ERS Congress 2022 Highlights: 3 Current Challenges in Asthma Clinical Research
The European Respiratory Society International Congress brought together the world’s respiratory experts to present and discuss the latest research, and PSI’s Senior Medical Advisor, Maxim Kosov, had the opportunity to attend. In his new white paper,?Respiratory Clinical Research: How to Navigate Therapeutic and Operational Challenges, he discusses the presentations and abstracts with the most significant advances in diagnostic and treatment approaches and how they can potentially influence clinical trials.
A number of these advances focused on asthma clinical research, the most common respiratory disease globally, which affects 264.4 million people and continues to be associated with death and disability even in the anti-inflammatory era.?The congress included updates on the immunology and possible mechanisms of the disease, target receptors, and the role of biologics in disease management and diagnostic approaches, particularly in pediatric asthma.
The proportion of patients misdiagnosed with asthma remains high, with overdiagnosis of up to 56% in adults and 54% in children and underdiagnosis of up to 70% in adults and 50% in children. There is no universal test to diagnose asthma, and despite the availability of effective inhaled therapies, many patients with asthma continue to have poor disease control, resulting in a significant burden on the patient and healthcare system. These challenges defined the agenda of the asthma section of the congress, which focused on the search for reliable diagnostic approaches and tools and optimization of therapy.
1. Optimizing Asthma Diagnostic Testing
One such example was the presentation by D. Lo (UK), “New and old tests for asthma diagnosis in primary care: from peak-flow to FeNO.”?Lo explained that none of the tests have perfect diagnostic accuracy, so they are “good for confirming, but not excluding asthma.” Results depend significantly on the timing of testing, and the optimal time to test is during or shortly after an acute attack. Using several methods in combination achieves the best results. These typically include spirometry plus bronchodilator reversibility, fraction of exhaled nitric oxide (FeNO), and peak flow variability tests in the primary care setting and indirect and direct challenge tests in the secondary care facilities.
The challenges of asthma testing include the costs of tests – approximately €60-€100 ($65-$108) per test, poor compliance during PEF monitoring, and limited options for testing young children. For example, spirometry can be successfully used in only 78% of 5-year-old children and FeNO in 18%. Spirometry and FeNO can be used in all children starting at age eight.
2. Biologics in Asthma Management
G. Brusselle (Belgium) spoke about the pathophysiological basis of using biologics in asthma management.?There are several clinical phenotypes of asthma, including early-onset asthma, with allergy as the main driver of the inflammation, and adult-onset asthma, where allergy does not play the leading role. There are also several inflammatory phenotypes, including eosinophilic inflammation, which can be either allergic or non-allergic, in Type-2-high asthma and neutrophilic asthma in Type 2-low asthma. These two different inflammatory phenotypes define different approaches to therapy based on the pathogenesis but also present a significant challenge for diagnosis.
For instance, non-invasive biomarkers exist for eosinophilic asthma: elevated FeNO and blood eosinophil count, which correlates with sputum eosinophils in asthma. No such biomarkers exist for neutrophilic asthma, and blood neutrophil count does not correlate with sputum neutrophil levels in asthma. Therapeutic targets in eosinophilic asthma are also clearly defined, including corticosteroids, type-2 cytokines, and IgE in allergic eosinophilic severe asthma. The targets are less clear in neutrophilic asthma, with the main ones being pro-inflammatory cytokines such as IL-1β, IL-6, and TNF.
领英推荐
3. The Role of Small Airway Disfunction (SAD) in Asthma
Knowing the mechanisms behind the disease is crucial to initiate the proper treatment, especially in the role of small airways in asthma. Small airways are defined as those less than 2 mm in diameter, and their involvement in the disease – so-called “small airway dysfunction” (SAD) – remains an unmet need in asthma diagnosis and management. SAD is already present before asthma is diagnosed and occurs at all severities of asthma and after allergen inhalation or smoking. It is associated with such conditions as hyperresponsiveness, exercise-induced asthma, exacerbations, and poor asthma control.
M. Kraft (USA) presented the results of the ATLANTIS study to determine the role of SAD in the clinical manifestation of asthma and to evaluate which clinical method or combination of methods can best assess this abnormality.iv?Most patients had Global Initiative for Asthma Strategy (GINA) steps 3 (26.5% of patients) and 4 (30.5% of patients), and only 4.8% had GINA step 5, the most severe form. 84% used a combination of inhaled corticosteroids.
The study revealed that SAD is present in 91% of the asthma population across all severities, particularly in more severe asthma cases, and can be used to help predict exacerbations. Kraft suggested that small airway lung function tests, including impulse oscillometry, body plethysmography, and spirometry, can be used in clinical practice.
Conclusion
The need for reliable methods for early diagnosis such as consistent biomarkers evaluation may provide a head start on effective treatment to help patients gain better disease control. If you’re looking for additional insights to be aware of when planning your respiratory trial, download our new white paper,?Respiratory Clinical Research: How to Navigate Therapeutic and Operational Challenges?today.
References