Research on Severe Asthma

Adult Severe Asthma Patients Treated in France Clinical Trial

— RAMSES  

Official title:

Research on Severe Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04077528
• Other study ID #: NI18033J
• Secondary ID: 2018-A03282-53
• Status: Recruiting
• Start date: September 10, 2019
• Est. completion date: September 2025

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Camille TAILLE, MD,PHD
• Phone: 01 40 25 68 63
• Email: camille.taille[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The French Society for Respiratory diseases (SPLF), through its Asthma and Allergy working group (G2A), wishes to set up a national cohort of severe asthma patients to describe this population and the use of step 4 and 5 treatment. This study also meets the demand for post - registration studies required by the Health Authorities for biotherapies and bronchial thermoplasty.

Other European or international cohorts of asthmatic patients exist and RAMSES could contribute to data sharing initiatives.

Description:

Severe asthma is defined by poorly controlled disease despite treatment with high doses of inhaled corticosteroids, in combination with at least a long acting beta agonist, after optimal management for at least 6 months by an asthma specialist. The diagnosis of severe asthma can only be made after a rigorous evaluation of 6 to 12 months, including the review of diagnosis and treatment, by a pulmonologist, to distinguish difficult asthma from severe asthma.

Severe asthma accounts for 3.5% to 5% of all asthma patients, a population estimated at 150 000 patients in France. This disease is responsible for significant health costs related to asthma treatments, comorbidities, hospitalizations and sick days. The management of severe asthma is complex, multidisciplinary and includes drug treatment, but also the management of side effects of treatment, including oral corticosteroid therapy, and comorbidities of asthma.

Until 2018, omalizumab,systemic continuous oral corticosteroid therapy or inclusion in a therapeutic trial were the ony possibilities offered to severe asthmatic patients beyond the usually recommended and optimized management. In 2018, mepolizumab and reslizumab have been marketed in France, then benralizumab in 2019. They will probably be followed by dupilumab and bronchial thermoplasty. New initiatives to change the history of the disease are also proposed such as specific immunotherapy or long-term use of macrolides. Respiratory rehabilitation is also part of the treatments to be evaluated in some groups of patients.

The description of the use of these treatments, as well as the evaluation of their effectiveness and tolerance in real life conditions is essential. Indeed, their use outside clinical trials raises a number of issues such as the optimal duration of treatment, the maintenance of efficacy over extended periods, the risk and the time to relapse when the treatment is stopped, the possibility to switch from one biotherapy to another in case of insufficient clinical response or to associate them which may prove to be an effective strategy in patients eligible for two biotherapies (allergic and eosinophilic patients).

The cost of these treatments is high. The pharmaco-economic evaluation of severe asthma and its management is another important element. For example, no economic evaluation of the use of omalizumab is currently available in France.

Lastly, the organization of a care network dedicated to severe asthma is being launched in France (severe asthma centers ), on the model of European countries, in order to improve the diagnosis and management of these patients and to reduce the burden of comorbidities of asthma and steroids side effects.It is therefore essential to set up a clinical research structure that will make it possible to obtain clinical data on this population of severe asthma patients and to evaluate all medical practices in real life conditions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with severe asthma : Meeting the definition of ATS-ERS: which requires a combination of high dose CSI and B2LDA.

Or receiving level 5 support (initiating treatment or already treated) :

• Long-term oral corticosteroids (> 6 months in the year prior to inclusion)

• And / or monoclonal antibody

• And / or bronchial thermoplasty

• And / or other complex costs corresponding to the level 5 treatments

• Consultant or hospitalized in one of the centers participating in RAMSES study

Exclusion Criteria:

