Beyond diagnosis: a narrative review of the evolving therapeutic role of medical thoracoscopy in the management of pleural diseases.

Background and Objective: Medical thoracoscopy (MT) is an endoscopic technique performed by interventional pulmonologists with a favorable safety profile and few contraindications, providing diagnostic and therapeutic intervention in a single sitting. This narrative review was designed to summarize the therapeutic role of MT based on the latest results from the available literature. Methods: Pertinent literature published in English, relative to human studies, between 2010-2022 was searched in Medline/PubMed and Cochrane databases. Publications regarded as relevant were considered for inclusion in this review; additional references were added based on the authors' knowledge and judgment. The review considered population studies, meta-analyses, case series, and case reports. Key Content and Findings: MT has mostly been described and is currently used globally in the diagnostic approach to exudative pleural effusion of undetermined origin. Carefully evaluating the literature, it is clear that there is initial evidence to support the use of MT in the therapeutic approach of malignant pleural effusion, pneumothorax, empyema, and less frequently hemothorax and foreign body retrieval. Conclusions: MT is an effective procedure for treating the clinical entities presented in this document; it must be carried out in selected patients, managed in centers with high procedural expertise. Further evidence is needed to assess the optimal indications and appropriate patients' profiles for therapeutic MT. The endpoints of length of hospital stay, surgical referral, complications and mortality will have to be considered in future studies to validate it as a therapeutic intervention to be applied globally.

Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies.

Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.

Environmental Impact of Bronchoscopy: Analysis of Waste Mass and Recyclability of Bronchoscopic Equipment and Consumables.

BACKGROUND: Greenhouse gases (GHGs) are significant contributors to climate change, and CO2 equivalent (CO2-e) is measured to compare emissions from GHGs. The healthcare sector contributes 4.4% of global CO2-e emissions, mainly with energy consumption and, in lesser extent, waste production. In this regard, bronchoscopy procedures produce a large amount of waste and are responsible for a significant consumption of energy. OBJECTIVE: We aimed at quantifying the impact on waste mass production, energy consumption, and recyclability of bronchoscopic procedures. METHODS: We conducted a prospective single-centre observational study; for each type of procedure (performed with either reusable or single-use instruments), the number of items used, their weight, and recyclability were evaluated, as well as the material of which recyclable waste was made of. We then calculated the total amount of waste produced, its recyclability, energy consumption, and CO2-e produced over 10 days of activity in our Interventional Pulmonology Unit. RESULTS: Sixty procedures generated 61,928 g of waste, of which only 15.8% was potentially recyclable. Single-use instruments generated nearly twofold more recyclable waste than reusable ones, 80% during the procedure phase. Reusable instruments generated 45% of waste during the reprocessing phase, of which 50% was recyclable. The recyclable material was totally composed of paper and plastic. During 10 days of activity, we consumed 64 kWh and produced more than 67 kg of CO2-e due to non-recyclable waste and energy consumption. CONCLUSIONS: Our results confirm the compelling need to recycle as many materials as possible, even if the amount of recyclable waste is limited. In this respect, official documents issued by international societies are urgently needed to align our activity with climate requirements and improve the sustainability of our work.

A Review: The Potential Involvement of Growth Arrest-Specific 6 and Its Receptors in the Pathogenesis of Lung Damage and in Coronavirus Disease 2019.

The tyrosine kinase receptors of the TAM family-Tyro3, Axl and Mer-and their main ligand Gas6 (growth arrest-specific 6) have been implicated in several human diseases, having a particularly important role in the regulation of innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells and this mechanism has been exploited by viruses for cell entry and infection. Coronavirus disease 2019 (COVID-19) is a multi-systemic disease, but the lungs are particularly affected during the acute phase and some patients may suffer persistent lung damage. Among the manifestations of the disease, fibrotic abnormalities have been observed among the survivors of COVID-19. The mechanisms of COVID-related fibrosis remain elusive, even though some parallels may be drawn with other fibrotic diseases, such as idiopathic pulmonary fibrosis. Due to the still limited number of scientific studies addressing this question, in this review we aimed to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms underlying COVID-19, with emphasis on the development of a fibrotic phenotype.

Endobronchial ultrasound: a pictorial essay.

BACKGROUND AND AIM: endobronchial ultrasound has gained widespread popularity in the last decade, becoming the primary technique for minimally invasive evaluation of the mediastinum and staging of lung cancer. Several tertiary and quaternary care institutes use this method, performed by trained and accredited specialists. Its main indications are (I) diagnosis and staging of lung cancer, (II) mediastinal lymphadenopathy diagnosis (III) sampling peripheral pulmonary lesions. CONCLUSIONS: this manuscript aims to describe the operational potential of both convex endobronchial ultrasound probe and radial endobronchial ultrasound probe technology, focusing on lung cancer. This narrative review is complemented with by the description of peculiar clinical cases in which endobronchial ultrasound played a pivotal role in reaching the diagnosis.

