A clinical trial comparing the difference between participants who are frequently monitored for their compliance with their inhaler medication and participants who receive only their routine care in people suffering from asthma or COPD

1. Annualised rate of airway disease exacerbations from baseline to 24 weeks, with exacerbations defined as:

1.1. Mild exacerbations (any one of):
1.1.1. Nocturnal awakening(s) on at least 2 nights
1.1.2. Increase in short-acting beta agonist (SABA) use for at least 2 nights
1.1.3. ≥20% decrease in peak expiratory flow on at least 2 nights compared to the optimal run-in peak flow reading
1.1.4. ≥20% decrease in FEV1 compared to optimal run-in FEV1 reading
1.1.5. A visit to the emergency department (ED)/trial team for increased symptoms but not requiring additional systemic corticosteroids.

1.2. Moderate-to-severe exacerbation (any one of):
1.2.1. Use of systemic corticosteroids ±antibiotics, or an increase from a stable maintenance dose, for at least 3 days. A period of 7 days or more between additional corticosteroids will be defined as a separate event
1.2.3. An episode of hospitalization or ED (emergency department) visit because of increased airways disease symptoms, requiring systemic corticosteroids ± antibiotics

Exacerbations will be captured via the electronic symptom diary supported by digital platform Atom5 and Nuvoair, with data collected three times per week to allow monitoring mild exacerbation events.

2. Annualised rate of all airway disease exacerbations from baseline visit to the study endpoint (24 weeks)

1. Secondary outcome measures from baseline (week 0) to week 24:
1.1. Pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) and FEV1/FVC measured at study visits (weeks 0,12 & 24) 
1.2. Compliance with biomarker algorithm-based treatment advisories during the trial (proportion of days in the month that participants adhere to algorithm-based treatment advisories over 24 weeks). Electronically monitored adherence profile (weeks 0, 4, 8,12 & 24)
1.3. St George’s Respiratory Questionnaire score (SGRQ) (weeks 0, 12 & 24)
1.4. Annualised rate of moderate to severe exacerbation events requiring oral corticosteroids or antibiotics

2. Exploratory (Clinical biomarkers):
To compare the following outcome measures between the biomarker intervention arm and the standard of care arm:
2.1. Additional exacerbation outcomes:
2.1.1. Time to first moderate-severe exacerbation
2.1.2. Hospital or Emergency Department (ED) admissions due to exacerbations of airway disease
2.2. Biomarkers:
2.2.1. Change in blood eosinophil counts (weeks 0, 12 & 24) 
2.3. Symptom questionnaires (Comparison of change over 24 weeks and responder analysis)
2.3.1. COPD Assessment Tool (CAT) for COPD participants
2.3.2. Asthma Control Test Score (ACT) for Asthma patients
2.3.3. Extended MRC dyspnoea score (eMRC) for participants with both asthma and COPD

3. Exploratory (Digital biomarkers):
The following digital biomarkers will be collected and assessed as exploratory analyses at Imperial College, London
3.1. Composite Exacerbation Endpoints:
Analysis of thrice weekly study acquired PEFR/FEV1, Reliever use and symptom scores with a view to deriving composite exacerbation endpoint measurements using threshold and slope-based indices. (weeks 0-12, 13-24 & 0-24)
3.2. Cough biomarker analysis (Nuvoair data):
3.2.1. Cough counts (weeks 0-12, 13-24 & 0-24)
3.2.2. Cough sound biomarkers (including frequency - median (range) and amplitude) (weeks 0-12, 13-24 & 0-24)
3.3. Physical activity monitoring biomarkers (Fitbit data):
3.3.1. Daily step count (weeks 0-12, 13-24 & 0-24)
3.3.2. Mean and standard deviation of daily heart rate (weeks 0-12, 13-24 & 0-24) Mean and standard deviation of daily energy expenditure (weeks 0-12, 13-24 & 0-24)
3.3.3. Sleep duration (weeks 0-12, 13-24 & 0-24)
3.4. Causal inference analyses using complier average causal effect (CACE) modelling of study adherence data and exacerbation events, with a view to understanding the impact of temporal variations in adherence to inhaled therapy and mild, moderate-severe, exacerbations.

4. Biobanking at stable disease state (with optional consent):
4.1. Collection of the following biological samples at the screening visit (week -34 to -22) and week 24
4.1.1. Blood (DNA PAXgene)
4.1.2. Urine
4.1.3. Serum
4.1.4. Plasma
4.1.5. Nasopharyngeal swab

5. Exacerbation profiling Sub-study (Optional)
A subgroup of trial participants (n = 100 participants, with 50 participants from each trial arm) will be analysed in greater depth if they report a moderate-severe exacerbation event.
Trial participants will be asked to report to their local trial site, should they require oral steroids or antibiotics for an exacerbation, preferably prior to initiating treatment
5.1. The following samples will be collected at these exacerbation visits:
5.1.1. Blood tests (FBC, C-Reactive Protein)
5.1.2. Spontaneous Sputum samples
5.1.3. Plasma
5.1.4. Nasopharyngeal swabs
5.1.5. Urine