Selection visit day -21 to -1: The diagnosis of COPD-B or BCNO will be verified. The inclusion criteria will be checked and it will be verified if there are any exclusion criteria (clinical record will be reviewed if necessary). The patient is invited to the study, will be given detailed information about it, and a copy of the informed consent for evaluation. If they agree to participate in the study, they will be asked to sign the consent in the indicated space, as well as two witnesses. If the patient does not have post-bronchodilator forced spirometry and a six-minute walk in the last 3 weeks, these tests will be performed in the COPD lung function laboratory. A symptom diary will be dispensed and training will be given on how to fill it out. The patient will be instructed to begin the washout time, which will be one week for long-acting bronchodilators (LAMA or LABA, or LAMA/LABA combination), and 3 weeks for inhaled steroids (or ICS/LABA, ICS/LAMA/LABA). During this period, patients will be able to use their rescue bronchodilator (SAMA, SABA, or combination) by schedule. They will be instructed in the identification of exacerbations and alarm symptoms and, if necessary, communicate with the principal investigator.

Randomization visit and initiation of treatment. (Visit 0, day 0): A complete patient history will be taken, with main emphasis on the recording of comorbidities and concomitant medication. Inclusion and exclusion criteria will be checked. The washout time of each bronchodilator will be confirmed, and once confirmed, baseline questionnaires will be performed: Measurement of dyspnea (mMRC scale) and health realated quality of life questionnaires (CAT and SGRQ). The history of exacerbations in the last 4 weeks will be verified. If the patient continue to meet the criteria, they will be selected and baseline respiratory function tests will begin: The tests will be performed between 7:00 to 8:00 AM in the following order: Exhaled fraction of nitric oxide (FeNO), impulse oscillometry, slow spirometry, forced spirometry, and simple plethysmography. The selection criteria will be confirmed and if they are a candidate, randomization will be carried out through the Redcap program. Patients will be assigned one of the four devices contemplated for the study. The first group will be assigned the device containing Vilanterol/Umeclidinium 25/62.5 mcg (Anoro) with a dose of one inhalation every 24 hours; the second group will be assigned the device containing Fluticasone/ Vilanterol/ Umeclidinium 100/25/62.5 mcg (Trelegy) with a dose of one inhalation every 24 hours; the third group will be assigned the device containing Beclomethasone/ Formoterol/ Glycopyrronium 100/6/12.5 mcg (Trimbow) with doses of two inhalations every 12 hours; the forth group will be assigned the device containing Budesonide/Formoterol/Glycopyrronium 160/4.8/7.2 mcg with doses of two inhalations every 12 hours. Each patient will be given a 100 μg salbutamol device as rescue medication.

Once the study medication is assigned, they will be instructed in technique and dosage, and a corresponding dose will be applied. A blood sample will be taken for a blood count and IgE test and Th2 and Th17 inflammatory profile cytokines. After 30 minutes of application of the study medication, impulse oscillometry, slow spirometry and forced spirometry will be performed. After 2 hours of application of study medication, impulse oscillometry, slow spirometry and forced spirometry will be performed. After 4 hours of application of study medication, impulse oscillometry, slow spirometry and forced spirometry will be performed. At the end of the respiratory function tests, the patient will be referred to the imaging service for tomography evaluation if it is not available with volumetry in the last year. Adverse events will be measured at baseline, for the safety outcome. The patient will be instructed in the use of the assigned medication, technique, frequency of use, as well as information and training on possible side effects. Visit 1 will be scheduled the next day without a window period.

Follow-up visit 1 (Visit 1, Day 1): Changes in respiratory symptoms, presence of adverse events, and use of concomitant medication will be questioned and documented. Symptom diary will be reviewed. It will be confirmed that the patient has not applied the morning dose of study medication. Dyspnea questionnaire (mMRC) and quality of life questionnaire (CAT) will be completed. Pulmonary function tests will be performed: FeNO, impulse oscillometry, slow spirometry, forced spirometry and simple plethysmography. Standard doses of SABA (400 mcg of salbutamol) will be applied and after 20 minutes post-bronchodilator tests of impulse oscillometry, slow spirometry and forced spirometry will be performed. The patient will be instructed in the technique of inhalation of study medication and a corresponding dose will be applied. Study medication will be provided for one month of treatment. A symptom diary will be provided and a follow-up visit 2 will be scheduled 30 days after the randomization visit.

Follow-up visit 2 (Visit 2, 30 days -2/+1 day): Exacerbations during the period, frequency of adverse events, newly diagnosed comorbidities and use of concomitant medication will be questioned and documented. Symptom diary will be reviewed. Devices dispensed at visit 1 will be reviewed to calculate adherence to treatment (≥80%). It will be confirmed that the patient has not applied the morning dose of study medication. Dyspnea questionnaire (mMRC), quality of life questionnaire (Saint George and CAT), and adherence to inhaled medication questionnaire (TAI) will be completed. Baseline pulmonary function tests will be performed: FeNO, impulse oscillometry, slow spirometry, forced spirometry and simple plethysmography. Short-acting bronchodilator (SABA) will be applied, the patient will be left to rest for 20 minutes. Post-bronchodilator tests will be initiated in the following order: impulse oscillometry, slow spirometry, forced spirometry. The patient will be instructed in the technique of inhalation of study medication and a corresponding dose will be applied. Study medication will be provided for two months of treatment. A symptom diary will be provided and a follow-up visit 3 will be scheduled 12 weeks after the randomization visit. Instructions for said visit will be given.

Follow-up visit 3 (Visit 3, 12 weeks -2/+1 day): Exacerbations during the period, frequency of adverse events, newly diagnosed comorbidities and use of concomitant medication will be questioned and documented. Symptom diary will be reviewed. Devices dispensed at visit 1 will be reviewed to calculate adherence to treatment (≥80%). It will be confirmed that the patient has not applied the morning dose of study medication. Dyspnea questionnaire (mMRC), quality of life questionnaire (Saint George and CAT), and adherence to inhaled medication questionnaire (TAI) will be completed. Baseline pulmonary function tests will be performed: FeNO, impulse oscillometry, slow spirometry, forced spirometry and simple plethysmography. Standard doses of SABA (400 mcg of salbutamol) will be applied and after 20 minutes post-bronchodilator tests of impulse oscillometry, slow spirometry and forced spirometry will be performed. Participation in the protocol will be terminated and monitoring by the NIRD Tobacco and COPD clinic will continue.