ABSTRACT
Case report Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe asthma in adults. Both diseases share key pathophysiological mechanisms that can involve type-2 inflammatory pathways. However, this is an uncommon presentation in pediatric patients. Dupilumab, a fully human monoclonal antibody against IL-4Ralpha, inhibits IL-4/ IL-13 signaling, which are key drivers of type-2 inflammation and interfere with both eosinophilic and allergic pathways. It is approved for patients >= 12-year- old with moderate to severe uncontrolled asthma, but its approval in CRSwNP is limited to adults. We report a case of a 12-year- old boy with severe uncontrolled asthma and highly symptomatic CRSwNP referred to our center in May 2021. He was sensitized to house dust mite and pollens, and a specific immunotherapy had been tried previously. He was treated with high dose inhaled corticosteroid, long-acting beta agonist, long-acting muscarinic antagonist, montelukast and daily intra-nasal corticosteroids. Furthermore, a bilateral endoscopic sinus surgery with polypectomy was performed in April 2021. Despite adherence to medication and surgical treatment, both diseases were uncontrolled with frequent exacerbations requiring unscheduled visits and multiple systemic corticosteroid courses. This led to failure to thrive and several missed school days. Oral corticosteroid (OCS) tapering was unachieved due to symptoms rebound and so maintenance therapy with prednisolone 10mg daily was attempted, with only a slight improvement. High levels of eosinophils (1010 cells/muL), FeNO (122 ppb) and IgE (2255 kU/L) were present. Treatment with subcutaneous dupilumab was started in July 2021. A clinical and analytical improvement was evident at the 3-month evaluation (Table 1). He was able to stop prednisolone, and no clinically relevant exacerbations occurred. He also was fully vaccinated and had an asymptomatic COVID-19 infection in December 2021. Patients with CRSwNP and comorbid asthma have a higher disease burden than patients with each disease alone. In this adolescent, dupilumab was effective as an add-on treatment, for both severe asthma and CRSwNP. It led to disease control, OCS withdrawal, reduced eosinophilic inflammation, improved lung function, smell recovery and absence of exacerbations during follow-up. Dupilumab, targeting the type 2 inflammatory process, may allow a better management of pediatric patients >=12 years old with severe CRSwNP and comorbid asthma. (Table Presented).
ABSTRACT
Background: Hymenoptera venom immunotherapy (VIT) is a safe and effective treatment for Hymenoptera venom allergy (HVA). Unexpected events, such as venom extracts shortage or COVID-19 pandemic, can impact HVA management, and a change in VIT supplier may became necessary. We aimed to evaluate the safety of switching VIT manufacturer without any dose adjustments. Method(s): A retrospective study of patients treated with VIT between 2013 and 2021, in the maintenance phase and without any previous systemic reactions was performed. All the patients switched to another manufacturer while keeping the same venom without any dose modification. All venom extracts were aqueous preparations. Demographic and clinical data were also analyzed. Result(s): A total of 40 patients were included (31 male, median age 44 years old);76% lived in a rural environment, 58% had apiaries <3km from home or work, and 18% were medicated with beta-blockers and/or angiotensin converting enzyme inhibitors. Most patients (68%) were treated with bee venom and the remaining wasp venom. The median time between the beginning of the maintenance phase and the switch to a different VIT supplier was 18 months [1-52 months]. A total of 42 changes between 4 suppliers were performed without any dose adjustments (39 Roxall to Leti;2 Stallergenes to Roxall;1 Inmunotek -> Roxall), with only local reaction reported. This healthy 50-year- old female patient treated with wasp VIT for 3-months in the maintenance phase, switched from Inmunotek to Roxall and presented a local reaction, similar to previous reactions with the former manufacturer. Two years later, she did not react when VIT was changed from Roxall to Leti. No systemic reactions occurred, and no one discontinued VIT. Conclusion(s): International recommendations regarding changing VIT supplier are scarce. Our results suggest that is safe to switch venom extracts from different manufacturers without the need for dose adjustment in patients on maintenance VIT without any previous systemic reactions.
ABSTRACT
Background: Covid-19 pandemic had an important impact on health care, in particular on the approach to respiratory diseases. Aim(s): To characterize asthmatics patients hospitalized in a tertiary hospital during Covid-19 pandemic. Method(s): Retrospective analysis of the clinical data of the patients hospitalized in our Hospital for asthma exacerbation during the first 12 months of Covid-19 pandemic (from March 2020 to February 2021) compared with the corresponding period before pandemic (from March 2019 to February 2020). In order to identify admitted patients for asthma, we used ICD9 and IC10 asthma diagnostic codes attributed to the main diagnosis. Result(s): A total of 56 hospitalizations were identified, corresponding to 53 patients, 81.1% females and 18.9% males, with a mean age of 47.3 years [ +/- 20.8 years;8-93 years]. Ten cases were excluded (missing information, in three, and other reason for admission, in seven). We identified 17 hospitalizations in the considered pandemic period and 39 in the pre-pandemic period, representing a significant reduction in asthma hospitalization during covid-19 pandemic (30.4% vs 69.6%, p < 0.001). When comparing the main characteristics between the two groups (pandemic vs pre-pandemic), namely age (47.1 vs 47.3 years, p = 0.972), gender (82.4% vs 79.5% female, p = 1.0), atopy (50.0% vs 64.5%, p = 0.366), hospitalization length (5.8 days vs 5.7 days, p = 0.9), previous therapy (37.5% vs 30.8% only SABA/LABA, p = 0.754), therapy after discharge (p = 0.842) or exacerbation trigger, no statistical differences were found. In both groups, viral respiratory tract infection was the main trigger for asthma exacerbation. In neither case SARS-CoV- 2 infection was identified. Conclusion(s): There was a significant decrease in asthma hospitalizations in the first 12 months of the Covid-19 pandemic, compared to the same period pre-pandemic. However no statistically significant differences were found between the characteristics of hospitalized patients in the two periods.
