Severe AsthmaIMPOSENCT05147155
Impulse Oscillometry Measurements in Severe Eosinophilic Asthmatics Before and After Anti-IL-5 Factor Initiation
An observational study of Severe Asthma, run by University of Thessaly at 1 site in Greece.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 82 yearsHealthy volunteers can take part
- Conditions the study is for
- Severe Asthma
- What is being tested?
- Mepolizumab
- Type of treatment
- Injection or infusion
- How many people
- 130 participants
- Where
- 1 siteGreece
- Study dates
- 19 Apr 2021to 23 Oct 2023
- How long will I take part?
- 26 Weeks
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 82 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The sample will consist of 40 patients between 18 and 82 years of age with uncontrolled severe eosinophilic asthma despite receiving high-dose ICS/LABA combination therapy.
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Greece1 site
External Unit of Asthma of Respiratory Medicine Department of the University of Thessaly in Greece
Larissa, Thessaly, 41110
About this study
Official title: How Much Severe is the Severe Asthma of Patients Who Will be Medicated With Mepolizumab? Μeasurement of Respiratory Mechanics by Means of Impulse Oscillometry in Severe Eosinophilic Asthmatics Before and After Mepolizumab Initiation
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.
Read the detailed description
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.
- Conditions
- Severe Asthma
- Being tested
- Mepolizumab
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabBiological
Also called Nucala
This will be a 2-year prospective study. Patients with uncontrolled severe asthma will receive mepolizumab according to standard of care and best clinical practice, which will be administered as a 100-mg subcutaneous dose every four weeks.
| Study group | Role | What they receive |
|---|---|---|
| Severe asthma patients | The sample will consist of 40 patients between 18 and 82 years of age with uncontrolled severe eosinophilic asthma despite receiving high dose ICS/LABA combination therapy who will receive mepolizumab, which will be administered as a 100-mg subcutaneous dose every four weeks Receives: Biological: Mepolizumab | |
| Control group 1 | Control group 1 will be a set of 50 healthy individuals matched for age and gender | |
| Control group 2 | Control group 2 will be a set of 40 patients with severe well-controlled asthma requiring high dose ICS/LABA combination therapy from becoming uncontrolled, as previously defined, matched for age and gender. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway Resistance at 5 Hz (R5) at Baseline (Pre-mepolizumab Initiation)
Measurements of R5 at baseline (pre-mepolizumab initiation). R5 was assessed using impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society
Measured: 0 months
Airway Resistance at 20 Hz (R20) at Baseline
Measurement of R20 at baseline - mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Measured: 0 months
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Baseline / (R5-R20) at Baseline
Measurement of R5-R20 at baseline. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at baseline, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Measured: 0 months
Reactance Area (AX) at Baseline
Measurement of AX at baseline. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at baseline using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Measured: 0 months
Resonant Frequency (Fres) at Baseline
Measurement of Fres at Baseline. Fres, the resonant frequency, is the point where the reactance of the respiratory system equals zero, indicating the balance between elastic and inertial forces in the lungs. Measurements were taken at baseline using impulse oscillometry. Values are reported in Hz and analyzed following guidelines from the European Respiratory Society
Measured: 0 months
Respiratory Reactance at 5 Hz (X5) at Baseline
Measurement of X5 at Baseline. X5, the respiratory reactance at 5 Hz, is a measure of the elastic properties of the lungs and the peripheral airways. It indicates how easily the lungs expand and contract during breathing. Measurements were taken at baseline using impulse oscillometry, with values expressed in kPa/L. Assessments followed European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Measured: 0 months
Airway Resistance at 5 Hz (R5) at Week 4.
Estimate the airway resistance measured at the 5 Hz frequency (R5) after four weeks from mepolizumab initiation (only severe uncontrolled asthma patients received mepolizumab). R5 was assessed using impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Measured: 4 weeks
Airway Resistance at 20 Hz (R20) at Week 4.
Estimate the airway resistance measured at the 20 Hz frequency (R20) after four weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society
Measured: 4 weeks
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 4/ R5-R20 at Week 4.
After four weeks of mepolizumab initiation, estimate the small airway resistance (R5- R20). R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted after 4 weeks from mepolizumab initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Measured: 4 weeks
Reactance Area (AX) at Week 4
Estimate the AX after four weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 4 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Measured: 4 weeks
Resonant Frequency (Fres) at Week 4.
