Childhood haematological and immunoglobulin trajectories and risk of asthma at 18 years.

Abstract

Asthma is an inflammatory airway disease originating in early life, but it is understudied whether childhood trajectories of haematological and immunoglobulin (Ig) measures associate with risk of developing asthma. We modelled trajectories of blood neutrophils, lymphocytes, eosinophils, platelets and Ig (IgE, IgA, IgM and IgG) measured at ages 4, 5, 6, 7, 12 and 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 birth cohort (n=411) and investigated association with asthma diagnosis, airway obstruction using spirometry (forced expiratory volume in 1 s (FEV)) and plethysmography (specific airway resistance (sRaw)), type 2 airway inflammation (fractional exhaled nitric oxide (FeNO)) and airway hyper-responsiveness (AHR) at age 18. We employed linear regression, linear mixed model (LMM) with variable slopes and intercepts and latent class trajectory (LCT) analysis adjusting for relevant confounders. In the LMM analyses, increasing blood neutrophils through childhood (slope, adjusted OR (aOR)=1.30 per 10 cells/L, 95% CI 1.01 to 1.68, p=0.040), higher eosinophils (intercept, aOR=1.51 per 10 cells/L, 95% CI 1.17 to 1.98, p=0.002), higher total IgE and increasing total IgE (intercept, aOR=1.28 per IgE g/L, 95% CI 1.00 to 1.63, p=0.049; slope, aOR=1.37, 95% CI 1.07 to 1.77, p=0.015) were significantly associated with asthma at age 18. Further, higher eosinophils (intercept, beta estimate=3.84 ppb per 10 cells/L, 95% CI 1.53 to 6.15, p=0.001), higher total IgE and increasing total IgE (intercept, beta estimate=3.91 ppb per g/L, 95% CI 1.64 to 6.18, p=0.001; slope, beta estimate=4.84, 95% CI 2.55 to 7.14, p=4.4×10⁵) were associated with higher FeNO, whereas higher platelet count (intercept, beta estimate=-0.07 L per 10 cells/L, 95% CI -0.12 to -0.03, p=0.002) was associated with lower FEVat age 18, and increasing total IgE was associated with increased AHR, that is, lower methacholine dose causing a 20% drop in FEV(slope, beta estimate=-0.75 per g/L, 95% CI -1.24 to -0.27, p=0.002). The LCT models confirmed that specific childhood trajectories of eosinophils and total IgE were associated with higher FeNO levels and increased AHR, and that a specific platelet count trajectory was associated with lower FEV. There were no consistent associations with trajectories of lymphocytes, IgG, IgA or IgM and no associations with sRaw. Trajectories of haematological and Ig measures throughout childhood, particularly platelet counts, eosinophils and total IgE, were associated with airway inflammation, reduced lung function and increased AHR at age 18.