Challenging the paradigm: Moving from umbrella labels to treatable traits in airway disease

Abstract

Airway diseases were initially described by nonspecific patterns of symptoms, for example “dry and wheezy” and “wet and crackly”. The model airway disease is cystic fibrosis, which has progressed from nonspecific reactive treatments such as antibiotics for airway infection to molecular sub-endotype, proactive therapies with an unequivocal evidence base, early diagnosis, and biomarkers of treatment efficacy. Unfortunately, other airway diseases lag behind, not least because nonspecific umbrella labels such as “asthma” are considered to be diagnoses not mere descriptions. Pending the delineation of molecular sub-endotypes in other airway disease the concept of treatable traits, and consideration of airway disease in a wider context is preferable. A treatable trait is a characteristic amenable to therapy, with measurable benefits of treatment. This approach determines what pathology is actually present and treatable, rather than using umbrella labels. We determine if airway inflammation is present, and whether there is airway eosinophilia which will likely respond to inhaled corticosteroids; whether there is variable airflow obstruction due to bronchoconstriction which will respond to β2-agonists; and whether there is unsuspected underlying airway infection which should be treated with antibiotics unless there is an underlying endotype which can be addressed, as for example an immunodeficiency. The context of airway disease should also be extrapulmonary comorbidities, social and environmental factors, and a developmental perspective, particularly this last aspect if preventive strategies are being contemplated. This approach allows targeted treatment for maximal patient benefit, as well as preventing the discarding of therapies which are useful for appropriate subgroups of patients. Failure to appreciate this almost led to the discarding of valuable treatments such as prednisolone.