What's the fuss about ‘Treatable Traits’?


Many of you will have come across the term ‘treatable traits’ - perhaps at a conference or from one of an increasing number of review articles on the subject. Some of you may even be designing your clinical services around this new treatment strategy, but what does it actually mean? And is it relevant to me in my everyday work supporting patients to live well with COPD and Asthma?

One size does not fit all

Proponents of the treatable traits strategy hail it as a new paradigm of personalised, precision medicine for chronic airways disease, moving us on from the historical limitations of a ‘magic bullet’ or ‘stepwise escalation’ strategies adopted in the 19th and 20th centuries.

There is no doubt that these old strategies had a huge impact, the ‘magic bullet’ served us well when the main threat to health was from infectious disease (millions of lives have been saved by an antibiotic targeting a suspectable pathogen). Then with the exponential rise in non-communicable diseases such as diabetes, vascular disease and of course, COPD heralded a drive to define and measure disease severity and then to escalate treatment in a stepwise way accordingly, perhaps the most recognisable example being the BTS/SIGN Asthma guidelines.

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However, we know from supporting patients with airways disease day to day in our clinics, that one size does not fit all. In the real world there is a complexity which may manifest itself from difficulties in confirming diagnosis to the individual variability in presentation and response to treatment.

This has prompted criticism of the current ‘stepwise approach’ which fails to account for this complexity and also does not incorporate recent discoveries in underlying biological mechanisms (often referred to as endotypes), for example TH2 driven airway inflammation characterised by raised exhaled nitric oxide and eosinophilia.

Multi-morbidity, largely driven by an ageing population and lifestyle factors is arguably the defining challenge for western healthcare. We now recognise that the majority of patients with COPD and severe asthma have multiple comorbidities, which appear to be associated with higher mortality, worse quality of life and increased healthcare utilisation. It is perhaps therefore not surprising that improvements in patient outcomes for asthma and COPD have flattened over recent decades (Fig 1.0). The big question is, will a treatable traits strategy help us meet this challenge of complexity and multimorbidity?


Number of COPD deaths per million, per year, by country (2001-2010)
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Figure 1. BLF. Chronic Obstructive Pulmonary Disease Statistics. https://statistics.blf.org.uk/copd#worldview


What are Treatable Traits?

“Treatable traits” is a strategy whereby patients are individually and systematically assessed for a specified set of treatable problems, and an individualised treatment programme is developed and implemented based on this multidimensional assessment. Proposed treatable traits relevant to chronic airways disease are split into 3 domains: Figure 2.0 

Domains assessed in Treatable Traits

  1. Airways (e.g fixed or reversible airflow obstruction, airway inflammation)
  2. Extrapulmonary or co-morbidities 
  3. Treatable behaviours and lifestyle risk factors. 

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Figure 2. Adapted from: Severe Asthma Toolkit. https://toolkit.severeasthma.org.au/resources/systematic-multidimensional-assessment-resources/

There will be many of you reading this who are perhaps not unreasonably thinking that this all sounds wonderful, but in the real world, how are we expected to adopt this approach without more time, resources and an extended multidisciplinary team?

The reality is that such a comprehensive, multi-dimensional assessment may be restricted to centralised specialist centres such as those commissioned by NHS England for Severe Asthma, but this perhaps ignores an uncomfortable truth that all of our patients with airways disease are likely to benefit from (and deserve) such a comprehensive management strategy. But is this affordable? Treatable traits enthusiasts may argue, can we afford not to?

Certainly, there is great appeal to us as healthcare professionals who by adopting a multidimensional assessment, are able to respond to the needs of the whole person and provide targeted holistic care.


What's the evidence?

The most familiar model for us in respiratory medicine come from the lessons learned from the improvements in survival in people living with Cystic Fibrosis.This turnaround has not just been down to new medicines but the multidimensional assessment and management strategies adopted by an extended multi-disciplinary team including doctors, nurse specialities, dieticians, psychologists, social worker, physiologists, physiotherapists and pharmacists. 

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There has been a systematic review and meta‐analysis of multidimensional assessment of severe asthma: Vanessa L. Clark et al. It looked at data from 26 studies including disease registries, cohorts and clinical trials which found that pooled results showed benefits in asthma‐related quality of life; asthma control and exacerbations, pre‐ and post‐multidimensional assessment and targeted treatment, but these strategies do appear to take time, with around 4 months needed for these benefits to become apparent.

Below is an example of how an intervention targeting one trait can achieve multiple positive outcomes, including health-related quality of life (HRQoL) and BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index. COPD: chronic obstructive pulmonary disease; CVD: cardiovascular disease.
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Treatable Traits: a new paradigm for 21st century management of crhonic airway diseases. Vanessa M. McDonald et al European Respiratory Journal 2019

Final thoughts


So, whether you are a ‘Treatable Traits’ enthusiast or sceptic, what is clear is that there are many challenges to overcome in order to improve the lives of our patients living with a significant burden of COPD and Asthma, but there is also reason to be optimistic.

It’s an exciting time to be involved in airways disease as we look to new ways of delivering precision medicine, recognising the complexities of the whole patient and have access to new and transformative medications which target underlying abnormal lung biology.



References
  1. The Kings Fund. (2019) Long-term conditions and multi-morbidity. https://www.kingsfund.org.uk/projects/time-think-differently/trends-disease-and-disability-long-term-conditions-multi-morbidity. [Accessed 10/09/2019].
  2. Cavaillès, A. et al (2013). Comorbidities of COPD. European Respiratory Review, 22(130), 454-475.https://err.ersjournals.com/content/22/130/454
  3. Serra-Batlles, J. et al (1998). Costs of asthma according to the degree of severity. European Respiratory Journal, 12(6), 1322-1326. https://erj.ersjournals.com/content/erj/12/6/1322.full.pdf
  4. British Lung Foundation. (2019) Chronic obstructive pulmonary disease (COPD) statistics https://statistics.blf.org.uk/copd#worldview. [Accessed 10/09/2019]
  5. Severe Asthma Toolkit (201. Systematic & Multidimensional Asthma Assessment Resources. https://toolkit.severeasthma.org.au/resources/systematic-multidimensional-assessment-resources/. [Accessed 10/09/2019]
  6. British Lung Foundation. (2019) Cystic Fibrosis statistics. https://statistics.blf.org.uk/cystic-fibrosis. [Accessed 10/09/2019]
  7. Clark, V. et al (2017). Multidimensional assessment of severe asthma: a systematic review and meta‐analysis. Respirology, 22(7), 1262-1275. https://doi.org/10.1111/resp.13134
  8. Vanessa M. McDonald et al (2019). Treatable Traits: a new paradigm for 21st century management of crhonic airway diseases. European Respiratory Journal 2019

Dr James Dodd has received an honorarium from GSK for developing this article/content.

PM-GB-CPU-WCNT-190020 - September 2019

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PM-GB-CAU-WCNT-190006
March 2019