Estimate Fres after four weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 4 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Measured: 4 weeks
Respiratory Reactance at 5 Hz (X5) at Week 4.
Estimate X5 after four weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, is a measure of the elastic properties of the lungs and peripheral airways, reflecting the ability of the respiratory system to expand and contract. Measurements were taken at Week 4 using impulse oscillometry. Values are reported in kPa/L and were analyzed according to European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Measured: 4 weeks
Airway Resistance at 5 Hz (R5) at Week 12
Estimate the airway resistance measured at the 5 Hz frequency (R5) after 12 weeks from the mepolizumab initiation. R5 was assessed using spirometry with impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Measured: 12 weeks
Airway Resistance at 20 Hz (R20) at Week 12
Estimate the airway resistance measured at the 20 Hz frequency (R20) after 12 weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Measured: 12 weeks
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 12 / R5-R20 at Week 12
Estimate small airway resistance (R5-R20) after 12 weeks from mepolizumab initiation. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at week 12 after mepolizuamb initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society.
Measured: 12 weeks
Reactance Area (AX) at Week 12
Estimate the AX after 12 weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 12 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Measured: 12 weeks
Resonant Frequency (Fres) at Week 12
Estimate Fres after12 weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 4 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Measured: 12 weeks
Respiratory Reactance at 5 Hz (X5) at Week 12
Estimate X5 after 12 weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, measures the elastic properties of the lungs and peripheral airways, reflecting the ability of the respiratory system to expand and contract. Measurements were taken at Week 12 using impulse oscillometry. Values are reported in kPa/L and analyzed according to European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Measured: 12 weeks
Airway Resistance at 5 Hz (R5) at Week 26.
Estimate the airway resistance measured at the 5 Hz frequency (R5) after 26 weeks from the initiation of mepolizumab. R5 was assessed using spirometry with impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Measured: 26 weeks
Airway Resistance at 20 Hz (R20) at Week 26.
Estimate the airway resistance measured at the 20 Hz frequency (R20) after 26 weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Measured: 26 weeks
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 26 / R5-R20 at Week 26.
Estimate the small airway resistance (R5-R20) after 26 weeks from mepolizumab initiation. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at Week 26 after mepolizumab initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Measured: 26 weeks
Reactance Area (AX) at Week 26.
Estimate AX after 26 weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 26 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Measured: 26 weeks
Resonant Frequency (Fres) at Week 26.
Estimate Fres after 26 weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 26 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Measured: 26 weeks
Respiratory Reactance at 5 Hz (X5) at Week 26.
Estimate X5 after 26 weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, reflects the elastic properties of the lungs and peripheral airways, indicating the ability of the respiratory system to expand and contract. Measurements were taken at Week 26 using impulse oscillometry. Values are reported in kPa/L and were analyzed following European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2021
- Study start19 Apr 2021
- Primary completion23 Oct 2023
- Study completion23 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe AsthmaStudies of the same condition, open and under way.
- More trials run by University of ThessalyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 130 participants (actual)
- Target duration
- 26 Weeks
Sponsor and investigators
- Lead sponsor
- University of Thessaly
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ourania Kotsiou, University of Thessaly
- Investigators
- Konstantinos I Gourgoulianis, Professor, Study director, University of Thessaly
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05147155
- Sponsor's protocol ID
- 15745/19-04-2021
- Acronym
- IMPOSE
- Status last verified
- Feb 2025
- First submitted
- 25 Jun 2021
- Last updated
- 24 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kotsiou OS, Kirgou P, Siachpazidou D, Bartziokas K, Tourlakopoulos K, Malli F, Pinaka M, Daniil Z, Gourgoulianis KI. Early benefit of mepolizumab on small airways in severe asthma: insights from the IMPOSE study. ERJ Open Res. 2025 Jun 23;11(3):00939-2024. doi: 10.1183/23120541.00939-2024. eCollection 2025 May.