• Patient does not accept the recording of his data in the cohort

• Patient not benefiting from health insurance coverage

• Patient under curatorship or tutorship

Related Conditions & MeSH terms

• Adult Severe Asthma Patients Treated in France
• Asthma

Locations

Country	Name	City	State
France	CHU Bichat	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients receiving asthma treatment	Severe asthma medication (high dose inhaled corticosteroids / B2LDA, Anti IgE antibody, Anti IL5 antibody, daily oral steroids…); Other asthma medications (long acting anticholinergics, montelukast, theophylline, inhaled corticoids); bronchial thermoplasty.	Previous treatment, collected at baseline
Primary	Dose of severe asthma treatments	Severe asthma medication (high dose inhaled corticosteroids / B2LDA, Anti IgE antibody, Anti IL5 antibody, daily oral steroids…)	At baseline
Primary	Duration of asthma treatments	Severe asthma medication (high dose inhaled corticosteroids / B2LDA, Anti IgE antibody, Anti IL5 antibody, daily oral steroids…); Other asthma medications (long acting anticholinergics, montelukast, theophylline, inhaled corticoids); bronchial thermoplasty.	Previous treatment, collected at baseline
Primary	Other medications	Number of patients receiving antidiabetics, Number of patients receiving antidepressants, Number of patients receiving anti-osteoporotic drugs, Number of patients receiving cardiovascular drugs.	At baseline
Primary	Asthma-related comorbidities	Prevalence of asthma related comorbidities such as chronic rhinosinusitis, nasal polyps, gastroesophageal reflux, obesity, obstructive sleep apnea respiratory infections, …	At baseline
Primary	Non-respiratory comorbidities	Prevalence of non-respiratory comorbidities such as osteoporosis, diabetes , cardiovascular diseases...	At baseline
Primary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 items, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled). Asthma is controlled when the total score is >20.	12 previous months, collected at baseline
Primary	Asthma exacerbations	Number of systemic corticosteroids (SC) courses	12 previous months, collected at baseline
Primary	Forced Expiratory Volume in 1 second (FEV1)	Mean FEV1, expressed in ml.	12 previous months, collected at baseline
Primary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	12 previous months, collected at baseline
Primary	Number of sick leaves due to asthma	Patient-reported sick leaves.	12 previous months, collected at baseline
Primary	Number of patients with long term disease status for asthma		At baseline
Primary	Intensive care unit hospitalization due to asthma exacerbation	At least one intensive care unit hospitalization for asthma	During life, collected at baseline
Secondary	Number of unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 6 months
Secondary	Number of patients with unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 6 months
Secondary	Number of unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 12 months
Secondary	Number of patients with unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 12 months
Secondary	Number of unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 24 months
Secondary	Number of patients with unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 24 months
Secondary	Number of unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 36 months
Secondary	Number of patients with unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 36 months
Secondary	Number of unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 60 months
Secondary	Number of patients with unscheduled healthcare visits or hospitalization	Inpatient hospitalizations due to asthma including intensive care unit, inpatient hospitalization for other reasons, emergency department visits and unscheduled ambulatory visits	At 60 months
Secondary	Daily dose of corticosteroids	Inhaled corticosteroids, oral corticosteroids (SC) in long term users	At 6 months
Secondary	Daily dose of corticosteroids	Inhaled corticosteroids, oral corticosteroids (SC) in long term users	At 12 months
Secondary	Daily dose of corticosteroids	Inhaled corticosteroids, oral corticosteroids (SC) in long term users	At 24 months
Secondary	Daily dose of corticosteroids	Inhaled corticosteroids, oral corticosteroids (SC) in long term users	At 36 months
Secondary	Daily dose of corticosteroids	Inhaled corticosteroids, oral corticosteroids (SC) in long term users	At 60 months
Secondary	Number of patients with at least 1 other asthma medication	Long acting beta 2 agonists, long acting anticholinergics, montelukast, macrolides, Anti IgE monoclonal antibodies, theophylline.	At 6 months
