Triaging treatable traits in asthma

The concept of treatable traits in airway disease has arisen from the recognition that asthma and COPD are syndromes encompassing a wide range of overlapping disorders, co-morbidities and environmental and behavioural factors, which can be identified and treated. Implementation of a treatable-traits approach to management has the potential to form the basis of a precision medicine strategy, in which specific investigations and treatments are tailored according to the characteristics of each individual patient. For asthma, specialist severe asthma clinics at tertiary hospitals have used this approach under the label of systematic or multidimensional assessment of traits. For severe asthma, it is associated with improvements in asthma control, quality of life and a reduction in severe exacerbations. However, there are very limited data from randomized controlled trials as to how to implement the treatabletraits approach in routine clinical practice and whether it is more effective than a guideline-directed approach. For asthma, to enable implementation of the treatable-traits approach in clinical practice, there are a number of practical issues that need to be addressed. First, which of the treatable traits are the most important and should be given priority in terms of investigation and treatment? The stark reality of this issue was brought into focus by the Australasian Severe Asthma Web-based Database (SAWD) study recently published in Respirology by McDonald et al. They reported the prevalence and exacerbation risk of 24 treatable traits, across pulmonary, extrapulmonary and behavioural/ risk factor domains in two distinct populations of severe and non-severe asthma. The list of treatable traits could be expanded by at least another eight, if characteristics addressed prior to enrolment in the SAWD study such as poor inhaler technique and nonadherence were included, or if other traits such as occupational or other sensitizing exposures, medication side effects, bacterial colonization, chronic bronchitis, cough reflex sensitivity and symptom perception, which were not routinely assessed in the SAWD study, were included. At a simplistic level, the clinical utility of specific treatable traits in asthma could be initially triaged by consideration of a number of fundamental criteria. Key triage criteria might include ease of diagnosis and what investigations are required, the prevalence in specific asthma populations, the burden of disease including exacerbation risk, the efficacy and safety of treatment, and resource requirements. The findings of McDonald et al. are informative in this regard, showing that different traits have differing relative importance in the two populations based on their prevalence and severity, and that it might be possible to triage the traits based on the key criteria proposed. For example, in terms of diagnostic criteria, neutrophilic airway inflammation could be excluded as sputum induction is not feasible in routine clinical practice, whereas eosinophilic inflammation can be readily assessed by measurement of fractional exhaled nitrous oxide (FeNO). Emphysema could be excluded as its prevalence is very low in both asthma groups based on severity. Systemic inflammation and gastro-oesophageal reflux disease (GORD) could be excluded as although they are measurable traits, they are either not amenable to treatment, or treatment does not lead to improvements in asthma outcomes. It is apparent that for some traits such as obstructive sleep apnoea and vocal cord dysfunction, in which investigations and treatment are resource intensive, simple screening questionnaires that have high sensitivity and specificity might have utility, particularly if completed prior to the consultation. A further consideration is that the proposed triage process is based in part on severe exacerbation risk, but other factors such as variable airflow obstruction leading to poor asthma control may also contribute to the burden of disease, and as a result may also warrant inclusion as a treatable trait. Another observation from the SAWD study is that the priority list of treatable traits may differ depending on the asthma population studied, or for that matter, if the population is broadened to encompass COPD. On the basis of the findings of the SAWD study, it is possible to produce a list of core treatable traits using arbitrary cut-off points, for example a prevalence of >5%, a significant risk of exacerbations (determined by adjusted incident rate ratio) as well as variable airflow obstruction, and treatment responsiveness. Using this hypothetical triage schema, the core treatable traits for severe asthma might include eosinophilic inflammation, prone to exacerbation, variable airflow obstruction, upper airway disease, vocal cord dysfunction, obstructive sleep apnoea, depression, anxiety and polypharmacy. A similar list could be derived for nonsevere asthma, with perhaps the exclusion of vocal cord dysfunction and obstructive sleep apnoea. A way forward would be to determine how to develop a practical system whereby each of the core traits is systematically addressed, utilizing the natural progression of enquiry within a clinical consultation, and then proceeding to targeted investigations, with the resources that are available. The system needs to be flexible enough to ensure that non-core traits of importance in individual patients might also be recognized in a clinical consultation, for example in adult-onset asthma, enquiry as to occupational exposures would be a mandatory requirement. The final step is to link such assessment with treatment recommendations, in which each