The Mixed Phenotype of Asthma and COPD: the Overlap Syndrome

Study Overview
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Brief Summary
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RATIONALE: In asthmatic subjects, smoking can lead to several changes in disease characterictics. in smokers of more than 20 pack-years, chronic obstructive pulmonary disease (COPD) can be associated with asthma, also called asthma-COPD overlap syndrome (ACOS). Increasing data support the concept that ACOS is a clinical entity. However, this should be further studied in order to better target therapy. AIM: The objective of this study is to evaluate the comparative features of ACOS METHODS: This will be a descriptive study comparing the features of the ACOS with the features of asthmatic subjects with an incomplete reversibility of airway obstruction (IRAO).The study will be done over 1 or 2 visits (within a week interval), according to subjects' availability. The visit will include completion of different questionnaires (asthma control asthma quality of life, medical history, exacerbations, etc.), a thoracic examination, allergy skin-prick tests, spirometry and bronchodilator response, lung volumes and compliance measurements, exhaled nitric oxide measurement, blood sampling and a sputum induction.

Official Title
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The Mixed Phenotype of Asthma and COPD: the Overlap Syndrome: A Comparison of Asthma Outcomes in Smoking vs Non-smoking Patients With an Incomplete Reversibility of Airway Obstruction (IRAO)

Conditions
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Asthma, COPD

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ALL SUBJECTS Subjects aged 45 years and older. Free of any other respiratory condition, except for asthma and/or COPD, which may interfere with the tests. Asthma that requires a baseline treatment with inhaled corticosteroids and/or additional asthma medication. Free of respiratory infection in the 4 weeks preceding the study. No changes in the asthma and COPD-related medications in the 4 weeks preceding the study. If female, not pregnant (or lactating). Able to adhere to study procedures. Able and willing to provide written informed consent to participate in the study, in accordance with international conference on harmonization (ICH) good clinical practice (GCP) requirements. ACOS SUBJECTS 1. Smokers or ex-smokers of at least 20 pack-years. 2. With an IRAO (see definitions section). IRAO SUBJECTS Long-life non-smokers or ex-smokers defined as someone who smoked less than 5 pack-years and who completely stopped smoking for at least 12 months before inclusion in the study. With an IRAO. Exclusion Criteria: ALL SUBJECTS With COPD without a past diagnosis of asthma. Unstable respiratory or non-respiratory condition. Any active chronic inflammatory disease. Any evidence of malignancy (active and/or treated) within the previous 5 years. Any significant concomitant illness or injury that would interfere with the subject's participation in the study. Any history of bronchial thermoplasty. IRAO SUBJECTS Use of any nicotine containing product within 1 year prior to study entry or a smoking history of > 5 pack-years.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ACOS smoking history >20 pack-years<br>Subjects with asthma-COPD overlap syndrome | |
| IRAO smoking history <5 pack-years<br>Subjects with an incomplete reversibility of airway obstruction | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total asthma control questionnaire (ACQ) score | Measurement of asthma control using a 0-6 scale. The questionnaire includes 6 questions. Total score is the mean of the scores from all questions. Total score ranges from 0 to 6. A lower score is better. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry results | Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC | Baseline | 
| Sputum eosinophil percentage | Percentage of sputum eosinophils | Baseline | 
| Concentration of Blood biomarkers | alpha 1 antitrypsine, C-reactive protein (CRP), fibrinogen | Baseline | 
| Asthma quality of life questionnaire (AQLQ) score | Measurement of asthma quality of life using the Mini asthma quality of life questionnaire. It is a 7-point scale questionnaire (where 1 is greatest impairment and 7 is least impairment) containing 15 uqestions divided into 4 domains : symptoms (5 items), activity limitation (4 items), emotional function (3 items), and exposure to environmental stimuli (3 items). during the last 2 weeks. The overall score is the mean of all the responses. Each domain score is calculated from the mean of the items that relate to it. | Baseline | 
| Number of patients with comorbidities | gastro-oesophageal reflux disease (GERD), obstructive sleep apnea (OSA), anxiety, depression | Baseline | 
| Number of asthma exacerbations in the previous year | emergency room (ER) visits, hospitalizations, oral corticosteroids treatment, unscheduled medical visits | Baseline | 
| Change from baseline total Asthma Control Questionnaire (ACQ) score at one-year follow-up | Measurement of asthma control using a 0-6 scale. The questionnaire includes 6 questions. Total score is the mean of the scores from all questions. Total score ranges from 0 to 6. A lower score is better. | Baseline to one-year follow-up | 
| Change from baseline number of exacerbations at one-year follow-up | emergency room (ER) visits, hospitalizations, oral corticosteroids treatment, unscheduled medical visits | Baseline to one-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phenotype, inflammation, pulmonary function, comorbidities