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1.
Front Immunol ; 13: 892277, 2022.
Article in English | MEDLINE | ID: covidwho-1933679

ABSTRACT

Coronavirus disease 2019 (COVID-19) vaccines effectively elicit humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthy populations. This immunity decreases several months after vaccination. However, the efficacy of vaccine-induced immunity and its durability in patients with severe asthma on biological therapy are unknown. In this study, we evaluated the effectiveness and durability of mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy. The study included 34 patients with severe asthma treated with anti-IgE (omalizumab, n=17), anti-IL5 (mepolizumab, n=13; reslizumab, n=3), or anti-IL5R (benralizumab, n=1) biological therapy. All patients were vaccinated with two doses of the BNT162b2 mRNA vaccine with a 6-week interval between the doses. We found that this COVID-19 vaccination regimen elicited SARS-CoV-2-specific humoral and cellular immunity, which had significantly declined 6 months after receipt of the second dose of the vaccine. The type of biological treatment did not affect vaccine-elicited immunity. However, patient age negatively impacted the vaccine-induced humoral response. On the other hand, no such age-related impact on vaccine-elicited cellular immunity was observed. Our findings show that treatment of patients with severe asthma with biological therapy does not compromise the effectiveness or durability of COVID-19 vaccine-induced immunity.


Subject(s)
Asthma , COVID-19 , Antibodies, Viral , Asthma/therapy , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Immunity, Humoral , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
2.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927925

ABSTRACT

Introduction: PrecISE is an ongoing Phase II clinical trial sponsored by the National Heart, Lung, and Blood Institute to investigate the efficacy of several treatments for severe asthma. The threat of COVID-19 has raised interest in obtaining reliable spirometry data for asthma research and clinical care in a remote, “no-touch” fashion. Prior studies of the accuracy of remote spirometry have not included real-time coaching. The PrecISE investigators hypothesized that remote spirometry with real-time video coaching could provide an accurate FEV1 for use as a study endpoint in a clinical trial setting. Methods: PrecISE network participants had remote spirometry post-bronchodilator (4 puffs of albuterol) measured with video coaching from trained research coordinators using the ZEPHYRx platform connected to MIR Spirobank Smart handheld spirometers. Remote spirometry measurements occurred within a +/- 3-day window from scheduled in-person PrecISE visits during which in-person spirometry with bronchodilator challenge was measured with standard equipment (Vyaire Medical). All measurements occurred during the screening/run-in period of the PrecISE protocol. Both remote and in-person spirometry was overread by the PrecISE Spirometry Core and only included in analysis if sessions met ATS acceptability and reproducibility criteria. Correlations between remote and in-person FEV1 and FVC were analyzed, and Bland-Altman plots generated. As a comparison, within subject biological variability was measured using data from separate in-person visits during the screening/run-in period. Results: A total of 128 pairs of remote/in-person spirometry data were obtained. The mean FEV1 for remote spirometry was 2.50 L (SD 0.81) and for inperson spirometry was 2.42 L (SD 0.80), with an estimated correlation of 0.95 (95% CI: 0.93, 0.97). The mean difference in FEV1 (in-person - remote) was -0.07 L (95% CI: -0.11, -0.03, SD 0.25). The mean FVC for remote spirometry was 3.72 L (SD 1.01) and for in-person spirometry was 3.53 L (SD 0.93), with an estimated correlation of 0.91 (95% CI: 0.87, 0.93). The mean difference in FVC (in-person - remote) was -0.19 L (95% CI: -0.27, -0.12, SD 0.42). A total of 142 pairs of repeated in-person spirometry measurements were performed (median time between measurements: 43 days), with mean difference in FEV1 of -0.01 L (95% CI: -0.06, 0.03) and FVC of -0.02 L (95% CI: -0.07, 0.03). Bland-Altman plots for FEV1 differences are shown in Figure 1. Conclusions: Remote spirometry with real-time video coaching provides a reliable FEV1 measurement which correlates closely with in-person spirometry and is suitable for use in clinical trials. (Figure Presented).

