Systematic Approach for the Diagnosis and Treatment of Obstructive Lung Diseases

Study Overview
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Brief Summary
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The differential diagnosis of asthma and COPD is sometimes difficult. Recently, an overlap syndrome has been defined based on the concurrence of asthma and COPD characteristics. These characteristics are based on expert opinions and have never been investigated nor validated prospectively. The investigators assume that the management strategy, the symptom burden and disease progression will differ between asthma, COPD and ACOS. Therefore, the study wants to establish baseline criteria for an appropriate disease definition and evaluate the potential impact on treatment and symptom control.

Detailed Description
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This study aims to test a diagnostic algorithm for obstructive airways diseases that may be used in daily practice to obtain a correct differential diagnosis and, hence, initiate an adequate therapy according to the current guidelines. The proposed algorithm will be used to categorize patients in 4 different diagnoses with specific treatment choices: asthma, obstructive asthma, overlap asthma with COPD, and COPD. The study will evaluate which tests and criteria contribute most to the diagnostic work-up and final diagnosis. Test battery for diagnosis spirometry with bronchodilator reversibility testing bodyplethysmography: spirometry, volumes, resistance, diffusing capacity exhaled NO blood sample CT scan of thorax (only when obstructive spirometry) histamine challenge (only when spirometry is not obstructive) induced sputum (not for protocol interpretation) Definition of endpoints Physician based diagnosis: diagnosis based on clinical exam and spirometry Algorithm based diagnosis: diagnosis based on clinical exam and test battery Final standard diagnosis diagnosis based on clinical exam, test battery and clinical evolution of 1 year.

Official Title
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Systematic Approach for the Diagnosis and Treatment of Obstructive Lung Diseases

Conditions
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Asthma, Chronic Obstructive Pulmonary Disease, Overlap Syndrome

Intervention / Treatment
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* Drug: LABA + LAMA
* Drug: ICS
* Drug: LABA + LAMA + ICS
* Drug: LABA + ICS
* Drug: other


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with respiratory symptoms suggestive of chronic airway disease Exclusion Criteria: Subjects with an immediate need for hospitalization or a treatment of systemic glucocorticoid or long-term antibiotics Subjects with pregnancy Subjects with clinically significant cardiovascular disease that warrants intervention Subject with concomitant pulmonary diseases (pulmonary embolism, interstitial lung disease etc..).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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 |
| --- | --- |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE<br>Patients with an obstructive spirometry and characteristics of chronic obstructive pulmonary disease Clinical intervention: Long acting B agonist (LABA) + Long acting muscarinic receptor antagonist (LAMA) inhaled therapy | Drug: LABA + LAMA<br>* An open label inhaled therapy is initiated once the diagnosis has been set based on clinical and testing criteria (algorithm). The treatment may be changed in function of the clinical evolution, which is left at the discretion of the general practitionar. Changes in treatment and treatment doses are registered during 1 year follow-up.<br>* Other names: dual bronchodilation;|
| ASTHMA<br>patients with asthma and a normal spirometry Clinical intervention: Inhaled corticosteroids (ICS) | Drug: ICS<br>* An open label inhaled therapy is initiated once the diagnosis has been set based on clinical and testing criteria (algorithm). The treatment may be changed in function of the clinical evolution, which is left at the discretion of the general practitionar. Changes in treatment and treatment doses are registered during 1 year follow-up.<br>* Other names: inhaled cortiscosteroids;|
| ASTHMA COPD OVERLAP SYNDROME<br>patients with an obstructive spirometry and characteristics of both COPD and Asthma Clinical Intervention: LABA + LAMA + ICS | Drug: LABA + LAMA + ICS<br>* An open label inhaled therapy is initiated once the diagnosis has been set based on clinical and testing criteria (algorithm). The treatment may be changed in function of the clinical evolution, which is left at the discretion of the general practitionar. Changes in treatment and treatment doses are registered during 1 year follow-up.<br>* Other names: triple therapy;|
| OBSTRUCTIVE ASTHMA<br>patients with an obstructive spirometry and characteristics of asthma Clinical Intervention: LABA + ICS inhaled therapy | Drug: LABA + ICS<br>* An open label inhaled therapy is initiated once the diagnosis has been set based on clinical and testing criteria (algorithm). The treatment may be changed in function of the clinical evolution, which is left at the discretion of the general practitionar. Changes in treatment and treatment doses are registered during 1 year follow-up.<br>* Other names: bronchodilator inhaled corticosteroid fixed combinations;|
| OTHER<br>patients with another diagnosis or healthy persons clinical Intervention: undefined - according to diagnosis | Drug: other<br>* An open label therapy or no therapy is initiated once the diagnosis has been set based on clinical and testing criteria (algorithm). The treatment may be changed in function of the clinical evolution, which is left at the discretion of the general practitionar. Changes in treatment and treatment doses are registered during 1 year follow-up.<br>* Other names: no inhalation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of the proposed diagnostic algorithm | % changes of algorithm diagnosis compared to physician based diagnosis (based on spirometry only) | after work-up at inclusion (at baseline) | 
| Accuracy of the proposed diagnostic algorithm (at one year follow-up) | % changes of algorithm diagnosis compared to final diagnosis (based on all tests with clinical evolution for 1 year)) | at one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in ACT/CAT-scores | Difference of ACT/CAT-score between arms at 3 months | 3 months | 
| Difference in ACT/CAT-scores | Difference of ACT/CAT-scores between arms at 1 year | 1 year | 
| Difference in Delta ACT/CAT scores (0 - 3 months) | Difference of delta ACT/CAT-scores (0 - 3 months) between arms | 3 months | 
| Difference in Delta ACT/CAT scores (0 - 1 year) | Difference of delta ACT/CAT-scores (0 - 1 year) between arms | 1 year | 
| specificity and sensitivity of individual criteria for final diagnosis | ROC curve analysis for individual criteria in predicting final diagnosis | 1 year | 
| independency of criteria for final diagnosis | Logistic regression analysis for criteria in predicting final diagnosis | 1 year |