Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis
Summary: Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exa...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224000567 |
| _version_ | 1827348267429527552 |
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| author | Theodore G. Liou Natalia Argel Fadi Asfour Perry S. Brown Barbara A. Chatfield David R. Cox Cori L. Daines Dixie Durham Jessica A. Francis Barbara Glover My Helms Theresa Heynekamp John R. Hoidal Judy L. Jensen Christiana Kartsonaki Ruth Keogh Carol M. Kopecky Noah Lechtzin Yanping Li Jerimiah Lysinger Osmara Molina Craig Nakamura Kristyn A. Packer Robert Paine, III Katie R. Poch Alexandra L. Quittner Peggy Radford Abby J. Redway Scott D. Sagel Rhonda D. Szczesniak Shawna Sprandel Jennifer L. Taylor-Cousar Jane B. Vroom Ryan Yoshikawa John P. Clancy J. Stuart Elborn Kenneth N. Olivier Frederick R. Adler |
| author_facet | Theodore G. Liou Natalia Argel Fadi Asfour Perry S. Brown Barbara A. Chatfield David R. Cox Cori L. Daines Dixie Durham Jessica A. Francis Barbara Glover My Helms Theresa Heynekamp John R. Hoidal Judy L. Jensen Christiana Kartsonaki Ruth Keogh Carol M. Kopecky Noah Lechtzin Yanping Li Jerimiah Lysinger Osmara Molina Craig Nakamura Kristyn A. Packer Robert Paine, III Katie R. Poch Alexandra L. Quittner Peggy Radford Abby J. Redway Scott D. Sagel Rhonda D. Szczesniak Shawna Sprandel Jennifer L. Taylor-Cousar Jane B. Vroom Ryan Yoshikawa John P. Clancy J. Stuart Elborn Kenneth N. Olivier Frederick R. Adler |
| author_sort | Theodore G. Liou |
| collection | DOAJ |
| description | Summary: Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome. |
| first_indexed | 2024-03-08T00:08:47Z |
| format | Article |
| id | doaj.art-0b6e6acfca2f4e87b4dbc09bc0ef7656 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T00:08:47Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0b6e6acfca2f4e87b4dbc09bc0ef76562024-02-17T06:42:02ZengElsevieriScience2589-00422024-03-01273108835Airway inflammation accelerates pulmonary exacerbations in cystic fibrosisTheodore G. Liou0Natalia Argel1Fadi Asfour2Perry S. Brown3Barbara A. Chatfield4David R. Cox5Cori L. Daines6Dixie Durham7Jessica A. Francis8Barbara Glover9My Helms10Theresa Heynekamp11John R. Hoidal12Judy L. Jensen13Christiana Kartsonaki14Ruth Keogh15Carol M. Kopecky16Noah Lechtzin17Yanping Li18Jerimiah Lysinger19Osmara Molina20Craig Nakamura21Kristyn A. Packer22Robert Paine, III23Katie R. Poch24Alexandra L. Quittner25Peggy Radford26Abby J. Redway27Scott D. Sagel28Rhonda D. Szczesniak29Shawna Sprandel30Jennifer L. Taylor-Cousar31Jane B. Vroom32Ryan Yoshikawa33John P. Clancy34J. Stuart Elborn35Kenneth N. Olivier36Frederick R. Adler37Adult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA; Primary Children’s Cystic Fibrosis Center, Division of Pediatric Pulmonology, Department of Pediatrics, University of Utah, 81 North Mario Capecchi Drive, Salt Lake City, UT 84113, USA; Corresponding authorCystic Fibrosis Center, Phoenix Children’s Hospital, 1919 East Thomas Road, Phoenix, AZ 85016, USAPrimary Children’s Cystic Fibrosis Center, Division of Pediatric Pulmonology, Department of Pediatrics, University of Utah, 81 North Mario Capecchi Drive, Salt Lake City, UT 84113, USASt. Luke’s Cystic Fibrosis Center of Idaho, 610 W. Hays Street, Boise, ID 83702, USAPrimary Children’s Cystic Fibrosis Center, Division of Pediatric Pulmonology, Department of Pediatrics, University of Utah, 81 North Mario Capecchi Drive, Salt Lake City, UT 84113, USANuffield College, 1 New Rd, Oxford OX1 1NF, UKDivision of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, University of Arizona Health Sciences, University of Arizona, 1501 N. Campbell Avenue, Room 3301, PO Box 245073, Tucson, AZ 85724, USANuffield College, 1 New Rd, Oxford OX1 1NF, UKAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USACystic Fibrosis Center, 3006 S. Maryland Pkwy, Suite #315, Las Vegas, NV 89109, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USAAdult Cystic Fibrosis Program, Division of Pulmonary, Critical Care and Sleep Medicine, DoIM MSC10-5550, 1 University of New Mexico, Albuquerque, NM 87131, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USAClinical Trial Service Unit & Epidemiological Studies