Annals of Allergy Asthma & Immunology最新文献

Background: Gestational diabetes mellitus (GDM) is associated with systemic processes that may disrupt fetal development and contribute to suboptimal lung function in offspring. Distinct from respiratory conditions such as asthma, lung function is a broad indicator of respiratory health and is predictive of long-term health outcomes. GDM has previously been associated with childhood asthma, but studies on childhood lung function are sparse.

Objective: To evaluate the association between GDM and respiratory outcomes in children, including lung function, wheeze, and asthma.

Methods: We studied mother-child dyads enrolled in a prospective pregnancy cohort (births 2007-2011) and followed to child age 8 to 9 years. We assessed GDM by chart review and measured child lung function using spirometry, characterizing the following outcomes: forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), FEV₁/FVC, and forced expiratory flow between 25% and 75% of vital capacity (FEF_25-75) (n = 722). We used multiple linear regression to evaluate associations between GDM and lung function z-scores. Then, we assessed child current asthma and wheeze by questionnaire (n = 892) and evaluated their association with GDM using multivariable logistic regression.

Results: GDM was identified in 6% of pregnancies. In children, median (IQR) FEV₁, FVC, FEV₁/FVC, and FEF_25-75 z-scores were -0.47 (-1.14, 0.22), -0.41 (-1.11, 0.31), -0.08 (-0.83, 0.61), and -0.34 (-1.02, 0.38), respectively. With adjustment, GDM-exposed children had lower FEV₁ (β = -0.28 [95% CI: -0.55, -0.00]) and FEF_25-75 (β = -0.43 [95% CI: -0.76, -0.10]) and increased odds of current asthma (odds ratio = 3.12 [95% CI: 1.55, 6.28]) compared with unexposed children. We observed no differences in other lung function measures.

Conclusion: GDM may be a risk factor for decreased lung function and childhood asthma.

Background: Undetectable IgE levels are a frequent feature of common variable immunodeficiency (CVID). However, not much is known regarding the role of IgE levels as a prognostic factor in patients with CVID.

Objective: To evaluate whether undetectable IgE levels would be associated with higher risk of noninfectious complications of CVID.

Methods: We compared clinical and laboratory outcomes in 60 patients with CVID with detectable IgE and 89 patients with CVID with undetectable IgE.

Results: Undetectable IgE was associated with significantly lower IgG, IgM, and IgA concentrations. In addition, these patients had significantly lower numbers of CD4+ T cells, total B cells, plasmablasts, and reduced memory and especially switch memory B cells, but no difference in CD21low B cells. Undetectable IgE was associated with a significantly higher frequency of autoimmune cytopenias and lymphoma and trends toward higher relative frequencies of serious bacterial infections and granulomatous disease.

Conclusion: Undetectable IgE is a readily available biomarker that in a patient with CVID may direct clinicians to be particularly vigilant for noninfectious complications of CVID.

Background: The airway epithelium is the primary structural and functional airway barrier and orchestrates innate immunity. Some children may have underlying epithelial vulnerabilities that contribute to the pathogenesis of acute wheeze and asthma (AWA).

Objective: To investigate the pediatric AWA epithelial environment and responses at time of exacerbation to elucidate cellular vulnerabilities; thus, a differentiated in vitro model with differentiated cell types is required.

Methods: Here, feasibility of establishing a differentiated model of primary nasal epithelial cells from children presenting to hospital with AWA was assessed. This was followed by examination of mucociliary differentiation, barrier integrity and function, viral receptor expression, and appropriate pro-inflammatory and antiviral cytokines compared with nasal epithelial cells derived from children who were non-wheezing non-atopic and non-wheezing with positive atopy.

Results: A differentiated pediatric AWA model was established with interparticipant heterogeneity reflected appropriately. The AWA model was of epithelial lineage and had mucociliary differentiation, barrier integrity and function, viral receptor expression, and the production of innate immune cytokines. However, the AWA epithelium had a more permeable paracellular barrier, higher expression of rhinovirus receptor ICAM1, intrinsically higher levels of pro-inflammatory and antiviral cytokines IL-6, IL-8, CCL5, CXCL10, and IFNL1, and potentially fewer cilia. Relationships between demographic and clinical data and AWA epithelial parameters were also identified.

Conclusion: Collectively, a differentiated epithelial model of pediatric AWA was established, and results indicated underlying epithelial vulnerabilities in these children. This platform may be used to investigate the role of the AWA epithelium in pathogen infections, disease etiology, and therapeutic pipelines.