Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Management of the patient with allergic and immunological disorders in the pandemic COVID-19 era.

The pandemic COVID-19 abruptly exploded, taking most health professionals around the world unprepared. Italy, the first European country to be hit violently, was forced to activate the lockdown in mid-February 2020. At the time of the spread, a high number of victims were quickly registered, especially in the regions of Northern Italy which have a high rate of highly-polluting production activities. The need to hospitalize the large number of patients with severe forms of COVID-19 led the National Health System to move a large number of specialists from their disciplines to the emergency hospital departments for the treatment of COVID-19. Furthermore, the lockdown itself has limited the possibility for general practitioners and pediatricians to be able to make outpatient visits and/or home care for patients with chronic diseases. Among them, the patient with atopic diseases, such as asthma, rhinitis and atopic dermatitis, is worthy of particular attention as she/he is immersed in a studded negative scenario with the onset of spring, a factor that should not be underestimated for those who suffer from pollen allergy. The Italian Society of Asthma Allergology and Clinical Immunology, to quickly deal with the lack of references and specialist medical procedures, has produced a series of indications for immunologic patient care that are reported in this paper, and can be used as guidelines by specialists of our discipline.

Spontaneous pneumomediastinum complicating severe acute asthma exacerbation in adult patients.

Objectives: The real incidence of pneumomediastinum (PNM) in adult patients with severe acute asthma exacerbation continues to be unknown. The current study aims to investigate the occurrence of PNM in an adult population of patients presenting a severe asthma attack and to evaluate the risk factors associated to its development. Methods: The 45 consecutive subjects who were admitted to our Division between January 1, 2015 and December 31, 2016 for severe acute asthma exacerbation underwent a diagnostic protocol including a standard chest X-ray and continuous monitoring of arterial oxygen saturation (SaO2) during the first 24 hours following admission. The patients showing persistence or deterioration of oxyhemoglobin desaturation were prescribed a chest Computed Tomographic (CT) scan. Results: Five out of the 45 patients (11.1%) with severe acute asthma exacerbation were diagnosed with PNM, in one case on the basis of an X-ray image and in four on the basis of a chest CT scan. Data analysis showed that the PNM patients were younger [21 (17-21) vs 49.5 (20-73) yrs; p < 0.001] and more likely to show sensitization to Alternaria (2/5 vs 0/40; p = 0.0101) with respect to their non-PNM counterparts. The duration of hospital stay was similar in the two groups [8 (4-12) vs 7 (3-15) days; p = 0.6939]. Conclusions: PNM is a common clinical entity in young adults with severe acute asthma exacerbation, particularly in those with unsatisfactory response to initial medical therapy. Although generally benign, patients with suspected PNM should be closely monitored because of the risk of developing severe hypoxemia.

Omalizumab for severe allergic asthma in clinical trials and real-life studies: what we know and what we should address.

Randomized clinical trials (RCTs) are the gold standard for the assessment of any therapeutic intervention. Real-life (R-L) studies are needed to verify the provided results beyond the experimental setting. This review aims at comparing RCTs and R-L studies on omalizumab in adult severe allergic asthma, in order to highlight the concurring results and the discordant/missing data. The results of a selective literature research, including "omalizumab, controlled studies, randomized trial, real-life studies" as key words are discussed. Though some similarities between RCTs and R-L studies strengthen omalizumab efficacy and safety outcomes, significant differences concerning study population features, follow-up duration, local adverse events and drop-out rate for treatment inefficacy emerge between the two study categories. Furthermore the comparative analysis between RCTs and R-L studies highlights the need for further research, concerning in particular long-term effects of omalizumab and its impact on asthma comorbidities.

Omalizumab management beyond clinical trials: the added value of a network model.