Unit and Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UKDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UKDepartment of Pediatrics, Children’s Hospital Colorado and University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, Aurora, CO 80045, USADivision of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Baltimore, MD 21205, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USAMontana Cystic Fibrosis Center, Billings Clinic, 2800 10th Avenue N, Billings, MT 59101, USADivision of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, University of Arizona Health Sciences, University of Arizona, 1501 N. Campbell Avenue, Room 3301, PO Box 245073, Tucson, AZ 85724, USACystic Fibrosis Center, 3006 S. Maryland Pkwy, Suite #315, Las Vegas, NV 89109, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USADivision of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USABehavioral Health Systems Research, Miami, FL 33133, USACystic Fibrosis Center, Phoenix Children’s Hospital, 1919 East Thomas Road, Phoenix, AZ 85016, USAAdult Cystic Fibrosis Program, Division of Pulmonary, Critical Care and Sleep Medicine, DoIM MSC10-5550, 1 University of New Mexico, Albuquerque, NM 87131, USADepartment of Pediatrics, Children’s Hospital Colorado and University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, Aurora, CO 80045, USADivision of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAMontana Cystic Fibrosis Center, Billings Clinic, 2800 10th Avenue N, Billings, MT 59101, USADivision of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA; Division of Pulmonology, Department of Pediatrics, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USAAdult Cystic Fibrosis Center, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, 26 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA; Primary Children’s Cystic Fibrosis Center, Division of Pediatric Pulmonology, Department of Pediatrics, University of Utah, 81 North Mario Capecchi Drive, Salt Lake City, UT 84113, USACystic Fibrosis Center, 3006 S. Maryland Pkwy, Suite #315, Las Vegas, NV 89109, USAFormer: Division of Pulmonary Medicine, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USASchool of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Health Sciences Building, Lisburn Rd, Belfast BT9 7AE, UKLaboratory of Chronic Airway Infection, Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health, 10 Center Drive MSC1454, Building 10-CRC, Room 1408A, Bethesda, MD 20892, USADepartment of Mathematics, 155 South 1400 East, University of Utah, Salt Lake City, UT 84112, USA; School of Biological Sciences, 257 South 1400 East, University of Utah, Salt Lake City, UT 84112, USASummary: Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome.http://www.sciencedirect.com/science/article/pii/S2589004224000567Health sciencesMedicineMedical specialtyrespiratory medicineOmics |
| spellingShingle | Theodore G. Liou Natalia Argel Fadi Asfour Perry S. Brown Barbara A. Chatfield David R. Cox Cori L. Daines Dixie Durham Jessica A. Francis Barbara Glover My Helms Theresa Heynekamp John R. Hoidal Judy L. Jensen Christiana Kartsonaki Ruth Keogh Carol M. Kopecky Noah Lechtzin Yanping Li Jerimiah Lysinger Osmara Molina Craig Nakamura Kristyn A. Packer Robert Paine, III Katie R. Poch Alexandra L. Quittner Peggy Radford Abby J. Redway Scott D. Sagel Rhonda D. Szczesniak Shawna Sprandel Jennifer L. Taylor-Cousar Jane B. Vroom Ryan Yoshikawa John P. Clancy J. Stuart Elborn Kenneth N. Olivier Frederick R. Adler Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis iScience Health sciences Medicine Medical specialty respiratory medicine Omics |
| title | Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| title_full | Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| title_fullStr | Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| title_full_unstemmed | Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| title_short | Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| title_sort | airway inflammation accelerates pulmonary exacerbations in cystic fibrosis |
| topic | Health sciences Medicine Medical specialty respiratory medicine Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224000567 |
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