Aeroallergen sensitization, Th2-skewed systemic immunity, and severe pneumonia in hospitalized children: a retrospective cohort study

Background Aeroallergen sensitization is common in children and is associated with a Th2-skewed immune response, but its relationship with community-acquired pneumonia (CAP) severity and systemic immune profiles remains incompletely characterized. This study compared systemic immune-inflammatory profiles and disease severity between sensitized and non-sensitized children hospitalized with CAP. Methods This retrospective cohort study included children aged 6 months to 14 years hospitalized with CAP (January 2019–December 2023). All participants had aeroallergen-specific IgE testing for six inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander, Alternaria alternata, and mixed grass pollen), serum cytokine assays, (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN- γ ), lymphocyte subsets, humoral immunity markers, infection biomarkers, and a respiratory nine-antibody panel. Patients were classified as sensitized or non-sensitized. Co-primary outcomes were wheezing and severe pneumonia. Multivariable logistic regression identified factors associated with severe disease. Results Of 2,351 children screened, 412 were included (median age 4.2 years; 56.3% male); 152 (36.9%) were sensitized. Excluded patients had shorter hospitalization than included patients. Sensitized children had higher rates of wheezing (46.1% vs. 20.8%, P < 0.001) and severe pneumonia (23.7% vs. 12.3%, P = 0.003). The distribution of pathogens identified by serology was similar between groups. Sensitized children had higher total IgE, IL-4, and IL-10 levels, lower IFN- γ levels, a lower IFN- γ /IL-4 ratio, and a higher CD4/CD8 ratio (all P < 0.01). In multivariable analysis, sensitization (aOR 2.08, 95% CI: 1.22–3.54), higher IL-6, and higher CD4/CD8 ratio were associated with severe CAP. Conclusions In this retrospective cohort, aeroallergen sensitization was associated with a Th2-skewed systemic cytokine profile and higher odds of severe pneumonia in children hospitalized with CAP. These associations were not explained by the pathogens identified by serology; however, the IgM panel omitted several common respiratory pathogens and has limited reliability, so definitive etiological conclusions cannot be drawn. Prospective studies with molecular diagnostics are needed to confirm these findings.