INTRODUCTION:Timely initiation of biologic therapies is crucial in the management of severe asthma. However, delays in diagnosis and access to advanced treatments are common in real-life settings. We investigated disease progression and trajectories, with a focus on the impact of treatment latency among patients with severe asthma. METHODS:This longitudinal observational analysis included adult patients with severe asthma enrolled in the Italian Registry on Severe Asthma (IRSA). Data were stratified by use and timing of biologic therapy. Two core analyses were conducted: (1) characterization of patients not receiving biologics; (2) evaluation of disease progression and the relationship with the timing of biologic initiation. RESULTS:At baseline, 43.7% of the 2,114 patients were not receiving biologics, despite having severe disease and a T2-high phenotype. The average time of progression from initial diagnosis to severe asthma was 17 years. The median time from severe asthma diagnosis to biologic initiation was 2 years (IQR: 0.9-4.2). At the 1-year follow-up, patients who initiated biologics after enrollment showed the most significant clinical improvements compared with patients without biologic treatment or already on biologics at baseline, including a 64.8% reduction in the number of exacerbations (p = 0.019), a mean reduction in annual exacerbation rate of 4.1 events (p < 0.001), and an increase of 6.3 points in ACT score (p < 0.001). CONCLUSION:Severe asthma often develops after a prolonged progression from initial symptom onset. Structured referral and earlier biologic initiation may be associated with better outcomes and potentially influence the clinical trajectory of severe asthma.

OBJECTIVES:Eosinophilic granulomatosis with polyangiitis (EGPA) and idiopathic hypereosinophilic syndrome (iHES) are systemic hypereosinophilic diseases largely overlapping. Type 2 (T2)-eosinophilic asthma is documented in 100% and 44-95% of EGPA and iHES patients, respectively, probably representing the beginning of the systemic eosinophilic disorders, as suggested by mepolizumab, effective in both asthma and EGPA/iHES. In this respect, there are no predictive biomarkers of progression from T2-eosinophilic asthma into EGPA/iHES. Immunoglobulins G type 4 (IgG4) take part in T2-eosinophilic inflammation, and elevated serum IgG4 have been previously documented in asthma, EGPA and HES. The objective of this study was to compare serum IgG4 between T2-eosinophilic asthma and EGPA/iHES in order to identify significant differences that could represent a reasonable background for prospective studies on IgG4 as potential predictive biomarker of progression from asthma to EGPA/iHES. METHODS:In this retrospective/cross-sectional case-control study, patients affected by T2-eosinophilic asthma or EGPA/iHES were consecutively enrolled. All patients underwent blood tests for serum IgG4. Asthmatics and EGPA/iHES patients were stratified upon serum IgG4 values (normal or elevated). RESULTS:62 patients were enrolled (27 asthmatics, 35 EGPA/iHES). The frequency of patients with elevated serum IgG4 was higher in the EGPA/iHES group than in the asthmatics (45.7% vs. 11.1%, p=0.003), as well as the mean serum IgG4 value (p=0.010). CONCLUSIONS:Elevated serum IgG4 seemed to discriminate between T2-eosinophilic asthma "alone" and T2-eosinophilic asthma evolved into EGPA/iHES. This finding could represent a reasonable background for prospective long-term studies on asthmatic naive patients aimed at investigating IgG4 as a potential predictive biomarker of progression from asthma to EGPA/iHES.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 μg/m3 (PM10), 20.1 ± 5.6 μg/m3 (PM2.5), 27.2 ± 9.7 μg/m3 (NO2), and 70.8 ± 4.2 μg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10 μg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 μg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.

Summary:Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

INTRODUCTION:Approximately 3-10% of people with asthma have severe asthma (SA). Patients with SA have greater impairment in daily life and much higher costs. Even if asthma affects the entire bronchial tree, small airways have been recognized as the major site of airflow limitation. There are several tools for studying small airway dysfunction (SAD), but certainly the most interesting is oscillometry. Despite several studies, the clinical usefulness of oscillometry in asthma is still in question. This paper aims to provide evidence supporting the use of oscillometry to improve the management of SA in clinical practice.AREAS COVERED:In the ATLANTIS study, SAD was strongly evident across all severity. Various tools are available for evaluation of SAD, and certainly an integrated use of these can provide complete and detailed information. However, the most suitable method is oscillometry, implemented for clinical routine by using either small pressure impulses or small pressure sinusoidal waves.EXPERT OPINION:Oscillometry, despite its different technological implementations is the best tool for determining the impact of SAD on asthma and its control. Oscillometry will also be increasingly useful for choosing the appropriate drug, and there is ample room for a more widespread diffusion in clinical practice.