PubMed 40551802
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How Much Severe is the Severe Asthma of Patients Who Will be Medicated With Mepolizumab? Μeasurement of Respiratory Mechanics by Means of Impulse Oscillometry in Severe Eosinophilic Asthmatics Before and After Mepolizumab Initiation
- ClinicalTrials.gov ID
- NCT05147155
- Acronym / sponsor ID
- IMPOSE / 15745/19-04-2021
- Conditions
- Severe Asthma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- University of ThessalyUniversity, hospital or other
- Study start
- 19 Apr 2021 (actual)
- Primary completion
- 23 Oct 2023 (actual)
- Study completion
- 23 Oct 2023 (actual)
- First posted
- 7 Dec 2021 (actual)
- Results
- Posted 24 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 26 Weeks
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Severe asthma patients | – | Biological: MepolizumabThe sample will consist of 40 patients between 18 and 82 years of age with uncontrolled severe eosinophilic asthma despite receiving high dose ICS/LABA combination therapy who will receive mepolizumab, which will be administered as a 100-mg subcutaneous dose every four weeks |
| Control group 1 | – | –Control group 1 will be a set of 50 healthy individuals matched for age and gender |
| Control group 2 | – | –Control group 2 will be a set of 40 patients with severe well-controlled asthma requiring high dose ICS/LABA combination therapy from becoming uncontrolled, as previously defined, matched for age and gender. |
Who may qualify
- Ages
- 18 to 82 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The sample will consist of 40 patients between 18 and 82 years of age with uncontrolled severe eosinophilic asthma despite receiving high-dose ICS/LABA combination therapy.
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
- pregnancy
- intention to become pregnant during the course of the study
- breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MepolizumabAlso: NucalaThis will be a 2-year prospective study. Patients with uncontrolled severe asthma will receive mepolizumab according to standard of care and best clinical practice, which will be administered as a 100-mg subcutaneous dose every four weeks. | Biological | Severe asthma patients |
Primary outcome
Airway Resistance at 5 Hz (R5) at Baseline (Pre-mepolizumab Initiation)
Time frame: 0 months
Measurements of R5 at baseline (pre-mepolizumab initiation). R5 was assessed using impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society
Airway Resistance at 20 Hz (R20) at Baseline
Time frame: 0 months
Measurement of R20 at baseline - mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Baseline / (R5-R20) at Baseline
Time frame: 0 months
Measurement of R5-R20 at baseline. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at baseline, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Reactance Area (AX) at Baseline
Time frame: 0 months
Measurement of AX at baseline. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at baseline using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Resonant Frequency (Fres) at Baseline
Time frame: 0 months
Measurement of Fres at Baseline. Fres, the resonant frequency, is the point where the reactance of the respiratory system equals zero, indicating the balance between elastic and inertial forces in the lungs. Measurements were taken at baseline using impulse oscillometry. Values are reported in Hz and analyzed following guidelines from the European Respiratory Society
Respiratory Reactance at 5 Hz (X5) at Baseline
Time frame: 0 months
Measurement of X5 at Baseline. X5, the respiratory reactance at 5 Hz, is a measure of the elastic properties of the lungs and the peripheral airways. It indicates how easily the lungs expand and contract during breathing. Measurements were taken at baseline using impulse oscillometry, with values expressed in kPa/L. Assessments followed European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Airway Resistance at 5 Hz (R5) at Week 4.
Time frame: 4 weeks
Estimate the airway resistance measured at the 5 Hz frequency (R5) after four weeks from mepolizumab initiation (only severe uncontrolled asthma patients received mepolizumab). R5 was assessed using impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Airway Resistance at 20 Hz (R20) at Week 4.
Time frame: 4 weeks
Estimate the airway resistance measured at the 20 Hz frequency (R20) after four weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 4/ R5-R20 at Week 4.
Time frame: 4 weeks
After four weeks of mepolizumab initiation, estimate the small airway resistance (R5- R20). R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted after 4 weeks from mepolizumab initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Reactance Area (AX) at Week 4
Time frame: 4 weeks
Estimate the AX after four weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 4 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Resonant Frequency (Fres) at Week 4.
Time frame: 4 weeks
Estimate Fres after four weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 4 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Respiratory Reactance at 5 Hz (X5) at Week 4.
Time frame: 4 weeks
Estimate X5 after four weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, is a measure of the elastic properties of the lungs and peripheral airways, reflecting the ability of the respiratory system to expand and contract. Measurements were taken at Week 4 using impulse oscillometry. Values are reported in kPa/L and were analyzed according to European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Airway Resistance at 5 Hz (R5) at Week 12
Time frame: 12 weeks
Estimate the airway resistance measured at the 5 Hz frequency (R5) after 12 weeks from the mepolizumab initiation. R5 was assessed using spirometry with impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Airway Resistance at 20 Hz (R20) at Week 12
Time frame: 12 weeks
Estimate the airway resistance measured at the 20 Hz frequency (R20) after 12 weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 12 / R5-R20 at Week 12
Time frame: 12 weeks
Estimate small airway resistance (R5-R20) after 12 weeks from mepolizumab initiation. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at week 12 after mepolizuamb initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society.
