Abstract We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.
Several criteria exist for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) as eosinophilic or non-eosinophilic. This study attempted to evaluate several criteria for defining eosinophilic CRSwNP from clinical and immunological perspectives.A cohort of 84 patients (73 patients with CRSwNP and 11 control patients) was retrospectively analyzed. Patients were divided into eosinophilic and non-eosinophilic CRSwNP based on four different criteria: eosinophils (EOS) accounting for more than 20% of the total inflammatory cells; ≥70 EOS per high-power field (HPF); >55 EOS/HPF; and ≥10 EOS/HPF. Preoperative clinical characteristics, the immunological profiles of 14 cytokines from nasal tissue, and postoperative outcomes were compared between eosinophilic and non-eosinophilic CRSwNP based on each criterion. These criteria were immunologically validated by using 14 cytokines to predict the performance of tissue eosinophilia with a random forest model.Patients with eosinophilic CRSwNP were significantly older when the criterion of ≥10 EOS/HPF or EOS >20% was used. The number of patients with aspirin intolerance was significantly higher in eosinophilic CRSwNP based on the criterion of EOS >20%. From an immunological perspective, non-type 2 inflammatory cytokines were significantly higher in non-eosinophilic CRSwNP with the criterion of EOS >20% of the total inflammatory cells. In addition, the criterion of EOS >20% of the total inflammatory cells resulted in the best prediction of eosinophilic CRSwNP, with an accuracy of 88.10% and area under the curve of 0.94.Clinical and immunological characteristics were different between eosinophilic and non-eosinophilic CRSwNP depending on a variety of criteria, and the.of this study should be taken into account when choosing the criterion for defining eosinophilic CRSwNP and interpreting the data accordingly.
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