• Individual patient plots of fractional exhaled Nitric Oxide (FeNO) (morning) [ Time Frame: From Day 1 to Day 169 (Treatment period). ]
  FeNO will be plotted over time for each patient.
• Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: From Day 1 to Day 169 (Treatment period) ]
  Symptoms scores will be plotted over time for each patient.
• Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: From Day 1 to Day 169 (Treatment period) ]
  Reliever use will be plotted over time for each patient.
• Individual patient plots of forced expiratory volume in 1 second (FEV1) (morning and evening) [ Time Frame: From Day 1 to Day 169 (Treatment period) ]
  FEV1 will be plotted over time for each patient.
• Individual patient plots of peak expiratory flow (PEF) (morning and evening) [ Time Frame: From Day 1 to Day 169 (Treatment period) ]
  PEF will be plotted over time for each patient.

• Individual patient plots of fractional exhaled Nitric Oxide (FeNO) (morning) [ Time Frame: From Day 1 to Day 168 (Treatment period). ]
  FeNO will be plotted over time for each patient.
• Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
  Symptoms scores will be plotted over time for each patient.
• Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
  Reliever use will be plotted over time for each patient.
• Individual patient plots of forced expiratory volume in 1 second (FEV1) (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
  FEV1 will be plotted over time for each patient.
• Individual patient plots of peak expiratory flow (PEF) (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
  PEF will be plotted over time for each patient.

• Individual patient plots of FeNO (morning) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 169) ]
  FeNO will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 169) ]
  Symptoms scores will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 169) ]
  Reliever use will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of FEV1 (morning and eveing) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 169) ]
  FEV1 will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of PEF (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 169) ]
  PEF will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

• Individual patient plots of FeNO (morning) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
  FeNO will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
  Symptoms scores will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
  Reliever use will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of FEV1 (morning and eveing) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
  FEV1 will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.
• Individual patient plots of PEF (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
  PEF will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

This is a randomised, active-comparator, open-label, parallel-group, multicentre phase IV exploratory study to characterise changes in airway inflammation, symptoms, lung function, and reliever use in asthma patients using SABA (salbutamol) or anti-inflammatory reliever (SYMBICORT®) as reliever medication in addition to SYMBICORT as daily asthma controller. Eligible patients diagnosed with asthma at least 6 months prior to the Screening Visit (Visit 1) and fulfilling all of the inclusion criteria and none of the exclusion criteria will continue into the Run-in Period. During the run-in period, patients will take their maintenance medication (ie, SYMBICORT [100/6 or 200/6 μg, × 2 BID]) and reliever salbutamol [100 μg, PRN]) using the connected inhalers. At Visit 2, patients will be assessed for randomisation criteria and, if met, will be randomised to receive either SYMBICORT as maintenance and reliever treatment or SYMBICORT as maintenance treatment and salbutamol as reliever treatment in a 1:1 ratio. Randomisation will be stratified by the patient's ongoing dose of ICS (low or medium) or long-acting β2-agonist (LABA) at study entry. This study will include a minimum of 3 site visits. Patients will be requested to come to the study site for 4 additional Event Visits (E1 to E4) at approximately 4-day intervals beginning after the first visit if they experience any one of the following 3 criteria: a) A severe exacerbation defined as use of systemic steroids for at least 3 days, emergency room visit, or inpatient hospitalisation due to asthma, b) Symptom worsening criteria based on CompEx evaluation - an asthma worsening identified by a combination of deteriorations in at least 2 variables (decrease in PEF of at least 15% compared with baseline, an increase of reliever medication of at least 1.5 occasions compared with baseline, or an increase in asthma symptoms of at least 1 compare with baseline or the absolute max score [=3]) at least 2 consecutive days, or c) A single day (in 24 hours) with 6 or more occasions of reliever medication use.

The duration of participation in the study will be 26 to 28 weeks (maximum) for each individual patient, including a 2-week Run-in Period, followed by a 24-week randomised Treatment Period and an additional follow-up period if the Event Visits fall within the final 2 weeks of the Treatment Period. The study plans to randomise a minimum of 60 patients to a maximum of 80 patients to achieve at least 54 patients completing the study. The study will be conducted at no less than 2 sites in the United Kingdom (UK). The estimated study duration is approximately 30 months.