Reactance Area (AX) at Week 12
Time frame: 12 weeks
Estimate the AX after 12 weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 12 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Resonant Frequency (Fres) at Week 12
Time frame: 12 weeks
Estimate Fres after12 weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 4 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Respiratory Reactance at 5 Hz (X5) at Week 12
Time frame: 12 weeks
Estimate X5 after 12 weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, measures the elastic properties of the lungs and peripheral airways, reflecting the ability of the respiratory system to expand and contract. Measurements were taken at Week 12 using impulse oscillometry. Values are reported in kPa/L and analyzed according to European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Airway Resistance at 5 Hz (R5) at Week 26.
Time frame: 26 weeks
Estimate the airway resistance measured at the 5 Hz frequency (R5) after 26 weeks from the initiation of mepolizumab. R5 was assessed using spirometry with impulse oscillometry. The values are reported in kPa/L/s and were analyzed following the guidelines of the European Respiratory Society.
Airway Resistance at 20 Hz (R20) at Week 26.
Time frame: 26 weeks
Estimate the airway resistance measured at the 20 Hz frequency (R20) after 26 weeks from mepolizumab initiation. R20 was measured using impulse oscillometry, representing airway resistance at 20 Hz. Values are reported in kPa/L/s, and assessments were conducted according to the standards outlined by the European Respiratory Society.
Difference Between Airway Resistance at 5 Hz (R5) and 20 Hz (R20) at Week 26 / R5-R20 at Week 26.
Time frame: 26 weeks
Estimate the small airway resistance (R5-R20) after 26 weeks from mepolizumab initiation. R5-R20 represents the difference between airway resistance at 5 Hz (R5) and 20 Hz (R20), measured using impulse oscillometry. This measure reflects peripheral airway resistance. Assessments were conducted at Week 26 after mepolizumab initiation, and values are reported in kPa/L/s following guidelines from the European Respiratory Society
Reactance Area (AX) at Week 26.
Time frame: 26 weeks
Estimate AX after 26 weeks from mepolizumab initiation. AX, the area of reactance derived from impulse oscillometry, represents the elastic and inertial properties of the lungs. Measurements were taken at Week 26 using standard protocols. Values are reported in kPa/L and analyzed following guidelines from the European Respiratory Society.
Resonant Frequency (Fres) at Week 26.
Time frame: 26 weeks
Estimate Fres after 26 weeks from mepolizumab initiation. Fres, the resonant frequency, is the point at which the reactance of the respiratory system equals zero, reflecting the balance between the elastic and inertial forces of the lungs. Measurements were taken at Week 26 using impulse oscillometry. Values are expressed in Hz and analyzed in accordance with European Respiratory Society guidelines.
Respiratory Reactance at 5 Hz (X5) at Week 26.
Time frame: 26 weeks
Estimate X5 after 26 weeks from mepolizumab initiation. X5, the respiratory reactance at 5 Hz, reflects the elastic properties of the lungs and peripheral airways, indicating the ability of the respiratory system to expand and contract. Measurements were taken at Week 26 using impulse oscillometry. Values are reported in kPa/L and were analyzed following European Respiratory Society guidelines. X5 is negative because the lungs store energy due to their elasticity, which results in a delayed response of airflow relative to pressure changes. This behavior is characteristic of a capacitive system, where elastic forces dominate at low frequencies. A less negative X5 means that the lung's elastic recoil is reduced, leading to decreased resistance to expansion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40551802Kotsiou OS, Kirgou P, Siachpazidou D, Bartziokas K, Tourlakopoulos K, Malli F, Pinaka M, Daniil Z, Gourgoulianis KI. Early benefit of mepolizumab on small airways in severe asthma: insights from the IMPOSE study. ERJ Open Res. 2025 Jun 23;11(3):00939-2024. doi: 10.1183/23120541.00939-2024. eCollection 2025 May.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Konstantinos I Gourgoulianis, Professor study director
University of Thessaly
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Asthma, run by University of Thessaly at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Airway Resistance at 5 Hz (R5) at Baseline (Pre-mepolizumab Initiation) (time frame: 0 months). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05147155, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025; AzTrials last refreshed its copy on 6 Nov 2026.