Research where it is most needed National Respiratory Strategy Richard Beasley Medical Research Institute of New Zealand

Circumstances associated with asthma deaths Delay in seeking medical help Lack of appreciation of severity (acute and chronic) Inadequate use ICS and oral steroids Over-reliance on beta agonists Discontinuity of care [Asthma Task Force Survey]

[Holt et al. Prim Care Respir J 2004]

[Holt et al. Prim Care Respir J 2004]

[Holt et al. Prim Care Respir J 2004]

Asthma self-management plans - questions Individual patient requirements Peak flow levels Peak flow vs symptoms Components leading to efficacy Doubling ICS Amount of detail Use by patients Other meds

SMART Single combination ICS/LABA inhaler for maintenance and reliever therapy

[Lancet 2006]

BUD/F 200/6 µg bd + formoterol prn BUD/F 200/6 µg bd + terbutaline prn BUD/F 200/6 µg bd + prn BUD/F 200/6 µg bd + formoterol prn BUD/F 200/6 µg bd + terbutaline prn ICS dose reduction (baseline 750 µg per day) Patients with beta agonist overuse excluded Severe exacerbations: ER, HA or oral steroids [Rabe et al. Lancet 2006]

[Rabe et al. Lancet 2006]

[NZ Med J 2008]

Indications [Taylor et al. NZ Med J 2008]

Contraindications [Taylor et al. NZ Med J 2008]

SMART Research Programme - Limitations Excluded high risk patients High baseline beta agonist use Limited generalisability Required significant bronchodilator reversibility Excluded smokers Step down in treatment Inadequate maintenance ICS No accurate measures of actual inhaler use Inability to assess risk of adverse effects Short term exposure Cumulative exposure

[Patel et al, Lancet Resp Med 2013]

Questions Overuse in setting of severe exacerbation? Delay in seeking medical review in severe exacerbations? Improve compliance with ICS therapy? Systemic corticosteroid exposure? Efficacy in patients at risk of severe exacerbations?

Methods A 24-week, open-label, parallel-group, randomised, controlled, trial undertaken at four primary healthcare practices and one hospital in New Zealand.

Design 303 asthma patients with exacerbation in previous 12 months Randomised to SMART or Standard regime SMART: budesonide/formoterol 200/6µg 2 actuations twice daily and 1 as required for relief Standard: budesonide/formoterol 200/6µg 2 actuations twice daily and salbutamol 1 to 2 as required for relief Study visits 0, 3, 10, 17, 24 weeks Electronic monitors to measure actual inhaler use

Electronic medication data Database: 282,466 actuations 2,642 monitors 49,1249 days treatment Complete data: 95% dispensed 98% returned

Primary outcome variable Proportion of subjects with at least one high-use beta agonist episode >16 actuations/day salbutamol >8 actuations/day bud/form (in addition to 4 maintenance doses) Limits of use requiring medical review defined by management plans Bronchodilator equivalence with repeat dosing in acute asthma

SMART resulted in fewer days with zero actuations of ICS (non-adherence) 24 vs 34 days RR 0.72 (0.55 to 0.95) P = 0.02

SMART reduced severe exacerbations 0.53 vs 0.77 per year RR 0.54 (0.36 to 0.82), P = 0.004

Interpretation The SMART regimen has a favourable risk-to-benefit profile and can be recommended for use in adults at risk of severe asthma exacerbations.

Asthma research priorities Prevalence  Morbidity  Mortality 

Worldwide prevalence of clinical asthma in children ≥ 10.0% > 5.0 – 9.9% > 0 – 4.9% > No standardised data available http://www.ginasthma.org/local/uploads/content/files/GINA_Appendix_2014_Jun11.pdf

Asthma Foundation research priorities Models of care for Maori and Pacific peoples Service evaluation of existing initiatives Strategies to prevent respiratory conditions (COPD, lung cancer, childhood bronchiectasis) Improve health literacy

Asthma Foundation research priorities Understanding OSA Improve diagnosis, assessment, treatment of COPD Health psychology and respiratory disease Effective of annual respiratory check Indicators to measure and monitor respiratory health outcomes