Severe hypereosinophilia in a patient treated with dupilumab and shift to mepolizumab: the importance of multidisciplinary management. A case report and literature review.

Type 2 inflammation is a heterogeneous condition due to the complex activation of different immunological pathways. Rapid progress in research to evaluate the efficacy of biologics for chronic rhinosinusitis with nasal polyps and asthma has led to the availability of effective therapeutic options. These drugs are safe, but temporary iatrogenic hypereosinophilia may sometimes be associated with clinical symptoms or organ damage. Here, we describe a case of severe hypereosinophilia in a patient with chronic rhinosinusitis with nasal polyps and asthma treated with dupilumab and a subsequent therapeutic shift to mepolizumab that led to maintenance of symptom control and concomitant normalization of blood eosinophil count.

Tezepelumab: patient selection and place in therapy in severe asthma.

Asthma is a disease characterised by heterogeneous and multifaceted airway inflammation. Despite the availability of effective treatments, a substantial percentage of patients with the type 2 (T2)-high, but mainly the T2-low, phenotype complain of persistent symptoms, airflow limitation, and poor response to treatments. Currently available biologicals target T2 cytokines, but no monoclonal antibodies or other specific therapeutic options are available for non-T2 asthma. However, targeted therapy against alarmins is radically changing this perspective. The development of alarmin-targeted therapies, of which tezepelumab (TZP) is the first example, may offer broad action on inflammatory pathways as well as an enhanced therapeutic effect on epithelial dysfunction. In this regard, TZP demonstrated positive results not only in patients with severe T2 asthma but also those with non-allergic, non-eosinophilic disease. Therefore, it is necessary to identify clinical features of patients who can benefit from an upstream targeted therapy such as anti-thymic stromal lymphopoietin. The aims of this narrative review are to understand the role of alarmins in asthma pathogenesis and epithelial dysfunction, examine the rationale underlying the indication of TZP treatment in severe asthma, summarise the results of clinical studies, and recognise the specific characteristics of patients potentially eligible for TZP treatment.

Comparison between clinical trials and real-world evidence studies on biologics for severe asthma.

In recent years, the more widespread availability of biological drugs with specific mechanisms of action has led to significant breakthroughs in the management of severe asthma. Over time, numerous randomised clinical trials have been conducted to evaluate the efficacy and safety of these biologics and define the eligibility criteria of patients suitable for various therapeutic options. These studies were conducted under controlled conditions not always applicable to real life. For this and other reasons, real-world evidence and pragmatic studies are required to provide useful information on the effectiveness of biological drugs and their safety, even in the long term. Because differences in outcomes have sometimes emerged between clinical trials and real-life studies, it is important to clarify the causes of these discrepancies and define the significance of the results of studies conducted in the course of daily clinical practice. Thus, a scientific debate is ongoing, and no consensus has been reached. The purpose of this narrative review is to analyse the differences between randomised trials and real-world evidence studies, focusing on their roles in guiding clinicians among different therapeutic options and understanding the reasons for the large discrepancies often found in the results obtained.

Usefulness of sleep events detection using a wrist worn peripheral arterial tone signal device (WatchPAT™) in a population at low risk of obstructive sleep apnea.

Due to the high prevalence of obstructive sleep apnea (OSA), it is recommended to use in-laboratory polysomnography (PSG) or a home sleep apnea test (HSAT) in uncomplicated adult subjects at high risk of OSA. The aims of the present study were to compare a HSAT device, a wrist worn peripheral arterial tone signal device (WatchPAT™-200 [WP]) with PSG and respiratory polygraphy (RP) in a low-risk population of OSA. A total of 47 adult subjects at low risk of OSA were simultaneously examined with the three different approaches in a single night. The sleep studies were scored independently and in a blinded fashion, then the results and the parameters (Respiratory Disturbance Index, apnea-hypopnea index [AHI] and oxygen desaturation index of 3%) were compared with several statistical analyses. The agreement between the sleep tools and correlation for the assessed parameters were analysed and compared with Bland and Altman plots and Pearson's coefficient (WP versus PSG, r = 0.86). For the severity of OSA ranked according to PSG, the Cohen's k was 0.60 and 0.82 for WP and RP, respectively. Specificity was higher for RP compared to WP for identifying the presence of OSA (AHIPSG cut-off ≥5 events/hr: 0.85 versus 0.73), while was quite similar in identifying patients who were more likely to be treated (AHIPSG cut-off ≥15 events/hr: 0.94 versus 0.96). Assessing the costs and the simplicity of the examination, the results of our present study demonstrate the usefulness of WP compared to PSG, especially in screening and follow-up for the ability to exclude subjects from treatment with continuous positive airway pressure (AHI <15 events/hr) in a population with a low pre-test risk of moderate-to-severe OSA.