None listed
Conditions
Brief summary
Asthma affects approximately 1:10 adults and 1:5 children. Although most subjects attained good control of their asthma with conventional treatment, there is a significant proportion who are resistant to conventional treatment and remain uncontrolled. Although there are several mechanisms that may explain incomplete asthma control, one important factor which is potentially easy to address, is the presence of severe small airways disease that is not effectively improved by inhaled corticosteroid treatment. The small airways are an important determinant of asthma control and severity. They are airways with an internal diameter of 2 mm or less and because of the branching nature of the airway tree, occupy a very large surface area compared to the larger and more proximal airways. We have recently shown that small airway function improves with high dose inhaled corticosteroid treatment in parallel with improving asthma control. Furthermore, asthma control and severity are strongly related to small airways function. It therefore follows that persisting small airways disease is an important determinant of severe asthma and that better treatment of the small airways will improve the treatment of severe asthma. The obvious problem with treating small airways that are severely affected by inflammation and tissue remodelling, is that it is difficult to deposit therapeutic aerosols there. This is because ventilation to those airways is poor, because of severe airway narrowing and closure. Therapeutic aerosols require ventilation to carry them to the target sites and so the worst affected airways receive less of the inhaled aerosols. There is a theoretical advantage of using fine particle aerosols, because they are more likely to be carried to areas where ventilation is poor. Particles greater than 3 – 5 um deposit in the medium to large airways, while smaller particles will be carried into smaller and narrowed airways. Therefore, we propose that small particle aerosols will be more effective in uncontrolled asthma than larger particle aerosols.
Interventions
The run-in period of this study will involve participants taking 200ug/day budesonide (Pulmicort Turbuhaler) for 4 weeks.
This will be followed by a two arm interventional study period which involves administration of budesonide modified into either small or large aerosols, for the treatment of asthma.
For both arm 1 (small aerosols ~1um) and arm 2 (large aerosols ~5um) participants will take 800ug/day of the study drug for a period of 12 weeks.
Adherence throughout the run-in period and the st
The run-in period of this study will involve participants taking 200ug/day budesonide (Pulmicort Turbuhaler) for 4 weeks. This will be followed by a two arm interventional study period which involves administration of budesonide modified into either small or large aerosols, for the treatment of asthma. For both arm 1 (small aerosols ~1um) and arm 2 (large aerosols ~5um) participants will take 800ug/day of the study drug for a period of 12 weeks. Adherence throughout the run-in period and the study period will be monitored with daily peak flow diaries to record lung function, daily asthma control questionnaires, and fortnightly phone calls from the research team.
Sponsors
Woolcock Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Current asthma defined as having a doctor diagnosis of asthma and asthma symptoms and asthma medication use in the last 12 months. 2. Be taking less than 400 ug of budesonide daily or alternative, with or without LABA. 3. Currently clinically stable. 4. Asthma Control Questionnaire (ACQ) score of >1.
Exclusion criteria
1. Current smoker (at least 1 cigarette/day >3 months) within the previous 12 months, or having past smoking history of >10 pack/years. 2. Had an asthma exacerbation (defined as an increase in asthma symptoms for >2 days requiring an increase in inhaled corticosteroid (ICS) treatment or administration of prednisone, within the last 6 weeks. 3. Admission to a hospital ward for 1 night or more for asthma, in the last 12 months. 4. Unable to provide written, informed consent. 5. Have significant co-existent pulmonary or cardiac disease that could, in the opinion of the Chief Investigators, affect small airway function and/or modify respiratory symptoms. These include but are not limited to emphysema, pulmonary fibrosis, pulmonary hypertension, bronchiectasis and heart failure. 6. Inability to satisfactorily use a pMDI after education on pMDI technique. 7. Taking >800ug budesonide equivalent.
Outcome results
None listed