Secondary	Number of patients with at least 1 other asthma medication	Long acting beta 2 agonists, long acting anticholinergics, montelukast, macrolides, Anti IgE monoclonal antibodies, theophylline.	At 12 months
Secondary	Number of patients with at least 1 other asthma medication	Long acting beta 2 agonists, long acting anticholinergics, montelukast, macrolides, Anti IgE monoclonal antibodies, theophylline.	At 24 months
Secondary	Number of patients with at least 1 other asthma medication	Long acting beta 2 agonists, long acting anticholinergics, montelukast, macrolides, Anti IgE monoclonal antibodies, theophylline.	At 36 months
Secondary	Number of patients with at least 1 other asthma medication	Long acting beta 2 agonists, long acting anticholinergics, montelukast, macrolides, Anti IgE monoclonal antibodies, theophylline.	At 60 months
Secondary	Asthma exacerbations	Systemic corticosteroids (SC) use or doubling the usual dose or at least 48 hours in SC long term users	6 months
Secondary	Asthma exacerbations	Systemic corticosteroids (SC) use or doubling the usual dose or at least 48 hours in SC long term users	At 12 months
Secondary	Asthma exacerbations	Systemic corticosteroids (SC) use or doubling the usual dose or at least 48 hours in SC long term users	At 24 months
Secondary	Asthma exacerbations	Systemic corticosteroids (SC) use or doubling the usual dose or at least 48 hours in SC long term users	At 36 months
Secondary	Asthma exacerbations	Systemic corticosteroids (SC) use or doubling the usual dose or at least 48 hours in SC long term users	At 60 months
Secondary	Number of patients reporting suboptimal treatment adherence	Patient-reported adherence to asthma treatment. Suboptimal treatment is defined as less treatment received than expected.	Through study completion, an average of 5 years
Secondary	Drug survival rate	Proportion of patients still exposed to treatment	At 6 month
Secondary	Drug survival rate	Proportion of patients still exposed to treatment;	At 12 months
Secondary	Time to drug discontinuation	Median time between the start of treatment and its definitive cessation	Reported at 6 month
Secondary	Time to drug discontinuation	Median time between the start of treatment and its definitive cessation.	Reported at 12 month
Secondary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).	At 6 months
Secondary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).	At 12 months
Secondary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).	At 24 months
Secondary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).	At 36 months
Secondary	Asthma control test (ACT)	Patient-reported asthma symptoms and control will be collected via the ACT questionnaire; a 5 item, self-administered survey that is designed to help the patient describe their asthma and how it affects their daily activities. ACT questionnaire is a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).	At 60 months
Secondary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	At 6 months
Secondary	Number of sick leaves due to asthma	Patient-reported sick leaves.	At 6 months
Secondary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	At 12 months
Secondary	Number of sick leaves due to asthma	Patient-reported sick leaves.	At 12 months
Secondary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	At 24 months
Secondary	Number of sick leaves due to asthma	Patient-reported sick leaves.	At 24 months
Secondary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	At 36 months
Secondary	Number of sick leaves due to asthma	Patient-reported sick leaves.	At 36 months
Secondary	Number of patients with at least 1 sick leaves due to asthma	Patient-reported sick leaves.	At 60 months
Secondary	Number of sick leaves due to asthma	Patient-reported sick leaves.	At 60 months
Secondary	St. George's Respiratory Questionnaire (SGRQ)	The St. George's Respiratory Questionnaire (SGRQ) is a self-reporting questionnaire validated for evaluating quality of life in asthma. The total score is expressed as a percentage, from 0%, no impairment of life quality, to 100%, maximal impairment.	At 6 months
Secondary	St. George's Respiratory Questionnaire (SGRQ)	The St. George's Respiratory Questionnaire (SGRQ) is a self-reporting questionnaire validated for evaluating quality of life in asthma. The total score is expressed as a percentage, from 0%, no impairment of life quality, to 100%, maximal impairment.	At 12 months
Secondary	St. George's Respiratory Questionnaire (SGRQ)	The St. George's Respiratory Questionnaire (SGRQ) is a self-reporting questionnaire validated for evaluating quality of life in asthma. The total score is expressed as a percentage, from 0%, no impairment of life quality, to 100%, maximal impairment.	At 24 months
