The 2025 edition of the American Academy of Allergy, Asthma and Immunology in San Diego provided a backdrop for a review of phenotypes in adult and pediatric asthma, a frequently discussed topic in Allergy/Pulmonary clinics, but always with caveats!
An opening seminar providing insight was entitled “Type 2 and Non-Type-2 Asthma and Beyond.” The clear takeaway message is that in pediatrics, a majority of the asthmatics have high Type-2, with an IL-4/IL-13 axis upregulation and an IL-5 contribution of eosinophilia, at least with pulmonary airway recoverability.
Non-Type 2 pediatric asthma presumably has airway eosinophilia, and — on occasion — peripheral eosinophilia. The triggers of exacerbations of pediatric asthma are often associated with new rhinovirus infection, primarily Rhinovirus C strains, and may have a respiratory syncytial virus origin. Asthma is possible in any child with recurrent wheezing illness and WARI (Wheezing Associated Respiratory illness), as discussed in a later symposium. Clearly, phenotyping of pediatric asthma as High or Low Type-2 is incomplete.
The majority of the seminar focused on adult asthma, with high-Type 2 being a holdover from childhood, and occasionally in young adults, obesity associated asthma, late onset adult asthma, and possibly neutrophilic asthma, although defining that on clinical grounds only is challenging. Leaving bronchioalveolar lavage cellularity recovery aside, clinical phenotyping of adult asthma has gaps, while cluster analysis of the Severe Asthma Program as identified 5 clusters of adult asthma.
A second seminar added to the definitions of phenotyping in children. A comprehensive review of WARI concluded by stating that pediatric asthma exisis is in the eye of the clinician, and no discernible characteristic can point in that direction. Largely, if asthma symptoms with new (rhinovirus) infections last long enough, asthma is likely, and by age 4-6 years, a pulmonary function may clue the likelihood, unless an impulse oscillometer test was available for a younger child. However, if long standing viral triggered wheezing persists without asthma treatment, pulmonary function is affected, possibly for life.
The same session discussed a review of the nasal transcriptome in ethnically consistent pediatric populations. In Puerto Rican and African American asthmatic populations, there was a clear group with High Type 2 in the IL-13 axis, but surprising, a large population of children had a High Helper Type 17 presence, with a neutrophilic gene positioning, and a third group were neither Type was identified. This clearly suggests neutrophils can play a role in pediatric asthma, either on a permanent or temporary basis. Identifying such, though, is not clearly clinically evident. It also re-emphasizes the genetic background of asthma.
The final seminar of interest to asthma phenotypes identification was a session on asthma and obesity. Clearly, obesity rates in many developed countries are increasing, which parallels rises in asthma incidence. Obesity has a clear-cut Type 1 (non-IL-13/IL-4) immunology, including: IL-6, IL-17, and the co-presence of obesity — either in pediatric or adult asthma — often co-exists. The presenters provided a clear picture of the inflammatory and anatomical pressure obesity may have on asthmatic lungs, complicating the phenotypic explanation of any one person’s asthma.
We left the conference with a refined explanation of asthma phenotyping and that phenotypes of asthma may be additive.
Dr Hopp has no conflicts of interest to report.
Illustration by April Brust
