Chinh T Nguyen

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Scholarly Contributions

Chapters

• Nguyen, C., & Cross, A. S. (2010). Chapter 63: Fever of Unknown Origin. In Infectious Diseases, Third Edition.

Journals/Publications

• , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , , ., et al. (2022). Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19: A Randomized Controlled Trial. Annals of Internal Medicine, 175(9), 1266-1274. doi:10.7326/m22-1503
• Ampel, N. M., Robey, I., & Nguyen, C. T. (2019). An Analysis of Skin Test Responses to Spherulin-Based Coccidioidin (Spherusol) Among a Group of Subjects with Various Forms of Active Coccidioidomycosis. Mycopathologia, 184(4), 533-538.
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  A reformulated skin test for coccidioidomycosis, Spherusol, was recently approved for use in the USA. We hypothesized that it could be useful in predicting severity of illness and outcome in various types of coccidioidomycosis.
• Ampel, N. M., Robey, I., Nguyen, C. T., Roller, B., August, J., Knox, K. S., & Pappagianis, D. (2019). Cytokine Release, Determined by a Multiplex Cytokine Assay, in Response to Coccidioidal Antigen Stimulation of Whole Blood among Subjects with Recently Diagnosed Primary Pulmonary Coccidioidomycosis. mSphere, 3(3).
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  The elements of the cellular immune response in human coccidioidomycosis remain undefined. We examined the release of an array of inflammatory proteins in response to incubation with a coccidioidal antigen preparation to ascertain which of these might be associated with diagnosis and outcome. Patients with a recent diagnosis of primary pulmonary coccidioidomycosis and a control group of healthy subjects were studied. Blood samples were incubated for 18 h with T27K, a soluble coccidioidal preparation containing multiple glycosylated antigens, and the supernatant was assayed for inflammatory proteins using the multiplex Luminex system. The presentation and course of illness were compared to the levels of the inflammatory proteins. Among the 31 subjects studied, the median time from diagnosis to assay was 15 days. Of the 30 inflammatory proteins measured, the levels of only 7 proteins, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor alpha (IL-1RA), interleukin-1β (IL-1β), interferon gamma (IFN-γ), IL-2, IL-13, and tumor necrosis factor alpha (TNF-α), were more than 10-fold above the levels seen without antigen stimulation. The levels of IFN-γ and IL-2 were significantly elevated in those subjects not receiving triazole antifungal therapy compared to those who were receiving triazole antifungal therapy. While the levels of IL-1RA were nonspecifically elevated, elevated levels of IL-13 were seen only in those with active pulmonary coccidioidomycosis. Only six cytokines were specifically increased in subjects with recently diagnosed primary pulmonary coccidioidomycosis. While IFN-γ, IL-2, and TNF-α have been previously noted, the finding of elevated levels of the innate cytokines GM-CSF and IL-1β could suggest that these, as well as IL-13, are early and specific markers for pulmonary coccidioidomycosis. Coccidioidomycosis, commonly known as Valley fever, is a common pneumonia in the southwestern United States. In this paper, we examined the release of 30 inflammatory proteins in whole-blood samples obtained from persons with coccidioidal pneumonia after the blood samples were incubated with a preparation made from the causative fungus, We found that six of these proteins, all cytokines, were specifically released in high concentrations in these patients. Three of the cytokines were seen very early in disease, and an assay for all six might serve as a marker for the early diagnosis of Valley fever.
• Roller, B., Ampel, N. M., Nguyen, C. T., Pappagianis, D., & Robey, I. F. (2016). Whole blood cytokine analysis in patients with recently diagnosed coccidioidomycosis. Open Forum Infectious Diseases, 3(suppl_1). doi:10.1093/ofid/ofw172.1266
• Ampel, N. M., Chavez, S., Johnson, S. M., Knox, K. S., Nesbit, L. A., Nguyen, C. T., & Pappagianis, D. (2015). Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis.. Clinical and vaccine immunology : CVI, 22(8), 917-22. doi:10.1128/cvi.00280-15