• Airway Inflammation
• Asthma

• Active Comparator: SYMBICORT as maintenance and reliever treatment
  Patients on ICS (low dose)/LABA prior to study entry (per GINA 2018 guidelines) will receive SYMBICORT (budesonide/formoterol 100/6 μg) × 2 twice a day (BID) for maintenance and as needed (PRN) for relief and patients on ICS (medium dose)/LABA prior to study entry (per GINA 2018 guidelines) will receive SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
  Intervention: Combination Product: SYMBICORT and salbutamol
• Active Comparator: SYMBICORT as maintenance, salbutamol as reliever treatment
  Patients on ICS (low dose)/LABA prior to study entry (per GINA 2018 guidelines) will receive SYMBICORT (budesonide/formoterol 100/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief and patients on ICS (medium dose)/LABA prior to study entry (per GINA 2018 guidelines) will receive SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
  Intervention: Combination Product: SYMBICORT and salbutamol

Inclusion Criteria:

1. Provision of signed and dated, written Informed Consent Form (ICF) prior to any study-related procedures, sampling, and analyses (at Visit 1).
2. Patient must be ≥18 years of age at the time of signing the ICF.
3. A physician diagnosis of asthma for a minimum ≥6 months prior to Visit 1.
4. Use of ICS (low or medium dose)/LABA (GINA 2018 guidelines) for asthma for ≥3 months prior to Visit 1.
5. Episode of asthma symptom worsening requiring overuse of reliever (more than the standard for the individual patient) at least once during the last 30 days prior to Visit 1.
6. The patient must be able to read speak, and understand local language; and be able to, in the Investigator's judgment, comply with the study protocol.
7. Able to perform home FeNO and spirometry assessments and complete the asthma symptom diary on a regular basis during the conduct of the study.
8. Asthma exacerbation history: patient reported history of one (or more) severe asthma exacerbation requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) in the 12 months prior to Visit 1.
9. Male and/or female
10. Negative pregnancy test (urine) for female patients of childbearing potential at Visit 1.

11. For randomisation at Visit 2, patients should fulfil the following criteria:

    1. Symptoms requiring reliever medication use for a minimum of 2 to a maximum 8 days out of the last 10 days of the Run-in Period.
    2. At least 80% overall compliance rate for performing FeNO and spirometry assessments and completing the asthma symptom diary during the Run-in Period.

Exclusion Criteria:

1. Any significant disease or disorder, or evidence of drug/substance abuse which in the Investigator's opinion would pose a risk to patient safety, interfere with the conduct of study, have an impact on the study results, or make it undesirable for the patient to participate in the study.
2. Any asthma worsening requiring change in asthma treatment other than the patient's prescribed reliever medication (SYMBICORT as Maintenance and Reliever Therapy [SMART] therapy, SABA, and/or short-acting anticholinergic agent) within 30 days prior to Visit 1.
3. Medical history of life- threatening asthma including intubation and intensive care unit admission.
4. Medical conditions (other than allergic rhinitis) or medications (other than ICS) that will influence FeNO, as judged by the Investigator.
5. Concurrent respiratory disease: presence of a known pre-existing, clinically important lung condition other than asthma (eg, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension).
6. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained (Visit 1) or during the screening/Run-in Period.
7. A severe asthma exacerbation (defined by an exacerbation resulting in ≥3 days of oral corticosteroids [or one depot intramuscular injection of a glucocorticosteroid], an urgent care or emergency room visit that results in systemic corticosteroids, or an inpatient hospitalisation due to asthma) within 30 days prior to screening.
8. Any disease state or procedure that may necessitate the use of oral/systemic corticosteroids during the Treatment Period, other than asthma.
9. Malignancy: a current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (patients that had localised carcinoma of the skin which was resected for cure will not be excluded).
10. Patients with a history/treatment of malignancy, and which in the Investigator's opinion could compromise the safety of the patient.
11. Other concurrent medical conditions: patients who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
12. Current smokers: previous smokers are allowed to be included provided that they stopped smoking >12 months prior to Visit 1 AND have a smoking history of ≤10 pack-years.
13. Alcohol/substance abuse: a history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
14. Participation in another clinical study with any marketed or investigational biologic drug within 4 months or 5 half-lives (whichever is longer) prior to Visit 1.
15. Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug during the last 30 days prior to Visit 1.
16. Patients with a known hypersensitivity to the study drugs or any of the excipients of the products.
17. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
18. Previous randomisation in the present study.
19. For women only: currently pregnant (confirmed with positive pregnancy test), breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the Investigator. Periodic abstinence, spermicides only, and the lactational amenorrhoea method are not acceptable methods of contraception.
20. Planned hospitalisation during the study that would interfere with study objectives as judged by the Investigator.