Second running title: Prediction of COPD-related exacerbations.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most important cause of death in high-income countries. Inappropriate use of COPD inhaled therapy, including the low adherence (only 10% to 40% of patients reporting an adequate compliance) may shrink or even nullify the proven benefits of these medications. As such, an accurate prediction algorithm to assess at national level the risk of COPD exacerbation might be relevant for general practictioners (GPs) to improve patient's therapy. METHODS: We formed a cohort of patients aged 45 years or older being diagnosed with COPD in the period between January 2013 to December 2021. Each patient was followed until occurrence of COPD exacerbation up to the end of 2021. Sixteen determinants were adopted to assemble the CopdEX(CEX)-Health Search(HS)core, which was therefore developed and validated though the related two sub-cohorts. RESULTS: We idenfied 63763 patients aged 45 years or older being diagnosed with COPD (mean age: 67.8 (SD:11.7); 57.7% males).When the risk of COPD exacerbation was estimated via CEX-HScore, its predicted value was equal to 14.22% over a 6-month event horizon. Discrimination accuracy and explained variation were equal to 66% (95% CI: 65-67%) and 10% (95% CI: 9-11%), respectively. The calibration slope did not significantly differ from the unit (p=0.514). CONCLUSIONS: The CEX-HScore was featured by fair accuracy for prediction of COPD-related exacerbations over a 6-month follow-up. Such a tool might therefore support GPs to enhance COPD patients' care, and improve their outcomes by facilitating personalized approaches through a score-based decision support system.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

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.

Safety of dupilumab in T2 airways conditions: focus on eosinophilia across trials and real-life evidence.

INTRODUCTION: Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, effectively blocks both IL-4 and IL-13 mediated pathways. Its introduction has represented a significant advancement in the treatment of severe asthma and other Type 2 (T2) conditions, including nasal polyps, atopic dermatitis, and eosinophilic esophagitis. To date, Dupilumab has demonstrated optimal efficacy and safety profile. AREAS COVERED: The safety profile of dupilumab has been extensively studied, especially for its effects on blood eosinophil count. Transient eosinophil increase during treatment is typically insignificant from a clinical point of view and related to its mechanism of action. Rare cases of hyper-eosinophilia associated with clinical conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) have been reported. Those cases are often related to the drug's steroid-sparing effect or the natural trajectory of the underlying disease rather than a direct cause-effect relationship with dupilumab. EXPERT OPINION: The management of hyper-eosinophilia during dupilumab treatment requires comprehensive diagnostic work-up and strict follow-up monitoring for early detection of systemic disease progression in order to avoid unnecessary discontinuation of an effective treatment. This approach highlights the importance of a personalized treatment.

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.

Antimicrobial Stewardship in COVID-19 Patients: Those Who Sow Will Reap Even through Hard Times.

BACKGROUND: Since the SARS-CoV-2 pandemic emerged, antimicrobial stewardship (AS) activities need to be diverted into COVID-19 management. METHODS: In order to assess the impact of COVID-19 on AS activities, we analyzed changes in antibiotic consumption in moderate-to-severe COVID-19 patients admitted to four units in a tertiary-care hospital across three COVID-19 waves. The AS program was introduced at the hospital in 2018. During the first wave, COVID-19 forced the complete withdrawal of hospital AS activities. In the second wave, antibiotic guidance calibration for COVID-19 patients was implemented in all units, with enhanced stewardship activities in Units 1, 2, and 3 (intervention units). In a controlled before and after study, antimicrobial usage during the three waves of the COVID-19 pandemic was compared to the 12-month prepandemic unit (Unit 4 acted as the control). Antibiotic consumption data were analyzed as the overall consumption, stratified by the World Health Organization AWaRe classification, and expressed as defined-daily-dose (DDD) and days-of-therapy (DOT) per 1000 patient-day (PD). RESULTS: In the first wave, the overall normalized DOT in units 2-4 significantly exceeded the 2019 level (2019: 587 DOT/1000 PD ± 42.6; Unit 2: 836 ± 77.1; Unit 3: 684 ± 122.3; Unit 4: 872, ± 162.6; p < 0.05). After the introduction of AS activities, consumption decreased in the intervention units to a significantly lower level when compared to 2019 (Unit 1: 498 DOT/1000 PD ± 49; Unit 2: 232 ± 95.7; Unit 3: 382 ± 96.9; p < 0.05). Antimicrobial stewardship activities resulted in a decreased amount of total antibiotic consumption over time and positively affected the watch class and piperacillin-tazobactam use in the involved units. CONCLUSIONS: During a pandemic, the implementation of calibrated AS activities represents a sound investment in avoiding inappropriate antibiotic therapy.

