Christian Bime

Interests

Teaching

Pulmonary Physiology and PathophysiologyPrinciples of Acute Critical Care

Research

Genetics of Acute Respiratory Distress Syndrome (ARDS)Translational ARDS researchHealth Disparities in ARDSAsthma Clinical TrialsAsthma, Obesity, and Aerobic Exercise

Courses

No activities entered.

Scholarly Contributions

Books

• Bime, C., Gurguis, C. I., Hecker, L., Wang, T., Desai, A., & Garcia, J. G. (2016). MicroRNAs in inflammatory lung diseases. Translating MicroRNAs to the clinic. Elsevier.

Chapters

• Celedon, J. C., & Bime, C. (2020). Respiratory Health in Migrants and Refugees. In Encyclopedia of Respiratory Medicine, 2nd Edition: Samuel Janes : CH 00063. Elsevier. doi:10.1016/B978-0-08-102723-3.00063-9
• Bime, C. (2019). Acute and Chronic Respiratory Failure. In Oncologic Critical Care(pp 1-31). Springer International Publishing.
• Bime, C., Gurguis, C. I., Hecker, L., Hecker, L., Wang, T., Wang, T., Garcia, J. G., Desai, A. A., Desai, A. B., & Desai, A. A. (2017). MicroRNAs in Inflammatory Lung Disease. In Translating MicroRNAs to the Clinic. Academic Press. doi:10.1016/B978-0-12-800553-8.00006-8
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  Inflammatory lung diseases include both acute inflammatory diseases such as acute respiratory distress syndrome (ARDS) and chronic inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis and sarcoidosis. Both acute and chronic inflammatory lung diseases are associated with airway inflammation and are influenced by a combination of environmental, genetic, and epigenetic components. Epigenetic regulation, including microRNA (miRNA), of gene expression contributes to inflammatory lung disease development and severity. With the advancement of “omics” technology, miRNA expression and function in inflammatory lung diseases have been well studied, leading to a clear conclusion that miRNAs are differentially expressed under inflammatory lung disease conditions and contribute to genomic dysregulation in these diseases. Here we summarized the most up-to-date findings of miRNA in the inflammatory lung diseases including asthma, ARDS, COPD, cystic fibrosis, and sarcoidosis, and clinical implications of miRNA in these diseases. miRNAs are valued to be served as biomarkers, diagnostic tools, as well as therapeutic targets of inflammatory lung diseases.
• Bime, C. (2016). Health Disparities in Asthma. In Health Disparities in Respiratory Medicine(pp 173-187). B. L. Gerald and E. C. Berry: Cham, Springer International Publishing.
• Bime, C., Gurguis, C. I., Hecker, L., Wang, T., Desai, A., & Garcia, J. G. (2016). MicroRNAs in inflammatory lung diseases.. In Translating MicroRNAs to the clinic(pp 135-177). Elsevier.

