Dataset Information

High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

ABSTRACT: Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4⁺ innate immune cells and another dominated by interferon (IFN)-γ⁺ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10⁺ macrophages. To better understand cellular mediators of severe asthma, we developed the Immune Cell Linkage through Exploratory Matrices (ICLite) algorithm to perform deconvolution of bulk RNA sequencing of mixed-cell populations. Signatures of mitosis and IL-7 signaling in CD206^-FcεRI⁺CD127⁺IL-4⁺ innate cells in one patient group, contrasting with adaptive immune response in T cells in the other, are preserved across technologies. Transcriptional signatures uncovered by ICLite identify T-cell-high and T-cell-poor severe asthma patients in an independent cohort, suggesting broad applicability of our findings.

SUBMITTER: Camiolo MJ

PROVIDER: S-EPMC8133874 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

Camiolo Matthew J MJ Zhou Xiaoying X Oriss Timothy B TB Yan Qi Q Gorry Michael M Horne William W Trudeau John B JB Scholl Kathryn K Chen Wei W Kolls Jay K JK Ray Prabir P Weisel Florian J FJ Weisel Nadine M NM Aghaeepour Nima N Nadeau Kari K Wenzel Sally E SE Ray Anuradha A

Cell reports 20210401 2

Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4<sup>+</sup> innate immune cells and another dominated by interferon (IFN)-γ<sup>+</sup> T cells, including tissue-resident memory cells. In contrast, BAL cells of a h ...[more]

PMID: 33852838

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Project description:IntroductionPrevious studies have demonstrated an association of low socioeconomic status with frequent asthma exacerbations. However, there have been no recent multicenter efforts to examine the relationship of insurance status - a proxy for socioeconomic status - with asthma severity and management in adults. The objective is to investigate chronic and acute asthma management disparities by insurance status among adults requiring emergency department (ED) treatment in the United States.MethodsWe conducted a multicenter chart review study (48 EDs in 23 U.S. states) on ED patients, aged 18-54 years, with acute asthma between 2011 and 2012. Each site underwent training (lecture, practice charts, certification) before reviewing randomly selected charts. We categorized patients into three groups based on their primary health insurance: private, public, and no insurance. Outcome measures were chronic asthma severity (as measured by ≥2 ED visits in one-year period) and management prior to the index ED visit, acute asthma management in the ED, and prescription at ED discharge.ResultsThe analytic cohort comprised 1,928 ED patients with acute asthma. Among these, 33% had private insurance, 40% had public insurance, and 27% had no insurance. Compared to patients with private insurance, those with public insurance or no insurance were more likely to have ≥2 ED visits during the preceding year (35%, 49%, and 45%, respectively; p<0.001). Despite the higher chronic severity, those with no insurance were less likely to have guideline-recommended chronic asthma care - i.e., lower use of inhaled corticosteroids (ICS [41%, 41%, and 29%; p<0.001]) and asthma specialist care (9%, 10%, and 4%; p<0.001). By contrast, there were no significant differences in acute asthma management in the ED - e.g., use of systemic corticosteroids (75%, 79%, and 78%; p=0.08) or initiation of ICS at ED discharge (12%, 12%, and 14%; p=0.57) - by insurance status.ConclusionIn this multicenter observational study of ED patients with acute asthma, we found significant discrepancies in chronic asthma severity and management by insurance status. By contrast, there were no differences in acute asthma management among the insurance groups.

Dataset Information

High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

Publications

High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

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