Asthma can be classified into T2 high and T2 low asthma based on the criteria for onset, with an estimated frequency of about 50% each. In addition, according to research by the Korean National Health Insurance Corporation, about 80-90% of asthma patients in Korea fall into the mild to moderate range.

Current guidelines recommend the use of inhaled steroid (ICS) treatment for all patients with mild to moderate asthma. However, ICS is a treatment targeted towards T2 high asthma, which is primarily caused by eosinophils, and may not be effective in T2 low asthma, which accounts for about 50% of patients. Despite this, the current guidelines recommend the use of ICS for T2 low asthma patients for life, leading to significant economic and public health losses due to the overuse of inhaled steroids.
Therefore, it is believed that in T2 low asthma patients in the mild to moderate range, treatment with bronchodilators without ICS may show inferior clinical results compared to ICS-containing treatment regimens.

A study with a similar concept has recently been published in the New England Journal of Medicine, proving the effectiveness of a similar concept to the proposed research topic. Therefore, it is believed that conducting this proposed study in Korea will not only lead to changes in international asthma guidelines, but also prevent the unnecessary overuse of ICS in Korean patients.

A multicenter prospective randomized controlled trial to generate evidence that bronchodilator therapy with long-acting muscarinic antagonist (LAMA) without inhaled steroids (ICS) is inferior to ICS-containing treatment regimens for mild T2 low asthma.

• Patients with mild asthma who maintain stability without worsening for more than three months on low-dose inhaled steroids, leukotriene receptor antagonists (LTRA), and/or prn budesonide/formoterol, will undergo blood eosinophil, allergen skin test, FeNO, and sputum analysis once to identify patients who meet the T2 low criteria. After the start of the study, the medications used in low-dose ICS and LTRA will be stopped, and the subjects will receive medication according to the study plan.
• Half of the 300 patients evaluated as T2 low/non-eosinophilic/non-allergic asthma will receive ICS treatment for 6 months and undergo a 2-month washout period to re-evaluate T2 low status before being treated with LAMA for 6 months and evaluated for treatment outcomes. The remaining asthma patients will receive LAMA treatment for 6 months, undergo a 2-month washout period to re-evaluate T2 low status, receive ICS treatment for 6 months, and then be evaluated for treatment outcomes. The primary outcome measure is the difference in treatment effectiveness between the two groups.

• Adult asthma patients between the ages of 19 and 80 years old.
• Definition of T2-low mild asthma patients (GINA step 1-2)
  • Absolute criterion: blood eosinophil count less than 300
  • (If the above absolute criterion is met, the patient is eligible for enrollment if they meet either FENO (less than 25) or sputum eosinophil (less than 3%) criteria)
  • The same criteria will be applied at the 6-month washout visit for re-evaluation.
• Patients who have been stable with low-dose ICS only, LRTA only, or PRN Ventolin, PRN budesonide/formoterol use for more than 3 months without exacerbation, and who meet the T2-low criteria after discontinuing medication for one month, or newly diagnosed with mild asthma and meet the T2-low criteria.
• FEV1 > 80%

Exclusion criteria

• Minors under the age of 18 or elderly patients over the age of 80.
• Smoking history of 10 PY or more or current smoker.
• Patients who have experienced an acute exacerbation requiring more than 30mg of total prednisolone within 6 months prior to study registration.
• Clinical respiratory diseases other than moderate asthma.
• Cases where assessment of asthma alone is difficult due to severe respiratory disease (lung cancer, Tb destroyed lung, interstitial lung disease, etc.).
• Hypereosinophilic syndrome, ABPA, EGPA, COPD.
• Pregnant women.
• Patients who cannot use LAMA medication due to side effects.
  • Severe benign prostate hypertrophy (BPH).
  • Glaucoma.
  • Renal disease.
• Cases with bladder neck obstruction.
• Patients diagnosed with significant cardiovascular disease or arrhythmia.
• Those who have experienced acute respiratory infection within the past month.
• Patients diagnosed with clinically significant liver, nervous system, or immune system diseases, etc.
• Patients who are currently receiving or require immunosuppressive or immune modulating agents, including steroids.
• Patients who have a hypersensitivity reaction to ICS or LAMA medication.
• Pregnant
• lactating women.
• Female study subjects who do not agree to use contraception from 1 month before the start of the study to the end of the study period.
• Patients who are taking or plan to take other investigational drugs or participate in other clinical trials within 1 month of the start of the study.

• Adult asthma patients between the ages of 19 and 80 years old.
• Definition of T2-low mild asthma patients (GINA step 1-2)
  • Absolute criterion: blood eosinophil count less than 300
  • (If the above absolute criterion is met, the patient is eligible for enrollment if they meet either FENO (less than 25) or sputum eosinophil (less than 3%) criteria)
  • The same criteria will be applied at the 6-month washout visit for re-evaluation.
• Patients who have been stable with low-dose ICS only, LRTA only, or PRN Ventolin, PRN budesonide/formoterol use for more than 3 months without exacerbation, and who meet the T2-low criteria after discontinuing medication for one month, or newly diagnosed with mild asthma and meet the T2-low criteria.
• FEV1 > 80%

Exclusion criteria

• Minors under the age of 18 or elderly patients over the age of 80.
• Smoking history of 10 PY or more or current smoker.
• Patients who have experienced an acute exacerbation requiring more than 30mg of total prednisolone within 6 months prior to study registration.
• Clinical respiratory diseases other than moderate asthma.
• Cases where assessment of asthma alone is difficult due to severe respiratory disease (lung cancer, Tb destroyed lung, interstitial lung disease, etc.).
• Hypereosinophilic syndrome, ABPA, EGPA, COPD.
• Pregnant women.
• Patients who cannot use LAMA medication due to side effects.
  • Severe benign prostate hypertrophy (BPH).
  • Glaucoma.
  • Renal disease.
• Cases with bladder neck obstruction.
• Patients diagnosed with significant cardiovascular disease or arrhythmia.
• Those who have experienced acute respiratory infection within the past month.
• Patients diagnosed with clinically significant liver, nervous system, or immune system diseases, etc.
• Patients who are currently receiving or require immunosuppressive or immune modulating agents, including steroids.
• Patients who have a hypersensitivity reaction to ICS or LAMA medication.
• Pregnant
• lactating women.
• Female study subjects who do not agree to use contraception from 1 month before the start of the study to the end of the study period.
• Patients who are taking or plan to take other investigational drugs or participate in other clinical trials within 1 month of the start of the study.