Journals/Publications

• Bermudez, T., Sammani, S., Song, J. H., Hernon, V. R., Kempf, C. L., Garcia, A. N., Burt, J., Hufford, M., Camp, S. M., Cress, A. E., Desai, A. A., Natarajan, V., Jacobson, J. R., Dudek, S. M., Cancio, L. C., Alvarez, J., Rafikov, R., Li, Y., Zhang, D. D., , Casanova, N. G., et al. (2022). eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling. Scientific reports, 12(1), 696.
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  Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.
• Bhakta, N. R., Kaminsky, D. A., Bime, C., Thakur, N., Hall, G. L., McCormack, M. C., & Stanojevic, S. (2022). Addressing Race in Pulmonary Function Testing by Aligning Intent and Evidence With Practice and Perception. Chest, 161(1), 288-297.
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  The practice of using race or ethnicity in medicine to explain differences between individuals is being called into question because it may contribute to biased medical care and research that perpetuates health disparities and structural racism. A commonly cited example is the use of race or ethnicity in the interpretation of pulmonary function test (PFT) results, yet the perspectives of practicing pulmonologists and physiologists are missing from this discussion. This discussion has global relevance for increasingly multicultural communities in which the range of values that represent normal lung function is uncertain. We review the underlying sources of differences in lung function, including those that may be captured by race or ethnicity, and demonstrate how the current practice of PFT measurement and interpretation is imperfect in its ability to describe accurately the relationship between function and health outcomes. We summarize the arguments against using race-specific equations as well as address concerns about removing race from the interpretation of PFT results. Further, we outline knowledge gaps and critical questions that need to be answered to change the current approach of including race or ethnicity in PFT results interpretation thoughtfully. Finally, we propose changes in interpretation strategies and future research to reduce health disparities.
• Garcia, A. N., Casanova, N. G., Valera, D. G., Sun, X., Song, J. H., Kempf, C. L., Moreno-Vinasco, L., Burns, K., Bermudez, T., Valdez, M., Cuellar, G., Gregory, T., Oita, R. C., Hernon, V. R., Barber, C., Camp, S. M., Martin, D., Liu, Z., Bime, C., , Sammani, S., et al. (2022). Involvement of eNAMPT/TLR4 signaling in murine radiation pneumonitis: protection by eNAMPT neutralization. Translational research : the journal of laboratory and clinical medicine, 239, 44-57.
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  Therapeutic strategies to prevent or reduce the severity of radiation pneumonitis are a serious unmet need. We evaluated extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a damage-associated molecular pattern protein (DAMP) and Toll-Like Receptor 4 (TLR4) ligand, as a therapeutic target in murine radiation pneumonitis. Radiation-induced murine and human NAMPT expression was assessed in vitro, in tissues (IHC, biochemistry, imaging), and in plasma. Wild type C57Bl6 mice (WT) and Nampt heterozygous mice were exposed to 20Gy whole thoracic lung irradiation (WTLI) with or without weekly IP injection of IgG (control) or an eNAMPT-neutralizing polyclonal (pAb) or monoclonal antibody (mAb). BAL protein/cells and H&E staining were used to generate a WTLI severity score. Differentially-expressed genes (DEGs)/pathways were identified by RNA sequencing and bioinformatic analyses. Radiation exposure increases in vitro NAMPT expression in lung epithelium (NAMPT promoter activity) and NAMPT lung tissue expression in WTLI-exposed mice. Nampt mice and eNAMPT pAb/mAb-treated mice exhibited significant histologic attenuation of WTLI-mediated lung injury with reduced levels of BAL protein and cells, and plasma levels of eNAMPT, IL-6,  and IL-1β. Genomic and biochemical studies from WTLI-exposed lung tissues highlighted dysregulation of NFkB/cytokine and MAP kinase signaling pathways which were rectified by eNAMPT mAb treatment. The eNAMPT/TLR4 pathway is essentially involved in radiation pathobiology with eNAMPT neutralization an effective therapeutic strategy to reduce the severity of radiation pneumonitis.
• Bose, S., Bime, C., Henderson, R. J., Blake, K. V., Castro, M., DiMango, E., Hanania, N. A., Holbrook, J. T., Irvin, C. G., Kraft, M., Peters, S. P., Reibman, J., Sugar, E. A., Sumino, K., Wise, R. A., Rogers, L., & , A. L. (2021). Biomarkers of Type 2 Airway Inflammation as Predictors of Loss of Asthma Control During Step-Down Therapy for Well-Controlled Disease: The Long-Acting Beta-Agonist Step-Down Study (LASST). The journal of allergy and clinical immunology. In practice, 8(10), 3474-3481.
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  Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking.
• Harris, D. T., Badowski, M., Jernigan, B., Sprissler, R., Edwards, T., Cohen, R., Paul, S., Merchant, N., Weinkauf, C. C., Bime, C., Erickson, H. E., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., Campion, J., , Chopra, M., et al. (2021). SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus. Biomedicines, 9(5).
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  SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
• Iii, A. G., Bime, C., Wisnivesky, J. P., Thakur, N., Shete, P., Sharma, S., Ruvalcaba, E., Roman, J., Riekert, K. A., Pakhale, S., Mageto, Y., Lovinsky-desir, S., Iii, A. G., Holguin, F., George, M., Ferreira, J., Celedon, J. C., Castro, L., Bime, C., & Appell, D. (2021). Enhancing Recruitment and Retention of Minority Populations for Clinical Research in Pulmonary, Critical Care, and Sleep Medicine: An Official American Thoracic Society Research Statement.. American journal of respiratory and critical care medicine, 204(3), e26-e50. doi:10.1164/rccm.202105-1210st
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  Background: Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions without appropriate knowledge of their usefulness in certain populations, and development of recommendations that are not broadly applicable.Goals: To develop best practices for recruitment and retention of racial/ethnic minorities for clinical research in pulmonary, critical care, and sleep medicine.Methods: The American Thoracic Society convened a workshop in May of 2019. This included an international interprofessional group from academia, industry, the NIH, and the U.S. Food and Drug Administration, with expertise ranging from clinical and biomedical research to community-based participatory research methods and patient advocacy. Workshop participants addressed historical and current mistrust of scientific research, systemic bias, and social and structural barriers to minority participation in clinical research. A literature search of PubMed and Google Scholar was performed to support conclusions. The search was not a systematic review of the literature.Results: Barriers at the individual, interpersonal, institutional, and federal/policy levels were identified as limiting to minority participation in clinical research. Through the use of a multilevel framework, workshop participants proposed evidence-based solutions to the identified barriers.Conclusions: To date, minority participation in clinical research is not representative of the U.S. and global populations. This American Thoracic Society research statement identifies potential evidence-based solutions by applying a multilevel framework that is anchored in community engagement methods and patient advocacy.
• Nikolich-zugich, J., Knox, K. S., Garcia, J. G., Casanova, N. G., Camp, S. M., Bime, C., Knox, K. S., Casanova, N. G., Nikolich-zugich, J., Knox, K. S., Garcia, J. G., Casanova, N. G., Camp, S. M., & Bime, C. (2021). Strategies to DAMPen COVID-19-mediated lung and systemic inflammation and vascular injury.. Translational research : the journal of laboratory and clinical medicine, 232, 37-48. doi:10.1016/j.trsl.2020.12.008
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  Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.
• Poeta, M. D., Lutrick, K., Hannun, Y. A., Bime, C., Zhang, H. H., Zec, M. M., You, J. K., Yao, G., Wang, X., Wang, Q., Sprissler, R., Snider, J. M., Snider, A. J., Sergeant, S., Seeds, M. C., Poeta, M. D., Parthasarathy, S., Mccall, C. E., Lutrick, K., , Luberto, C., et al. (2021). Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality.. The Journal of clinical investigation, 131(19). doi:10.1172/jci149236
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  There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.
• Snider, J. M., You, J. K., Wang, X., Snider, A. J., Hallmark, B., Zec, M. M., Seeds, M. C., Sergeant, S., Johnstone, L., Wang, Q., Sprissler, R., Carr, T. F., Lutrick, K., Parthasarathy, S., Bime, C., Zhang, H. H., Luberto, C., Kew, R. R., Hannun, Y. A., , Guerra, S., et al. (2021). Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality. The Journal of clinical investigation, 131(19).
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  There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.
• Sun, B., Sammani, S., Martin, D., Desai, A. A., Valera, D. G., Sun, X., Sun, B., Song, J. H., Sammani, S., Quijada, H., Oita, R. C., Natarajan, V., Moreno-vinasco, L., Mascarenhas, J. B., Martin, D. R., Liu, Z., Kempf, C. L., Jacobson, J. R., Hernon, V. R., , Garcia, J. G., et al. (2021). Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody.. The European respiratory journal, 57(5). doi:10.1183/13993003.02536-2020
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  The severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target..Wild-type C57BL/6J or endothelial cell (EC)-cNAMPT -/- knockout mice (targeted EC NAMPT deletion) were exposed to either a lipopolysaccharide (LPS)-induced ("one-hit") or a combined LPS/ventilator ("two-hit")-induced acute inflammatory lung injury model. A NAMPT-specific monoclonal antibody (mAb) imaging probe (99mTc-ProNamptor) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were used in vitro and in vivo..Immunohistochemical, biochemical and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both pre-clinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb or mAb significantly attenuated inflammatory lung injury (haematoxylin and eosin staining, bronchoalveolar lavage (BAL) protein, BAL polymorphonuclear cells, plasma interleukin-6) in both pre-clinical models. In vitro human lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption. In vivo studies in wild-type and EC-cNAMPT -/- mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both pre-clinical ARDS models..These findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.
• Sun, B., Song, J. H., Mascarenhas, J. B., Liu, Z., Garcia, J. G., Cress, A. E., Bime, C., Valera, D. G., Sun, X., Sun, B., Song, J. H., Sammani, S., Quijada, H., Oita, R. C., Natarajan, V., Moreno-vinasco, L., Mascarenhas, J. B., Martin, D., Liu, Z., , Kempf, C. L., et al. (2021). Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody.. The European respiratory journal, 57(5), 2002536. doi:10.1183/13993003.02536-2020
  More info

  The severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target..Wild-type C57BL/6J or endothelial cell (EC)-cNAMPT -/- knockout mice (targeted EC NAMPT deletion) were exposed to either a lipopolysaccharide (LPS)-induced ("one-hit") or a combined LPS/ventilator ("two-hit")-induced acute inflammatory lung injury model. A NAMPT-specific monoclonal antibody (mAb) imaging probe (99mTc-ProNamptor) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were used in vitro and in vivo..Immunohistochemical, biochemical and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both pre-clinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb or mAb significantly attenuated inflammatory lung injury (haematoxylin and eosin staining, bronchoalveolar lavage (BAL) protein, BAL polymorphonuclear cells, plasma interleukin-6) in both pre-clinical models. In vitro human lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption. In vivo studies in wild-type and EC-cNAMPT -/- mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both pre-clinical ARDS models..These findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.
• Thakur, N., Lovinsky-Desir, S., Appell, D., Bime, C., Castro, L., Celedón, J. C., Ferreira, J., George, M., Mageto, Y., Mainous III, A. G., Pakhale, S., Riekert, K. A., Roman, J., Ruvalcaba, E., Sharma, S., Shete, P., Wisnivesky, J. P., & Holguin, F. (2021). Enhancing Recruitment and Retention of Minority Populations for Clinical Research in Pulmonary, Critical Care, and Sleep Medicine: An Official American Thoracic Society Research Statement. American journal of respiratory and critical care medicine, 204(3), e26-e50.
  More info

  Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions without appropriate knowledge of their usefulness in certain populations, and development of recommendations that are not broadly applicable. To develop best practices for recruitment and retention of racial/ethnic minorities for clinical research in pulmonary, critical care, and sleep medicine. The American Thoracic Society convened a workshop in May of 2019. This included an international interprofessional group from academia, industry, the NIH, and the U.S. Food and Drug Administration, with expertise ranging from clinical and biomedical research to community-based participatory research methods and patient advocacy. Workshop participants addressed historical and current mistrust of scientific research, systemic bias, and social and structural barriers to minority participation in clinical research. A literature search of PubMed and Google Scholar was performed to support conclusions. The search was not a systematic review of the literature. Barriers at the individual, interpersonal, institutional, and federal/policy levels were identified as limiting to minority participation in clinical research. Through the use of a multilevel framework, workshop participants proposed evidence-based solutions to the identified barriers. To date, minority participation in clinical research is not representative of the U.S. and global populations. This American Thoracic Society research statement identifies potential evidence-based solutions by applying a multilevel framework that is anchored in community engagement methods and patient advocacy.
• Weinkauf, C. C., Sprissler, R., Spier, C. M., Sam, A., Rischard, F., Paul, S., Parthasarathy, S., Natt, B., Mosier, J., Merchant, N., Knox, K. S., Knepler, J. L., Jernigan, B., Insel, M., Harris, D. T., Erickson, H. E., Edwards, T., Dake, M. D., Cristan, E., , Cohen, R., et al. (2021). SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus.. Biomedicines, 9(5), 539. doi:10.3390/biomedicines9050539
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  SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
• Weinkauf, C. C., Sprissler, R., Spier, C. M., Sam, A., Rischard, F., Paul, S., Parthasarathy, S., Natt, B., Mosier, J., Merchant, N., Knox, K. S., Knepler, J. L., Jernigan, B., Insel, M., Harris, D. T., Erickson, H. E., Edwards, T., Dake, M. D., Cristan, E., , Cohen, R., et al. (2021). SARS-CoV-2 Rapid Antigen Testing of Symptomatic and Asymptomatic Individuals on the University of Arizona Campus.. Biomedicines, 9(5). doi:10.3390/biomedicines9050539
  More info

