U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

Abstract

Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

Severe asthma: phenotyping to endotyping or vice versa?

“…Although the authors have already reported clinical and pathological clustering analyses [15], and found four phenotypes not much different from those previously reported [20,21], they reasoned that clustering severe asthma using clinical features may not only not provide a precise definition of severe asthma, but may even preclude the collection of adequate information on the underlying mechanisms of each phenotype. Indeed, significant overlap of inflammatory profiles and inflammatory mechanisms is present across clinical clusters.…”

“…It would be important to revisit the clinical phenotype recently identified from the U-BIOPRED cohort [15] and assess the consistency/concordance with the transcriptomic clusters reported here and evaluate their clinical relevance. A possible validation would be to show differences in outcomes among the three TAC groups in a validation set.…”

“…There is also significant overlap across clinical clusters, inflammatory profiles, and inflammatory mechanisms [1,[14][15][16][17][18]. Severe asthma is likely to represent several endotypes (subtypes of disease defined by a molecular mechanism), each associated with distinct clinical features, divergent underlying molecular mechanisms, and individual treatment responsesendotypes that still need to be defined.…”

“…Severe asthma is likely to represent several endotypes (subtypes of disease defined by a molecular mechanism), each associated with distinct clinical features, divergent underlying molecular mechanisms, and individual treatment responsesendotypes that still need to be defined. Furthermore, although severe asthma can be classified into different phenotypes based on age of onset, atopy, and other parameters determined by clinical, immunological and molecular assessments [1,12,[15][16][17][18], the stability and natural history of these clinical phenotypes are poorly understood. In some cases, severe asthma seems to be severe from the beginning, both in children and adults, while in other cases an event such as viral infection changes a mild asthma phenotype to a much more severe one.…”

“…Because of the size and selection of the subpopulation of asthmatics (only those capable of producing readable sputum), the limited number of control subjects, and the lack of correlation with multiple clinical, biological and translational data and pathological features, the study should be considered exploratory and hypothesis generating. In particular, the results must be considered specific for the type of patients examined, because in some respects they are a selected subgroup of the U-BIOPRED cohort [15,18]. The study could possibly be extended by separately analysing, e.g., smokers and nonsmokers, considering the importance of overlap between asthma and chronic obstructive pulmonary disease [24], selecting patients with different ages of onset, or simply comparing gene profiles in adult-onset severe asthma with those in childhood-onset severe asthma.…”