Sex differences in excessive oral corticosteroid exposure in poor adherent adult asthmatics overusing short-acting ß-2 agonists.

BACKGROUND: We know that excessive short-acting ß2-agonists (SABA) use in asthma may be associated to high exacerbation risks. We studied whether such excessive SABA consumption is connected with different higher oral corticosteroid (OC) prescriptions in the two sexes. METHODS: In our prescribing database, we searched subjects aged 18-40 years that were prescribed at least one SABA package/year and/or at least two ICS or two ICS/LABA boxes/year to identify asthmatics. Their OC prescriptions/year were also examined. Subjects were divided into 4 groups according to SABA packages/year prescribed (0, 1-2,3-6 and ≥7), considering sexes separately. RESULTS: Individuals recruited were 9,102. Subjects with at least one OC prescription were higher in each group and were females (P<0.001). The OC packages/year number was also more elevated in women especially those with >7 SABA prescriptions/year (0.96 in males vs. 2.64 in females, P<0.001). 94.7%/93.6% males/females, who never used SABA, took at least one ICS/LABA (mean 5.84/5.48 packages/year), while the subject percentage adhering to ICS/LABA dropped to 28-47% (mean 0.94-3.82 packages/year) in those who used SABA (P<0.001). Higher SABA prescriptions were associated with an increasing OC dispensation (ß=0.057, P<0.0001). We observed also a greater risk of using >3 OC packages/year in subjects with 3-6 (OR: 2.98 [95% CI: 2.19-4.06], P<0.001) and ≥7 (OR: 3.49 [95% CI: 2.39-5.10], P<0.001) SABA prescriptions compared to those that never used SABA. Besides, we found that using ICS (OR:0.51 [95% CI: 0.35-0.75], P<0.001) or ICS/LABA (OR:0.07 [95% CI: 0.05-0.09], P<0.001) may significantly reduce SABA prescriptions. CONCLUSIONS: Poor adherence to maintenance treatment appears to associated with excessive SABA prescriptions that may lead to a higher OC consumption particularly noticeable in women.

Variation in costs due to virtual switching from free- to fixed-triple LABA/LAMA/ICS combinations among COPD patients: an analysis using a primary care database.

Chronic obstructive pulmonary disease (COPD) is a condition with a relevant clinical and economic burden. Only 10% to 40% of COPD patients reporting a regular use of respiratory medications, including those who suffered from severe disease being prescribed with triple combination therapy, nominally long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid (ICS). The recent market launch of fixed-triple LABA/LAMA/ICS therapy might contribute to improve medications adherence and costs containment, given the use of a single instead of two or three inhalers. Few data are available on costs due to triple therapy prescribed for COPD. In specific, there are no studies providing data on the potential costs saving whether COPD patients exposed to free-triple combination therapy were switched to fixed-triple combination. In this respect, we simulated some scenarios of virtual switching and calculated the related cost savings.

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management.

INTRODUCTION: Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. It is currently indicated for the treatment of asthma, moderate-to-severe atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophilia has been reported as a potential adverse event in treated patients. AREAS COVERED: A selective search on PubMed and Medline up to January 2022 was performed, by focusing on dupilumab-induced hypereosinophilia described in clinical trials, real-life studies, and case reports. The possible mechanisms underlying dupilumab-induced hypereosinophilia and the eosinophil-related morbidity have also been explored. EXPERT OPINION: Dealing with dupilumab-induced hypereosinophilia represents a clinical challenge for clinicians managing patients on dupilumab therapy. An algorithm for the practical management of dupilumab-induced hypereosinophilia has been proposed, in order to properly investigate potential eosinophil-related morbidity and avoid unnecessary drug discontinuation.

