Benralizumab monotherapy was insufficient to induce remission in patients with active eosinophilic granulomatosis with polyangiitis.

Eosinophils play an important pathogenetic role in the development of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA has long been treated with systemic corticosteroids and immunosuppressive agents. However, in recent years, biologic agents targeting eosinophils (anti-IL-5 antibody; mepolizumab) have also been used. Evidence regarding the effectiveness of using benralizumab, anti-IL-5 receptor α monoclonal antibody that depletes eosinophils via antibody-dependent cell-mediated cytotoxicity, has been growing. Benralizumab is used as a steroid-sparing treatment option for EGPA. Clinical studies have evaluated the effects of using mepolizumab or benralizumab in combination with steroids for the treatment of EGPA. However, to date, there have been no reports of using biologics alone. Herein, we describe the case of a patient with active EGPA refractory to benralizumab monotherapy. The patient achieved significant improvement in symptoms after administration of corticosteroids during hospitalization. Benralizumab monotherapy might not be considered a therapeutic option for patients with active EGPA in whom corticosteroids are initially indicated.

Retropharyngeal edema: A rare manifestation of eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by excessive eosinophil accumulation in the peripheral blood and affected tissues with development of granulomatous vasculitic organ damage. Although upper airway and neck involvement is seen in patients with EGPA, retropharyngeal inflammation has never been reported. We report a case of retropharyngeal edema in a 70-year-old woman with EGPA. Her symptoms improved and the retropharyngeal edema disappeared on computed tomography following treatment. EGPA should be considered as a differential diagnosis in patients with asthma presenting with neck swelling and dysphagia.

Prompt Reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19.

Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown. Methods: In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab. Results: A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab. Conclusion: Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19.

Scoring system for identifying Japanese patients with COVID-19 at risk of requiring oxygen supply: A retrospective single-center study.

INTRODUCTION: Japan is facing the threat of medical system collapse due to the rapid spread of coronavirus disease 2019 (COVID-19). The present scoring system may help assess disease severity and oxygen supply requirements in COVID-19 patients. METHODS: Data on patient characteristics at baseline and throughout hospitalization for COVID-19 were extracted from medical records. Disease severity was dichotomized into two categories without or with oxygen supply as asymptomatic, mild, and moderate illness (AMMI), and severe and critical illness (CSI). The AMMI and CSI groups were compared. Predictors of disease severity, previously identified in the outpatient setting, were included in multivariable logistic regression analysis; the obtained coefficients were converted to integers and assigned a score. RESULTS: A total of 206 patients diagnosed with COVID-19 were included in this study. Correlation between COVID-19 severity and medical information was examined by comparing AMMI and CSI. Age, hemodialysis, and C-reactive protein (CRP) levels were candidate predictors of the need for oxygen supply in patients with COVID-19. Coefficients associated with age, hemodialysis, and CRP were as follows: 1 × age (in years, coded as 0 for values of <50, and as 1 for values of ≥50) + 1 × hemodialysis (coded as 0 for "no", and as 1 for "yes") + 1 × CRP (in mg/dL, coded as 0 for values of <1.0, and as 1 for values of ≥1.0). Patients with scores of ≥2 points required oxygen supply (sensitivity, 68.4%; specificity, 79.0%) CONCLUSION: The present model can help predict disease severity and oxygen requirements in COVID-19 patients in Japan.

COVID-19 in a Patient With Severe Eosinophilic Asthma on Benralizumab Therapy: A Case Report and Review of Literature.

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.

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study.

INTRODUCTION: The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. METHODS: All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients' records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. RESULTS: Data from 61 patients (16 Pt-CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt-CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt-CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt-CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt-CSI than in Pt-MMI (P = 0.013). Among the 16 Pt-CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died. CONCLUSIONS: The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.

Rapid effect of benralizumab for severe asthma with chronic rhinosinusitis with nasal polyps.