  SARS-CoV-2, the cause of COVID19, has caused a pandemic that has infected more than 80 M and killed more than 1.6 M persons worldwide. In the US as of December 2020, it has infected more than 32 M people while causing more than 570,000 deaths. As the pandemic persists, there has been a public demand to reopen schools and university campuses. To consider these demands, it is necessary to rapidly identify those individuals infected with the virus and isolate them so that disease transmission can be stopped. In the present study, we examined the sensitivity of the Quidel Rapid Antigen test for use in screening both symptomatic and asymptomatic individuals at the University of Arizona from June to August 2020. A total of 885 symptomatic and 1551 asymptomatic subjects were assessed by antigen testing and real-time PCR testing. The sensitivity of the test for both symptomatic and asymptomatic persons was between 82 and 90%, with some caveats.
• Witzl, A., Wilson, J., Wilson, C., Welsby, I., Vojnik, R., Tekin, A., Shaw, M., Sen, A., Rogers, A. J., Ribet, J., Reineck, L., Patel, R., Patel, N. M., Nicolau, L., Murray, R., Murray, J. E., Murphy, T., Mosier, J., Moran, K. M., , Matthay, M. A., et al. (2021). The ARREST Pneumonia Clinical Trial. Rationale and Design.. Annals of the American Thoracic Society, 18(4), 698-708. doi:10.1513/annalsats.202009-1115sd
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  Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).
• Bime, C., Camp, S. M., Casanova, N., Oita, R. C., Ndukum, J., Lynn, H., & Garcia, J. G. (2020). The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility. Translational research : the journal of laboratory and clinical medicine, 226, 105-115.
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  Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into "personalized" medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.
• Bime, C., Casanova, N. G., Nikolich-Zugich, J., Knox, K. S., Camp, S. M., & Garcia, J. G. (2020). Strategies to DAMPen COVID-19-mediated lung and systemic inflammation and vascular injury. Translational research : the journal of laboratory and clinical medicine.
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  Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.
• Casanova, N. G., Gonzalez-Garay, M. L., Sun, B., Bime, C., Sun, X., Knox, K. S., Crouser, E. D., Sammani, N., Gonzales, T., Natt, B., Chaudhary, S., Lussier, Y., & Garcia, J. G. (2020). Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas. Respiratory research, 21(1), 321.
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  Despite the availability of multi-"omics" strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.
• Chaudhary, S., Natt, B., Bime, C., Knox, K. S., & Glassberg, M. K. (2020). Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused. Frontiers in medicine, 7, 539.
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  After decades of research, two therapies for chronic fibrotic lung disease are now approved by the FDA, with dozens more anti-fibrotic therapies in the pipeline. A great deal of enthusiasm has been generated for the use of these drugs, which are by no means curative but clearly have a favorable impact on lung function decline over time. Amidst a flurry of newly developed and repurposed drugs to treat the coronavirus disease 2019 (COVID-19) and its accompanying acute respiratory distress syndrome (ARDS), few have emerged as effective. Historically, survivors of severe viral pneumonia and related acute lung injury with ARDS often have near full recovery of lung function. While the pathological findings of the lungs of patients with COVID-19 can be diverse, current reports have shown significant lung fibrosis predominantly in autopsy studies. There is growing enthusiasm to study anti-fibrotic therapy for inevitable lung fibrosis, and clinical trials are underway using currently FDA-approved anti-fibrotic therapies. Given the relatively favorable outcomes of survivors of virus-mediated ARDS and the low prevalence of clinically meaningful lung fibrosis in survivors, this perspective examines if there is a rationale for testing these repurposed antifibrotic agents in COVID-19-associated lung disease.
• Chaudhary, S., Natt, B., Bime, C., Knox, K. S., & Glassberg, M. K. (2020). Corrigendum: Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused. Frontiers in medicine, 7, 604640.
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  [This corrects the article DOI: 10.3389/fmed.2020.00539.].
• Miller, D. C., Bime, C., Partharsarathy, S., & Mosier, J. M. (2020). High-Flow Oxygen Therapy Concepts: Time to Standardize Nomenclature and Avoid Confusion. Journal of intensive care medicine, 35(5), 519-523.
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  High-flow nasal oxygen systems are rapidly being adopted as an initial noninvasive treatment for acute respiratory failure. However, the term "high-flow nasal cannula" is nonspecific and leads to imprecise communication between physicians, respiratory therapists, and nurses with the potential for patient harm. In this viewpoint and a brief review of the technology, we argue for a change in nomenclature in order to reduce the chance for future clinical, administrative, and research misunderstanding surrounding high-flow nasal oxygen systems.
• Miller, D. C., Pu, J., Kukafka, D., & Bime, C. (2020). Failure of High Flow Nasal Cannula and Subsequent Intubation Is Associated With Increased Mortality as Compared to Failure of Non-Invasive Ventilation and Mechanical Ventilation Alone: A Real-World Retrospective Analysis. Journal of intensive care medicine, 885066620968041.
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  Despite the increasing use of high flow nasal cannula oxygenation systems (HFNC) in clinical practice, little is known about its role in all cause respiratory failure as compared to traditional non-invasive ventilation (BiPAP). Furthermore, the effect of HFNC on mortality is unknown.
• Perkins, B., Huckleberry, Y., Bogdanich, I., Leelathanalerk, A., Huckleberry, A., Konecnik, M., Miller, D. C., Bailey, M., & Bime, C. (2020). Evaluation of Inpatient Opioid Prescribing Resulting in Outpatient Opioid Prescriptions for Previously Opioid-Naive Internal Medicine Patients. Journal of pharmacy practice, 897190020961290.
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  Little data exist regarding inpatient opioid prescriptions as a potential contribution to the current opioid crisis. While pain management is essential to inpatient care, the ease of which opioids may be prescribed for all levels of pain may contribute to unnecessary inpatient exposure and new outpatient prescriptions. The aim of this study was to observe patterns of opioid prescribing potentially leading to new opioid prescriptions at hospital discharge for previously opioid-naive patients.
• Quijada, H., Bermudez, T., Kempf, C. L., Valera, D. G., Garcia, A. N., Camp, S. M., Song, J. H., Franco, E., Burt, J. K., Sun, B., Mascarenhas, J. B., Burns, K., Gaber, A., Oita, R. C., Reyes Hernon, V., Barber, C., Moreno-Vinasco, L., Sun, X., Cress, A. E., , Martin, D., et al. (2020). Endothelial eNAMPT Amplifies Preclinical Acute Lung Injury: Efficacy of an eNAMPT-Neutralising mAb. The European respiratory journal.
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  The SARS-CoV-2/COVID-19 pandemic has highlighted the serious unmet need for effective therapies that reduce ARDS mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor 4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target.
• Rajagopal, K., Keller, S. P., Akkanti, B., Bime, C., Loyalka, P., Cheema, F. H., Zwischenberger, J. B., El Banayosy, A., Pappalardo, F., Slaughter, M. S., & Slepian, M. J. (2020). Advanced Pulmonary and Cardiac Support of COVID-19 Patients: Emerging Recommendations From ASAIO-A "Living Working Document". ASAIO journal (American Society for Artificial Internal Organs : 1992), 66(6), 588-598.
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  The severe acute respiratory syndrome (SARS)-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 (COVID)-19 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of COVID-19; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from ASAIO. Of note, this is a "living document," which will be updated periodically, as additional information and understanding emerges.
• Rajagopal, K., Keller, S. P., Akkanti, B., Bime, C., Loyalka, P., Cheema, F. H., Zwischenberger, J. B., El Banayosy, A., Pappalardo, F., Slaughter, M. S., & Slepian, M. J. (2020). Advanced Pulmonary and Cardiac Support of COVID-19 Patients: Emerging Recommendations From ASAIOa Living Working Document. Circulation. Heart failure, 13(5), e007175.
