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1.
Laryngo- Rhino- Otologie ; 101:S180, 2022.
Article in English | EMBASE | ID: covidwho-1967655

ABSTRACT

Introduction The use of biologics has been described as an effective therapy in phase 3 studies in severe CRSwNP. Relatively unexplored is the post-covid syndrome in CRSwNP patients. Method Case presentation. Results Presentation of a 75-year-old patient with CRSwNP, asthma, ASA intolerance and eosinophilic granulomatosis with polyangiitis. Drug therapy with daily 1-5 mg prednisolone oral and inhalation therapy with formoterol/ beclomethasone. In February 2021, the patient was diagnosed with SARS-CoV-2 infection. For four days, the patient was admitted to a hospital with pronounced physical weakness without respiratory insufficiency. Anosmia has long been known because of CRSwNP. After Covid-19 illness, the patient reported severe sleep impairment and a severe state of exhaustion compatible with a post-covid syndrome. In addition, the patient was impaired by a severe nasal obstruction. At presentation in the rhinological consultation 7 months after Covid-19 illness, severe nasal polyps (NP overall score 8) and anosmia were detected. Dupilumab therapy (anti IL-4/IL-13 antibody) was initiated for severe CRSwNP. In the course of 2 months, an improved quality of life with less nasal obstruction as well as a reduced NP overall score of 6 were shown. Furthermore, the sleep impairment and exhaustion of the patient did not improve. Conclusion Dupilumab therapy improves quality of life in patients with severe CRSwNP, which may be especially important in post-covid syndrome.

2.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846

ABSTRACT

Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

3.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927832

ABSTRACT

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and small-vessel vasculitis. We report a case of EGPA in an adolescent with uncontrolled asthma who was receiving montelukast. Case: A 12-year-old boy who is known to have asthma and allergic rhinitis which were previously controlled on ICS, intranasal steroids, and prolonged use of montelukast for 4 years. He presented with cough and nasal blockage for 2 months. He also reported an increase in the frequency of asthma attacks and received multiple courses of systemic steroids. Subsequently, his asthma controller medications were upgraded to ICS/LABA few weeks prior to admission. His symptoms were also associated with weight loss, diarrhoea and haematochezia. He was vitally stable and maintained oxygen saturation on room air. Physical examination revealed nasal polyps, purple skin flat lesions on palms and feet (Figure1), and bilateral crackles on chest auscultation. His blood investigations were significant for leukocytosis with marked eosinophilia (11x103/uL, (51%)), high inflammatory markers and total-IgE (1975 kU/L). Initial chest XR showed bilateral interstitial thickening and small pleural effusions (Figure2). Chest CT showed centrilobular nodules and peripheral ground-glass opacities, tree-in-bud appearance with no peripheral sparing in addition to moderate pericardial effusion and bilateral mild pleural effusion (Figure3). Sinus CT showed extensive sino-nasal polyposis with pansinusitis (Figure4). Initial echocardiography showed moderate pericardial effusion with normal biventricular function. Patient was started on IV furosemide. During his hospitalization, patient developed chest pain. His serial troponin was rising and LV contractility was depressed. ECG showed ST-segment depression. Therefore, EGPA with cardiac involvement was suspected. Cardiac MR showed features of a peri-myocarditis. IVIG was commenced for suspicion of coronary artery involvement, which was later disputed by cardiac cath. He was also started on IV pulse steroids at a dose of 30 mg/kg for 3 days which resulted in dramatic decrease in troponin level, eosinophil count and CRP. Skin biopsy, which was later performed after administration of steroids, showed perivascular non-necrotizing granulomas. His ANA, ANCA and COVID-19 PCR came negative. Serum chemistries and urine microscopy were unremarkable. Patient was later started on Rituximab with significant clinical, serological and radiological (Figure5,6) improvement after 10-months of follow-up. Discussion: EGPA is rare but should be considered in children with uncontrolled asthma, eosinophilia and rhino-sinusitis. This case shows the importance of being aware that montelukast could cause EGPA, in spite of the uncertainty about its mechanism. (Figure Presented).