3.
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.

4.
Respir Med ; 200: 106916, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1907739

ABSTRACT

Patients with respiratory diseases suffer more from problems of severe psychiatric comorbidity than the general population. Asthma might cause psychiatric disorders and affect patients' quality of life negatively. Previous studies reported that mental disorders prevail in asthmatic patients, causing anxiety, depression, and suicidal risk. The aim of this study is to evaluate in real life the prevalence of psychological comorbidities in asthmatics with severe asthma treated by biologicals (Benralizumab, Mepolizumab, Omalizumab). This study starts with the hypothesis that psychological distress, anxiety, depression and suicidal risk in severe asthma patients decreases if treated by biologicals. This study involves a sample of 90 patients (32 males, 58 females and aged 53.92 ± 15.92) suffering from severe asthma and treated with the biological drugs of Benralizumab, Mepolizumab, Omalizumab during Covid-19 pandemic. At the beginning of the treatment (T0) and after 16 weeks (T1), there have been reported results from both clinical disease control, assessed using the ACT, and psychological disorders, assessed with the PSS, HADS and C-SSRS. In the sample of these patients treated with biologicals for severe asthma, the study reported a significant change in all observed parameters, including asthma control (ACT), stress (PSS), anxiety (HADS-A) and depressive symptoms (HADS-D, despite Covid-19 pandemic. In addition, there was a significant improvement in disease management, perceived stress, anxiety and depressive symptoms after a 16 week treatment for severe asthma, independent from the type of biologic drugs used during the pandemic.

5.
J Allergy Clin Immunol Pract ; 2022 Jun 23.
Article in English | MEDLINE | ID: covidwho-1907243

ABSTRACT

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.

6.
J Asthma Allergy ; 15: 623-632, 2022.
Article in English | MEDLINE | ID: covidwho-1869275

ABSTRACT

Introduction: The increase in drugs available for severe uncontrolled asthma and the lifestyle of these patients make it necessary to implement self-administration programs of these therapies at home. Benralizumab, a monoclonal antibody targeting IL5R, was authorized in Spain for poorly controlled severe eosinophilic asthma. The possibility of administration at home was approved in March 2020 in Spain. The aim of the Auto-Benra study was to evaluate the usability and satisfaction of the benralizumab prefilled syringe and autoinjector and assessing the effectivity of these devices in uncontrolled severe eosinophilic asthma (SEA) in home-self administration. Methods: This is a retrospective, observational multicenter study uncontrolled SEA patients treated with benralizumab at least with 3 doses self-administered at home before April 30, 2021. Reliability and satisfaction with benralizumab at home were evaluated with subcutaneous administration assessment questionnaire (SQAAQ) and visual analogic scales (VAS). Effectiveness was evaluated in all patients with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual exacerbation rate, oral corticosteroid treatment (OCS) and asthma-related hospitalizations and emergency visits. Results: Fifty-four patients across 9 hospitals in Spain were included. The mean SQAAQ score was 6.89 (±0.16) points. Patients and their caregivers and doctors report excellent satisfaction by VAS, with no differences between benralizumab devices used (prefilled syringe and autoinjector). Severe exacerbation rate decreased by 65% (p = 0.0007) after benralizumab treatment. ACT score improved on average 6.27 ± 5.35 points (p < 0.0001) and the mean MiniAQLQ increased up to 1.58 ± 1.47 points (p < 0.0001). Twenty-four patients were OCS-dependent and at the end of study 14 patients get complete OCS withdrawal. Conclusion: AUTO-BENRA study supports the use of benralizumab at home given the excellent results of satisfaction and usability by patients and their caregivers.