Secondary	St. George's Respiratory Questionnaire (SGRQ)	The St. George's Respiratory Questionnaire (SGRQ) is a self-reporting questionnaire validated for evaluating quality of life in asthma. The total score is expressed as a percentage, from 0%, no impairment of life quality, to 100%, maximal impairment.	At 36 months
Secondary	St. George's Respiratory Questionnaire (SGRQ)	The St. George's Respiratory Questionnaire (SGRQ) is a self-reporting questionnaire validated for evaluating quality of life in asthma. The total score is expressed as a percentage, from 0%, no impairment of life quality, to 100%, maximal impairment.	At 60 months
Secondary	Asthma Quality of Life Questionnaire (AQLQ) overall score by Visit	The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions.	At 6 months
Secondary	Asthma Quality of Life Questionnaire (AQLQ) overall score by Visit	The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions.	At 12 months
Secondary	Asthma Quality of Life Questionnaire (AQLQ) overall score by Visit	The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions.	At 24 months
Secondary	Asthma Quality of Life Questionnaire (AQLQ) overall score by Visit	The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions.	At 36 months
Secondary	Asthma Quality of Life Questionnaire (AQLQ) overall score by Visit	The AQLQ is a 32-item disease-specific questionnaire that has been designed to measure the functional impairments that are most troublesome to adults with asthma. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions.	At 60 months
Secondary	EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) index score and health state assessment	EQ-5D is a standardized instrument for measuring generic health status. The EQ-5D questionnaire has two components: health state description and evaluation.; In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". Pain/discomfort dimension asks how much pain or discomfort the person has, and anxiety/depression dimension asks how anxious or depressed the person is. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) scale.; In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).	At 6 months
Secondary	EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) index score and health state assessment	EQ-5D is a standardized instrument for measuring generic health status. The EQ-5D questionnaire has two components: health state description and evaluation.; In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". Pain/discomfort dimension asks how much pain or discomfort the person has, and anxiety/depression dimension asks how anxious or depressed the person is. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) scale.; In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).	At 12 months
Secondary	EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) index score and health state assessment	EQ-5D is a standardized instrument for measuring generic health status. The EQ-5D questionnaire has two components: health state description and evaluation.; In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". Pain/discomfort dimension asks how much pain or discomfort the person has, and anxiety/depression dimension asks how anxious or depressed the person is. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) scale.; In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).	At 24 months
Secondary	EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) index score and health state assessment	EQ-5D is a standardized instrument for measuring generic health status. The EQ-5D questionnaire has two components: health state description and evaluation.; In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". Pain/discomfort dimension asks how much pain or discomfort the person has, and anxiety/depression dimension asks how anxious or depressed the person is. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) scale.; In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).	At 36 months
Secondary	EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) index score and health state assessment	EQ-5D is a standardized instrument for measuring generic health status. The EQ-5D questionnaire has two components: health state description and evaluation.; In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". Pain/discomfort dimension asks how much pain or discomfort the person has, and anxiety/depression dimension asks how anxious or depressed the person is. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) scale.; In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).	At 60 months