BACKGROUND: The anti-interleukin (IL)-5 agent benralizumab has recently become available for treatment of severe asthma with promising results; however, it appears effective only in specific subgroups of asthma patients. Severe asthma with chronic rhinosinusitis/nasal polyps (CRSwNP or eosinophilic chronic rhinosinusitis, ECRS) is a severe eosinophilic asthma phenotype that necessitates individualized treatment. OBJECTIVE: To assess differences in response to benralizumab between severely eosinophilic asthma patients with and without CRSwNP. METHODS: Seventeen outpatients with severe eosinophilic asthma treated with benralizumab for 1 year were evaluated at the Osaka Habikino Medical Center. Blood eosinophil count, Asthma Control Questionnaire 5 (ACQ5), Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), and spirometry were recorded at weeks 0, 4, 16, 24, and 50. RESULTS: ACQ5 and AQLQ in CRSwNP(+) groups improved significantly after 4, 16, 24, and 50 weeks (p = 0.0195, 0.0156, 0.0117, and 0.0078 and p = 0.0098, 0.0098, 0.0029, and 0.0098, respectively) of benralizumab treatment. ACQ5 in CRSwNP(-) groups did not improve significantly after benralizumab treatment, but AQLQ improved significantly after 24 (p = 0.0313) and 50 weeks (p = 0.0313). Forced expiratory volume in 1s (FEV1) predicted in CRSwNP(+) groups were improved significantly after 4 weeks (p = 0.0137), 16 weeks (p = 0.0127), 24 weeks (p = 0.0098) and 50 weeks (p = 0.0420) of benralizumab treatment. %FEV1 in CRSwNP(-) groups were improved significantly after 24 weeks (p = 0.0313) and 50 weeks (p = 0.0313) of benralizumab treatment (Fig. 3). Forced vital capacity (FVC) predicted in CRSwNP(+) groups were improved significantly after 24 weeks (p = 0.0195) and %FVC in CRSwNP(-) groups improved significantly after 50 weeks (p = 0.0313) of benralizumab treatment. Maximum mid-expiratory flow rate predicted in CRSwNP(+) groups were improved significantly after 16 (p = 0.0137 and 50 weeks (p = 0.0371) of benralizumab treatment. CONCLUSIONS: Benralizumab can exert a very rapid therapeutic action, detectable 4 weeks after treatment initiation in patients with severe eosinophilic asthma with CRSwNP. However, severe eosinophilic asthma without CRSwNP takes longer to respond to benralizumab treatment.

Eosinophils depletion therapy for severe asthma management following favorable response to mepolizumab.

We described three severe asthmatics whose asthma symptoms were rapidly improved by benralizumab following favorable response to mepolizumab. Benralizumab-induced eosinophil depletion contributed to clinical improvement of severe asthma after mepolizumab-induced eosinophil reduction; thus, prior favorable responses to mepolizumab may predict benralizumab efficacy.

Flare of eosinophilic granulomatosis with polyangiitis related to pregnancy: Case report and review of the literature.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by excessive eosinophil accumulation in the peripheral blood and affected tissues with development of granulomatous vasculitic organ damage. It is strongly associated with asthma and ear-nose-throat disease. It often affects patients between the ages of 40 and 60 years. It is unknown whether pregnancy impacts the disease activity of EGPA, including initial diagnosis or relapse. Because of its rarity and age of susceptibility, there are few reported cases describing pregnancy in women with quiescent or active EGPA. Here, we describe a young woman who experienced EGPA relapse during pregnancy and subsequently underwent an elective caesarean section for non-reassuring fetal status at 37 weeks without complication.

Serum soluble interleukin-2 receptor as a biomarker in immunoglobulin G4-related disease.

OBJECTIVES: Serum soluble interleukin-2 (IL-2) receptor (sIL-2R) might reflect disease activity in immunoglobulin G4-related disease (IgG4-RD). We aimed to elucidate the clinical significance of blood markers, including sIL-2R, in patients with IgG4-RD. METHODS: We enrolled 59 patients with IgG4-RD and investigated the association between blood markers (white blood cells, C-reactive protein, sIL-2R, IgG, IgG4, IgE, total hemolytic complement), and clinical indices. RESULTS: At baseline, serum sIL-2R (Rs = 0.532, p < .001) and IgG4 (Rs = 0.545, p < .001) levels showed significant correlation to the number of organs involved. During follow-up period (median, 70 months; range, 7-195 months), 40 patients were treated with corticosteroids. Receiver operating characteristic (ROC) analysis showed that baseline sIL-2R levels most accurately predicted patients requiring glucocorticoid treatment (area under the ROC curve, 0.807). Among the 46 patients who improved, sIL-2R and IgG4 levels decreased in 42 and 41 patients, respectively. Among them, serum sIL-2R levels decreased to a normal range in 42 patients (91%), whereas IgG4 levels normalized in 19 (41%). CONCLUSION: The serum sIL-2R level is a potential biomarker for IgG4-RD that may reflect the number of involved organs and may predict patients requiring glucocorticoid treatment.

