Evaluation of switching or simultaneous use of biologic treatment in patients with severe chronic rhinosinusitis with nasal polyps and severe asthma. Considerations in clinical decision making.

Introduction: Type 2 targeting biologics have reached the market first for asthma and since 2019 also for CRSwNP. As clear guidelines and predictors for optimal biological choice are missing, patients are sometimes required to switch biologic therapy in order to find the optimal treatment result. In this paper, we evaluate reasons for switching biologics and the treatment effects after each sequential switch.

Identifying risk factors for COPD and adult-onset asthma: an umbrella review.

Background: COPD and adult-onset asthma (AOA) are the most common noncommunicable respiratory diseases. To improve early identification and prevention, an overview of risk factors is needed. We therefore aimed to systematically summarise the nongenetic (exposome) risk factors for AOA and COPD.

Multi-set Pre-processing of Multicolor Flow Cytometry Data.

Flow Cytometry is an analytical technology to simultaneously measure multiple markers per single cell. Ten thousands to millions of single cells can be measured per sample and each sample may contain a different number of cells. All samples may be bundled together, leading to a 'multi-set' structure.

Correction: Synergistic activation of pro-inflammatory type-2 CD8 T lymphocytes by lipid mediators in severe eosinophilic asthma.

This article was originally published under standard licence, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the paper have been modified accordingly.

Multi-dimensional flow cytometry analysis reveals increasing changes in the systemic neutrophil compartment during seven consecutive days of endurance exercise.

Endurance exercise is associated with a transient increase in neutrophil counts in the peripheral blood. Here we investigate the impact of intensified endurance exercise on the neutrophil compartment. We hypothesized that intensified endurance exercise leads to mobilization of neutrophil subsets, which are normally absent in the blood.

Automated flow cytometric identification of disease-specific cells by the ECLIPSE algorithm.

Multicolor Flow Cytometry (MFC)-based gating allows the selection of cellular (pheno)types based on their unique marker expression. Current manual gating practice is highly subjective and may remove relevant information to preclude discovery of cell populations with specific co-expression of multiple markers. Only multivariate approaches can extract such aspects of cell variability from multi-dimensional MFC data.

Synergistic activation of pro-inflammatory type-2 CD8 T lymphocytes by lipid mediators in severe eosinophilic asthma.

Human type-2 CD8 T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8CRTH2 (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma.

A field-applicable method for flow cytometric analysis of granulocyte activation: Cryopreservation of fixed granulocytes.

Upon activation granulocytes upregulate several adhesion molecules (CD11b) and granule proteins (CD35, CD66b) and shed surface l-selectin (CD62L). These changes in expression, as assessed by flow cytometry, can be used as markers for activation. Whereas these markers are usually studied in fresh blood samples, a new method is required when samples are collected at a field site with no direct access to a flow cytometer.

Novel data analysis method for multicolour flow cytometry links variability of multiple markers on single cells to a clinical phenotype.

Multicolour Flow Cytometry (MFC) produces multidimensional analytical data on the quantitative expression of multiple markers on single cells. This data contains invaluable biomedical information on (1) the marker expressions per cell, (2) the variation in such expression across cells, (3) the variability of cell marker expression across samples that (4) may vary systematically between cells collected from donors and patients. Current conventional and even advanced data analysis methods for MFC data explore only a subset of these levels.

Emerging Biologics in Severe Asthma.

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by persistently elevated sputum and/or blood eosinophils and by a significant response to treatments that suppress eosinophilia.

Evidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma.

Two recent phase III trials in patients with severe eosinophilic asthma have shown that anti-interleukin 5 (IL-5) therapy with mepolizumab reduces the frequency of asthma attacks, improves symptoms and allows patients to reduce oral glucocorticoid use without loss of control of asthma. An earlier large 616 patient Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) study had shown that the only variables associated with treatment efficacy were a prior history of asthma attacks and the peripheral blood eosinophil count. The link between blood eosinophil counts and treatment efficacy is biologically obvious given that IL-5 has a pivotal role in eosinophil production, proliferation and chemotaxis.

Clinical utility of asthma biomarkers: from bench to bedside.

Asthma is a chronic disease characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. The disease is very heterogeneous in onset, course, and response to treatment, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted clinical biomarkers to assess the nature and severity of the disease.