Development of a Quantitative Measure of Lung Disease Severity in STAT3 Hyper-Ige Syndrome

IntroductionProgressive lung disease remains the leading cause of morbidity and mortality in patients with STAT3 hyper-IgE syndrome (HIES), despite optimal supportive care. Forced expiratory volume in 1 second (FEV1) is a readily available quantitative measure of lung function that is known to predict survival across various lung diseases.MethodsAll FEV1 values (% predicted based on Global Lung Function Initiative equations) from STAT3 HIES patients enrolled in a natural history protocol (NCT00006150) were collected. Measurements were obtained prior to hematopoietic stem cell or lung transplantation, when applicable. A generalized additive model was used to plot the trajectory of FEV1 (% predicted) in the cohort. FEV1 (% predicted) at age 20 years was estimated using a Bayesian approach, and its association with time to death was analyzed using Cox proportional hazards models.ResultsA total of 1,056 FEV1 values (% predicted) were collected from 161 patients with STAT3 HIES. The longitudinal progression of FEV1 (% predicted) with age was modeled and adjusted for known factors affecting lung function, including scoliosis and lung surgery. For further analysis, we focused on patients with at least one FEV1 measurement between age 14 and 30 (n = 111), which enabled estimation of FEV1 (% predicted) at age 20, the physiological peak of lung function, across the cohort. We first showed a strong correlation between observed and estimated FEV1 (% predicted) at age 20 (Spearman’s rho = 0.959, p < 0.001). We then demonstrated that the FEV1 (% predicted) at age 20 significantly correlated with time to death (hazards ratio = 0.962, p = 0.029).ConclusionIn STAT3 HIES, estimated FEV1 (% predicted) at 20 years of age serves as a quantitative measure of lung disease severity and may facilitate identification of patients with extreme lung phenotype for further mechanistic investigation and therapeutic studies.Figure 1.Longitudinal changes in FEV1 with age among patients with STAT3 HIES.