Severe asthma: Phenotyping to endotyping or vice versa?

The most recent definition of asthma is that it is a heterogeneous disease, usually characterised by chronic airway inflammation, defined by a history of chronic respiratory symptoms that vary over time, both in frequency and intensity, and associated with variable airflow limitation [1]. Admittedly, asthma is used as an umbrella term, like anaemia, arthritis and cancer. This highlights the importance of taking an individualised approach to a patient's diagnosis and management, using genomics, proteomics, and “humanomics” as emphasised in the GINA guidelines [2]. The vague definition reflects our poor understanding of the underlying mechanisms of the disease, particularly of its more severe expressions. In the guidelines, they are included in steps 4 and 5 of treatment. This might imply that so-called severe asthma is at the extreme of a continuum of severity, something which has never been demonstrated in prospective studies. In contrast to this concept are the observations that: 1) the vast majority of asthmatics (>95%) are treatable [1] and have little if any excessive risk of progression or death [3]; 2) severe asthma improves through intervention on modifiable risk factors [4], particularly because of its undertreatment [1, 5]; and 3) mortality for asthma is not increased nor increasing [6, 7]. Nonetheless, severe asthma is a major health and social burden, even in childhood and adolescence [1, 8].