The pathogenic role of p-ANCA in eosinophilic granulomatosis with polyangiitis (EGPA) is a long-standing matter of debate. In this work, we report our real-life experience with EGPA patients, treated with biologics targeting type 2 (T2)-eosinophilic inflammation (Mepolizumab, Benralizumab, Dupilumab). Interestingly, we observed EGPA extrarespiratory relapses only in p-ANCA-positive patients (2/5 cutaneous vasculitis, 3/5 constitutional symptoms), with new rise of p-ANCA and normal eosinophil blood count. Notably, revising our cohort with the new ACR 2022 criteria, these five patients were the only ones to satisfy the entry criterion of vasculitis’ defined diagnosis at disease onset. These observations may suggest that biologics, selectively turning off T2 inflammation, may have unmasked p-ANCA exclusive role in the pathogenesis of vasculitis in EGPA. Therefore, we raise the question whether EGPA vasculitis exists only in p-ANCA-positive patients, and whether p-ANCA-negative disease is “only eosinophils without vasculitis”.

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choices or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy.

BACKGROUND:According to expert consensus, the time interval between Hymenoptera venom immunotherapy (VIT) injections can be extended up to 12 weeks, without significant impact on efficacy and safety. However, the coronavirus disease 2019 pandemic caused longer delays, and no recommendations are available to manage this huge extension. OBJECTIVES:To provide advice on how to resume VIT safely after a long delay from the last injection considering the potential risk factors for side effects, without starting again with the induction phase. METHODS:All the patients who delayed VIT because of the pandemic were consecutively enrolled in this single-center study. The time extension was decided according to their risk profile (eg, long prepandemic time interval, severe pre-VIT reaction, older age, multitreatments), and correlation analyses were performed to find potential risk factors of side effects. RESULTS:The mean delay from the pre- (7 weeks) to the postpandemic VIT interval (15.5 weeks) was 8.5 weeks. The total amount of the prepandemic VIT maintenance dose was safely administered in 1 day in 78% of patients, whereas only 3, of 87, experienced side effects, and their potential risk factors were identified in bee venom allergy and recent VIT initiation. CONCLUSIONS:In a real-world setting, long VIT delays may be safe and well tolerated, but more caution should be paid in resuming VIT in patients with long prepandemic maintenance interval, severe pre-VIT reaction, recent VIT initiation, older age, multidrug treatments, and bee venom allergy. This is useful in any case of long, unplanned, and unavoidable VIT delay.

Introduction: The Global Initiative for Asthma recommend Tiotropium (TIO) Respimat add-on therapy for patients with uncontrolled severe asthma (SA) (step5). Randomized double blinded studies showed that Tiotropium-Respimat added to high dose Inhaled Cortico-Steroids (ICS)/ Long-Acting β2-Agonists (LABA) treatment significantly improved lung function thus extending the time to the first asthma exacerbation and reducing frequency. Aim: To assess the use of triple inhaler therapy in Allergy and Pulmonology Departments adhering to the Italian Registry of Severe Asthma (IRSA). Methods: We analysed 1218 patients enrolled in the IRSA. All patients provided written informed consent. Results: 1215 patients (477 male, 738 female) were included in the analysis. 41% patients were treated with ICS/LABA/TIO and 59% with ICS/LABA. Patients taking Triple therapy had a worse lung function (FEV1 67%±21 vs 75%±20; p<0.001), high number of exacerbation/year (3.9±4 vs 2.8±3; p>0.001) and were regularly treated with systemic steroids (37% vs 28%). However, they had reduced IgE levels (520±1475 vs 561±1194). In addition, 57% of ICS/LABA/TIO patients used biologics compared to 66% of LABA/ICS patients. Conclusions: To reduce exacerbations, LABA/LAMA/ICS are recommended in patients with uncontrolled SA. Moreover, the optimization of inhaler therapy is mandatory before starting biological treatment approach. IRSA network revealed a low percentage of patients treated with triple combination therapy also in those using biologics. Additionally, IRSA Centres used to prescribe triple therapy especially to patients with more SA and a non-allergic phenotype.

