Background The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animals models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. Methods We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. Results Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyperresponsiveness in response to methacholine indistinguishable from eosinophilic wild type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon restoration of peripheral eosinophils. Conclusions Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses.

Background In the age of COVID-19 and enforced social distancing, changes in patterns of trauma were observed but poorly understood. Our aim was to characterize traumatic injury mechanisms and acuities in 2020 and compare to years prior at our Level 1 trauma center. Materials and Methods Trauma patients triaged in 2016 through 2020 from January to May were reviewed. Patient demographics, level of activation (1 vs. 2), ISS, and mechanism of injury were collected. Data from 2016 through 2019 was combined, averaged by month, and compared to data from 2020 using Chi-squared analysis. Results During the months of interest, 992 trauma patients were triaged in 2020 and 4,311 in 2016-2019. The numbers of penetrating and Level 1 trauma activations in January – March of 2020 were similar to average numbers for the same months during 2016 through 2019. In April 2020, there was a significant increase in incidence of penetrating trauma compared to the prior four-year average (27% vs. 16%, p<0.002). Level 1 trauma activations in April 2020 also increased, rising from 17% in 2016 through 2019 to 32% in 2020 (p<0.003). These findings persisted through May of 2020 with similarly significant increases in penetrating and high-level trauma. Conclusion In the months after the initial spread of COVID-19, there was a perceptible shift in patterns of trauma. The significant increase in penetrating and high acuity trauma may implicate a change in population dynamics, demanding a need for thoughtful resource allocation at trauma centers nationwide in the context of a global pandemic.

No abstract

No abstract