Measure of lung dielectric proprieties in patients with Idiopathic Pulmonary Fibrosis: correlation with clinical, radiological and pulmonary functional parameters.

BACKGROUND: Dielectric properties of biological tissues are biophysical parameters; in lung they change with amount of air, blood and parenchyma. Remote Dielectric Sensing (ReDS™) technology measures dielectric properties of lung tissues quantifying the content of fluids inside the scan volume. We aimed to evaluate the reliability of ReDS™ measure in Idiopathic Pulmonary Fibrosis (IPF) patients and in healthy volunteers, and to investigate the correlation of ReDS™ score with clinical, radiological and functional parameters. METHODS: We conducted a prospective observational study, including 52 patients with diagnosis of IPF and 17 healthy volunteers; for each patient we recorded: complete functional evaluation, dyspnoea score (mMRC scale), Usual Interstitial Pneumonia (UIP) Computed Tomography (CT) pattern (UIP definite or probable) and ReDS™ measure (expressed in %). RESULTS: ReDS™ measure was reported as correct both in patients and controls, the firsts with higher scores (33.8% vs 29.1%, p = 0.003). In IPF patients we observed a significant inverse correlation with ReDS™ score and Forced Vital Capacity (FVC), Vital Capacity (VC) and Total Lung Capacity (TLC) measures and, when we considered only patients with UIP definite CT pattern, the correlation was inverse with FVC, VC, TLC, DLCO. In IPF patients the higher was mMRC dyspnoea index, the higher was ReDS™ score. No significant correlations were observed between ReDS™ score and functional parameters in healthy controls. DISCUSSION: We demonstrated a correlation of ReDS™ scores with some functional (mainly indicative or diagnostic for restriction) and clinical parameters in IPF patients; the score was correlated with density of tissues possibly quantifying tissue fibrosis in IPF patients.

Idiopathic Pulmonary Fibrosis and Post-COVID-19 Lung Fibrosis: Links and Risks.

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated molecular patterns generating pro-fibrotic pathways or downregulating anti-fibrotic agents. Post-COVID pulmonary fibrosis (PCPF) is an emerging clinical entity, following SARS-CoV-2 infection; it shares many clinical, pathological, and immune features with IPF. Similarities between IPF and PCPF can be found in intra- and extracellular physiopathological pro-fibrotic processes, genetic signatures, as well as in the response to antifibrotic treatments. Moreover, SARS-CoV-2 infection can be a cause of acute exacerbation of IPF (AE-IPF), which can negatively impact on IPF patients' prognosis. In this narrative review, we explore the pathophysiological aspects of IPF, with particular attention given to the intracellular signaling involved in the generation of fibrosis in IPF and during the SARS-CoV-2 infection, and the similarities between IPF and PCPF. Finally, we focus on COVID-19 and IPF in clinical practice.

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Combining three-dimensional fluoroscopy guide system with single-use bronchoscopes for diagnosis of peripheral lesions: First two cases.

Pulmonary Peripheral Lesions (PPLs) diagnosis is usually performed using a guidance system in combination with bronchoscopes and diagnostic tools. We report two cases of PPLs sampling procedures combining the use of the single-use bronchoscope Ambu aScope 5 Broncho and CIOS 3D Spin Mobile (Siemens Healthineers) fluoroscopy system. A 69-year-old-female was found to have a lesion located in right B6 segment and a 73-year-old-male with a mass in the upper right lobe. We used for both cases a single-use bronchoscope to reach the correct area and the fluoroscopy system to guide peripheral transbronchial aspiration needle (TBNA) sampling. After the confirmation of the correct location of the TBNA tool, the sampling was performed. Rapid onsite evaluation (ROSE) confirmed the adequacy of the sample for molecular analysis and the final diagnosis. Thus, the use of ever-new disposable bronchoscopes for sampling peripheral lesions is a viable alternative to reusable bronchoscopes for advanced bronchoscopy procedures.

Interventional pulmonology techniques in lung transplantation.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.

Vitamin D in Systemic Sclerosis: A Review.

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis.

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07-7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19-7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

Keep on tailoring CMV management in lung transplantation: 24 versus 12-month CMV hyperimmune globulins regimen effects in combined universal prophylaxis.

