James L Knepler

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Scholarly Contributions

Journals/Publications

• 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.
• Low, S., Sam, A. R., & Knepler, J. L. (2018). ENDOBRONCHIAL VALVES THERAPY FOR ADVANCED EMPHYSEMA: A META-ANALYSIS. JOURNAL OF BRONCHOLOGY AND INTERVENTIONAL PULMONOLGY.
• Knepler, J. L. (2018). Endobronchial Valves Therapy for Advanced Emphysema: A Meta-Analysis of Randomized Trial. Journal of Bronchology & Interventional Pulmonology.
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  AbstractBACKGROUND:Trials suggest that bronchoscopic lung volume reduction (BLVR) with endobronchial valve (EBV) implantation may produce similar effects as lung volume reduction surgery, by inducing atelectasis and reducing hyperinflation through a minimally invasive procedure. This study sought to investigate the efficacy and safety of BLVR with EBV for advanced emphysema.METHODS:We searched PubMed, EMBASE, Web of Science, CINAHL, ClinicalTrials.gov, and Cochrane Library databases for randomized controlled trials comparing EBV implantation versus standard medical treatment or sham bronchoscopy. The main outcome of interest was the percentage change of forced expiratory volume in 1 second.RESULTS:Data analyzed from 5 randomized controlled trials with 703 patients revealed improvement in percentage change of forced expiratory volume in 1 second in EBV group compared with control group [weighted mean difference (WMD)=11.43; 95% confidence interval (CI), 6.05-16.80; P
• Natt, B., Knepler, J. L., Kazui, T., & Mosier, J. M. (2017). The use of extracorporeal membrane oxygenation in the bronchoscopic management of critical upper airway obstruction. J Bronchology Interv Pulmonol, 24(1), e12-e14.
• Natt, B., & Knepler, J. L. (2016). Medical image of the week: endobronchial valves. Southwest Journal of Pulmonary and Critical Care, 13(1), 34-35.
• Natt, B., & Knepler, J. L. (2016). Medical image of the week: lung entrapment. Southwest Journal of Pulmonary and Critical Care, 13(1), 36-37.
• 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.
• Ganesh, A., Omar, M., Knepler, J. L., & Snyder, L. S. (2015). Medical image of the week: nocardiosis. Southwest J Pulm Crit Care.
• Knepler, J. L. (2015). Medical Image of the Week: Carcinoid at the Carina. Southwest Journal of Pulmonary and Critical Care Medicine. doi:http://dx.doi.org/10.13175/swjpcc052-15
• Moller, D. R., Koth, L. L., Maier, L. A., Morris, A., Drake, W., Rossman, M., Leader, J. K., Collman, R. G., Hamzeh, N., Sweiss, N. J., Zhang, Y., O'Neal, S., Senior, R. M., Becich, M., Hochheiser, H. S., Kaminski, N., Wisniewski, S. R., & Gibson, K. F. (2015). Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol. Annals of the American Thoracic Society, 12(10), 1561-71.
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  Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.
• Mosier, J. M., Malo, J., Sakles, J. C., Hypes, C. D., Natt, B., Snyder, L., Knepler, J., Bloom, J. W., Joshi, R., & Knox, K. (2015). The impact of a comprehensive airway management training program for pulmonary and critical care medicine fellows. A three-year experience. Annals of the American Thoracic Society, 12(4), 539-48.
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  Airway management in the intensive care unit (ICU) is challenging, as many patients have limited physiologic reserve and are at risk for clinical deterioration if the airway is not quickly secured. In academic medical centers, ICU intubations are often performed by trainees, making airway management education paramount for pulmonary and critical care trainees.
• Strange, C., Senior, R. M., Sciurba, F., O'Neal, S., Morris, A., Wisniewski, S. R., Bowler, R., Hochheiser, H. S., Becich, M. J., Zhang, Y., Leader, J. K., Methé, B. A., Kaminski, N., & Sandhaus, R. A. (2015). Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals of the American Thoracic Society, 12(10), 1551-60.
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  Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220).

Poster Presentations

• Natt, B., Malo, J., Snyder, L. S., Knepler, J. L., Knox, K. S., & Mosier, J. M. (2015, May/Spring). Advanced Airway Management in Critical Care Fellowship Training. ATS International Conference. Denver, CO.