ABSTRACT
Benralizumab is a humanized, afucosylated IgG1k monoclonal antibody directed against the α subunit of IL-5R. It inhibits IL-5, the main regulator of the biology of eosinophils, from binding to its specific receptor. Moreover, it directly targets and depletes eosinophils and other IL-5R + cells by inducing antibody-dependent cell-mediated cytotoxicity, differentiating it from the other IL-5 ligand targeted therapies. We report a case of a 61-year-old woman with severe eosinophilic asthma and rhinosinusitis, referred to our department in 2014. Blood eosinophilia (560 cells/μL) and normal total IgE levels (57 kU/L) were present. She was on GINA step-5 treatment with additional aminophylline 225mg twice daily. Control was not achieved despite good compliance with frequent asthma exacerbations requiring emergency department visits, multiple systemic corticosteroid courses and hospitalizations. Maintenance therapy with prednisolone 5mg daily was attempted with only a slight improvement. Although no more hospitalizations were required, she continued to have several asthma exacerbations. Treatment with subcutaneous Benralizumab 30mg was started in October 2020. The subsequent administration was skipped because the patient had COVID-19. An interval of approximately 3 months (82 days) separated the first 2 administrations. Regardless of our recommendation, the patient decided to discontinue systemic corticosteroids and aminophiline. Evaluation before the 2nd administration showed that blood eosinophils decreased to 0 cells/μL and clinical improvement that was established by disease control and health-related quality of life questionnaires (see table I) Although maintained eosinopenia after an isolated intravenous administration of Benralizumab has been reported, to our knowledge this is the first case related to a single subcutaneous administration in a previously eosinophilic patient. Additionally, clinical improvement was sustained in spite of stepping down her maintenance therapy. This case raises questions regarding the possibility and success of patient-oriented scheduling of Benralizumab administration as an alternative to the current treatment regimen. (Table Presented).
ABSTRACT
Background: Mepolizumab, a humanized monoclonal antibody against IL-5, is a therapeutic option in patients with severe eosinophilic asthma. Its efficacy has been shown in clinical trials. Our aim is to present data from our center to corroborate this evidence in the complexity of real-life patients. Method: A retrospective study of patients with severe eosinophilic asthma treated with mepolizumab in our center was performed. We collected data regarding demographics, eosinophilic blood count, FEV 1 , fractional exhaled nitric oxide (FeNO), clinically significant exacerbations [need to start or increase oral corticosteroids (OCS), emergency department visit and/or hospitalization], OCS and safety profile, before and after patients started mepolizumab. Results: A total of 12 patients were included (9 female, mean age 53.7 ± 8.9 years old);10 patients had concomitant chronic rhinosinusitis with nasal polyps. Mepolizumab was administered in a dose of 100 mg every 4 weeks, except for 2 patients diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) (300 mg every 4 weeks). The mean duration of treatment was 13.75 months [3 - 28 months]. Due to COVID-19 pandemics restriction it was not possible to assess absolute eosinophilic count in 2 patients, as well as FeNO and FEV 1 in 2 different patients after treatment. The mean value before and after treatment for each outcome were the following: absolute eosinophilic blood count, from 537.5/μl to 116/μl ( p = 0.005);FEV 1 , from 1.44L to 1.84L ( p = 0.036);FeNO, from 62.27ppm to 41.8ppm ( p = 0.260);clinically significant exacerbations, from 2.83 in the previous year to 0.25 ( p = 0.007). Prior to treatment, 8 patients were treated with daily OCS, and after starting mepolizumab 3 of them were able to stop OCS and the others reduced daily dose (mean dose reduction 64.7%, ranging from 25% to 98.5%). The only side effect reported was sporadic headache, and no one discontinued treatment. Conclusion: In our sample, we observed a significant reduction in eosinophilic blood count, clinically significant exacerbations and OCS use, as well as improvements in FEV 1 , in patients with severe eosinophilic asthma treated with mepolizumab, with a good safety profile. This information supports data from clinical trials and early real-life experience in other populations.
ABSTRACT
The SARS-CoV-2 pandemic spread worldwide in a short period causing an extremely high number of infected people and numerous fatalities. Portugal as many other countries declared a State of National Emergency and applied quarantine measures soon after the WHO declaration of pandemic. As result we had to deal with dramatic and unexpected changes affecting our clinical activity on an unprecedented scale. A Contingency Plan was immediately planned, comprising new approaches and strategies, to assure the health care needs of our allergic patients and the safety of both health care providers and patients. Additionally, we needed to consider the intensive participation of most of the doctors and nurses of our Department in COVID-19 related activities. The Contingency Plan was also particularly difficult to elaborate since no recommendations or guidelines were available at that time. We believe that sharing this experience with other Allergy and Clinical Immunology Departments may prove to be useful in case of a second wave of COVID-19 infection or another future pandemic.