A proof-of-concept single group study of an anti-inflammatory reliever therapy stepwise approach to the pharmacological treatment of adult asthma.

The AIR Algorithm Study is a prospective, single-centre, open label, single group study aimed at assessing the utility of the Anti-Inflammatory Reliever (AIR) therapy stepwise approach to the pharmacological treatment of adult asthma (AIR Algorithm). 100 participants will be assigned to the AIR Algorithm for 52 weeks. The AIR Algorithm uses a single combined budesonide-formoterol (Symbicort Turbuhaler 200/6 micrograms) dry powder inhaler and a stepwise change in treatment according to asthma symptoms. The AIR Algorithm treatment steps are: 1) Step 1 - one actuation as required (PRN) for the relief of symptoms with no regular maintenance therapy. 2) Step 2 - one actuation PRN and one actuation twice daily as regular maintenance therapy. 3) Step 3 - one actuation PRN and two actuations twice daily as regular maintenance therapy. At enrolment, participants will be allocated an AIR Algorithm treatment step according to their pre-enrolment asthma therapy based on the Global Initiative for Asthma (GINA) 2018 criteria: 1) AIR Algorithm Step 1 - pre-enrolment GINA Step 1 therapy (Short-Acting Beta-Agonist [SABA] monotherapy). 2) AIR Algorithm Step 2 - pre-enrolment GINA Step 2 and 3 therapy (Inhaled Corticosteroid [ICS] plus SABA reliever or low dose ICS/Long-Acting Beta-Agonist [LABA] plus SABA reliever). 3) AIR Algorithm Step 3 - pre-enrolment GINA Step 4 therapy (medium or high dose ICS/LABA plus SABA reliever). Treatment steps will be adjusted throughout the trial in accordance with a participant’s reported inhaler use and whether they have experienced an asthma attack. All treatment step changes will be based on participant self-report. All study inhalers will also be fitted with Turbu+ electronic monitors that record patterns of inhaler use. Participants will: 1) ‘Step down’ if they report using two or fewer actuations per week for symptom relief. Step 1 represents the lowest level of treatment. 2) Remain on the same treatment step if they report using greater than two, but seven or fewer actuations per week for symptom relief. 3) ‘Step up’ if they report using greater than seven actuations per week for symptom relief or if they have an asthma attack. For the purposes of this study an asthma attack is defined as a deterioration in asthma symptoms severe enough to warrant the use or prescription of systemic corticosteroids, such as a course of prednisone. If a participant on Step 3 meets the requirements for stepping up, they will remain on the same treatment and be referred to a specialist respiratory clinic on study completion. The study will be conducted in two phases: 1) Phase One will cover the first 26 weeks with treatment steps reviewed and adjusted by study staff at study visits every 13 weeks. 2) Phase Two will cover week 26 to week 52 when participants will be encouraged to adjust their own treatment step. At 26 weeks, during a study visit, study staff will provide participants with a written asthma management plan detailing the AIR algorithm and explain to participants how and when to review and adjust their own treatment step. From week 26 to week 39 participants will be asked to review their treatment monthly. Between week 39 and week 52 participants will be encouraged to adjust their treatment as often as they feel necessary. In order to assist participant self-report over the 52-week duration of the study, Asthma Diary Cards and a MyCap mobile app alternative have been developed specifically for this study. Participants will be encouraged to record details of: 1) Urgent medical reviews due to asthma. 2) Courses of systemic corticosteroids for asthma. 3) Changes to any medications. 4) Self-adjusted treatment step changes. Two additional sub-studies are planned alongside the AIR Algorithm study: 1) The AIR Tutorial sub-study (AIR-T) - an embedded randomised controlled sub-study designed assess whether interactive comic tutorials can help adult patients with asthma understand and adhere to an anti-inflammatory reliever therapy regimen. All 100 participants enrolled in the AIR Algorithm parent study will undergo randomisation, with 50 participants allocated to receive the interactive comic tutorials. These materials have been designed specifically for this study and will cover the rationale of the AIR Algorithm concept, when to seek medical help and how to self-manage care using the AIR Algorithm. 2) The AIR Qualitative sub-study (AIR-Q) - a qualitative sub-study to enhance understanding of the findings of the main study, and to explore patient attitudes to the treatment regimen. A subset of participants will be invited for an optional interview at the end of the trial. Recruitment will be purposive, based on a sampling framework that includes high and low levels or reported treatment satisfaction, specific AIR Algorithm treatment steps, withdrawal status, age group and gender, in order to enrol a broad distribution of participants. The interviewer will use the existing study data to select participants to be approached for interview, according to the sampling framework, timing of study visits, and the participants already interviewed.