BACKGROUND: In lung transplantation (LTx), Cytomegalovirus (CMV) management is based on prophylaxis or pre-emptive therapy. CMV hyperimmune globulins (CMV IG) added to prophylactic antiviral agents reduce CMV manifestations and acute rejection. The length of prophylaxis regimens is variable among studies with different results. METHODS: We conduced, after demonstrating efficacy of 12 months prophylaxis on acute rejections and CMV pneumonia, a single center retrospective study comparing, during the second year after LTx, clinical effects of a long (24 months) versus short (12 months) course of combined CMV prophylaxis scheme, based on antiviral agents and CMV IG. RESULTS: We included 120 patients, 70 received a long (24 months) and 50 a short (12 months) prophylaxis. The long prophylaxis group, at 18th month, had a lower rate of neutrophilic alveolitis in BAL (63.6% vs. 94.4%, P=0.029). No other statistically significant differences were observed among the two groups of patients although we observed a reduction in both CMV (56.4% vs. 76.0% P=n.s.) and bacterial infections (23.7% vs. 32.0%, P=n.s.) during the 18th month of follow-up. We did not observe differences among two groups in acute rejection rate on transbronchial lung biopsies. CONCLUSIONS: The combined long prophylaxis course based on antiviral agents and CMV IG provides a reduction trend in CMV or bacterial infections even if not statistically significant. The significant reduction in neutrophilia in BAL compared to the cohort undergoing prophylaxis for 12 months should be carefully interpreted. An 18-month prophylaxis could be a good suggestion to be tested by other larger prospective studies.

Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort.

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of "Maggiore della Carità" University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5−53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8−252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6−54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1−99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9−103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4−204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

Baseline plasma SARS-CoV-2 RNA detection predicts an adverse COVID-19 evolution in moderate to severe hospitalized patients.

BACKGROUND: SARS-CoV-2 is a single-stranded RNA virus, known to be the causative agent of COVID-19. As the resulting disease shows a very heterogeneous range of clinical manifestations, the identification of early biomarkers allowing patients stratification according to the expected disease severity is still an unmet clinical need. METHODS: In this observational prospective cohort study, 137 consecutive patients, testing positive for SARS-CoV-2 infection by nasopharyngeal swab RT-PCR or antigenic test, were enrolled to evaluate their plasma viral load at the time of hospitalization. RESULTS: Even if all of them had a molecular diagnosis of COVID-19, only 29 patients showed a detectable plasma SARS-CoV-2 RNAemia. Such viremic patients also showed other clinical and laboratory finding alterations (increased troponin I, IL-6, RDW-CV, and creatinine levels along with decreased platelet count and glomerular filtration rate). A plasma detectable RNA viral load predicted in hospital death or ICU admission with an odds ratio of 3.53 (CI: 1.44-8.64, P=0.0058), while the lack of a detectable viral load was associated with a faster recovery, with an odds ratio of 4.06 (CI: 1.72-9.59, P=0.0014). These findings were confirmed in multivariate models including age, sex and baseline National Early Warning Score 2 and arterial oxygen tension over inspired oxygen fraction ratio. CONCLUSIONS: Our data thus suggest that plasma viral RNA load at the time of hospital admission could represent a useful independent biomarker allowing early patients' stratification according to the expected disease evolution, and driving clinical decisions tailored on the specific needs of the individual patient.

Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality?

Chronic obstructive pulmonary disease (COPD) is a complex disease which consists in the reduction of the airflow and leads to the disruption of the pulmonary tissue due to a chronic inflammation. The progression of the disease is characterized by an exacerbation of the symptoms and the presence of life-threatening systemic complications, such as stroke and ischemic heart disease, with a progressive decline in lung function which can deeply impact the quality of life. Mortality represents the most important COPD outcome, with an increased risk in patients with cardiovascular comorbidities. The efficacy and safety of triple inhaled therapy were demonstrated by numerous controlled trials. Above all, many robust data are now available on the effectiveness of the triple therapy to reduce mortality in COPD patients.

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database.

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1-17.8] vs. 7.9 [3.8-12.9] ng/mL and 34.8 [26.4-47.5] vs. 29.8 [22.1-41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00-1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00-1.02] and 1.04 [1.02-1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00-1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02-1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.

Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center.

INTRODUCTION: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased annual exacerbations (AE) and improved asthma control test (ACT). METHODS: In 90 SEA patients being treated with a biological drug, clinical examination, ACT, blood eosinophils count and spirometry were assessed before (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4) months from the start of biological therapy. Patients were considered responders (R) or non-responders (NR) to biologics depending on whether or not they had less than two AE and a 20% increase in the ACT after 12 months of treatment. RESULTS: 75% of the patients were R, 25% NR. In R patients, biological therapy add-on was followed by significant improvement in AE and ACT throughout the whole follow-up period. The percentage of patients on oral corticosteroids (OCS) dropped from 40% to 12%. By contrast, the NR patients were shifted to another biological drug after 12 months of therapy, as they still had high AE and nearly unchanged ACT; 40% of them still needed OCS treatment. The predictors of switching to another biological drug were three or more AE, ACT below 17, nasal polyposis and former smoking (p < 0.05). In NR, the shift to another biological drug was followed by a significant decrease in AE and an increase in the ACT. DISCUSSION: This real-life study confirms the long-term efficacy of biologics in most SEA patients and indicates that even in non-responders to a first biological drug, it is worth trying a second one. It is hoped that the availability of additional biologics with different targets will help improve the personalization of SEA therapy.