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  The severe acute respiratory syndrome-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of coronavirus disease 2019; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from American Society for Artificial Internal Organs. Of note, this is a living document, which will be updated periodically, as additional information and understanding emerges.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., Aini, T. E., Rischard, F., , Campion, J., et al. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. medRxiv : the preprint server for health sciences.
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  We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
• Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., , Campion, J., et al. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925-933.e4.
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  We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
• Thakur, N., Lovinsky-Desir, S., Bime, C., Wisnivesky, J. P., & Celedón, J. C. (2020). The Structural and Social Determinants of the Racial/Ethnic Disparities in the U.S. COVID-19 Pandemic. What's Our Role?. American journal of respiratory and critical care medicine, 202(7), 943-949.
• Bime, C., Casanova, N., Oita, R. C., Ndukum, J., Lynn, H., Camp, S. M., Lussier, Y., Abraham, I., Carter, D., Miller, E. J., Mekontso-Dessap, A., Downs, C. A., & Garcia, J. G. (2019). Development of a biomarker mortality risk model in acute respiratory distress syndrome. Critical care (London, England), 23(1), 410.
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  There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome.
• Goel, K., Bailey, M., Borgstrom, M., Parthasarathy, S., Natt, B., Berry, C., & Bime, C. (2019). Trends in Chronic Obstructive Pulmonary Disease Hospitalization and In-Hospital Deaths in the United States by Sex: 2005 to 2014. Annals of the American Thoracic Society, 16(3), 391-393.
• Insel, M., Natt, B., Mosier, J., Malo, J., & Bime, C. (2019). The Association of Non-Cardiac ECMO With Influenza Incidence: A Time Series Analysis. Respiratory care, 64(3), 279-284.
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  The 2009 H1N1 influenza epidemic saw a rise in the use of extracorporeal membrane oxygenation (ECMO) as a supportive therapy for refractory ARDS. We sought to determine whether ECMO utilization follows a seasonal pattern that matches the influenza season, and whether it can further be explained by the incidence of each influenza subtype.
• Lynn, H., Sun, X., Casanova, N., Gonzales-Garay, M., Bime, C., & Garcia, J. G. (2019). Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality. Antioxidants & redox signaling, 31(14), 1027-1052.
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  Acute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.
• Bime, C., Malo, J., Mosier, J. M., Natt, B., & Insel, M. (2018). The Association of Non-Cardiac ECMO With Influenza Incidence: A Time Series Analysis.. Respiratory Care.
• Bime, C., Pouladi, N., Sammani, S., Batai, K., Casanova, N., Zhou, T., Kempf, C. L., Sun, X., Camp, S. M., Wang, T., Kittles, R. A., Lussier, Y. A., Jones, T. K., Reilly, J. P., Meyer, N. J., Christie, J. D., Karnes, J. H., Gonzalez-Garay, M., Christiani, D. C., , Yates, C. R., et al. (2018). Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor. American journal of respiratory and critical care medicine, 197(11), 1421-1432.
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  Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches.
• Dill, J., Bixby, B., Ateeli, H., Sarsah, B., Goel, K., Buckley, R., Finkelshteyn, I., Thajudeen, B., Kadambi, P. V., & Bime, C. (2018). Renal replacement therapy in patients with acute respiratory distress syndrome: a single-center retrospective study. International journal of nephrology and renovascular disease, 11, 249-257.
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  Patients with acute respiratory distress syndrome (ARDS) who develop acute kidney injury have increased mortality and frequently require renal replacement therapy (RRT). The optimal timing for initiation of RRT after onset of ARDS to improve survival is not known.
• Gaefke, C. L., Carr, T. F., Borgstrom, M., & Bime, C. (2018). Disparities in Risk of Hospitalization for Food Anaphylaxis in the United States. The Journal of Allergy and Clinical Immunology, 141(2), AB89. doi:10.1016/j.jaci.2017.12.285
• Kempf, C., Bime, C., Pouladi, N., Zhou, T., Sammani, S., Casanova, N., Batai, K., Batai, K., Casanova, N., Sammani, S., Zhou, T., Pouladi, N., Kempf, C., & Bime, C. (2018). GWAS in African Americans identifies the Selectin P Ligand gene, SELPLG, as an ARDS risk gene. American J Respiratory Critical Care Medicine.
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  Rationale: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches.Objectives: To identify genetic susceptibility targets for ARDS.Methods: A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort.Measurements and Main Results: Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg−/− mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation.Conclusions: These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.
• Roman, J., Viegi, G., Schenker, M., Ojeda, V. D., Pérez-Stable, E. J., Nemery, B., Annesi-Maesano, I., Patel, S. R., La Grutta, S., Holguin, F., Moughrabieh, A., Bime, C., Lindberg, A., Migliori, G. B., de Vries, G., Ramírez, J., Aliberti, S., Feldman, C., & Celedón, J. C. (2018). Research Needs on Respiratory Health in Migrant and Refugee Populations. An Official American Thoracic Society and European Respiratory Society Workshop Report. Annals of the American Thoracic Society, 15(11), 1247-1255.
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  Migrants represent a diverse population comprising workers, students, undocumented individuals, and refugees. Worldwide, approximately 1 billion people were considered migrants in 2016. Notably, about 65 million of these migrants were forcibly displaced from their homes, and 20 million were considered refugees. While the geopolitical consequences of such migration continue to be considered, less is known about the impact of these events on the respiratory health of migrants and refugees. In recognition of this knowledge gap, the American Thoracic Society and the European Respiratory Society brought together investigators with diverse and relevant expertise to participate in a workshop and develop a consensus on research needs on the respiratory health of migrants and refugees. The workshop focused on environmental and occupational hazards, chronic noninfectious diseases, and respiratory infectious diseases, which were presented by experts in three distinct sessions, each culminating with panel discussions. A writing committee collected summaries prepared by speakers and other participants, and the information was collated into a single document. Recommendations were formulated, and differences were resolved by discussion and consensus. The group identified important areas of research need, while emphasizing that reducing the burden of pulmonary, critical care, and sleep disorders in migrants and refugees will require a concerted effort by all stakeholders. Using best research practices, considering how research impacts policies affecting migrant and refugee populations, and developing new approaches to engage and fund trainees, clinical investigators, and public health practitioners to conduct high-quality research on respiratory health of migrants and refugees is essential.
• Shrestha, M. P., Bime, C., & Taleban, S. (2018). Decreasing Clostridium difficile-Associated Fatality Rates Among Hospitalized Patients in the United States: 2004-2014. The American journal of medicine, 131(1), 90-96.
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  Clostridium difficile infection has emerged as a major public health problem in the United States over the last 2 decades. We examined the trends in the C. difficile-associated fatality rate, hospital length of stay, and hospital charges over the last decade.
• Bime, C., Fiero, M., Lu, Z., Oren, E., Berry, C. E., Parthasarathy, S., & Garcia, J. G. (2017). High Positive End-Expiratory Pressure Is Associated with Improved Survival in Obese Patients with Acute Respiratory Distress Syndrome. The American journal of medicine, 130(2), 207-213.
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  In acute respiratory distress syndrome, minimizing lung injury from repeated collapse and reopening of alveoli by applying a high positive end-expiratory pressure improves oxygenation without influencing mortality. Obesity causes alveolar atelectasis, thus suggesting that a higher positive end-expiratory pressure might be more protective among the obese. We hypothesized that the effect of applying a high positive end-expiratory pressure on mortality from acute respiratory distress syndrome would differ by obesity status.
• Bime, C., Natt, B., Desai, H., Poongkunran, C., & Borgstrom, M. (2017). Reply: Racial Disparities in Acute Respiratory Distress Syndrome Mortality. Annals of the American Thoracic Society, 14(2), 300-301.
