impulse oscillometry measurements in severe eosinophilic asthmatics before and after anti-il-5 factor initiation

Conditions: Severe Asthma

Summary: eosinophilic inflammation in the small airways of patients with severe asthma is considered to be an important marker of disease severity. in clinical trials, treatment with mepolizumab reduces exacerbation rates by almost a half along with modest improvements in symptom scores and forced expiratory volume in 1 s (fev1) early after the first month of commencing mepolizumab treatment. however, there is an apparent discrepancy between major patient-reported outcomes and lung function that should be explored. it has recently been reported that mepolizumab improves small airway function in severe eosinophilic asthma as detected by multiple-breath nitrogen washout test. the improvement in small airway function was seen rapidly after the first mepolizumab injection and was associated with a sustained response in the majority of patients. however, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues leading the committee to conclude that multiple-breath nitrogen washout test is not ready for use as a clinical trial endpoint in asthmatics. the investigators hypothesize that early improvement in small airway function may be a significant contributor to the therapeutic response of anti-il-5 monoclonal antibody therapy in patients with severe uncontrolled eosinophilic asthma. the investigators speculate that sad could be effectively evaluated using ios. consequently, this study could lead to novel sad subtypes with possible clinical relevance in the context of treatment with anti-il-5 factor. the investigators hypothesize that healthy individuals and patients with severe controlled asthma would disclose a lesser extent of sad than patients with severe uncontrolled eosinophilic asthma with or without fixed airway obstruction.

asthma is an inflammatory condition impacting the entire bronchial tree, with small airways playing a crucial role. small airways, defined as those less than 2 mm in diameter, are significantly involved in all stages of asthma, particularly severe cases. this region, known as the silent zone, is often linked with poor asthma control, increased severity, and a higher risk of exacerbations. structural changes at the peribronchiolar level, such as increased stiffness due to remodeling, contribute to the disease's pathogenesis. these changes are associated with more frequent exacerbations and poorer quality of life. small airways account for a significant portion of airway resistance, particularly in obstructive diseases like asthma. for example, resistance in small airways can constitute up to 51% of total airway resistance in severe asthma cases. despite their importance, measuring small airway inflammation and dysfunction remains challenging. various tests, including spirometry and impulse oscillometry (ios), are used, but each has limitations in detecting and evaluating small airway disease (sad). methods more refined techniques like ios are employed to better understand and treat sad. ios measures airway resistance and reactance during breathing without patient effort, offering a detailed analysis more sensitive to small airway changes than traditional spirometry. this technique is crucial for identifying different subtypes of sad and is associated with asthma severity stages and control. in clinical practice, forced oscillation technique (fot) devices, including newer models that utilize multiple sound frequencies, are becoming popular for assessing respiratory impedance in diseases like asthma. these devices, particularly ios, help differentiate between small and large airway obstructions and are easier to use in diverse patient groups, including the elderly and children. research focus recent studies have highlighted the effectiveness of new treatments like mepolizumab in improving small airway function in severe eosinophilic asthma. this improvement, detectable through methods like the multiple-breath nitrogen washout test, occurs quickly after treatment begins and is sustained over time. however, gaps in standardization and device choice remain challenges. study objectives and design the upcoming study will investigate early changes in respiratory mechanics using ios in patients with severe eosinophilic asthma starting on mepolizumab. this 2-year prospective cohort study will involve 40 patients with severe asthma, matched controls for age and gender, and will assess various respiratory parameters and asthma control metrics. measurements will be taken at multiple points to gauge the treatment's effectiveness and its impact on lung function. ethical considerations the study will adhere to ethical standards, with informed consent obtained from all participants and approval from relevant ethical bodies. the goal is to enroll patients efficiently and effectively, leveraging networks of healthcare providers and educational programs to support patient recruitment and data collection. conclusion this research aims to enhance our understanding of sad in severe asthma and improve treatment outcomes through innovative diagnostic techniques and targeted therapies. by focusing on the small airways, which play a significant role in asthma pathology but are challenging to study, this work could lead to more effective management strategies for those most affected by this condition.

Eligibility criteria:
inclusion criteria: * written informed consent * male or female outpatient aged 18 to 82 years inclusive * history of bronchial asthma for at least six months as defined by ats criteria. * the patients will be required to have one or more of the following objective physiological criteria: positive results on methacholine or mannitol challenge during the previous year, bronchodilator reversibility to 400 mg of inhaled salbutamol of fev1 ≥12% and 200ml or peak flow variability of ≥20% over two weeks. * diagnosis of severe asthma, defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy. * all patients will be medicated with at least 880 μg of fluticasone propionate or the equivalent by inhalation per day and at least three months of treatment with an additional controller. patients will be allowed to continue their anti-asthma therapy throughout the study. * patients should have uncontrolled asthma commencing mepolizumab treatment, based on investigator assessment, including one or both of the following: * poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma), defined as acq consistently ⩾1.5 or act\<20. * frequent exacerbations (≥2/year) requiring oral corticosteroids, or severe exacerbations (≥1/year) requiring hospitalization or burst of systemic corticosteroids (≥3 days). * all patients will have an eosinophil count of at least 150 cells per microliter in the peripheral blood at screening or at least 300 cells per microliter at some time during the previous year. exclusion criteria: principal exclusion criteria: * diseases and health status: clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation suffering from copd (i.e., chronic bronchitis or emphysema) and/or other relevant lung diseases causing alternating impairment in lung function * asthmatic patients and healthy controls currently smoking or with a smoking pack history greater than 10 will be excluded. common exclusion criteria: * pregnancy * intention to become pregnant during the course of the study * breastfeeding * participation in another study within the 30 days preceding and during the present study * known or suspected non-compliance, alcohol or drug abuse * inability to follow the procedures of the study, e.g., due to language problems, psychological disorders