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16. Circulating Metabolic Profile in Idiopathic Pulmonary Fibrosis: Data from the IPF-PRO Registry

Author

Summer, Ross, Todd, Jamie, Neely, Megan, Lobo, L. Jason, Namen, Andrew, Newby, L. Kristin, Shafazand, Shirin, Suliman, Sally, Hesslinger, Christian, Keller, Sascha, Leonard, Thomas, Palmer, Scott M, Ilkayeva, Olga, Muehlbauer, Michael, Newgard, Christopher, Roman, Jesse, Summer, Ross, Todd, Jamie, Neely, Megan, Lobo, L. Jason, Namen, Andrew, Newby, L. Kristin, Shafazand, Shirin, Suliman, Sally, Hesslinger, Christian, Keller, Sascha, Leonard, Thomas, Palmer, Scott M, Ilkayeva, Olga, Muehlbauer, Michael, Newgard, Christopher, and Roman, Jesse

Abstract

BACKGROUND: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF. METHODS: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF and controls and to determine associations between metabolite levels and measures of disease severity in patients with IPF. Unadjusted and adjusted univariable Cox regression models were used to evaluate associations between circulating metabolites and the risk of mortality or disease progression among patients with IPF. RESULTS: Levels of 64 metabolites and 5 clinical analytes were significantly different between patients with IPF and controls. Among analytes with greatest differences were non-esterified fatty acids, multiple long-chain acylcarnitines, and select ceramides, levels of which were higher among patients with IPF versus controls. Levels of the branched-chain amino acids valine and leucine/isoleucine were inversely correlated with measures of disease severity. After adjusting for clinical factors known to influence outcomes, higher levels of the acylcarnitine C:16-OH/C:14-DC were associated with all-cause mortality, lower levels of the acylcarnitine C16:1-OH/C14:1DC were associated with all-cause mortality, respiratory death, and respiratory death or lung transplant, and higher levels of the sphingomyelin d43:2 were associated with the risk of respiratory death or lung transplantation. CONCLUSIONS: IPF has a distinct circulating metabolic profile characterized by increased

Published
2024

22. Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry

Author

Summer, Ross, primary, Todd, Jamie L., additional, Neely, Megan L., additional, Lobo, L. Jason, additional, Namen, Andrew, additional, Newby, L. Kristin, additional, Shafazand, Shirin, additional, Suliman, Sally, additional, Hesslinger, Christian, additional, Keller, Sascha, additional, Leonard, Thomas B., additional, Palmer, Scott M., additional, Ilkayeva, Olga, additional, Muehlbauer, Michael J., additional, Newgard, Christopher B., additional, and Roman, Jesse, additional

Published
2024
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25. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases

Author

Johnson, Sindhu R., Bernstein, Elana J., Bolster, Marcy B., Chung, Jonathan H., Danoff, Sonye K., George, Michael D., Khanna, Dinesh, Guyatt, Gordon, Mirza, Reza D., Aggarwal, Rohit, Allen, Aberdeen, Assassi, Shervin, Buckley, Lenore, Chami, Hassan A., Corwin, Douglas S., Dellaripa, Paul F., Domsic, Robyn T., Doyle, Tracy J., Falardeau, Catherine Marie, Frech, Tracy M., Gibbons, Fiona K., Hinchcliff, Monique, Johnson, Cheilonda, Kanne, Jeffrey P., Kim, John S., Lim, Sian Yik, Matson, Scott, McMahan, Zsuzsanna H., Merck, Samantha J., Nesbitt, Kiana, Scholand, Mary Beth, Shapiro, Lee, Sharkey, Christine D., Summer, Ross, Varga, John, Warrier, Anil, Agarwal, Sandeep K., Antin‐Ozerkis, Danielle, Bemiss, Bradford, Chowdhary, Vaidehi, Dematte D'Amico, Jane E., Hallowell, Robert, Hinze, Alicia M., Injean, Patil A., Jiwrajka, Nikhil, Joerns, Elena K., Lee, Joyce S., Makol, Ashima, McDermott, Gregory C., Natalini, Jake G., Oldham, Justin M., Saygin, Didem, Lakin, Kimberly Showalter, Singh, Namrata, Solomon, Joshua J., Sparks, Jeffrey A., Turgunbaev, Marat, Vaseer, Samera, Turner, Amy, Uhl, Stacey, and Ivlev, Ilya

Abstract

We provide evidence‐based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high‐resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6‐minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend againstscreening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend againstmonitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Published
2024
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26. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases

Author

Johnson, Sindhu R., Bernstein, Elana J., Bolster, Marcy B., Chung, Jonathan H., Danoff, Sonye K., George, Michael D., Khanna, Dinesh, Guyatt, Gordon, Mirza, Reza D., Aggarwal, Rohit, Allen, Aberdeen, Assassi, Shervin, Buckley, Lenore, Chami, Hassan A., Corwin, Douglas S., Dellaripa, Paul F., Domsic, Robyn T., Doyle, Tracy J., Falardeau, Catherine Marie, Frech, Tracy M., Gibbons, Fiona K., Hinchcliff, Monique, Johnson, Cheilonda, Kanne, Jeffrey P., Kim, John S., Lim, Sian Yik, Matson, Scott, McMahan, Zsuzsanna H., Merck, Samantha J., Nesbitt, Kiana, Scholand, Mary Beth, Shapiro, Lee, Sharkey, Christine D., Summer, Ross, Varga, John, Warrier, Anil, Agarwal, Sandeep K., Antin‐Ozerkis, Danielle, Bemiss, Bradford, Chowdhary, Vaidehi, Dematte D'Amico, Jane E., Hallowell, Robert, Hinze, Alicia M., Injean, Patil A., Jiwrajka, Nikhil, Joerns, Elena K., Lee, Joyce S., Makol, Ashima, McDermott, Gregory C., Natalini, Jake G., Oldham, Justin M., Saygin, Didem, Lakin, Kimberly Showalter, Singh, Namrata, Solomon, Joshua J., Sparks, Jeffrey A., Turgunbaev, Marat, Vaseer, Samera, Turner, Amy, Uhl, Stacey, and Ivlev, Ilya

Abstract

We provide evidence‐based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. Thirty‐five recommendations were generated (including two strong recommendations) for first‐line SARD‐ILD treatment, treatment of SARD‐ILD progression despite first‐line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis–ILD as a first‐line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first‐line ILD treatment in all other SARDs. This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Published
2024
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33. PIMT is a novel and potent suppressor of endothelial activation

Author

Zhang, Chen, primary, Guo, Zhi-Fu, additional, Liu, Wennan, additional, Kazama, Kyosuke, additional, Hu, Louis, additional, Sun, Xiaobo, additional, Wang, Lu, additional, Lee, Hyoungjoo, additional, Lu, Lin, additional, Yang, Xiao-Feng, additional, Summer, Ross, additional, and Sun, Jianxin, additional

Published
2023
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34. All supplemental figures tables and legends from The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria

Author

Schultz, Christopher W., primary, McCarthy, Grace A., primary, Nerwal, Teena, primary, Nevler, Avinoam, primary, DuHadaway, James B., primary, McCoy, Matthew D., primary, Jiang, Wei, primary, Brown, Samantha Z., primary, Goetz, Austin, primary, Jain, Aditi, primary, Calvert, Valerie S., primary, Vishwakarma, Vikalp, primary, Wang, Dezhen, primary, Preet, Ranjan, primary, Cassel, Joel, primary, Summer, Ross, primary, Shaghaghi, Hoora, primary, Pommier, Yves, primary, Baechler, Simone A., primary, Pishvaian, Michael J., primary, Golan, Talia, primary, Yeo, Charles J., primary, Petricoin, Emanuel F., primary, Prendergast, George C., primary, Salvino, Joseph, primary, Singh, Pankaj K., primary, Dixon, Dan A., primary, and Brody, Jonathan R., primary

Published
2023
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48. 68-year old man with progressive weakness and ventilator dependent respiratory failure: a case report of sporadic late onset nemaline myopathy

Author

Kirupaharan, P., Kramer, Daniel, Gandler, Alan, Kenyon, Lawrence C, Summer, Ross, Kirupaharan, P., Kramer, Daniel, Gandler, Alan, Kenyon, Lawrence C, and Summer, Ross

Abstract

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy. Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to our hospital, he was found to have elevated muscle specific enzymes, prompting evaluation for neuromuscular causes of respiratory failure. He was also found to have elevated HMG-CoA Reductase (HMGCR) antibodies. Ultimately, a right quadriceps muscle biopsy was performed and electron microscopy identified nemaline bodies within skeletal myofibers. Given the clinical course and other histopathologic findings, he was diagnosed with Sporadic late-onset nemaline myopathy (SLONM). Conclusion: The diagnosis of neuromuscular disease in patients with ventilator dependent respiratory failure is challenging. A detailed history of a patient's clinical course prior to hospitalization is key and may raise suspicion for underlying neuromuscular pathology. Further evaluation in non-critically ill patients may include pulmonary function, electromyography and confirmatory muscle biopsy. Sporadic late onset nemaline myopathy remains a rare disease entity which rarely presents with respiratory failure and lacks effective treatment.

Published
2022

49. The profibrotic and senescence phenotype of old lung fibroblasts is reversed or ameliorated by genetic and pharmacological manipulation of Slc7a11 expression

Author

Ritzenthaler, Jeffrey D., primary, Torres-Gonzalez, Edilson, additional, Zheng, Yuxuan, additional, Zelko, Igor N., additional, van Berkel, Victor, additional, Nunley, David R., additional, Kidane, Biniam, additional, Halayko, Andrew J., additional, Summer, Ross, additional, Watson, Walter H., additional, and Roman, Jesse, additional

Published
2022
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