7.
Biomedicines ; 9(12)2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1785519

ABSTRACT

BACKGROUND: The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. PATIENTS AND METHODS: Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. RESULTS: In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). CONCLUSION: The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

8.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-332520

ABSTRACT

The COVID-19 vaccines effectively elicit humoral and cellular immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a healthy population. This immunity decreases several months after the vaccination. However, the efficacy of the vaccine-induced immunity and its durability in patients with severe asthma on biological therapy is unknown. In this study, we evaluated the effectiveness and durability of the mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy. The study included 37 patients with severe asthma treated with anti-IgE (omalizumab, n=18), anti-IL5 (mepolizumab, n=14;reslizumab, n=4), or anti-IL5R (benralizumab, n=1) biological therapy. All patients were vaccinated with two doses of BNT162b2 mRNA vaccine (Comirnaty) at a 6-week period between the doses. We found that the COVID-19 vaccination elicited SARS-CoV-2-specific humoral and cellular immunity, which significantly declined 6 months after the second dose of the vaccine. The type of biological treatment did not affect the vaccine-elicited immunity. However, the patients' age negatively impacted the vaccine-induced humoral response. On the other hand, no such age-related impact was observed on the vaccine-elicited cellular immunity. Our findings showed that biological therapy of patients with severe asthma does not compromise the effectiveness and durability of the COVID-19 vaccine-induced immunity.

9.
Children (Basel) ; 9(3)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1715146

ABSTRACT

Currently, asthma represents the most common chronic disorder in children, showing an increasingly consistent burden worldwide. Childhood asthma, similar to what happens in adults, is a diversified disease with a great variability of phenotypes, according to genetic predisposition of patients, age, severity of symptoms, grading of risk, and comorbidities, and cannot be considered a singular well-defined disorder, but rather a uniquely assorted disorder with variable presentations throughout childhood. Despite several developments occurring in recent years in pediatric asthma, above all, in the management of the disease, some essential areas, such as the improvement of pediatric asthma outcomes, remain a hot topic. Most treatments of the type 2 (T2) target phenotype of asthma, in which IL-4, IL-5, and IL-13 modulate the central signals of inflammatory reactions. Although, there may be an unresolved need to identify new biomarkers used as predictors to improve patient stratification using disease systems and to aid in the selection of treatments. Moreover, we are globally facing many dramatic challenges, including climate change and the SARS-CoV2 pandemic, which have a considerable impact on children and adolescent asthma. Preventive strategies, including allergen immunotherapy and microbiome evaluation, and targeted therapeutic strategies are strongly needed in this population. Finally, the impact of asthma on sleep disorders has been reviewed.

10.
European Respiratory Journal ; 58:2, 2021.
Article in English | Web of Science | ID: covidwho-1708442
11.
European Respiratory Journal ; 58:2, 2021.
Article in English | Web of Science | ID: covidwho-1707652
13.
J Allergy Clin Immunol ; 149(2): 455-465, 2022 02.
Article in English | MEDLINE | ID: covidwho-1676782

ABSTRACT

Severe asthma is a heterogeneous disease encompassing different phenotypes and endotypes. Although patients with severe asthma constitute a small proportion of the total population with asthma, they largely account for the morbidity and mortality associated with asthma, indicating a clear unmet need. Being distinct from mild and moderate disease, new insights into the immunopathogenesis of severe asthma are needed. The disease endotypes have provided better insights into the immunopathogenic mechanisms underlying severe asthma. Current stratified approach of treating severe asthma based on phenotypes is met with shortcomings, necessitating unbiased multidimensional endotyping to cope with disease complexity. Therefore, in this review, we explore the distinct endotypes and their mechanistic pathways that characterize the heterogeneity observed in severe asthma.


Subject(s)
Asthma/immunology , Airway Remodeling , Asthma/etiology , Asthma/therapy , Autophagy/physiology , Bronchial Thermoplasty , Humans , Mitochondria/physiology , Obesity/complications , Th17 Cells/immunology , Th2 Cells/immunology
14.
J Asthma Allergy ; 14: 1511-1525, 2021.
Article in English | MEDLINE | ID: covidwho-1662468

ABSTRACT

BACKGROUND: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action. METHODS: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II-VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III-V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum pro-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings. RESULTS: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopathological changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13. CONCLUSION: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.