Does allergic rhinitis make a difference to the respiratory resistance and reactance of asthma?

BACKGROUND: Concomitant allergic rhinitis (AR) in asthmatic patients can contribute to increased asthma exacerbations and poorer symptom control. A recent study indicated that impulse oscillometry is a more sensitive measure of change in airway function than spirometry, but this has not been used to compare asthmatic patients with or without AR. OBJECTIVE: We used impulse oscillometry (Mostgraph-01) to examine the impact of AR on asthma. METHODS: Impulse oscillometry and spirometry were assessed in 50 patients with asthma only and 95 patients with asthma and AR. RESULTS: Mean age in the asthma only group was significantly higher than in the asthma with AR group. Therefore, analysis of covariance adjusted for age was used to compare between these two groups. Percentage of mean forced expiratory volume in 1 s (FEV1), respiratory resistance at 5 Hz (R5) minus respiratory resistance at 20 Hz (R20), and resonant frequency (Fres) in the asthma with AR group were significantly less severe than in the asthma only group. Parameters of resistance and reactance were correlated with age and body mass index only in the asthma with AR group but not in the asthma only group. Correlations were observed between rate of change of maximum mid-expiratory flow and impulse oscillometry values of R5 and Fres in the asthma only group, but not between the rate of change of FEV1 and impulse oscillometry values. CONCLUSION: Asthma with AR was associated with higher lung function and better values of resistance and reactance than asthma only.

Effectiveness of omalizumab in a patient with severe asthma, low serum IgE level, and lack of sensitized allergens induced by oral steroid therapy: the usefulness of impulse oscillation for assessment of omalizumab therapy.

BACKGROUND: Omalizumab is a humanized monoclonal anti-IgE antibody that was recently approved for the treatment of severe allergic asthma. However, omalizumab is not licensed for allergic asthma in patients with a low serum IgE level (<30 IU/mL) or negative results for specific allergen tests. CASE HISTORY: We present a patient with severe asthma and low serum IgE levels who had negative results for specific allergens induced by oral steroid therapy. Omalizumab administration improved asthma exacerbated forced expiratory volume in 1 s (FEV(1)) and respiratory resistance measurements based on the impulse oscillation technique (Mostgraph-01). The response to omalizumab therapy was evidenced by a decrease in airway resistance at 1 month. CONCLUSIONS: The findings of this case report indicate that omalizumab treatment had beneficial effects in a patient with severe asthma and low total serum IgE levels with negative results for specific IgE, which may have been induced by long-term corticosteroid administration.

[An adolescent case of pulmonary MAC infection, found 3 years later from bone marrow transplantation for myelodysplastic syndrome].

Mycobacterium avium complex (MAC) pulmonary infection is usually seen in elderly persons. We encountered a rare case of MAC pulmonary disease seen in a 19-year-old adolescent. The patient had received bone marrow transplantation at the age of 16 for myelodysplastic syndrome. Subsequently, he developed constrictive bronchiolitis and has been treated with corticosteroid and taclorimus. At age 19, small or fine nodules and a cavitary nodule in right lung were detected on the chest radiograph and computed tomography. Afterwards, Mycobacterium avium was detected by bronchoscopic examination and sputum examination and he was diagnosed as MAC pulmonary infection. MAC pulmonary infection in a young person at the age of 19 is an extremely rare case, in which constrictive bronchiolitis, immunosuppression by corticosteroid and tacrolimus, and diabetes mellitus were considered as critical predisposing factors.