• Dalen, J. E., Alpert, J. S., Dill, J., Desai, H., Dalen, J. E., Bime, C., Bhupinder, N., & Alpert, J. S. (2017). Pulmonary Embolism With Right Ventricular Dysfunction: Who Should Receive Thrombolytic Agents?. Journal of vascular surgery. Venous and lymphatic disorders, 5(2), 298. doi:10.1016/j.jvsv.2017.01.009
• Natt, B., Dalen, J. E., Alpert, J. S., Natt, B., Dill, J., Desai, H., Dalen, J. E., Bime, C., & Alpert, J. S. (2017). Pulmonary Embolism with Right Ventricular Dysfunction: Who Should Receive Thrombolytic Agents?. The American journal of medicine, 130(1), 93.e29-93.e32. doi:10.1016/j.amjmed.2016.07.023
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  Appropriate management of pulmonary embolism patients with right ventricular dysfunction is uncertain. Recent guidelines have stressed the need for more data on the use of thrombolytic agents in the stable pulmonary embolism patient with right ventricular dysfunction. The objective of this study is to investigate the hypothesis that thrombolytic therapy in hemodynamically stable pulmonary embolism patients with right ventricular dysfunction is not associated with improved mortality..We did a retrospective analysis using multi-institutional observational data from the Nationwide Inpatient Sample database. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes were used to identify the patients with pulmonary embolism and right ventricular dysfunction. In-hospital mortality was defined as the primary outcome of interest..Over the 4 years of the study period, 3668 patients with right ventricular dysfunction and pulmonary embolism were found, of which 3253 patients were identified as having hemodynamically stable right-sided heart failure with pulmonary embolism. There was no significant difference in mortality between hemodynamically stable pulmonary embolism patients with right ventricular dysfunction who received thrombolytic agents compared with those who did not. When outcomes were assessed for patients with right ventricular dysfunction and hemodynamic instability, a significant improvement in mortality was noted for patients with right ventricular dysfunction who received thrombolytic agents, which confirmed previous reports that thrombolytic therapy decreases mortality in pulmonary embolism patients who are hemodynamically unstable..Our data support the use of less aggressive treatment for stable pulmonary embolism patients with right ventricular dysfunction. These results argue against the reflexive use of thrombolytic agents in stable pulmonary embolism patients with right ventricular dysfunction.
• Natt, B., Desai, H., Bime, C., Dill, J., Dalen, J. E., & Alpert, J. S. (2017). The Reply. The American journal of medicine, 130(4), e165.
• Shrestha, M. P., Bime, C., & Taleban, S. (2017). Decreasing Clostridium difficile-Associated Fatality Rates Among Hospitalized Patients in the United States: 2004-2014. Am J Med. doi:10.1016/j.amjmed.2017.07.022
• Toosizadeh, N., Berry, C., Bime, C., Najafi, B., Kraft, M., & Mohler, J. (2017). Assessing upper-extremity motion: An innovative method to quantify functional capacity in patients with chronic obstructive pulmonary disease. PloS one, 12(2), e0172766.
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  Assessment of functional capacity is important in directing chronic obstructive pulmonary disease (COPD) care (e.g., rehabilitation and discharge readiness), and in predicting outcomes (e.g., exacerbation, hospitalization, and mortality). The 6-minute walk distance (6MWD) test for functional capacity assessment, may be time-consuming and burdensome.
• Bime, C., Gerald, J. K., Wei, C. Y., Holbrook, J. T., Teague, W. G., Wise, R. A., & Gerald, L. B. (2016). Measurement characteristics of the childhood Asthma-Control Test and a shortened, child-only version. NPJ primary care respiratory medicine, 26, 16075.
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  The childhood Asthma-Control Test (C-ACT) is validated for assessing asthma control in paediatric asthma. Among children aged 4-11 years, the C-ACT requires the simultaneous presence of both parent and child. There is an unmet need for a tool that can be used to assess asthma control in children when parents or caregivers are not present such as in the school setting. We assessed the psychometric properties and estimated the minimally important difference (MID) of the C-ACT and a modified version, comprising only the child responses (C-ACTc). Asthma patients aged 6-11 years (n=161) from a previously completed multicenter randomised trial were included. Demographic information, spirometry and questionnaire scores were obtained at baseline and during follow-up. Participants or their guardians kept a daily asthma diary. Internal consistency reliabilities of the C-ACT and C-ACTc were 0.76 and 0.67 (Cronbach's α), respectively. Test-retest reliabilities of the C-ACT and C-ACTc were 0.72 and 0.66 (intra-class correlation), respectively. Significant correlations were noted between C-ACT scores and ACQ scores (Spearman's correlation r=-0.56, 95% CI (-0.66, -0.44), P
• Bime, C., Poongkunran, C., Borgstrom, M., Natt, B., Desai, H., Parthasarathy, S., & Garcia, J. G. (2016). Racial Differences in Mortality from Severe Acute Respiratory Failure in the United States, 2008-2012. Annals of the American Thoracic Society, 13(12), 2184-2189.
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  Racial disparities in health and healthcare in the United States are well documented and are increasingly recognized in acute critical illnesses such as sepsis and acute respiratory failure.
• Bime, C., Zhou, T., Wang, T., Slepian, M. J., Garcia, J. G., & Hecker, L. (2016). Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis. Pulmonary circulation, 6(2), 196-201.
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  Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)-associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies.
• Desai, H., Natt, B., Bime, C., Dill, J., Dalen, J. E., & Alpert, J. S. (2016). Pulmonary Embolism with Right Ventricular Dysfunction: Who Should Receive Thrombolytic Agents?. The American journal of medicine.
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  Appropriate management of pulmonary embolism patients with right ventricular dysfunction is uncertain. Recent guidelines have stressed the need for more data on the use of thrombolytic agents in the stable pulmonary embolism patient with right ventricular dysfunction. The objective of this study is to investigate the hypothesis that thrombolytic therapy in hemodynamically stable pulmonary embolism patients with right ventricular dysfunction is not associated with improved mortality.
• Desai, H., Natt, B., Kim, S. S., & Bime, C. (2016). Decreased In-hospital Mortality after Lobectomy Using Video-Assisted Thoracoscopic Surgery Compared to Open Thoracotomy.. Annals of American Thoracic Society.
• Desai, H., Natt, B., Kim, S., & Bime, C. (2016). Decreased In-hospital Mortality after Lobectomy Using Video-Assisted Thoracoscopic Surgery Compared to Open Thoracotomy. Annals of the American Thoracic Society.
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  There is a paucity of data regarding the optimal surgical approach for lung lobectomy. Lobectomy performed by video-assisted thoracoscopic surgery (VATS) has been associated with lower morbidity as compared to thoracotomy. However, no multicenter studies have shown improved mortality with VATS lobectomy compared to open surgical lobectomy.
• Ghazala, L., Bime, C., Cortopassi, F., Golden, T., & Berry, C. E. (2016). Inhaler preferences in older adults with chronic lung disease. Southwest Journal of Pulmonary and Critical Care Medicine, 13, 225-234.
• Huthayfa, A., Bime, C., & Gerald, J. K. (2016). Tucson Critical Care Journal Club: Albumin Use in the Critical Care Unit. Southwest J Pulm Crit Care.
• Malaisamy, S., Dalal, B., Bimenyuy, C., & Soubani, A. O. (2016). The clinical and radiologic features of nodular pulmonary sarcoidosis. Lung, 187(1), 9-15.
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  Nodular sarcoidosis is an uncommon presentation of sarcoidosis. Our objective was to describe the clinical characteristics of a large cohort of patients with nodular sarcoidosis.
• Natt, B. S., Desai, H., Singh, N., Poongkunran, C., Parthasarathy, S., & Bime, C. (2016). Extracorporeal Membrane Oxygenation for ARDS: National Trends in the United States 2008-2012. Respiratory care, 61(10), 1293-8.
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  Recent advances in technology and protocols have made the use of extracorporeal membrane oxygenation (ECMO) a viable rescue therapy for patients with ARDS who present with refractory hypoxemia. Despite the lack of strong evidence supporting the use of ECMO in ARDS, its use seems to be increasing. We sought to determine recent trends in the use of ECMO for ARDS. We also assessed trends in mortality among patients with ARDS in whom ECMO was used.