15.
Immunotargets Ther ; 10: 419-430, 2021.
Article in English | MEDLINE | ID: covidwho-1662467

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues to spread across the world. Since the beginning of the pandemic, the question of whether asthma is a risk factor for getting the infection or for poor outcomes motivated a great debate. In the field of severe asthma and its treatment during COVID-19 pandemic, several issues are also pending. A literature review focused on the management of severe asthma patients in the context of COVID-19 is performed. The available evidence suggests that severe asthma patients do not have an increased risk of poor COVID-19 outcomes and that it is safe to treat asthmatic patients with inhaled corticosteroids (ICS) and biologics during the pandemic, even though some studies indicate that high doses of ICS may predispose to COVID-19. The chronic use of oral corticosteroid (OCS) might be associated with poor COVID-19 outcomes, although there is no complete agreement. There is very limited evidence concerning the use of triple therapy for asthma in the context of this pandemic. Ultimately, severe asthma patients should maintain their medication during the COVID-19 pandemic, including biologic agents. More studies are needed to address the role of asthma medications and asthma's different phenotypes on the incidence and course of COVID-19.

16.
JACCP Journal of the American College of Clinical Pharmacy ; 4(12):1679-1680, 2021.
Article in English | EMBASE | ID: covidwho-1616009

ABSTRACT

Introduction: Medication adherence and prescribing among Medication Therapy Management (MTM)-eligible older adults with asthma have not been well studied. Research Question or Hypothesis: Was adherence among older adults affected by the COVID-19 pandemic? What patient characteristics and medications are associated with adherence and asthma exacerbations? Study Design: Retrospective observational cohort. Methods: MTM-eligible older patients with asthma diagnoses were included. Patients with chronic obstructive pulmonary disease were excluded. Proportion of days covered (PDC) determined adherence. High adherence was defined as PDC ≥80%. Medication adherence during January-July 2019 and January-July 2020 was compared. Conditional logistic regression assessed relationships between characteristics and medication use with high adherence to inhaled corticosteroids (ICS) and asthma exacerbations. Results: Total of 2320 patients studied;497 were with moderate and 156 with severe asthma. In 2019, proportions were low of patients with high adherence to controller medications with moderate (38-54%) and severe asthma (46-63%). In 2020, proportions remained low of patients with high adherence with moderate (30-49%) and severe asthma (46-65%). High adherence was associated with higher number of prescribers (Odds Ratio: (OR) 1.4-1.75, p ≥0.04), increasing days-supply of systemic corticosteroids (OR: 1.33-1.44, p ≥0.03), long-acting-beta-agonists (LABA) use (OR: 1.65, p<0.001) and montelukast (OR: 1.25, p=0.04). Among patients with moderate and severe asthma, high adherence to ICS was associated with asthma exacerbations and LABA use. In this same cohort, exacerbations were associated with increasing short-acting-beta-agonists (SABA) dispenses (OR: 1.62-2.47, p ≥0.02) and albuterol nebulizer use (OR: 2.25, p<0.001). Conclusion: Asthma medication adherence among older adults with moderate and severe asthma was alarmingly low in 2019 and remained low during the COVID-19 pandemic in 2020. Asthma exacerbations among these patients were associated with SABA fills and albuterol nebulizers. MTM programs can electronically identify suboptimal medication use by utilizing these findings to improve outcomes among patients with asthma.

17.
Cureus ; 13(12): e20644, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1614251

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can develop eosinopenia. Eosinophils have various functions, including immunoregulation and antiviral activity, in addition to modulation of an inflammatory reaction. Benralizumab is an anti-interleukin-5Rα monoclonal antibody that selectively depletes eosinophils through enhanced antibody-dependent cell-mediated cytotoxicity. Whether eosinophil depletion affects COVID-19 prognosis is yet to be elucidated. Here, we present a case of a 60-year-old patient with severe asthma on benralizumab therapy, who tested positive for an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient experienced an asymptomatic COVID-19 course without deterioration of asthma control. Eosinophil depletion did not contribute to a deterioration of the clinical status. Comorbidities play a major role in the severity of COVID-19 in patients with asthma. The findings of our case and a literature review revealed that benralizumab therapy is not associated with a significant negative impact on the disease course in COVID-19 patients.