BACKGROUND: Omalizumab is effective and safe in severe allergic asthma. Few data are available about its impact on lung function and on asthma comorbidities, long-term follow-up of treated patients, adherence, non-responders profile, and optimal treatment duration. OBJECTIVE: We aimed at evaluating omalizumab-related clinical outcomes and unmet needs in a real-life setting. METHODS: We created a collaborative network (NEONet - North East Omalizumab Network) involving 9 Allergy and Respiratory referral centres for severe asthma placed in the North-East of Italy. Patients' data were entered into a common study database shared by all the participating physicians. A preliminary retrospective analysis was performed. RESULTS: Patients come from a common well-defined geographical and environmental district providing a homogeneous population sample. A moderate but statistically significant improvement of the FEV1, and an increasing proportion of exacerbations-free patients were observed since the treatment start. These findings were independent of the baseline severity of bronchial obstruction. A positive impact of omalizumab on rhinitis in patients with both asthma and rhinitis was detected. Moreover the efficacy of omalizumab on asthma seemed not to be affected by the baseline severity of rhinitis. CONCLUSION: Our retrospective analysis represents a preliminary report from the NEONet activity. It confirmed omalizumab efficacy and provided some new insights about its impact on lung function and on comorbid rhinitis. The network approach, under a prospective view, allows creating a large uniform database, by means of a standardized shared tool for data collecting, and joining a multidisciplinary expertise.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

Severe Asthma, Telemedicine, and Self-Administered Therapy: Listening First to the Patient.

Severe asthma patients are at an increased risk of major complications and they need to be monitored regularly. The COVID-19 pandemic has notably impacted on the health care resources. The telemedicine approach applied to the follow-up of asthmatic patients has been proven to be effective in monitoring their disease and their adherence to the therapy. The aim of our study was to investigate the satisfaction of severe asthma patients before the activation of a telemedicine management, as well as their current experience with self-administration of injection therapy. An ad hoc questionnaire was developed and sent by e-mail to 180 severe asthma patients. Most of subjects, 82%, were confident with the idea of doing self-measurements and self-managing their disease. Further, 77% of subjects favoured to carry out virtual visits and telemedicine. Regarding the home treatment, 93% of patients considered the self-injection therapy easy, 94% of subjects felt safe, and 93% were not worried while self-administering. Only mild adverse events were reported in 22% of patients after self-administration. Our results showed an agreement between what is considered necessary and practicable by healthcare personnel and what is perceived by the severe asthma patients in terms of treatment and monitoring of the disease with Telehealth. Biologics have a safety profile and can be easily self-administred at home.

COVID-19 Vaccination in Patients with Severe Asthma on Biologic Treatment: Safety, Tolerability, and Impact on Disease Control.

BACKGROUND: COVID-19 vaccination has been recommended for severe asthmatics. We aimed to evaluate the safety, tolerability, and impact on disease control and patient's quality of life of the mRNA SARS-CoV-2/COVID-19 vaccine in severe asthma patients regarding biologic treatment. METHODS: Severe asthmatic patients regularly managed by two big allergy and respiratory referral centers were offered to undergo Pfizer COVID 19 vaccination at the hospital site. Patients filled in an adverse events questionnaire after the first and second dose, as well as the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ). RESULTS: Overall, 253 patients were vaccinated; only 16 patients refused. No serious events were detected. Less than 20% of patients reported side effects, most of which were classified as very common side effects. No differences were reported according to the ongoing biologic drug. A significant improvement in both ACT and AQLQ was observed between the first and the second dose administration. CONCLUSIONS: Our data confirm the optimal safety and tolerability profile of mRNA SARS- CoV-2/COVID-19 in severe asthma patients on biologic treatment, as well as their positive attitude towards COVID-19 vaccination. The negligible proportion of patients reporting side effects and the absence of asthma exacerbations are relevant to support the COVID-19 vaccination campaign in severe asthma patients worldwide.

Asthma in a large COVID-19 cohort: Prevalence, features, and determinants of COVID-19 disease severity.