• Natt, B., Natt, B., Desai, H., & Bime, C. (2016). Outcome of Patients With Pulmonary Hypertension Undergoing Elective, Non-Cardiac Surgery: A Propensity-Matched Study. Chest, 150(4), 37A. doi:10.1016/j.chest.2016.08.044
• Pouladi, N., Bime, C., Garcia, J. G., & Lussier, Y. A. (2016). Complex genetics of pulmonary diseases: lessons from genome-wide association studies and next-generation sequencing. Translational research : the journal of laboratory and clinical medicine, 168, 22-39.
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  The advent of high-throughput technologies has provided exceptional assistance for lung scientists to discover novel genetic variants underlying the development and progression of complex lung diseases. However, the discovered variants thus far do not explain much of the estimated heritability of complex lung diseases. Here, we review the literature of successfully used genome-wide association studies (GWASs) and identified the polymorphisms that reproducibly underpin the susceptibility to various noncancerous complex lung diseases or affect therapeutic responses. We also discuss the inherent limitations of GWAS approaches and how the use of next-generation sequencing technologies has furthered our understanding about the genetic determinants of these diseases. Next, we describe the contribution of the metagenomics to understand the interactions of the airways microbiome with lung diseases. We then highlight the urgent need for new integrative genomics-phenomics methods to more effectively interrogate and understand multiple downstream "omics" (eg, chromatin modification patterns). Finally, we address the scarcity of genetic studies addressing under-represented populations such as African Americans and Hispanics.
• Dill, J., Gerald, J. K., Bime, C., & Knepler, J. L. (2015). September 2015 Tucson pulmonary journal club: genomic classifier for lung cancer. .. Southwest J Pulm Crit Care. doi:doi: http://dx.doi.org/10.13175/swjpcc125-15 PDF
• Dill, J., Gerald, J. K., Bime, C., & Knepler, J. L. (2015). Tucson pulmonary journal club: genomic classifier for lung cancer.. Southwest J Pulm Crit Care.
• Dill, J., Gerald, J., & Knepler, J. (2015). A bronchial genomic classifier for the diagnostic evaluation of lung cancer.. Southwest Journal of Pulmonary & Critical Care, 11(3), 119-20.
• Ganesh, A., Bime, C., & Gerald, J. (2015). Fibrinolysis for patients with intermediate-risk pulmonary embolism. Southwest Journal of Pulmonary & Critical Care, 10(2), 97-8.
• Ganesh, A., Bime, C., & Gerald, J. K. (2015). Tucson pulmonary journal club: fibrinolysis for Pulmonary Embolus. Southwest J Pulm Crit Care.
• Gordon, J. S., Berry, C. E., Sekhon, K., Gordon, J. S., Golden, T., Ghazala, L., Gerald, L. B., Bime, C., & Berry, C. E. (2015). Cross Sectional Survey of Electronic Cigarettes Use Among Ambulatory COPD Patients. Chest, 148(4), 1076A. doi:10.1378/chest.2256166
• Hecker, L., Bime, C., Zhou, T., Wang, T., Slepian, M., & Garcia, G. (2015). Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis. Pulmonary Circulation, 0(0).
• Kempf, C., Bime, C., Zhou, T., Pouladi, N., Casanova, N., Sammani, S., Batai, K., Batai, K., Sammani, S., Casanova, N., Pouladi, N., Zhou, T., Kempf, C., & Bime, C. (2018). GWAS in African Americans identifies the Selectin P Ligand gene, SELPLG, as an ARDS risk gene. American J Respiratory Critical Care Medicine.
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  Rationale: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches.Objectives: To identify genetic susceptibility targets for ARDS.Methods: A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort.Measurements and Main Results: Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg−/− mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation.Conclusions: These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.
• Malaisamy, S., Dalal, B., Bimenyuy, C., & Soubani, A. O. (2015). The clinical and radiologic features of nodular pulmonary sarcoidosis. Lung, 187(1), 9-15.
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  Nodular sarcoidosis is an uncommon presentation of sarcoidosis. Our objective was to describe the clinical characteristics of a large cohort of patients with nodular sarcoidosis.
• Natt, B., Poongkunran, C., Singh, N., Poongkunran, C., Natt, B., Desai, H., & Bime, C. (2015). ARDS Prevalence and Survival Trends in the United States; 2008-2012. Chest, 148(4), 1-7. doi:10.1378/chest.2278583
• Natt, B., Poongkunran, C., Singh, N., Raz, Y., Poongkunran, C., Natt, B., Desai, H., & Bime, C. (2015). Extracorporeal Membrane Oxygenator Use in ARDS; Trends From 2008-2012. Chest, 148(4), 292A. doi:10.1378/chest.2278195
• Poongkunran, C., John, S. G., Kannan, A. S., Shetty, S., Bime, C., & Parthasarathy, S. (2015). A meta-analysis of sleep-promoting interventions during critical illness. The American journal of medicine, 128(10), 1126-1137.e1.
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  Sleep quality and quantity are severely reduced in critically ill patients receiving mechanical ventilation with a potential for adverse consequences. Our objective was to synthesize the randomized controlled trials (RCTs) that measured the efficacy of sleep-promoting interventions on sleep quality and quantity in critically ill patients.
• Poongkunran, C., Natt, B., Singh, N., Poongkunran, C., Natt, B., Desai, H., Borgstrom, M., & Bime, C. (2015). 679: INCREASED MORTALITY IN ARDS PATIENTS REQUIRING CONTINUOUS RENAL REPLACEMENT THERAPY. Critical Care Medicine, 43, 171. doi:10.1097/01.ccm.0000474507.38895.79
• Soler, X., Searing, D. A., Santiago, M. T., Morgan, W. J., Knox, K. S., Goodwin, J. L., Ezmigna, D. R., Daines, M. O., Berry, C. E., Zheng, G., Zagaja, V., Yasin, R., Xu, B., Wu, N., Wu, E. Y., Wolf, D., Wise, R. A., Williams, J., Wences, J. A., , Welter, J., et al. (2015). Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial.. JAMA, 313(20), 2033-43. doi:10.1001/jama.2015.5024
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  Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control..To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease..Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24..Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks..The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation..Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement..Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma..clinicaltrials.gov Identifier: NCT01052116.
• Bime, C., Sun, K., Ulliman, E., & Hypes, C. (2014). Medical image of the week: secondary pneumonia presenting as hemoptysis. Southwest J Pulm Crit Care.
• Natt, B., Berry, C. E., Bime, C., & Gerald, J. K. (2014). Tucson critical care journal club: early goal-directed therapy. Southwest J Pulm Crit Care.
• Natt, B., Berry, C. E., Bime, C., & Gerald, J. K. (2014). Tucson critical care journal club: early goal-directed therapy. Southwest Journal of Pulmonary and Critical Care.
• Strawter, C., Berry, C. E., Bime, C., & Gerald, J. K. (2014). Tucson critical care journal club: esmolol in septic shock. Southwest J Pulm Crit Care.
• Bime, C., Nguyen, J., & Wise, R. A. (2012). Measures of asthma control. Current opinion in pulmonary medicine, 18(1), 48-56.
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  Over the past decade, the concept of asthma control as distinct from asthma severity has been clearly defined. Well controlled asthma is the goal of therapy in all asthma patients. This review is a comprehensive description of the tools currently available for a methodical assessment of different aspects of asthma control in clinical practice and research.
• Bime, C., Wei, C. Y., Holbrook, J. T., Sockrider, M. M., Revicki, D. A., & Wise, R. A. (2012). Asthma symptom utility index: reliability, validity, responsiveness, and the minimal important difference in adult asthmatic patients. The Journal of allergy and clinical immunology, 130(5), 1078-84.
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  The evaluation of asthma symptoms is a core outcome measure in asthma clinical research. The Asthma Symptom Utility Index (ASUI) was developed to assess the frequency and severity of asthma symptoms. The psychometric properties of the ASUI are not well characterized, and a minimal important difference (MID) is not established.
• Bime, C., Wei, C. Y., Holbrook, J., Smith, L. J., & Wise, R. A. (2012). Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Primary care respiratory journal : journal of the General Practice Airways Group, 21(4), 398-404.
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  Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations.
• Wise, R. A., Teague, W. G., Nguyen, J. M., Holbrook, J. T., & Bime, C. (2012). Reliability, Validity, and Responsiveness of the Asthma Control Questionnaire among Pediatric Patients. The Journal of Allergy and Clinical Immunology, 129(2), AB206. doi:10.1016/j.jaci.2011.12.194
• Hammad, H., Bimenyuy, C., Rau, S., & Siddiqui, F. (2006). Upper Extremity Venous Thrombosis after Infliximab Therapy. American Journal of Gastroenterology.