Secondary	Hospital Anxiety and Depression scale	The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.	At 6 months
Secondary	Hospital Anxiety and Depression scale	The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.	At 12 months
Secondary	Hospital Anxiety and Depression scale	The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.	At 24 months
Secondary	Hospital Anxiety and Depression scale	The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.	At 36 months
Secondary	Hospital Anxiety and Depression scale	The HADS is a fourteen item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.	At 60 months
Secondary	Long term adverse Events associated with corticosteroid therapy.	Frequency of relevant medical events such as osteoporosis, diabetes, cardiovascular disease.	60 months
Secondary	Asthma-related comorbidities	Prevalence of comorbidities such as rhinosinusitis, obesity, gastroesophageal reflux, sleep obstructive apnea syndrome, …	At 6 months
Secondary	Asthma-related comorbidities	Prevalence of comorbidities such as rhinosinusitis, obesity, gastroesophageal reflux, sleep obstructive apnea syndrome, …	At 12 months
Secondary	Asthma-related comorbidities	Prevalence of comorbidities such as rhinosinusitis, obesity, gastroesophageal reflux, sleep obstructive apnea syndrome, …	At 24 months
Secondary	Asthma-related comorbidities	Prevalence of comorbidities such as rhinosinusitis, obesity, gastroesophageal reflux, sleep obstructive apnea syndrome, …	At 36 months
Secondary	Asthma-related comorbidities	Prevalence of comorbidities such as rhinosinusitis, obesity, gastroesophageal reflux, sleep obstructive apnea syndrome, …	At 60 months
Secondary	Death and cause of death		At 6 months
Secondary	Death and cause of death		At 12 months
Secondary	Death and cause of death		At 24 months
Secondary	Death and cause of death		At 36 months
Secondary	Death and cause of death		At 60 months
Secondary	Post-procedural adverse Events associated with bronchial thermoplasty	Frequency of post-procedure medical events such as hemoptysis, respiratory symptoms, asthma, prolonged hospitalization	Up to 24 hours following the procedure
Secondary	Post-procedural adverse Events associated with bronchial thermoplasty	Frequency of post-procedure medical events such as hemoptysis, respiratory symptoms, asthma, prolonged hospitalization.	From 24 hours to 1 month following the procedure
Secondary	Long term adverse events associated with bronchial thermoplasty	Frequency of long term medical events such as bronchial stenosis.	60 months
Secondary	Events of special interest	Frequency of special interest events including new onset malignancy, severe infection, anaphylaxis.	From treatment initiation to 3 months following treatment initiation
Secondary	Events of special interest	Frequency of special interest events including new onset malignancy, severe infection, anaphylaxis.	From 3 months to 12 months following treatment initiation
Secondary	Events of special interest	Frequency of special interest events including new onset malignancy, severe infection, anaphylaxis.	From 3 to 5 years following treatment initiation
Secondary	Blood eosinophil count		At baseline
Secondary	Total immunoglobulin E (IgE)		At baseline
Secondary	Chest computed tomography scan	Dates and description of major findings.	At baseline
Secondary	Forced Vital Capacity (FVC)		At baseline
Secondary	Forced Vital Capacity (FVC)		At 6 months
Secondary	Forced Vital Capacity (FVC)		At 12 months
Secondary	Forced Vital Capacity (FVC)		At 24 months
Secondary	Forced Vital Capacity (FVC)		At 36 months
Secondary	Forced Vital Capacity (FVC)		At 60 months
Secondary	Forced Expiratory Volume in 1 second (FEV1)		At 6 months
Secondary	Forced Expiratory Volume in 1 second (FEV1)		At 12 months
Secondary	Forced Expiratory Volume in 1 second (FEV1)		At 24 months
Secondary	Forced Expiratory Volume in 1 second (FEV1)		At 36 months
Secondary	Forced Expiratory Volume in 1 second (FEV1)		At 60 months
Secondary	FEV1/FVC ratio		At baseline
Secondary	FEV1/FVC ratio		At 6 months
Secondary	FEV1/FVC ratio		At 12 months
Secondary	FEV1/FVC ratio		At 24 months
Secondary	FEV1/FVC ratio		At 36 months
Secondary	FEV1/FVC ratio		At 60 months
Secondary	RV/TLC ratio		At baseline
Secondary	RV/TLC ratio		At 6 months
Secondary	RV/TLC ratio		At 12 months
Secondary	RV/TLC ratio		At 24 months
Secondary	RV/TLC ratio		At 36 months
Secondary	RV/TLC ratio		At 60 months
Secondary	Fractional exhaled nitric oxide (FENO)		At baseline
Secondary	Costs of severe asthma management	Total amount of money, expressed in euros, reimbursed by Social Security ( for treatments, medical visits, radiological or laboratory examinations).	Through study completion, an average of 5 years