Serum LPC 22:6 is associated with paediatric asthma phenotypes and attenuates HDM-induced airway inflammation

Lipid metabolism is altered in asthma, but the clinical relevance of individual lysophosphatidylcholine (LPC) species across paediatric disease states remains uncertain. We examined serum LPC 22:6 patterns, phenotype associations and effects in allergic airway inflammation. Untargeted serum lipidomics compared independently recruited acute-exacerbation, 1-week post-treatment, remission and non-asthmatic control groups ( n = 30 each). Associations were evaluated in the three asthma groups ( n = 90) using Spearman correlation, covariate-adjusted rank-based partial Spearman correlation and multivariable regression. Functional effects were assessed in house dust mite (HDM)-exposed C57BL/6J mice given intravenous LPC 22:6 at 120 or 240 µg/kg ( n = 12 per group). Twenty-nine annotated LPC species and phosphatidylcholine profiles showed stage-associated distribution patterns across the clinical groups. LPC 22:6 was highest in the 1-week post-treatment group (4.02 [SD 0.64] arbitrary units), compared with acute exacerbation (3.39 [1.13]), remission (2.96 [0.91]) and controls (2.81 [0.94]; overall P < 0.001). Among children with asthma, adjusted partial correlations linked higher LPC 22:6 to higher FEV1/FVC ( r = 0.62, 95% CI 0.46 to 0.73; P < 0.001) and lower FeNO ( r =-0.31; P = 0.004), FnNO ( r =-0.49; P < 0.001) and total IgE ( r =-0.35; P = 0.001). After covariate adjustment, each 1-SD higher LPC 22:6 was associated with a 5.71-percentage-point higher FEV1/FVC (95% CI 4.42 to 6.99; P < 0.001). In HDM-exposed mice, LPC 22:6 reduced pulmonary inflammation, mucus production, serum total IgE, airway hyperresponsiveness and pulmonary inflammatory cytokine responses. Serum LPC 22:6 showed stage-associated variation and was associated with respiratory and inflammatory phenotypes in children with asthma. Experimental LPC 22:6 administration attenuated HDM-induced airway inflammation in mice. These findings nominate a candidate phenotype-associated lipid and warrant longitudinal, targeted and mechanistic studies. Not applicable.