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

Hat Yai Medical Education Center

Status: Enrolling

Conditions: Parasympathetic Nervous System Diseases; Asthma; Airway Remodeling; Airway Obstruction

Treatments: Drug: Salbutamol; Drug: Salbutamol plus Ipratropium Bromide; Drug: Ipratropium Bromide; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05550402

454554

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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60 participants in 4 patient groups, including a placebo group

Salbutamol then ipratropium

Active Comparator group

Description:

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.

Treatment:

Drug: Ipratropium Bromide

Drug: Salbutamol

Ipratropium then salbutamol

Active Comparator group

Description:

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.

Treatment:

Drug: Ipratropium Bromide

Drug: Salbutamol

Salbutamol plus ipratropium

Active Comparator group

Description:

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)

Treatment:

Drug: Salbutamol plus Ipratropium Bromide

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Other: Placebo