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Allergic Immune Diseases and the Risk of Mortality Among Patients Hospitalized for Acute Infection*

Verhoef, Philip A. MD, PhD, FACP, FAAP1,2; Bhavani, Sivasubramanium V. MD1; Carey, Kyle A. MPH1; Churpek, Matthew M. MD, MPH, PhD, ATSF1

doi: 10.1097/CCM.0000000000004020
Clinical Investigations

Objectives: The immune response during sepsis remains poorly understood and is likely influenced by the host’s preexisting immunologic comorbidities. Although more than 20% of the U.S. population has an allergic-atopic disease, the type 2 immune response that is overactive in these diseases can also mediate beneficial pro-resolving, tissue-repair functions. Thus, the presence of allergic immunologic comorbidities may be advantageous for patients suffering from sepsis. The objective of this study was to test the hypothesis that comorbid type 2 immune diseases confer protection against morbidity and mortality due to acute infection.

Design: Retrospective cohort study of patients hospitalized with an acute infection between November 2008 and January 2016 using electronic health record data.

Setting: Single tertiary-care academic medical center.

Patients: Admissions to the hospital through the emergency department with likely infection at the time of admission who may or may not have had a type 2 immune-mediated disease, defined as asthma, allergic rhinitis, atopic dermatitis, or food allergy, as determined by International Classification of Diseases, 9th Revision, Clinical Modification codes.

Interventions: None.

Measurements and Main Results: Of 10,789 admissions for infection, 2,578 (24%) had a type 2 disease; these patients were more likely to be female, black, and younger than patients without type 2 diseases. In unadjusted analyses, type 2 patients had decreased odds of dying during the hospitalization (0.47; 95% CI, 0.38–0.59, p < 0.001), while having more than one type 2 disease conferred a dose-dependent reduction in the risk of mortality (p < 0.001). When adjusting for demographics, medications, types of infection, and illness severity, the presence of a type 2 disease remained protective (odds ratio, 0.55; 95% CI, 0.43–0.70; p < 0.001). Similar results were found using a propensity score analysis (odds ratio, 0.57; 95% CI, 0.45–0.71; p < 0.001).

Conclusions: Patients with type 2 diseases admitted with acute infections have reduced mortality, implying that the type 2 immune response is protective in sepsis.

1Department of Medicine, University of Chicago, Chicago, IL.

2Department of Pediatrics, University of Chicago, Chicago, IL.

*See also p.1808.

Drs. Verhoef and Churpek were involved in study concept and design, obtained funding, and supervised the study. Dr. Churpek was involved in acquisition of data. Dr. Verhoef was involved in the first drafting of the article, had full access to all the data in the study, and took responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Carey and Churpek were involved in administrative, technical, and material support. All authors were involved in critical revision of the article for important intellectual content and statistical analysis; analysis and interpretation of data.

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Dr. Verhoef is supported by a career development award from the National Heart, Lung, and Blood Institute (NHLBI) (K08 HL132109) and was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR002389 that funds the Institute for Translational Medicine. Dr. Bhavani is supported by the Research Training in Respiratory Biology award from NHLBI (T32HL007605). Dr. Churpek is supported by a career development award from the NHLBI (K08 HL121080) and an R01 from National Institute of General Medical Sciences (R01 GM123193). Dr. Churpek has a patent pending (ARCD. P0535US.P2) for risk stratification algorithms for hospitalized patients, and he received research support from EarlySense (Tel Aviv, Israel). Drs. Verhoef and Churpek received support for article research from the NIH. Mr. Carey has disclosed that he does not have any potential conflicts of interest.

Address requests for reprints to: Philip A. Verhoef, MD, PhD, FACP, FAAP, Kaiser Permanente Internal Medicine Residency Program, Room 3D04, 2828 Pa'a Street, Honolulu, HI 96819. E-mail:

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