Proceedings Publications

• Lynn, H., Liao, S. Y., Garcia, J. G., Casanova, N. G., & Bime, C. (2020). Longitudinal and Multi-Omics Analysis Identified Gene Sets Associated with Acute Respiratory Distress Syndrome Mortality. In C59. DISSECTING ACUTE LUNG INJURY AND ARDS.
• Oita, R. C., Ndukum, J., Miller, E. J., Lynn, H., Lussier, Y. A., Garcia, J. G., Downs, C. A., Dessap, A. M., Casanova, N. G., Carter, D., Camp, S. M., Bime, C., & Abraham, I. (2020). A Prognostic Biomarker-Based Panel for Patient Stratification in Adults with Acute Respiratory Distress Syndrome. In A104. LUNGS, BUGS, AND THE DIAPHRAGM: TRANSLATIONAL STUDIES IN THE ICU.
• Pu, J., Miller, D. C., Kukafka, D., & Bime, C. (2020). Patients with Acute Respiratory Failure Who Fail High Flow Nasal Cannula Before Intubation Have a Higher Mortality Compared to Invasive Mechanical Ventilation Alone. In A40. CRITICAL CARE: FROM HFNC TO ECMO.
• Sammani, S., Oita, R. C., Kempf, C. L., Garcia, J. G., Casanova, N. G., Camp, S. M., & Bime, C. (2020). Selectin P Ligand Gene Knockout Mice (Selplg-/-) Exhibit Attenuated LPS-Induced Lung Injury and Increased Selectin P (Selp) Expression. In A104. LUNGS, BUGS, AND THE DIAPHRAGM: TRANSLATIONAL STUDIES IN THE ICU.
• Casanova, N. G., Sun, X., Lynn, H., Garcia, J. G., Ganay, M. G., Coletta, D., Casanova, N. G., & Bime, C. (2019). The mTOR Pathway Genes Are Differentially Methylated in African- and Hispanic- Americans Who Fail to Survive Acute Respiratory Distress Syndrome (ARDS). In C59. GENETIC AND EPIGENETIC MECHANISMS IN PULMONARY FIBROSIS.
• Miller, D., Johnston, C. B., Insel, M., Fain, M., & Bime, C. (2019). Regional Differences in Do Not Resuscitate Status and Inpatient Mortality Among Patients in US Hospitals: Analysis Using Nationwide Data from 2014. In A22. FACILITATING PALLIATIVE AND END-OF-LIFE CARE.
• Wise, R. A., Wei, C. Y., Sockrider, M., Nguyen, J., Holbrook, J. T., & Bime, C. (2012). Asthma Symptom Utility Index: Reliability, Validity, Responsiveness And The Minimally Important Clinical Difference In Adult Asthma Patients. In D41. DEVELOPING AND IMPROVING MEASURES TO ASSESS AND CHANGE BELIEFS, SKILLS, BEHAVIORS AND OUTCOMES.
• Wise, R. A., Wei, C. Y., Sugar, E. A., & Bime, C. (2012). Repeatability Of Fractional Concentration Of Exhaled Nitric Oxide (FeNO) Using The NIOX MINO And The Agreement Between Two NIOX MINO Machines. In D39. EVALUATION AND MONITORING OF ASTHMA AND COPD.
• Wise, R. A., Wei, C. Y., Smith, L. J., Holbrook, J. T., & Bime, C. (2011). Dietary Intake Of Soy Genistein Is Associated With Asthma Control And Lung Function In Asthma Patients. In C33. CLINICAL PROFILES AND SEVERITY OF ASTHMA.

Presentations

• Bime, C., Gerald, L. B., Stern, D., Garcia, D. L., & Lowe, A. (2018, May). Home based exercise intervention versus remote asthma care guidance via telephone/text message in obese asthmatics. American Thoracic Society International Conference. San Diego, CA: American Thoracic Society.
• Lowe, A., Garcia, D. L., Stern, D., Gerald, L. B., & Bime, C. (2018, May). Feasibility of home based exercise intervention with remote guidance for obese asthmatics. American Thoracic Society International Conference. San Diego, CA: American Thoracic Society.

Poster Presentations

• Shrestha, M. P., Bime, C., & Taleban, S. (2017, Oct/ Fall). Decreasing Clostridium difficile-Associated Mortality Rates Among Hospitalized Patients in the Unites States: 2004-2014. WCOG. Orlando: ACG.
• Desai, H., Natt, B., & Bime, C. (2016, May/Spring). Decreased in-hospital mortality after lobectomy using video-assisted thoracoscopic surgery compared to open thoracotomy. ATS International Conference. San Francisco, CA.
• Berry, C. E., Berry, C. E., Ghazala, L., Ghazala, L., Mohler, M. J., Mohler, M. J., Bime, C., & Bime, C. (2015, June). Frailty features are common in ambulatory patients with COPD and may be associated with respiratory muscle weakness. COPD9USA. Chicago, IL.
• Ghazala*, L., Ghazala*, L., Ghazala*, L., Gordon, J. S., Gordon, J. S., Gordon, J. S., Berry, C. E., Berry, C. E., Berry, C. E., Bime, C., Bime, C., Bime, C., Gerald, L. B., Gerald, L. B., Gerald, L. B., Golden*, T., Golden*, T., Golden*, T., Sekhon*, K., , Sekhon*, K., et al. (2015, October). Cross-section survey of electronic cigarette use among ambulatory COPD patients. CHEST.
• Ghazala, L., Bime, C., Cortopassi, F., Baalachandran, R., Oren, E., Berry, C. E., Ghazala, L., Bime, C., Cortopassi, F., Baalachandran, R., Oren, E., & Berry, C. E. (2015, May). Inhaler Device Preferences In Older Adults With Chronic Lung Disease. American Thoracic Society. Denver, CO.
• Natt, B., Desai, H., Poongkunran, C., & Bime, C. (2015, October/Fall). Extracorporeal Membrane Oxygenator Use in ARDS. CHEST Annual Meeting. Montreal, Québec, Canada.
• Natt, B., Desai, H., Singh, N., Poongkunran, C., & Bime, C. (2015, October/Fall). ARDS Prevalence and Survival Trends in the United States; 2008-2012. CHEST Annual Meeting. Montreal, Québec, Canada.
• Toosizahdeh, N., Berry, C. E., Bime, C., Najafi, B., Mohler, M. J., Toosizahdeh, N., Berry, C. E., Bime, C., Najafi, B., & Mohler, M. J. (2015, May). An Association between Frailty and Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease (COPD) – Application of a Routine Frailty Assessment Approach using Wearable Technology. American Aging Association. Marina del Rey, CA.

Others

• Bime, C., Bhupinder, N., Singh, N., Desai, H., Poongkunran, C., Parthasarathy, S., & Garcia, G. (2015, Jan). Racial and ethnic differences in Acute Respiratory Distress Syndrome mortality in the United States.
• Bime, C., Oren, E., Fierro, M., Berry, C., Parthasarathy, S., & Garcia, G. (2015, Jan). Obesity, Positive End-Expiratory Pressure, and Acute Respiratory Distress Syndrome Survival - Submitted to Journal of Critical Care Medicine. Journal of Critical Care Medicine.
• Bime, C., Wei, R., & Gerald, J. (2015, Jan). Measurement characteristics of the Childhood Asthma Control Test (C-ACT) and a shortened, child-only version (C-ACTc).. Nature Publication Journals Primary Care Respiratory Medicine.
• Natt, B., Singh, N., Desai, H., Poongkunran, C., Parthasarathy, S., & Bime, C. (2015, Jan). Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: National Trends in the United States 2008-2012. Respiratory Care Journal.
• Toosizahdeh, N., Berry, C., Bime, C., Najafi, B., & Mohler, J. (2015, Jan). An Association between Frailty and Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease (COPD) – Application of a Routine Frailty Assessment Approach using Wearable Technology. Journal of COPD.
• Bime, C., Oren, E., Fierro, M., Berry, C., Parthasarathy, S., & Garcia, G. (2015, March). High versus low PEEP and ARDS survival: Effect modification by BMI. ATS 2015 Denver, CO.
• Chazala, L., Bime, C., Baalachandran, R., Cortopassi, F., Oren, E., Golden, T., & Berry, C. (2015, March). Inhaler Device Preferences in Older Adults with Chronic Lung Disease. ATS, Denver, CO.
• Desai, H., Poongkunran, C., Singh, N., & Bime, C. (2016, February). ARDS Prevalence and Survival Trends in the United States; 2008-2012. ACCP 2015 Montreal, Canada.
• H, D., N, B., & N, S. (2015, October). Extracorporeal Membrane Oxygenator use in ARDS; trends from 2008-2012. ACCP 2015 Montreal, Canada.
• Bimenyuy, C., & Kuaban, C. (2001, 2001). The correlation between radiographic aspects of pulmonary tuberculosis and degree of HIV associated immune-suppression. MD. Thesis Presentation FMSB.