Background: Very few studies have examined whether marital/relationship status affects respiratory diseases. Objective: Assess the association of relationship status (Rstatus: domestic partnership/civil union/marriage, cohabitation with non-partners, being single) with current (CA) and past asthma (PA), allergic (AR) and non-allergic rhinitis (NAR), and chronic bronchitis (CB). Methods: Data were collected in the frame of GEIRD, a population-based, multicase-control survey. Among 2531 subjects (age 21–86, female 50%) who underwent standardized interviews, skin prick and lung function tests, 575 cases of CA, 268 cases of PA, 968 cases of AR, 462 cases of NAR, 265 cases of CB without airflow obstruction and 832 controls were identified. The association of Rstatus with respiratory diseases was evaluated by logistic regression for CB and multinomial regression for CA and PA and for AR and NAR, adjusting for sex, age, smoking, education, employment status, the centre and the interaction between sex and relationship status. Results: The Rstatus was not associated with CA and PA, nor with AR and NAR. An interaction between sex and Rstatus (p=0.004) was identified when considering CB. After adjustment for potential confounders, in women living with non-partners and in single women the likelihood of CB was significantly higher than in women in a domestic partnership/civil union/marriage (OR=2.81, 95%C.I.:1.62-4.87 and OR=2.71, 95%C.I.:1.43-5.14, respectively). There was no association between the Rstatus and CB in men. Conclusions: These findings suggest a higher risk of chronic bronchitis in women without a partner, while relationship status has not been found to be associated with asthma or rhinitis in both sexes.

Background Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated. Aims To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis. Methods We investigated 2887 subjects aged 20–84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed “gastritis or stomach ulcer (confirmed by gastroscopy)” or “gastroesophageal reflux disease, hiatal hernia or esophagitis”. The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression. Results The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56–5.62) and sinusitis (RRR = 3.70, 2.62–5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37–2.35).. Conclusion The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

Introduction: Comorbidities in patients affected by severe asthma (SA) have different impact on asthma symptoms control. Moreover, prevalence rate of SA comorbidities are often increased by chronic Oral-Steroids (OCS) treatments. Aim: We evaluated the prevalence of comorbidities in patients enrolled in the Italian Registry of Severe Asthma (IRSA). Methods: 1218 patients were analysed and comorbidities were evaluated in four main treatments groups: (A) Long-Acting β2-Agonists+Inhaled-Cortico-Steroids (LABA+ICS), (B) LABA+ICS+other drugs, (C) LABA+ICS+Other drugs+Biologics, (D) OCS for over three months +Other drugs. Results: 1196 patients were analysed and one comorbidity affected 88% of subjects. Most common comorbidities were: sinusitis (52%), gastroesophageal reflux (GER) (44%), nasal polyposis (44%), hypertension (31%), obesity (20%), osteoporosis (20%), cataract (9%), diabetes (7%). Group D had more comorbidities with a prevalence of osteoporosis and cataract compared to other groups (D vs B and D vs C, p<0.001). Diabetes was common in Group B (8.5%) and D (8.4%). Obesity, GER and hypertension were equally distributed among Groups Conclusions: SA patients showed high comorbidities prevalence and reduced symptoms control. Moreover, chronic use of OCS strongly influences comorbidities rate. For those reasons, Biologics treatment optimization and OCS sparing interventions should be considered to reduce related comorbidities.

Introduction: Severe asthma (SA) has relevant pharmacological and socio-economic impact. Besides an adequate inhalation therapy, patients frequently require oral corticosteroids (OCS) for asthma control. However, log-term OCS use is associated with adverse effects. Aim: We assessed asthma control and the characteristics of patients treated with OCS in Allergy and Pulmonology Departments adhering to the Italian Registry of Severe Asthma (IRSA). Methods: IRSA is an Italian, multicenter, transversal/retrospective, non-interventional, observational study on patients ≥14years affected by SA according to GINA Guidelines. Data on asthma control and patients regularly treated with OCS were analysed. Results: Overall, 1216 patients (477 male, 739 female) were included in the analysis. According to the Asthma Control Test scoring, 409 patients were controlled with a mean FEV1 78±21%. As add-on to inhalation therapy, 383 patients took OCS: Dexamethasone 0.7%, Deflazacort 1.6%, Betamethasone 2.7%, Methylprednisolone 8.5%, Prednisone 17.6%. Among patients, 15% treated with OCS were controlled and 40% were uncontrolled asthmatics. Patients with uncontrolled asthma had high eosinophilia (577cells/ul ± 800) compared with controlled (432cells/ul ± 632). Moreover, patients with eosinophilia (n=675) took OCS in 34.5% of cases, and only 60% were treated with biologics. Conclusions: Despite high-dose inhalation therapy plus additional controllers or OCS, only 34% of patients affected by SA had controlled asthma. Moreover, 31% of subjects daily took OCS. Of note, uncontrolled patients had a high eosinophilia and few were properly treated with biologics.