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  The outcome of coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal disseminated coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active coccidioidomycosis (for both, P < 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all, P < 0.05). The cytokine profile among patients with active coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time.
• Ampel, N. M., Johnson, S. M., Nesbit, L. A., Nguyen, C. T., & Pappagianis, D. (2014). 1355Th1 responses in persons with disseminated coccidioidomycosis depend on serology titer and time from diagnosis but Th17 responses are persistent. Open Forum Infectious Diseases, 1(suppl_1), S354-S355. doi:10.1093/ofid/ofu052.901
• Nguyen, C., Lillehoj, E. P., Hyun, S. W., Feng, C., Zhang, L., Liu, A., Guang, W., Sun, W., Luzina, I. G., Webb, T. J., Atamas, S. P., Passatini, A., Twaddel, W. S., Puche, A. C., Wang, L. X., Cross, A. S., & Goldblum, S. E. (2014). Human airway epithelia express catalytically active NEU3 sialidase. Am J Physiol Lung Cell Mol Physiol, 1;3069, L876-86.
• Aw, P. P., Duong, K. T., Farrar, J., Hammond, J., Hibberd, M. L., Hoang, L. T., Huynh, H. L., Javanbakht, H., Klumpp, K., Merson, L., Nagarajan, N., Nguyen, T. T., Nguyen, Q. T., Nguyen, N. M., Nguyen, D. T., Nguyen, C. T., Nguyen, C. V., Petric, R., Pham, M. P., , Phung, L. K., et al. (2013). A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients.. The Journal of infectious diseases, 207(9), 1442-50. doi:10.1093/infdis/jis470
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  Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo..We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with
• Nesbit, L. A., Knox, K. S., Nguyen, C. T., Roesch, J., Wheat, L. J., Johnson, S. M., Pappagianis, D., Chavez, S., & Ampel, N. M. (2013). Immunological Characterization of Bronchoalveolar Lavage Fluid in Patients With Acute Pulmonary Coccidioidomycosis. JOURNAL OF INFECTIOUS DISEASES, 208(5), 857-863.
• Nesbit, L. A., Knox, K. S., Nguyen, C. T., Roesch, J., Wheat, L. J., Johnson, S. M., Pappagianis, D., Chavez, S., & Ampel, N. M. (2013). Immunological characterization of bronchoalveolar lavage fluid in patients with acute pulmonary coccidioidomycosis. The Journal of infectious diseases, 208(5), 857-63.
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  The specific cellular immunological characteristics of bronchoalveolar lavage (BAL) fluid in acute pulmonary coccidioidomycosis have not been defined.
• Nguyen, C., Barker, B. M., Hoover, S., Nix, D. E., Ampel, N. M., Frelinger, J. A., Orbach, M. J., & Galgiani, J. N. (2013). Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis. Clinical microbiology reviews, 26(3), 505-25.
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  Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.
• Nguyen, C., Feng, C., Zhang, L., Vogel, S. N., Goldblum, S. E., Blackwelder, W. C., & Cross, A. S. (2013). Neuraminidase reprograms lung tissue and potentiates lipopolysaccharide-induced acute lung injury in mice. J Immunol.
• Adhikari, R. P., Ajao, A. O., Aman, M. J., Chen, W. H., Johnson, J. K., Karauzum, H., Lydecker, A. D., Nguyen, C., Roghmann, M. C., & Sarwar, J. (2012). Lower antibody levels to Staphylococcus aureus exotoxins are associated with sepsis in hospitalized adults with invasive S. aureus infections.. The Journal of infectious diseases, 206(6), 915-23. doi:10.1093/infdis/jis462
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  Staphylococcus aureus has numerous virulence factors, including exotoxins that may increase the severity of infection. This study was aimed at assessing whether preexisting antibodies to S. aureus toxins are associated with a lower risk of sepsis in adults with S. aureus infection complicated by bacteremia..We prospectively identified adults with S. aureus infection from 4 hospitals in Baltimore, MD, in 2009–2011. We obtained serum samples from prior to or at presentation of S. aureus bacteremia to measure total immunoglobulin G (IgG) and IgG antibody levels to 11 S. aureus exotoxins. Bacterial isolates were tested for the genes encoding S. aureus exotoxins using polymerase chain reaction (PCR)..One hundred eligible subjects were included and 27 of them developed sepsis. When adjusted for total IgG levels and stratified for the presence of toxin in the infecting isolate as appropriate, the risk of sepsis was significantly lower in those patients with higher levels of IgG against α-hemolysin (Hla), δ-hemolysin (Hld), Panton Valentine leukocidin (PVL), staphylococcal enterotoxin C-1 (SEC-1), and phenol-soluble modulin α3 (PSM-α3)..Our results suggest that higher antibody levels against Hla, Hld, PVL, SEC-1, and PSM-α3 may protect against sepsis in patients with invasive S. aureus infections.
