Professor Richard Beasley

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Professor Richard Beasley University of Otago Director Medical Research Institute of New Zealand Wellington 14:00-14:55 WS #111: Towards Precision Medicine in Asthma -Treatable Traits 15:05-16:00 WS #121: Towards Precision Medicine in Asthma -Treatable Traits (Repeated)

Treatable Traits in airways disease Richard Beasley

Conflicts of Interest Chair, Asthma & Respiratory Foundation (New Zealand) Adult Asthma Guidelines: A Quick Reference Guide Member, Global Initiative for Asthma Assembly Funding/support: AstraZeneca, Cephalon, Genentech, GSK, Novartis, Sanofi

The Problem Airways disease is classified by diagnostic labels such as asthma and COPD, including chronic bronchitis and emphysema. Asthma and COPD are probably not single diseases, but syndromes made up of a complex of multiple related disorders that overlap. Current definitions may not reflect actual phenotypes of airways disease.

Why is it important? Specific phenotypes inform Underlying mechanisms Risk factors Natural history Monitoring Treatment

What is required? Multidimensional assessment of patients with airways disease which identifies clinical characteristics for which specific treatment strategies are based.

Treatable traits Specific characteristics of patients including phenotypes of airways disease, overlapping disorders, comorbidities, environmental and lifestyle factors, that potentially contribute to respiratory health, that are potentially amenable to specific treatments.

[The Lancet 2006]

[Wenzel, Lancet 2006]

Inhaled steroid responsiveness PC 20 doubling dose Eosinophilic 5.5 Non-eosinophilic 0.5 [Berry et al. Thorax 2007]

[NEJM 2009]

[Haldar et al. NEJM 2009]

[Lancet Respir 2016]

[Ortega et al. Lancet Respir 2016]

Case 45 year old woman with atopic asthma, Step 3 ICS/LABA treatment and repeat courses of oral steroids for exacerbations, anxiety/depression. Step up to moderate or high dose ICS/LABA treatment

Potential treatable traits Eosinophilic asthma Psychogenic vocal cord dysfunction Allergic bronchopulmonary aspergillosis Chronic rhinosinusitis Occupational asthma Adherence, inhaler technique

Challenge To develop a system whereby the treatable traits are assessed and managed in a primary or secondary care setting.

[ERS Task Force. ERJ 1999]

[ATS. Am J Respir Crit Care Med 2000]

[Robinson et al. Eur Respir J 2003]

[Lancet 2006]

[Holgate & Polosa. Lancet 2006]

[Thorax 2011]

[Bel et al. Thorax 2011]

[Bel et al. Thorax 2011]

[Bel et al. Thorax 2011]

[Bel et al. Thorax 2011]

[Rev Respir Med 2016]

Comorbidities and severe asthma Comorbidity Questionnaires Sensitivity (%) Specificity (%) Sinonasal disease (includes rhinosinusitis and allergic rhinitis) Sinonasal Q naire 90 94 Allergic rhinitis Score for allergic rhinitis 74 83 Dysfunctional breathing Nijmegen 91 95 Paradoxical vocal fold movement Pittsburgh vocal cord dysfunction index 83 95 Obstructive sleep apnoea Berlin Q naire 86 77 Anxiety/depression Hospital anxiety & depression score 80 80 Gastroesophageal reflux GR disease Q naire 65 71 [Wark et al. Exp Rev Respir Med 2016]

A Quick Reference Guide Richard Beasley, Bob Hancox, Matire Harwood Kyle Perrin, Betty Poot, Janine Pilcher, Jim Reid Api Talemaitoga, Darmiga Thayabaran

Treatable Traits Overlapping disorders: COPD Bronchiectasis Allergic bronchopulmonary aspergillosis Dysfunctional breathing, e.g. vocal cord dysfunction Comorbidities: Obesity Gastro-oesophageal reflux disease Rhinitis Sinusitis Depression/anxiety [Agusti et al. ERJ 2016]

Treatable Traits Environmental: Smoking Occupational exposures Provoking factors e.g. aspirin, other NSAIDs Behavioural: Adherence Inhaler technique [Agusti et al. ERJ 2016]