Citations

ABSTRACT Introduction Changes in peripheral eosinophils follow endoscopic sinus surgery (ESS) in chronic rhinosinusitis with nasal polyps (CRSwNP), with and without aspirin sensitivity. Cytometry by time‐of‐flight (CyTOF) identifies more immune cell subsets than conventional assays or clinical testing. We hypothesized that ESS‐associated changes in peripheral immune cell subsets differ between aspirin‐tolerant (AT)‐CRSwNP and aspirin‐exacerbated respiratory disease (AERD) as measured by CyTOF. Methods Pre‐ and post‐ESS peripheral blood from patients with CRSwNP ( n = 13) or with AERD ( n = 15) was analyzed for immune cell populations using a 37‐marker CyTOF panel. CITRUS analysis identified cell clusters most predictive of patient group or sample timepoint. Results In the combined cohort of 28 patients, circulating CD4 + naïve T cells and CD194 + neutrophils increased after ESS, while eosinophils decreased. When stratified by disease, CD4 + naïve T cells increased in both AERD and CRSwNP post‐ESS; however, eosinophils decreased after ESS only in CRSwNP. Neutrophil subsets showed a mixed response in both patient groups after ESS. Dendritic cells increased in CRSwNP but not in AERD after ESS. Individual timepoint analyses showed more CD141 + monocyte‐derived DCs (moDCs) in CRSwNP than in AERD pre‐ and post‐ESS. Pre‐ESS, both CD185 + and CD194 + neutrophils were higher in AERD compared to CRSwNP. Conclusion CD141 + moDCs were more prevalent in CRSwNP versus AERD, both before and after ESS. Naïve CD4 + T cells increased, and neutrophil subsets changed in all groups after ESS, but eosinophils decreased only in CRSwNP. Our study points to possible systemic immune effects of ESS and candidate immune signatures in CRSwNP and AERD.

India saw an unprecedented and rapid rise of invasive coronavirus-associated mucormycosis (CAM) during the delta COVID-19 surge. There is little known about the pathophysiology and if there is a direct causation between the COVID-19 infection and invasive CAM. While the traditional risk factors such as uncontrolled diabetes and other immunocompromising conditions are recognised, there could be several COVID-19-induced phenomena that may predispose the patients to develop CAM and are yet unrecognised. It has been proposed that prior severe COVID-19 is associated with invasive CAM. This could be due to the increased use of immunomodulators or the direct effects of the COVID-19 infection. We report four patients with CAM during the delta surge who did not have prior known COVID-19 infection but on subsequent testing had positive antibodies suggesting past asymptomatic infection. We report the quantitative abnormalities in lymphocyte subsets in all four patients and report CD19+ B cell lymphopenia and reduced percentage of CD27+ CD45RA+ naïve helper T cells. CAM may occur in patients after asymptomatic COVID-19 infection, in the absence of systemic corticosteroid and immunomodulator use, and may reflect underlying immune abnormalities possibly attributable to or unmasked by prior COVID-19 infection.

Background: It remains unclear if asthma is a risk factor associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19). Methods: We performed a comprehensive database search for studies published from January 1, 2019, to October 2, 2020. We included studies that evaluated outcomes among patients with COVID-19 and underlying asthma. Outcomes of interest included the need for hospitalization, length of hospitalization, intensive care unit (ICU) admission, and death. The meta-analysis was conducted by using random-effects methodology. Results: A total of 389 studies were identified through data base searches. After abstract and full-text screening, 16 observational studies with 92,275 patients were included in the analysis. Of the 16 studies, 15 were retrospective and 1 was a prospective cohort study. The average age was 39.6 years, with 48% female patients. Six of the studies included pediatric patients, and one of these studies only evaluated pediatric patients. One study only evaluated pregnant patients. Among patients with COVID-19, the presence of asthma was not associated with any significant increase in risk of hospitalization (odds ratio [OR] 1.46 [95% confidence interval {CI}, 0.29-7.28]), length of hospitalization (1.59 days [‐0.55 to 3.74]), ICU admission (OR 1.65 [95% CI, 0.56-4.17]), or death (OR 0.73 [95% CI, 0.38-1.40]). The overall risk of bias of the included studies was high. Conclusion: Among the patients with COVID-19, asthma did not seem to significantly increase the risk of hospitalization, length of hospitalization, ICU admission, or death.

Objective To provide a comprehensive state‐of‐the‐art review of the emerging role of urine leukotriene E4 (uLTE4) as a biomarker in the diagnosis of chronic rhinosinusitis (CRS), aspirin‐exacerbated respiratory disease (AERD), and asthma. Data Sources Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Review Methods A state‐of‐the‐art review was performed investigating the role of uLTE4 as a diagnostic biomarker, predictor of disease severity, and potential marker of selected therapeutic efficacy. Conclusions uLTE4 has been shown to be a reliable and clinically relevant biomarker for CRS, AERD, and asthma. uLTE4 is helpful in ongoing efforts to better endotype patients with CRS and to predict disease severity. Implications for Practice Aside from being a diagnostic biomarker, uLTE4 is also able to differentiate aspirin‐tolerant patients from patients with AERD and has been associated with objective disease severity in patients with CRS with nasal polyposis. uLTE4 levels have also been shown to predict response to medical therapy, particularly leukotriene‐modifying agents.

ObjectivesUrine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin‐exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin‐tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP.MethodsA retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund‐Mackay CT score, spirometry and lab values) were collected.ResultsAmong the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P< .001), aspirin sensitivity (P< .001), worse Lund‐Mackay CT scores (P= .002) and other objective markers of disease severity including serum IgE (P= .05), presenting blood eosinophil level (P< .001), and the highest recorded eosinophil level (P< .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (Rrange 0.31–0.52) than the aspirin tolerant CRSwNP group (Rrange −0.30–0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores).ConclusionElevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient‐reported symptom measures.Level of Evidence3Laryngoscope, 131:961–966, 2021

A critical goal of multidisciplinary scientific teams is to integrate knowledge from diverse disciplines for the purpose of developing novel insights and innovations. For example, multidisciplinary translational teams (MTTs) which typically include physicians, biologists, statisticians, and informaticians, aim to integrate biological and clinical knowledge leading to innovations for improving health outcomes. However, such teams face numerous barriers in integrating multidisciplinary knowledge, which is further exacerbated by the explosion of molecular and clinical data generated from millions of patients. Here, we explore the use of a visual analytical representation to help MTTs integrate molecular and clinical data with the goal of accelerating translational insights. The results suggest that the visual analytical representation functioned as a “computational evolving boundary object” which (a) evolved through several emergent states that progressively helped integrate diverse disciplinary knowledge, (b) enabled team members to play primary and supportive roles in evolving the data representation resulting in a more egalitarian team structure, and (c) enabled the team to arrive at novel translational insights leading to domain and methodology publications. However, the interventions also revealed limitations in the approach motivating new visual analytical approaches. These results suggest (a) implications for theory related to modeling computational evolving boundary objects (CEBOs) as an instance of team-centered informatics, and (b) implications for practice related to the design and use of interactive features that enable teams to fluidly evolve CEBOs through emergent states, with the goal of deriving novel insights from large multiomics datasets.