Integrating supportive care into the multidisciplinary management of lung cancer: we can't wait any longer.

INTRODUCTION: Due to important achievements in terms of diagnostic and therapeutic tools and the complexity of the disease itself, lung cancer management needs a multidisciplinary approach. To date, the classical multidisciplinary team involves different healthcare providers mainly dedicated to lung cancer diagnosis and treatments. Nevertheless, the underlying disease and related treatments significantly impact on patient function and psychological well-being. In this sense, supportive care may offer the best approach to relieve and manage patient symptoms and treatment-related adverse events. AREAS COVERED: Evidence reports that exercise, nutrition, smoking cessation, and psychological well-being bring many benefits in patients with lung cancer, from both a physical and socio-psychological points of view, and potentially improving their survival. Nevertheless, supportive care is rarely offered to patients, and even less frequently these needs are discussed within the multidisciplinary meeting. EXPERT OPINION: Integrating supportive care as part of the standard multidisciplinary approach for lung cancer involves a series of challenges, the first one represented by the daily necessity of specialists, such as kinesiologists, dietitians, psycho-oncologists, able to deliver a personalized approach. In the era of precision medicine, this is an essential step forward to guarantee comprehensive and patient-centered care for all patients with lung cancer.

Future Perspectives of Revaluating Mild COPD.

In 2020, COPD was the third leading cause of death worldwide. Lung function is central for the diagnosis of this disease, and COPD severity is still partially classified based on airflow obstruction, which can range from "mild" (GOLD 1 group, FEV1 ≥80% predicted) to "very severe" (GOLD 4, FEV1 <30% predicted). However, the term "mild COPD" needs to be carefully analyzed. Several studies have shown that even in the presence of a mild obstruction, patients can have significant symptoms, physiological deterioration, evidence of emphysema, and suffer from recurrent exacerbations. Small airways pathology significantly correlates with the presence of symptoms, and it has been demonstrated that the onset of bronchiolitis occurs earlier than that of emphysema. These damages have long been known to not be detectable with conventional tests, and exclusive reliance on spirometry is not enough to adequately study and stage a patient with "mild COPD." Therefore, early identification of COPD is of utmost importance in the light of modifying the natural course of the disease. However, patients with early lung damage are yet to be included and studied in interventional clinical trials.

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE).

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (-35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments.

Multidisciplinary management of type 2 inflammatory diseases.

Greater understanding of molecular pathophysiology has led to the recognition that an excessive type 2 inflammatory response is at the basis of the pathophysiology of several inflammatory diseases including atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). Given the availability of biological agents that can permit management of specific disease endotypes, this reinforces the need for detailed characterization of these diseases through a multidisciplinary approach. Herein, these three conditions are briefly overviewed and practical guidance for a multidisciplinary approach to management is presented. Since type 2 inflammation is suppressed by steroids, drugs such as glucocorticoids have long been the workhorse of medical therapy. However, steroids have well-known local and systemic adverse effects, especially when used at high doses over prolonged periods of time, which is problematic when treating chronic diseases such as AD, asthma, and CRSwNP. Moreover, a substantial proportion of patients remain refractive to therapy. In the attempt to overcome these limitations, greater understanding of the molecular mechanisms of type 2 inflammation have led to the development of targeted biological drugs such as dupilumab, a fully human monoclonal antibody that targets the α chain of the IL-4 receptor. Dupilumab represents a unique therapy for type 2 inflammatory diseases and to date is the only therapy approved for AD, asthma, and CRSwNP. In terms of multidisciplinary management of type 2 inflammatory conditions, the main healthcare professionals involved include a dermatologist, pneumologist or allergologist, and ENT specialist. The model proposed herein takes into account the complex management of patients with type 2 inflammatory conditions and the new biological agents available. A multidisciplinary team can provide a central point for patient management, improve outcomes and specialist referrals, reduce costs, and guarantee that the most appropriate therapeutic decisions are made, as well as aid in management of adverse events. The multidisciplinary model should be structured and dedicated, but at the same time simple and flexible in order to not risk slowing down the patient's care. At present, it is believed that a structured multidisciplinary approach is currently the best means to optimize care of patients with type 2 inflammatory conditions.

Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study.

BACKGROUND: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients. METHODS: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed. RESULTS: 465 patients (54% males, 51% hospitalized) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalization and ICU stay vs. non-hospitalized status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress. CONCLUSIONS: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.

Lung cancer and interstitial lung diseases: the lack of prognostic impact of lung cancer in IPF.

Lung Cancer (LC) is the first cause of death worldwide. Recently increased interest in interstitial lung diseases (ILD) has highlighted an association with lung cancer, offering interesting insights into the pathogenesis of the latter. Describe the association between lung cancer and ILD and evaluate the impact of LC on survival in these populations. We collected clinical, radiological, histologic data of 53 cases of advanced pulmonary fibrosis with lung cancer: 17 with UIP pattern (usual interstitial pneumonia, UIP/IPF-LC) and 36 with non-UIP pattern (ILD-LC). Adenocarcinoma was the most frequent histological subtype of lung cancer in all three groups and in UIP/IPF-LC developed in the lung periphery and in an advanced fibrosis context. Patients with DLCO% < 38% showed survival < 10 months, irrespective of group and development of carcinoma in UIP/IPF does not necessarily affect survival, unlike in SR-ILD. Our results confirm that the oncogenic mechanism is closely linked to fibrotic and inflammatory processes and that the development of carcinoma affects survival in SR-ILD but not in IPF.

ARIA-ITALY multidisciplinary consensus on nasal polyposis and biological treatments.

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Assessment of COVID-19 progression on day 5 from symptoms onset.

BACKGROUND: A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. METHODS: Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. RESULTS: A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66-0.81) for predicting disease progression by day-11. CONCLUSION: An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians' decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

Organization, Clinical and Management Indicators on the First Year of Activity of an Outpatient Clinic Dedicated to the Diagnosis and Treatment of Severe Asthma in Italy.

PURPOSE: A Regional Technical Commission was set in 2017 by Veneto region (Italy) to provide opinions and recommendations on drug prescriptions and to implement treatment-pathway guidelines for severe asthma. In this observational study, we describe the first structured, integrated, multidisciplinary, patient-centered outpatient clinic for the care of severe-asthma patients in Italy, and characterize patients referring to the center for specialist visits. PATIENTS AND METHODS: To characterize patients that accessed the outpatient clinic in 2018, data on demographic characteristics, treatments, severity of asthma, phenotypes, and relevant comorbidities by phenotype were collected. Use of biologic agents and indicators of the performance of the outpatient clinic were described. RESULTS: A structured multidisciplinary outpatient pathway for taking charge of patients and for administration and monitoring of biological agents was developed. A total of 146 patients accessed the outpatient clinic in 2018: 62.3% had uncontrolled asthma upon admission and 27.4% were already being treated with biologic agents. Among patients with uncontrolled asthma, 66% had severe uncontrolled asthma, 22% had moderate-severe uncontrolled asthma, and 12% had mild-moderate uncontrolled asthma. Main asthma phenotypes in uncontrolled-asthma patients were allergic (58% of patients), eosinophilic (22%), allergic plus eosinophilic (10%) and non-atopic asthma (10%). Among patients affected by severe asthma, 47% had allergic asthma, 28% had eosinophilic asthma, 13% had allergic plus eosinophilic asthma, and 12% had non-atopic asthma. Nasal polyps were more frequent in eosinophilic and allergic plus eosinophilic asthma, while gastro-esophageal reflux disease was more frequent in non-atopic asthma. CONCLUSION: This structure of an outpatient clinic for the treatment of severe asthma, with its dedicated pathway and multidisciplinary approach, may allow a stricter control of asthma and optimization of therapies, as well as minimization of drug misuse.