Role of Parasympathetic Activity in Mild to Severe Asthma With Fixed Airway Obstruction (PARASMA Study)

Study Overview
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Brief Summary
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In asthma, the significant role of pathogenesis is chronic airway inflammation, bronchial hyperresponsiveness, and variable airflow obstruction. Asthma with irreversible or fixed airflow obstruction (FAO) is a clinical phenotype resulting from chronic airway inflammation with having longer disease duration, suggesting that airway remodeling contributes to the decline in lung function seen in individuals with asthma. Although this condition frequently occurs in patients with severe asthma, there are pieces of evidence occurring in those with mild to moderate asthma. According to previous research, low lung function, FEV1 less than 60% predicted, is a robust independent predictor of subsequent asthma attacks and other asthma outcomes, including asthma control and SABA use. In a recent study, the patients with mild to moderate asthma who received mild to medium dosed inhaled corticosteroid plus long-acting beta-2 agonist with or without asthma control showed evidence of FAO with or without bronchodilator reversibility. Therefore parasympathetic activity may be affected by FAO in those patients. The autonomic nervous system plays an essential role in asthma, especially from the parasympathetic, promoting bronchoconstriction and regulating airway inflammation and remodeling. This study hypothesizes that a cholinergic mechanism may play a significant role in FAO across patients with mild, moderate, and severe asthma. This might increase the fundamental evidence leading to early-step treatment with anti-cholinergic medication in early asthma severity driven by FAO.

Official Title
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Comparison of Parasympathetic Activity in Mild, Moderate, and Severe Asthma With Fixed Airway Obstruction

Conditions
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Asthma, Airway Obstruction, Airway Remodeling, Parasympathetic Nervous System Diseases

Intervention / Treatment
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* Drug: Salbutamol
* Drug: Ipratropium Bromide
* Drug: Salbutamol plus Ipratropium Bromide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthmatic patients classified by severity Mild (achieved control with using low-dose ICS or as-needed ICS-formoterol) or Moderate (achieved controlled with using low-dose ICS/LABA or Severe ((achieved controlled with using medium to high dose ICS/LABA) Post-bronchodilator (Salbutamol) FEV1/FVC ratio less than 0.75 or below the Lower Limit of Normal (LLN) and Post-bronchodilator (Salbutamol) FEV1 predicted < 80% with or without bronchodilator response History of smoking less than 10 pack-years or current smoking Patients who able to do spirometry without contraindication asthma control was defined by ACQ6 < 1.5 Exclusion Criteria: Contraindication for spirometry Chest x-ray suggested any chronic lung diseased Contraindication for anticholinergic drug History of asthma exacerbation within 12 weeks before visit 1 History of taking LAMA within 6 months before visit 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Salbutamol then ipratropium<br>Visit 1, After predosed spirometry is done, the patients will be received 4 puffs of salbutamol. 30 minutes later, if they meet the criteria of fixed airway obstruction based on ATS criteria, then they will continue to undergo serial spirometry at 1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of ipratropium and do spirometry at 4.5 and 5 hours. | Drug: Salbutamol<br>* Visit 1, After predosed spirometry is done, the patients will be received 4 puffs of salbutamol. 30 minutes later, if they meet the criteria of fixed airway obstruction based on ATS criteria, then they will continue to undergo serial spirometry at 1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of ipratropium and do spirometry at 4.5 and 5 hours.<br>* Other names: ventolin;Drug: Ipratropium Bromide<br>* Visit 2, After predosed spirometry is done, the patients will be received 4 puffs of ipratropium they will continue to undergo serial spirometry at 30 minutes,1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours.<br>* Other names: Atrovent;|
| Active Comparator: Ipratropium then salbutamol<br>Visit 2, After predosed spirometry is done, the patients will be received 4 puffs of ipratropium they will continue to undergo serial spirometry at 30 minutes,1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours. | Drug: Salbutamol<br>* Visit 1, After predosed spirometry is done, the patients will be received 4 puffs of salbutamol. 30 minutes later, if they meet the criteria of fixed airway obstruction based on ATS criteria, then they will continue to undergo serial spirometry at 1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of ipratropium and do spirometry at 4.5 and 5 hours.<br>* Other names: ventolin;Drug: Ipratropium Bromide<br>* Visit 2, After predosed spirometry is done, the patients will be received 4 puffs of ipratropium they will continue to undergo serial spirometry at 30 minutes,1, 2, 3, and 4 hours. Then, the patients requested to be administered 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours.<br>* Other names: Atrovent;|
| Active Comparator: Salbutamol plus ipratropium<br>Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm). Then, the patients requested to be administered 4 puffs of ipratropium and 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours (Salbutamol plus ipratropium) | Drug: Salbutamol plus Ipratropium Bromide<br>* Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm). Then, the patients requested to be administered 4 puffs of ipratropium and 4 puffs of salbutamol and do spirometry at 4.5 and 5 hours (Salbutamol plus ipratropium arm)<br>|
| Placebo Comparator: Placebo<br>Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm). | Other: Placebo<br>* Visit 3, After predosed spirometry is done, the patients will be received 4 puffs of a placebo, and they will do spirometry at 30 minutes, 1 and 2 hours (Placebo arm).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average FEV1 | FEV1 determined from serial spirometry and calculated on the basis of area under the curve | 6 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 at 6 h | FEV1 at 6 hours post-dose | 6 hour | 
| Maximum FEV1 | Maximum FEV1 over the 6-hour serial assessments | 6 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, fixed airway obstruction, spirometry, parasympathetic activity, well controlled