Introduction: Severe Asthma (SA) affects 5% of the asthma population and patients have frequent exacerbations and inadequate asthma control although appropriate treatment. Biological therapies represent a major advancement in the management of SA however, due to the heterogeneity of clinical outcomes and phenotypes the use of specific biomarkers is pivotal to identify the most effective treatment. Aim: We evaluated how Italian Allergists and Pulmonologists approach SA patients and manage biomarkers for asthma phenotyping and the identification of the most appropriate treatment. Methods: AAIITO and AIPO-ITS submitted a multiple choice survey questions to Allergy and Pulmonology Departments adhering to the Italian Registry of Severe Asthma. Results: The 87.85% of Centers used biomarkers in clinical practice considering useful in the diagnosis of SA (99.07%). Blood eosinophils count (97.78%), total serum IgE (85.56%) and exhaled Nitric Oxide (72.22%) are the most used. High IgE are related to uncontrolled atopic asthma phenotype, with a positivity to perennial allergens, potentially treatable with Omalizumab. On the contrary, high levels of blood eosinophils identified a phenotype suitable for treatment with Mepolizumab. Low values of eosinophils and IgE characterized patients who could benefit from thermoplastics. Periostin and IL5 are considered possible future effective biomarkers. Centers declared to manage 35 SA patients/Center and to be authorized for monoclonal antibodies therapies (84.5%). Conclusions: A close collaboration between Allergists and Pulmonologists is pivotal to recognize the importance of biomarkers in the diagnosis, phenotyping and monitoring of SA.

Background: Hymenoptera stings are accountable for significant morbidity and deterioration in health-related quality of life due to the allergic reactions they cause, the most severe of which can culminate in fatal anaphylaxis. The availability of high quality venom extracts for use in the diagnosis and treatment of insect venom allergy has improved the prognosis and the health-related quality of life of venom-allergic patients. All over the world subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy with an early, sustained and long-term efficacy. Even though the type of insect responsible for allergic reactions may be different from Europe and US and therefore also the type of extract, nevertheless indications and contraindications are quite similar, as well as treatment protocols and treatment duration. However, neither the efficacy nor the safety of the treatment are optimal, especially with regard to bee venom immunotherapy, and so there is considerable room for further improvement in these important areas. Purpose: This review presents the current practice of venom immunotherapy in Europe and United States discussed at the EAACI (European Academy of Allergy and Clinical Immunology) Allergy School on Insect Venom held in Groningen in April 2019.

