Mepolizumab as a glucocorticoid-sparing agent in eosinophilic granulomatosis with polyangiitis (EGPA): is a lower dose sufficient?

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of small-vessel vasculitis characterized by asthma, hyper-eosinophilia, and progressive multiorgan involvement. EGPA is traditionally treated using glucocorticoids, either alone or in combination with conventional immunosuppressants. Mepolizumab, a novel anti-interleukin (IL)-5 agent, has been approved as an add-on therapy for adult patients with EGPA. The recommended dose of mepolizumab is 300 mg (subcutaneous [SC]) every 4 weeks. CASE STUDY: The present report discusses three cases of refractory and/or relapsing EGPA in patients regularly taking a stable dose of prednisolone, all of whom were successfully treated with a lower-than-recommended dose of mepolizumab (100 mg SC, every 4 weeks). RESULTS: Treatment with a low dose of mepolizumab enabled us to gradually reduce glucocorticoid doses. In addition, patients treated with low doses of mepolizumab exhibited better asthma control and experienced sustained relapse-free periods. Responses to 100 mg of mepolizumab were comparable to those previously observed in patients taking the recommended dose of 300 mg. CONCLUSION: Our findings suggest that mepolizumab at a third of the recommended dose can achieve reasonable clinical efficacy in the long-term treatment of EGPA in some patients. Initiation of mepolizumab therapy in the early, eosinophilic phase of EGPA-which is characterized by asthma, marked blood eosinophilia, pulmonary infiltrates, and sinonasal abnormalities-may help to prevent the deleterious side-effects of long-term glucocorticoid use while reducing the cost of EGPA treatment.

Longitudinal analysis of chest Q-SPECT/CT in patients with severe COVID-19.

INTRODUCTION: Patients with COVID-19 have an increased risk for microvascular lung thrombosis. In order to evaluate the type and prevalence of perfusion defects, we performed a longitudinal analysis of combined perfusion single-photon emission and low-dose computed tomography (Q-SPECT/CT scan) in patients with COVID-19 pneumonia. METHODS: Consecutive patients with severe COVID-19 (B.1.1.7 variant SARS-CoV-2) and respiratory insufficiency underwent chest Q-SPECT/CT during hospitalization, and 3 months after discharge. At follow-up (FU), Q-SPECT/CT were analyzed and compared with pulmonary function tests (PFT), blood analysis (CRP, D-dimers, ferritin), modified Medical Research Council (mMRC) dyspnea scale, and high-resolution CT scans (HRCT). Patients with one or more segmental perfusion defects outside the area of inflammation (PDOI) were treated with anticoagulation until FU. RESULTS: At baseline, PDOI were found in 50 of 105 patients (47.6 %). At FU, Q-SPECT/CT scans had improved significantly (p < 0.001) and PDOI were recorded in 14 of 77 (18.2 %) patients. There was a significant correlation between mMRC score and the number of segmental perfusion defects (r = 0.511, p < 0.001), and a weaker correlation with DLCO (r = -0.333, p = 0.002) and KCO (r = -0.373, p = 0.001) at FU. Neither corticosteroid therapy nor HRCT results showed an influence on Q-SPECT/CT changes (p = 0.94, p = 0.74). CRP, D-Dimers and ferritin improved but did not show any association with the FU Q-SPECT/CT results (p = 0.08). CONCLUSION: Segmental mismatched perfusion defects are common in severe COVID-19 and are correlated with the degree of dyspnea. Longitudinal analyses of Q-SPECT/CT scans in severe COVID-19 may help understand possible mechanisms of long COVID and prolonged dyspnea.

Investigating the role of obstructive pulmonary diseases and eosinophil count at admission on all-cause mortality in SARS-CoV-2 patients : A single center registry-based retrospective cohort study.

INTRODUCTION: The impact of asthma and chronic obstructive pulmonary disease (COPD) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) infection is not clearly defined. Blood eosinophil count is a standard diagnostic test which, according to the previously published literature, might have a potential prognostic role on mortality in patients with SARS-CoV­2 infection. AIM: To investigate the potential prognostic value of peripheral blood eosinophil count on all-cause mortality of patients hospitalized with SARS-CoV­2 infection, as well as to assess the impact of asthma or COPD premorbidity on all-cause mortality. MATERIAL AND METHODS: We conducted a retrospective registry-based cohort study. Survival analysis was performed by employing the Cox proportional hazards regression model at 30 days of follow-up. Prognostic value of eosinophil count on all-cause mortality was assessed using receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 5653 participants were included in the study. Our model did not reveal that pre-existing asthma or COPD is a statistically significant covariate for all-cause mortality but, indicated that higher eosinophil count at admission might have a protective effect (hazard ratio, HR 0.13 (95% confidence interval, CI 0.06-0.27), p = 0.0001). ROC curve analysis indicates cut-off value of 20 cells/mm3 (81% specificity; 30.9% sensitivity). CONCLUSION: Our results indicate that eosinophil count at hospital admission might have a potential prognostic role for all-cause mortality at 30 days of follow-up; however this was not demonstrated for pre-existing obstructive lung diseases.

Are We Missing the Opportunity to Disseminate GOLD Recommendations Through AECOPD Discharge Letters?

