The purpose of the study is to enroll participants with uncontrolled asthma to evaluate the large and small airways and drug delivery utilizing two study drugs:

• Beclometasone dipropionate/Formoterol fumarate dihydrate/Glycopyrronium bromide (BDP/FF/G) or Trimbow
• Fluticasone furoate/Umeclidinium/Vilanterol (FluF/UMEC/VI ) or Trelegy Ellipta

The study will comprise of 5 visits. A screening visit (V1, Week -2), with baseline assessment. At the randomization visit (V2, Week 0), patients will be randomized in a 1:1 ratio to receive one of the following treatments for 8 weeks:

• BDP/FF/G 100/6/12.5 mcg pMDI, two inhalations twice-daily
• FluF/UMEC/VI 100/62.5/25 mcg DPI, one inhalation once-daily

A subsequent visit will be performed at 8 weeks (V3), where participants will undergo spirometry, oscillometry, and imaging. Participants will then stop the assigned treatment and undergo a washout period of 4 weeks using an unrelated maintenance ICS/LABA combination inhaler.

Following the washout period, at the next visit (V4, Week 12) participants will then be crossed over to the other treatment they did not receive at randomization.

At the final visit (V5, Week 20), patients will once again undergo spirometry, oscillometry, and imaging. In the event of premature study discontinuation, an early termination (ET) visit will be conducted and the Investigator must fill in the "Study Termination" page in the eCRF, reporting the main reason for withdrawal.

Participants who were previously screened and found ineligible due to transient or correctable conditions (e.g., recent exacerbation) may be considered for rescreening twice. Rescreening must be approved by the Principal Investigator and documented in the subject's screening log.

Rescreening will follow the same procedures as the initial screening, including informed consent, unless otherwise specified in the protocol. The reason for rescreening and any changes in eligibility status must be clearly documented in the case report form (CRF) and source documents.

Inclusion Criteria:

• Subject's written informed consent obtained prior to any study-related procedure.

• Patients aged ≥ 18 and ≤ 75 years

• Confirmed diagnosis of asthma (patients must have a documented history of asthma for at least 1 year with diagnosis before the age of 40 and/or pre-bronchodilator FEV1 between 50-80% of their predicted normal value, after appropriate washout from bronchodilators)

• Symptomatic on ICS/LABA treatment with ACT <20

• No exacerbations in the past 3 months requiring treatment with systemic corticosteroids or emergency department visit/ in-patient hospitalization

• The ability to be trained and correctly use a pressurized Meter Dose Inhaler (pMDI) and Dry Powder Inhaler (DPI)

• To have a cooperative attitude and the ability to perform the required outcomes measurements (e.g. spirometry maneuvers in sitting and supine position) and the ability to understand the risks involved

• WOCBP fulfilling one of the following criteria:

  1. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
  2. WOCBP with physician confirmed non-fertile male partners (contraception is not required in this case).

• Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile, e.g. amenorrheic for ≥12 consecutive months without alternative medical cause). Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges).

Exclusion Criteria:

• Pregnant or lactating female
• Patients who had an exacerbation, defined as a sustained and acute deterioration of subject's symptoms and signs (dyspnea, cough and/or sputum production/purulence) that was either moderate, i.e. require treatment with systemic (oral/IV/IM) corticosteroids and/or antibiotics, or severe, i.e. require hospitalization, if their associated treatment/hospitalization occurred within 3 months prior to V1
• Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake
• History of near fatal asthma or of a past hospitalization for asthma in intensive care unit which, in the judgement of the Investigator, may have placed the patient at undue risk
• Patients using systemic corticosteroid medication in the 4 weeks or slow-release corticosteroids in the 12 weeks, prior to screening
• Patients who suffer from COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) document
• History of a diagnosis of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which may have interfered with study evaluations
• Current smokers or current use of electronic cigarettes or ex-smokers with total cumulative exposure equal or more than 10 pack-years or having stopped smoking one year or less prior to screening visit
• Patients who had clinically significant cardiovascular condition according to investigator's judgement, such as but not limited to: congestive heart failure (NYHA class >2), acute ischemic heart disease in the last year prior to study screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained meant lasting more than 30 seconds or ending only with external action, or led to hemodynamic collapse; non-sustained meant >3 beats <30 seconds, and or ending spontaneously, and or asymptomatic), high degree impulse conduction blocks (>2nd degree atrioventricular block type 2). Similarly, patients affected by persistent, long standing or paroxysmal AF were not considered for enrollment
• Patients who are unable to undergo imaging procedures for CT scans or MRI or demonstrate intolerance to Xenon gas
• Patients who have participated in a recent therapeutic trial (within past 6 months)
• Patients who have a milk protein allergy