Good clinical practice in clinical interventional studies

Good clinical practice (GCP) guidelines should always be implemented and obeyed in clinical interventional studies. In this mini-review, we will address several burning questions relating to GCP in a concise ‘frequently asked questions’ format.While compliance to current rules and regulations is our mission, we also wish to play devil’s advocate attempting to translate the rules into sizeable chunks using a high dose of common sense

Non-invasive Biomarkers in Asthma: Promises and Pitfalls

The asthma concept has evolved throughout the years: one major step in asthma management is the recognition of the chronic (airway) inflammation; another major step is further understanding of asthma heterogeneity and subsequent development of targeted therapies. While the concept of chronic inflammation, airway structural changes and their variability over time are widely accepted, their measurement and monitoring have gone through many hardships

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.</p

An Algorithm for Strategic Continuation or Restriction of Asthma Medication Prior to Exercise Challenge Testing in Childhood Exercise Induced Bronchoconstriction

Exercise induced bronchial (EIB) constriction is a common and highly specific feature of pediatric asthma and should be diagnosed with an exercise challenge test (ECT). The impact of EIB in asthmatic children's daily lives is immense, considering the effects on both physical and psychosocial development. Monitoring childhood asthma by ECT's can provide insight into daily life disease burden and the control of asthma. Current guidelines for bronchoprovocation tests restrict both the use of reliever and maintenance asthma medication before an exercise challenge to prevent false-negative testing, as both have significant acute bronchoprotective properties. However, restricting maintenance medication before an ECT may be less appropiate to evaluate EIB symptoms in daily life when a diagnosis of asthma is well established. Rigorous of maintenance medication before an ECT according to guidelines may lead to overestimation of the real, daily life asthma burden and lead to an inappropiate step-up in therapy. The protection against EIB offered by the combined acute and chronic bronchoprotective effects of maintenance medication can be properly assessed whilst maintaining them. This may aid in achieving the goal of unrestricted participation of children in daily play and sports activities with their peers without escalation of therapy. When considering a step down in medication, a strategic wash-out of maintenance medication before an ECT aids in providing objective support of potential discontinuation of maintenance medication

Allergen bronchoprovocation test:an important research tool supporting precision medicine

PURPOSE OF REVIEW: Allergen bronchoprovocation test (ABT) has been used to study asthma pathophysiology and as a disease-modelling tool to assess the properties and efficacy of new asthma drugs. In view of the complexity and heterogeneity of asthma, which has driven the definition of several phenotypes and endotypes, we aim to discuss the role of ABT in the era of precision medicine and provide guidance for clinicians how to interpret and use available data to understand the implications for the benefits of asthma treatment. RECENT FINDINGS: In this review, we summarize background knowledge and applications of ABT and provide an update with recent publications on this topic. In the past years, several studies have been published on ABT in combination with non-invasive and invasive airway samplings and innovative detection techniques allowing to study several inflammatory mechanisms linked to Th2-pathway and allergen-induced pathophysiology throughout the airways. SUMMARY: ABT is a valuable research tool, which has strongly contributed to precision medicine by helping to define allergen-triggered key inflammatory pathways and airway pathophysiology, and thus helped to shape our understanding of allergen-driven asthma phenotypes and endotypes. In addition, ABT has been instrumental to assess the interactions and effects of new-targeted asthma treatments along these pathways

Application of nitric oxide measurements in clinical conditions beyond asthma.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma