Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis.

INTRODUCTION: Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. METHODS: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. RESULTS: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. CONCLUSIONS: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.

The Real Impact of Age on Mortality in Critically Ill COVID-19 Patients.

OBJECTIVE: The impact of severe infection from COVID-19 and the resulting need for life support in an ICU environment is a fact that caused immense pressure in healthcare systems around the globe. Accordingly, elderly people faced multiple challenges, especially after admission to the ICU. On this basis, we performed this study to assess the impact of age on COVID-19 mortality in critically ill patients. MATERIALS AND METHODS: In this retrospective study, we collected data from 300 patients who were hospitalized in the ICU of a Greek respiratory hospital. We split patients into two age groups using a threshold of 65 years old. The primary objective of the study was the survival of patients in a follow up period of 60 days after their admission to the ICU. Secondary objectives were to determine whether mortality is affected by other factors, including sepsis and clinical and laboratory factors, Charlson Comorbidity Index (CCI), APACHE II and d-dimers, CRP, etc. Results: The survival of all patients in the ICU was 75.7%. Those in the <65 years old age group expressed a survival rate of 89.3%, whereas those in the ≥65 years old age group had a survival rate of 58% (p-value < 0.001). In the multivariate Cox regression, the presence of sepsis and an increased CCI were independent predictors of mortality in 60 days (p-value < 0.001), while the age group did not maintain its statistical significance (p-value = 0.320). CONCLUSIONS: Age alone as a simple number is not capable of predicting mortality in patients with severe COVID-19 in the ICU. We must use more composite clinical markers that may better reflect the biological age of patients, such as CCI. Moreover, the effective control of infections in the ICU is of utmost importance for the survival of patients, since avoiding septic complications can drastically improve the prognosis of all patients, regardless of age.

Fungal Infections in Critically Ill COVID-19 Patients: Inevitabile Malum.

Patients with severe COVID-19 belong to a population at high risk of invasive fungal infections (IFIs), with a reported incidence of IFIs in critically ill COVID-19 patients ranging between 5% and 26.7%. Common factors in these patients, such as multiple organ failure, immunomodulating/immunocompromising treatments, the longer time on mechanical ventilation, renal replacement therapy or extracorporeal membrane oxygenation, make them vulnerable candidates for fungal infections. In addition to that, SARS-CoV2 itself is associated with significant dysfunction in the patient's immune system involving both innate and acquired immunity, with reduction in both CD4+ T and CD8+ T lymphocyte counts and cytokine storm. The emerging question is whether SARS-CoV-2 inherently predisposes critically ill patients to fungal infections or the immunosuppressive therapy constitutes the igniting factor for invasive mycoses. To approach the dilemma, one must consider the unique pathogenicity of SARS-CoV-2 with the deranged immune response it provokes, review the well-known effects of immunosuppressants and finally refer to current literature to probe possible causal relationships, synergistic effects or independent risk factors. In this review, we aimed to identify the prevalence, risk factors and mortality associated with IFIs in mechanically ventilated patients with COVID-19.

Acid-Base Disturbances in Patients with Asthma: A Literature Review and Comments on Their Pathophysiology.

Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the resulting hypoxemia along with the circulatory compromise due to heart-lung interactions can reduce tissue oxygenation, with a particular impact on respiratory muscles that have increased energy needs due to the increased workload. Thus, anaerobic metabolism may ensue, leading to lactic acidosis. Additionally, chronic hypocapnia in asthma can cause a compensatory drop in plasma bicarbonate concentration, resulting in non-anion gap acidosis. Indeed, studies have shown that in acute severe asthma, metabolic acid-base disorders may occur, i.e., high anion gap or non-anion gap metabolic acidosis. This review briefly presents studies that have investigated acid-base disorders in asthma, with comments on their underlying pathophysiology.