• Cross, A. S., Hyun, S. W., Miranda-Ribera, A., Feng, C., Liu, A., Nguyen, C., Zhang, L., Luzina, I. G., Atamas, S. P., Twaddell, W. S., Guang, W., Lillehoj, E. P., Puché, A. C., Huang, W., Wang, L. X., Passaniti, A., & Goldblum, S. E. (2012). NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not. The Journal of biological chemistry, 287(19), 15966-80.
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  The microvascular endothelial surface expresses multiple molecules whose sialylation state regulates multiple aspects of endothelial function. To better regulate these sialoproteins, we asked whether endothelial cells (ECs) might express one or more catalytically active sialidases. Human lung microvascular EC lysates contained heat-labile sialidase activity for a fluorogenic substrate, 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (4-MU-NANA), that was dose-dependently inhibited by the competitive sialidase inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid but not its negative control. The EC lysates also contained sialidase activity for a ganglioside mixture. Using real time RT-PCR to detect mRNAs for the four known mammalian sialidases, NEU1, -2, -3, and -4, NEU1 mRNA was expressed at levels 2700-fold higher that those found for NEU2, -3, or -4. Western analyses indicated NEU1 and -3 protein expression. Using confocal microscopy and flow cytometry, NEU1 was immunolocalized to both the plasma membrane and the perinuclear region. NEU3 was detected both in the cytosol and nucleus. Prior siRNA-mediated knockdown of NEU1 and NEU3 each decreased EC sialidase activity for 4-MU-NANA by >65 and >17%, respectively, and for the ganglioside mixture by 0 and 40%, respectively. NEU1 overexpression in ECs reduced their migration into a wound by >40%, whereas NEU3 overexpression did not. Immunohistochemical studies of normal human tissues immunolocalized NEU1 and NEU3 proteins to both pulmonary and extrapulmonary vascular endothelia. These combined data indicate that human lung microvascular ECs as well as other endothelia express catalytically active NEU1 and NEU3. NEU1 restrains EC migration, whereas NEU3 does not.
• Lillehoj, E. P., Hyun, S. W., Feng, C., Zhang, L., Liu, A., Guang, W., Nguyen, C., Luzina, I. G., Atamas, S. P., Passaniti, A., Twaddell, W. S., Puche, A. C., Wang, L., Cross, A. S., & Goldblum, S. E. (2012). NEU1 Sialidase Expressed in Human Airway Epithelia Regulates Epidermal Growth Factor Receptor (EGFR) and MUC1 Protein Signaling. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(11), 8214-8231.
• Nguyen, C., Feng, C., Zhan, M., Cross, A. S., & Goldblum, S. E. (2012). Bacillus anthracis-derived edema toxin (ET) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway. BMC microbiology, 12, 2.
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  A common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (PMNs) in infected tissues in the face of abundant circulating PMNs. A major virulence determinant of anthrax is edema toxin (ET), which is formed by the combination of two proteins produced by the organism, edema factor (EF), which is an adenyl cyclase, and protective antigen (PA). Since cAMP, a product of adenyl cyclase, is known to enhance endothelial barrier integrity, we asked whether ET might decrease extravasation of PMNs into tissues through closure of the paracellular pathway through which PMNs traverse.

Poster Presentations

• Pappagianis, D., Ampel, N., Nguyen, C., Robey, I., & Roller, B. (2016, Oct). Whole blood cytokine analysis in patients with recently diagnosed coccidioidomycosis. IDWeek 2016. New Orleans, LA: Infectious Diseases Society of America.