18.
Psychoneuroendocrinology ; 131, 2021.
Article in English | EMBASE | ID: covidwho-1611981

ABSTRACT

Background: Strong genetic and epidemiological evidence supports an asthma-PTSD association, however, contributory immune mediators/mechanisms are unclear. Here, we examined a direct role of severe asthma associated Th17/ IL-17A in regulating PTSD-relevant behaviors using mouse aeroallergen house dust mite (HDM) models. Methods: 3 strategies were used: 1) BALBc-C5a receptor treatment that shifts Th2 mild asthma phenotype to Th17/IL17a expansion;2) IL-17a receptor knockout mice and 3) sufficiency testing with intracerebroventricular (ICV) administration of recombinant IL17a effects on behavior. Fear conditioning and extinction, maze exploration and social behaviors were assessed. Results: Absence of IL-17 signaling attenuated HDM effects on fear extinction while induction of Th17/IL-17 in the BALBc/anti-C5aR1 treated mice resulted in compromised fear extinction. ICV IL-17a promoted an anxiogenic phenotype and impaired social behaviors. Preliminary evidence suggests a role of cortical mechanisms (under investigation). Conclusion: Overall, our work highlights severe asthma inflammatory mediator IL17a in regulating PTSD-relevant behaviors. Beyond asthma-PTSD, our findings have relevant implications for other pulmonary (e.g. COVID-19) and autoimmune inflammatory conditions and PTSD risk.

19.
Russian Journal of Allergy ; 18(1):6-17, 2021.
Article in Russian | Scopus | ID: covidwho-1599949

ABSTRACT

BACKGROUND: Biologicals use in severe asthma (SA) is associated with targeted therapy (TT) availability problem. Ensuring the availability of biologicals can be resolved within the territorial compulsory medical insurance program (TCMIP) in day-stay or round-the-clock hospital. AIMS: This study aimed to develop and implement a program for immunobiological therapy (IBT) introduction for SA in Sverdlovsk Region (SR). MATERIALS AND METHODS: Program for introduction of IBT for SA was developed in SR in 2018 to provide patients with expensive biologicals within the TCMIP. Program includes the following: SA prevalence study in SR;practitioners training in differential diagnosis of SA;organization of affordable therapy for patients with SA;registration of patients with SA сreation and maintenance;and selection and management of patients with SA in accordance with federal clinical guidelines. RESULTS: Atopic phenotype in SA was detected in 5%, eosinophilic ― in 2.3% of all analyzed cases of asthma (n=216). Practitioners of SR were trained in differential diagnosis of SA. Orders of the Ministry of Health of SR were issued as follows: regulating the procedure for referring patients with SA to IBT, with a list of municipal medical organizations providing IBT in a day-stay or round-the-clock hospital;approving regional registration form of patients with SA requiring biologicals use;ungrouping of clinical and statistical groups of day-stay hospital was depending on INN and dosage of biologicals;and selecting patients with SA for TT and including them in the regional register. Initiating of TT in round-the-clock hospital and continuation therapy in day-stay hospital provides a significant savings in compulsory medical insurance funds. CONCLUSIONS: IBT introduction for SA in SR is carried out within the framework of the developed program. Principle of decentralization brings highly specialized types of medical care closer to patients making it possible to provide routine medical care in “allergology-immunology” profile in the context of restrictions caused by coronavirus disease 2019 pandemic. © 2020 Pharmarus Print Media All rights reserved.

20.
Allergologie ; 44(1):54-80, 2021.
Article in German | Web of Science | ID: covidwho-1572877

ABSTRACT

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodennatitis. and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic vi- ral and bacterial infections and, if necessary. the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.

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