4.
Italian Journal of Medicine ; 16(SUPPL 1):71, 2022.
Article in English | EMBASE | ID: covidwho-1912982

ABSTRACT

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis. Discussion: A 58-years man was admitted to the Emergency Department in January 2022 for myalgia and weakness of lower limbs in recent COVID-19 infection. He had a clinical history of allergic asthma and eosinophilic pneumonia (ANCA negative) diagnosed as secondary to sensitization work-related in 2001. Blood test showed a severe hypereosinophilia (absolute eosinophil count: 9875/microL) and elevated creatine kinase (CK: 7555 U/L). He was hospitalized in HUB COVID. During hospitalization reported paraesthesia of upper and lower limbs and fever;blood test showed elevation of inflammation markers. Autoimmune screening showed a antineutrophil cytoplasmic antibodies positivity (ANCA anti-MPO 178UI/mL). A sinus CT showed nasal polyposis. A neurological evaluation and electromyography were performed with the evidence of polyneuropathy. Muscle biopsy showed eosinophil-associated vascular occlusion and eosinophilassociated tissue damage. The investigation excluded renal, cardiac, pulmonary and gastro-intestinal involvement. A steroid therapy (Prednisone 1 mg/kg/die) was started with clinical improvement. Conclusions: EGPA is a multisystemic disorder, typically suspected based on a combination of clinical findings, such as asthma, nasal and sinus symptoms, peripheral neuropathy, and eosinophilia ≥1500/microL. ANCA antibodies are positive in around 40% of patients and diagnosis can often be challenging and delayed.

5.
Allergy, Asthma and Clinical Immunology ; 18(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1865820

ABSTRACT

The proceedings contain 88 papers. The topics discussed include: investigating the prevalence, accuracy of self reporting, and mental health impacts of allergic disease in health care professional students during the COVID 19 pandemic;triple therapy (LAMA, ICS and LABA) in asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta analysis;serum biomarkers and staphylococcus aureus carriage in ragweed induced allergic rhinitis using the nasal allergen challenge model;the role of gut microbiota in mediating allergic asthma in infants;The 12 SQ HDM SLIT tablet shows similar safety and efficacy across geographies, ethnic and age groups;dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps: results from the SINUS trials;and time varying effects of allergy on the childhood asthma risk: a retrospective cohort study.

6.
Cardiogenetics ; 12(2):133-141, 2022.
Article in English | EMBASE | ID: covidwho-1818054

ABSTRACT

Eosinophilic pancarditis (EP) is a rare, often unrecognized condition caused by endomyocardial infiltration of eosinophil granulocytes (referred as eosinophilic myocarditis, EM) associated with pericardial involvement. EM has a variable clinical presentation, ranging from asymptomatic cases to acute cardiogenic shock requiring mechanical circulatory support (MCS) or chronic restrictive cardiomyopathy at high risk of progression to dilated cardiomyopathy (DCM). EP is associated with high in‐hospital mortality, particularly when associated to endomyocardial thrombosis, coronary arteries vasculitis or severe left ventricular systolic dysfunction. To date, there is a lack of consensus about the optimal diagnostic algorithm and clinical management of patients with biopsy‐proven EP. The differential diagnosis includes hypersensitivity myocarditis, eosinophil granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome, parasitic infections, pregnancy‐related hypereosinophilia, malignancies, drug overdose (particularly clozapine) and Omenn syndrome (OMIM 603554). To our knowledge, we report the first case of pancarditis associated to eosinophilic granulomatosis with polyangiitis (EGPA) with negative anti‐neutrophil cytoplasmic antibodies (ANCA). Treatment with steroids and azathioprine was promptly started. Six months later, the patient developed a relapse: treatment with subcutaneous mepolizumab was added on the top of standard therapy, with prompt disease activity remission. This case highlights the role of a multimodality approach for the diagnosis of cardiac involvement associated to systemic immune disorders.

