Severe acute asthma at the pediatric intensive care unit: can we link the clinical phenotypes to immunological endotypes?

Figures & data

Table 1. Studies assessing risk factors for severe acute asthma at PICU

Study	Design	Patients	Controls	Age range (years)	Gender	Ethnicity	Age	Previous admission	ICS	Patient delay	Weight	Atopy	IgE	ETS
81	Case–control	Children ventilated for severe acute asthma	Children with non-life threatening exacerbation	1–16	Matched	Matched	Matched	+^1	+	nm	nm	+^2	nm^3	-
17	Case–control	Children with severe acute asthma at PICU	Children with non-life threatening exacerbation	1–16	-	Matched	-	+^4	nm	+	-	+^5	+	ns
22	Retrospective	Children with severe acute asthma at PICU	Children with mild asthma at PICU	2–18	ns	+^6	+^7	+^7	nm	nm	-	nm	nm	nm
16	Retrospective case–control	Children with severe acute asthma at PICU	Children with non-life threatening exacerbation	Unclear	Male preponderance	+^8	nm	+	-	nm	nm	+	nm	+
18	Prospective cohort	Children with severe acute asthma at PICU	Children with non-life threatening exacerbation	1–16	-	-	>4 years	+^9	+	nm	nm	+	+	+
4	Retrospective cohort study	Patients with severe acute asthma admitted to the PICU	Patients with severe acute asthma admitted to a general ward	2–18	-	+^10	2–4 years	+	+^11	nm	nm	-	-	-

Table 2. Immunological endotypes

Group	Endotype	Triggers	Cellular component	Biomarkers	Clinical characteristics
Type 2 High
	Allergic eosinophilic	Allergens	Airway epithelial cells, Type 2 lymphocytes, eosinophils	IL-4, IL-5, IL-13, alarmins (IL-25 and IL-33), TSLP*, IgE	Common in children. Moderate-to-good response to corticosteroids. Atopic association.
	Non-allergic eosinophilic	Pollutants, microbes	Airway epithelial cells, Innate lymphoid cells (ILCs) Eosinophils	Alarmins (IL-25, IL-33), TSLP, prostaglandin D2	Less common in children. Relatively insensitive to steroids.
Type 2 Low
	Paucigranulocytic	Environmental factors (tobacco smoke), allergens		Oxidative stress	Insensitive to corticosteroids.
	Neutrophilic	Microbes, viruses	Th17 lymphocytes Neutrophils	Il-8, IL-17, Il-21, IL-22	Bacterial airway colonization. Relatively insensitive to steroids.

IL, interleukin; TSLP, thymic stromal lymphopoetin.

Figure 1. Potential precision medicine strategies for severe acute asthma at the PICU. Immunophenotyping might help to monitor disease, diagnose type of asthma and/or guide treatement. Eo, eosinophil; FENO, fraction of exhaled nitric oxide; IL, interleukin, ILC2, type 2 innate lymphoid cells; Th2, T helper 2 cell.