To the Editor, Severe asthma (SA) is a chronic disease affecting around 3-8% of adult asthma population in Europe, with the refractory form estimated to occur in 0.1% of the general population (1,2). SA is characterized by increased use of healthcare resources (i.e. emergency room/hospital admissions, access to intensive care units (ICU), use of biologics) due to exacerbations compared to the less severe form. In the current SARS-CoV-2 pandemic, there is an ongoing debate on the role of asthma and use of immunomodulating drugs, like corticosteroids and biologics, on COVID-19 outcomes. According to available data on COVID-19 hospitalizations, asthma seems to play little role on the clinical severity or access to health resources, unlike other chronic conditions such as hypertension, obesity and chronic obstructive pulmonary disease (3). However, to date, no information is available on the burden of SA on COVID-19 severity and hospitalization rates.A questionnaire was submitted to the Italian Registry of Severe Asthma (IRSA) network (4), assessing the prevalence and clinical characteristics of patients with SA who contracted COVID-19 during the outbreak in Italy (February 24th - May 18th 2020), and 41 out of 78 centers distributed evenly among different Italian regions participated to the survey (Figure 1a).Among the 558 subjects surveyed, 7 subjects contracted COVID-19 (1.25% of the national sample), with an average age of 54.5 years: 5 isolated at home/received home care (71.5%), while 2 subjects were admitted to the hospital (28.5%), none required accessed to ICU and no deaths were reported. All COVID-19 subjects with SA came from 2 regions of Northern Italy (6 Lombardy, 1 Emilia-Romagna, 3.7% of the regional population), all showing one or more comorbidities, and were treated with high-dose inhaled corticosteroids plus long-acting beta-2 agonists (ICS-LABA) and biologics (see Table 1).We then compared our results with data provided by the Italian Department for Civil Protection in the same time period from the affected geographic areas (5), and we observed that the frequency of COVID-19 among subjects referred to IRSA centers strongly correlated with the prevalence of SARS-CoV-2 infection in the corresponding province (Figure 1b). Furthermore, the hospitalization rate in COVID-19-SA subjects was not significantly different from the general population (24.1%, 23.6-24.6 95% C.I.; p=0.25, Chi-squared test). Lastly, we could not observe a significantly increased COVID-19 frequency in subjects undergoing high-dose ICS-LABA and biologics compared to SA treated with ICS-LABA alone (p=0.09, Fisher exact test).These findings from the IRSA registry offer some insights on the susceptibility to SARS-CoV-2 infection, access to healthcare resources and mortality by SA patients.Given the low prevalence of SA in Italy (2), we expected less COVID-19-SA cases per region than what reported by the IRSA survey. However, we observed that the geographic location of COVID-19-SA patients mostly reflected the bimodal distribution of the COVID-19 outbreak in Italy, mainly clustered in Lombardy and neighboring regions, where the highest cumulative COVID-19 cases were recorded (>500/100000 cases per inhabitants) (5). In these areas, the prevalence of positive cases by province also strongly correlated with the frequency of COVID-19-SA patients observed in each IRSA center (Figure 1b), suggesting that patients with SA most likely contract the infection when high circulation of the virus within the area of residence is present. The lack of positive cases reported in Southern regions further proves this hypothesis, and demonstrates the efficacy of the lockdown measures adopted to contain the further spread of the virus.Our results also suggest no increased risk of contracting COVID-19 in SA treated with biologics compared to ICS-LABA alone. Although there is currently no strong evidence that biologics used in asthma might affect the risk of contracting COVID-19, new evidence suggests a protective effect of inhaled corticosteroids against viral entry by ACE2 receptor downregulation, that are usually prescribed at a high dose in SA (6), thus a possible explanation to the lack of observed differences in our cohort.Despite the severity of asthma and reported comorbidities, no ICU admissions were reported, and hospital admissions in COVID-19-SA subjects did not differ from the median rate observed in the same geographic areas (5). Furthermore, we could observe no difference in the median monthly hospitalization rate of SA patients in 2019 compared to 2020 in Lombardy region where both hospital-admitted subjects reside (0.97 vs 0.9%, IRSA data).Our result is consistent with recent literature, showing that asthma in Western countries was not associated with an increased hospitalization rate and ICU admissions due to COVID-19 (3,8). It is still debated if a protective effect of Th2-inflammation in a significant proportion of asthma sufferers (7), or concomitant anti-inflammatory therapy could be the reasons for such outcomes (6). However, if asthma patients with COVID-19 require intubation, the duration of hospitalization was shown to be longer than average (8).As for the role of biologics in COVID-19 disease progression, we could not observe an increase in hospital admissions in patients with SA treated with biologics compared to the general population, with the majority isolating at home and requiring no additional treatment. Considering that, in areas with high prevalence of SARS-CoV-2 infection, 68.2% of SA subjects were treated with either omalizumab or mepolizumab, our observations further prove the safety of biologics during the COVID-19 pandemic.Lastly, we did not observe any deaths in our cohort, but we speculate that this outcome is most likely due to the small sample size and younger average age. In fact, advanced age seems to be the most determining risk factor on mortality due to COVID-19 compared to other causes. (9)Taken together, our results point at a neutral role of SA in the COVID-19 disease course and hospital admissions. One major strengths of our study is that, by using a fast and inexpensive tool, we could outline the salient features of severe asthma and COVID-19 at a national level, while the major weakness is the limited number of SA subjects diagnosed with COVID-19, that could lead to sampling bias and low accuracy. Further confirmation of these results with an increased sample size is therefore warranted

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