BACKGROUND: Asthma prevalence among COVID-19 patients seems to be surprisingly low. However the clinical profile of COVID-19 asthmatic patients and potential determinants of higher susceptibility/worse outcome have been scarcely investigated. We aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity. METHODS: Medical records of patients admitted to COVID-Units of six Italian cities major hospitals were reviewed. Demographic and clinical data were analyzed and compared according to the COVID-19 outcome (death/need for ventilation vs discharge at home without requiring invasive procedures). RESULTS: Within the COVID-Units population (n = 2000) asthma prevalence was 2.1%. Among the asthmatics the mean age was 61.1 years and 60% were females. Around half of patients were atopic, blood eosinophilia was normal in most of patients. An asthma exacerbation in the 6 months before the Covid-Unit admittance was reported by 18% of patients. 24% suffered from GINA step 4-5 asthma, and 5% were under biologic treatment. 31% of patients were not on regular treatment and a negligible use of oral steroid was recorded. Within the worse outcome group, a prevalence of males was detected (64 vs 29%, p = 0.026); they suffered from more severe asthma (43 vs 14%, p = 0.040) and were more frequently current or former smokers (62 vs 25%, p = 0.038). CONCLUSIONS: Our report, the first including a large COVID-19 hospitalized Italian population, confirms the low prevalence of asthma. On the other side patients with GINA 4/5 asthma, and those not adequately treated, should be considered at higher risk.

Mepolizumab for severe eosinophilic asthma: a real-world snapshot on clinical markers and timing of response.

Background: Few studies have provided real-world evidence of mepolizumab efficacy and safety. We aimed to evaluate mepolizumab for severe eosinophilic asthma in daily clinical practice.Research design and methods: Patients included in the RINOVA (Interdisciplinary Network for the management of severe asthma in Veneto region, Italy) database were investigated. Blood eosinophil count, forced expiratory volume in 1 second, % of predicted (FEV1%), fractional exhaled nitric oxide (FeNO), asthma control test (ACT), oral steroid (OCS) intake, and exacerbation rate were evaluated during mepolizumab treatment.Results: 69 patients were enrolled (mean age: 55.1 years; 60.9% females). A significant improvement was detected at one month with respect to blood eosinophils (median level at baseline: 710/µl; -620/µl, p < 0,001), FEV1% (median value at baseline 87; range: 79-101; +4, p = 0.001) and ACT (median value at baseline 18; range: 14-20.5;+4, <0.001). A significant reduction of FeNO was observed six months after the treatment start, when the exacerbation rate and the mean OCS dose significantly decreased (respectively: Δ reduction -3; p < 0.001 and -5 mg; p < 0.001).Conclusions: Our study provides real-world evidence of mepolizumab safety and confirms its dramatic steroid sparing effect. The greatest clinical change (ACT and FEV1) was observed within the first month.

Fibromyalgia in Italian patients with primary Sjögren's syndrome.

OBJECTIVE: To assess the prevalence of fibromyalgia in primary Sjögren's syndrome and to evaluate the clinical differences between patients affected with both primary fibromyalgia and primary Sjögren's syndrome and those affected only with primary fibromyalgia. METHODS: Clinical features of fibromyalgia were evaluated in 100 consecutive outpatients with primary Sjögren's syndrome and, as controls, in 90 patients with non-insulin-dependent diabetes mellitus, in 75 patients with primary fibromyalgia and in 30 healthy subjects. RESULTS: Fibromyalgia was recorded in 22% of patients with primary Sjögren's syndrome, in 12.2% with diabetes and in 3.3% of healthy controls. In the primary Sjögren's syndrome group the prevalence was significantly higher than in healthy controls (P < 0.01), but not significantly different than in diabetes. Moreover, primary Sjögren's syndrome with fibromyalgia and primary fibromyalgia patients did not differ with respect to the number of tender points, while the mean pain threshold was lower in the latter (P = 0.05). Purpura, hypergammaglobulinemia, rheumatoid factor, and a focus score > or = 1 on lip biopsy were significantly more frequent in primary Sjögren's syndrome patients without than with fibromyalgia. CONCLUSIONS: As recently reported by other authors, our study confirms the moderate increase of fibromyalgia prevalence in primary Sjögren's syndrome. Typical fibromyalgic findings are quite similar to those of primary fibromyalgia, but surprisingly, primary Sjögren's syndrome patients with fibromyalgia show a less severe global involvement than those with primary Sjögren's syndrome alone.