Introduction: Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) lead to poor outcomes and increased burden for patients and healthcare systems. The Global Initiative for COPD (GOLD) includes specific recommendations for AECOPD interventions, discharge criteria, and follow-up. Aligning the AECOPD discharge letters (DL) with GOLD guidelines could facilitate dissemination of recommendations among general practitioners (GPs). Purpose: This study was conducted to assess the compliance of DL with the GOLD recommendations in Croatia. Methods: Pre-pandemic DL of patients presenting for AECOPD to emergency room (ER) were analyzed and stratified by clinical decision to hospitalize (HDL) or discharge patients for outpatient treatment (ERDL). Experienced pulmonologists checked the information from DL against guidelines by using online study-specific questionnaires. Results: In total, 225 HDL and 368 ERDL were analyzed. In most cases, the GOLD ABCD categories (85% HDL, 92% ERDL) or the spirometry-based degree of severity (90% HDL, 91% ERDL) were not included. The number of AEs in the previous year was recorded, but the specific frequent exacerbator phenotype not explicitly stated. The AE phenotype was included in two thirds of HDL and one third of ERDL. The blood eosinophil count was frequently available, but not considered decision-relevant information. Adjustments of previous maintenance therapy, mostly escalation, were recommended in 58.4% HDL and 27.9% ERDL, respectively. Education on proper use of inhalers was recommended only in 15.6% of HDL. Smoking cessation measures were advised in 23.1% HDL and 7.9% ERDL; pulmonary rehabilitation in 35.6% HDL and 0.8% ERDL. Early follow-up was frequently advised (>50%), but rarely appointed. Conclusion: Significant deficiencies in compliance with the GOLD guidelines were identified, translating into a missed opportunity for GPs to become acquainted with GOLD recommendations. These findings emphasize the necessity to increase compliance with guidelines first at specialist level and consequent standardization of DL.

A Combination of Ultrasound Characteristics with Macroscopic and Biochemical Features to Diagnose the Etiology of Lymphocytic Pleural Effusions.

OBJECTIVES: The primary aim of this study was to improve the diagnosis of lymphocytic pleural effusions (LPEs) by combining their ultrasound characteristics with their macroscopic and biochemical features. METHODS: This prospective, single-center, clinical observational study was conducted over a period of three years. The possible malignant etiology of LPEs was assessed using several diagnostic criteria: 1. ultrasound characteristics of the LPEs; 2. typical combinations of macroscopic and ultrasound features; and 3. the logistic regression method with three parameters-pleural nodularity, absence of fibrin, and serum protein concentration. RESULTS: Eighty-four patients with LPEs were included in this study. Pleural nodularity (first criterion) was an ultrasound characteristic that yielded the best individual results (p < 0.001) in the differentiation of malignant and nonmalignant etiologies of LPEs (accuracy 73.81%). The combination of the second and third criteria yielded the best results in the prediction of a malignant etiology of LPEs (sensitivity 90.48%, specificity 83.33%, PPV 84.44%, NPV 89.74%, accuracy 86.90%). Based on the results of this prospective study, a protocol for the diagnostic procedure of lymphocytic pleural effusions without a definitive fluid diagnosis has been proposed. CONCLUSIONS: A combination of the ultrasound characteristics of LPEs and their macroscopic and biochemical features has improved the predictive accuracy for the malignant etiology of LPEs.

Attitudes of Croatian pulmonologists concerning obstacles to earlier, more appropriate use of biologics in severe asthma: Survey results.

AIMS: Biologics have been proven efficacious for patients with severe asthma (SA). It is essential to diagnose such individuals correctly. This study was designed to survey pulmonologists to identify barriers to early diagnosis and subsequent appropriate use of biologics for SA in Croatia. METHODS: A pulmonologist group with expertise in SA developed the initial list of questions, with the final questionnaire created according to a 2-round Delphi method. The resulting survey consisted of 23 items consequently divided into 4 domains: 1) Pulmonologists' demographics and professional experiences; 2) Concerns about asthma management; 3) Attitudes toward SA diagnosis; and 4) Beliefs and attitudes regarding the use of biologics in managing SA. The given answers represented the respondents' estimates. RESULTS: Eighty-four surveys were analyzed, with pulmonologists observing that general practitioners often inaccurately diagnose asthma and treat acute exacerbations. Although specialist centers are capably and correctly equipped, the time to diagnose patients with SA is approximately 3.5 months, with initial use of biologics delayed an additional 2 months. The primary indications for prescribing biologics are conventional therapy with oral glucocorticoids (91.7%) and frequent acute exacerbations (82.1%). In addition to improper diagnosis (64.3%), many patients with SA do not receive the indicated biologics owing to strict administrative directives for reimbursement (70.2%) or limited hospital resources (57.1%). LIMITATIONS: The limitations of this survey include the subjective nature of the collected data, the relatively small sample size, and the lack of the biologic efficacy evaluation. CONCLUSIONS: Croatian pulmonologists observed that a significant number of patients with SA who are eligible for biologics are not prescribed them, largely because of an inaccurate and/or delayed diagnosis, a delayed referral to a specialist center, highly restrictive criteria for reimbursement, and/or institutional budgetary limitations.