Kinki University

The genetic factors contributing to exacerbations in type 2-low asthma are not well understood.

We sought to clarify the association between variants in gasdermin B/orosomucoid-like 3 (GSDMB/ORMDL3) on 17q21 and exacerbations in type 2-low asthma.

This follow-up study of the multicenter Kinki Hokuriku Airway disease Conference (KiHAC) enrolled adults with asthma who were receiving inhaled corticosteroids. It examined associations between asthma exacerbations requiring systemic corticosteroids over 2 years and clinical and genetic factors in patients with the type 2-low endo-genotype, defined by serum periostin levels lower than 95 ng/mL and the IL4RA rs8832 A allele. Exacerbation risks were also evaluated in patients with the type 2-low genotype, defined by both the POSTN rs3829365 C allele and the IL4RA rs8832 A allele, using the KiHAC and replication cohorts. The genetic variant rs7216389 in GSDMB was the primary focus for assessing genetic risk.

A total of 115 patients with the type 2-low endo-genotype were analyzed (mean age, 62 years; 76.5% female). During the 2-year follow-up, 32 patients experienced 1 or more exacerbation. Multivariate analysis identified the rs7216389 TT genotype, recent exacerbations, female sex, and higher body mass index as independent risk factors for asthma exacerbations in patients with the type 2-low endo-genotype. The association between the rs7216389 TT genotype and exacerbations was confirmed in patients with the type 2-low genotype in the KiHAC (n = 89) and replication (n = 125) cohorts.

The rs7216389 TT variant on 17q21 may be an independent risk factor for exacerbations in adults with type 2-low asthma, highlighting the role of GSDMB in its pathophysiology.

Owing to advances in prenatal diagnoses, the overall outcome of congenital diaphragmatic hernia (CDH) can be estimated; however, practical clinical information among CDH survivors for counselling families were lacking. The present study analyzed the overall outcome of prenatally diagnosed left isolated CDH, using a Japanese CDH Study Group (JCDHSG) database.

Prenatally diagnosed patients with left isolated CDH (n = 511), registered in our JCDHSG database from 2006 to 2021 were retrospectively reviewed. Prenatal diagnoses were divided into three categories depending on the observed-to-expected lung-to-head circumference ratio and liver herniation (extremely severe + severe [ES + S], n = 94; moderate [Mo], n = 156, and Mild [Mi], n = 261). The primary outcomes were the survival and intact discharge rates. Intact discharge was defined as CDH survivors without home-based medical care at discharge. The secondary outcomes included the operation timing, ventilation duration, and hospitalization duration.

The overall survival rate at discharge was 86.9 % (444/511). Among survivors at discharge, the intact discharge rate was 80.6 % (358/444). The survival and intact discharge rates varied significantly by disease severity. Among CDH survivors, the median operation timing was consistent across severity grades, however, the median duration of ventilation (26, 20, and 10 days for ES + S, Mo, and Mi, respectively, p < 0.001) and length of hospitalization duration (83, 65, and 39 days for ES + S, Mo, and Mi, respectively, p < 0.001) differed significantly.

Prenatal diagnoses, categorized by disease severity correlated well with the stratified clinical outcomes. These data support accurate prenatal family counselling with prognostic prediction in prenatally diagnosed left isolated CDH patients.

Original Research, Clinical Research.

LEVEL Ⅲ Retrospective Comparative Study.