...