7.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):487-488, 2021.
Article in English | EMBASE | ID: covidwho-1570381

ABSTRACT

Background: Rapid development of vaccines to prevent coronavirus disease 2019 (COVID-19) has become a global imperative. Two mRNA vaccines have been recently approved by European Medicines Agency: BNT162b2 and mRNA-1273 COVID-19 vaccine. They have demonstrated safety in 1-3 phase clinical trials but data in asthmatics vaccinated in real-life is scarce. We sought to assess the change in asthma control before and 4 weeks after the administration of mRNA vaccine against COVID-19 in adults diagnosed with mild to severe asthma. Method: We performed an observational descriptive study of asthmatic healthcare workers who were vaccinated in our Allergy Department. Asthma severity were measured following Spanish Guideline on the Management of Asthma (GEMA) criteria. Asthma control was evaluated prior to vaccination and 4 weeks after vaccination using Asthma Control Test (ACT) questionnaire. The mRNA vaccines were administered under medical supervision and 30 minutes observation. Results: We recorded a total of 52 asthmatic healthcare workers who receive COVID-19 vaccination in our Allergy Department. The mean age was 52.3 years (range 21-66) and 46 (88.5%) were female. Ten (19.2%) and 42 (80.8%) subjects received BNT162b2 and mRNA-1273 COVID-19 vaccine, respectively. Twenty patients (38.5%) had intermittent asthma, 8 (15.4%) mild, 18 (34.6%) moderate, and 6 (11.5%) severe asthma. One patient was receiving oral corticosteroids and one biologic treatment. Coexisting allergic diseases were common: 26 (50%) had allergic rhinitis, 5 (9.6%) atopic dermatitis, 18 (34.6%) food allergy, 19 (36.5%) drug allergy. Other comorbidities were cardiovascular disease (23.1%), obesity (21.2%), autoimmunity (19.2%) and nasal polyposis (5.8%). The ACT before vaccination was 24.2 (range 21-25, SD 1.4). We detected 2 (3.8%) patients with ACT<20 who were vaccinated once ACT was ≥20. Four weeks after the first and second dose of mRNA vaccine, ACT was 23.4 (range 10-25, SD 2.6) and 23.8 (range 12-25, SD 2.5), respectively. We found no statistical significant differences in ACT changes among intermittent, mild, moderate, and severe asthma. Conclusion: In our experience, asthma exacerbation after mRNA vaccination is infrequent and not related to asthma severity. Asthmatic population can safely receive mRNA vaccines against COVID-19.

8.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):169-170, 2021.
Article in English | EMBASE | ID: covidwho-1570344

ABSTRACT

Background: Vasospasm due to eosinophilic coronary periarteritis (VECP) can cause not only vasospastic angina but also myocardial infarction and sudden cardiac death. It is usually resistant to conventional treatment of coronary disease and responds to systemic corticosteroids. The role that may have the monoclonal antibodies reducers eosinophils is unknown. Method: A 52-year-old female with chronic rhinosinusitis with nasal polyposis, moderate persistent bronchial asthma and Aspirinexacerbated respiratory disease(AERD), without atopy, had been treated with inhaled and intranasal fluticasone, oral montelukast and inhaled formoterol. In July 2019, she arrived at the emergency room with an acute coronary syndrome. Results: The procedures performed revealed high levels of troponin 16717ng/L(0- 47ng/L), and abnormal electrocardiogram (alteration of repolarization in II, III and aVF). Marked eosinophilia of 750cells/ mm3 was noticed. She was treated with oral vasodilators and aspirin, which due to her AERD required rapid desensitization, being effective. However, she continued with recurrent chest pain and electrocardiographic abnormalities. Diagnostic coronary angiography revealed vasospasm in the right coronary artery without atheromatous lesions. Type 2 myocardial infarction secondary to VECP was suspected and prednisone 30mg/day was started with complete resolution of chest pain. She developed a Cushing syndrome and prednisone dose was reduced, but chest pain and eosinophilia(1000/mm3) reappeared, and prednisone 20mg/day was reintroduced. It was decided to discontinue corticosteroids and treatment was begun with anti-IL-5(benralizumab) in May 2020, reducing eosinophilia( 0/mm3) from the first dose. At 6 months we suspended prednisone without new episodes of pain. In August 2020, she was visited due to SARS-CoV-2 infection without symptoms of bronchospasm or pneumonia and received the 4th dose of benralizumab without complications. Conclusion: An acute coronary syndrome refractory to conventional medications with normal coronary arteries and eosinophilia, with a history of chronic rhinosinusitis/polyposis, asthma and/or AERD, VECP should be considered and early treatment with corticosteroids could save lives. This is the first case to our knowledge in which anti IL 5 has been used for VECP to control of the eosinophilic disorder. Likewise, it was administrated during the SARS-CoV-2 infection without complications.

9.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):171-172, 2021.
Article in English | EMBASE | ID: covidwho-1570339

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.

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