Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis

作者：Fernando J. Martínez, Eric Yow, Kevin R. Flaherty, Laurie D. Snyder, Michael T. Durheim, Stephen R. Wisniewski, Frank C. Sciurba, Ganesh Raghu, Maria M. Brooks, Dong‐Yun Kim, Daniel F. Dilling, Gerard J. Criner, Hyun Kim, Elizabeth A. Belloli, Anoop M. Nambiar, Mary Beth Scholand, Kevin J. Anstrom, Imre Noth, CleanUP-IPF Investigators of the Pulmonary Trials Cooperative, Rebecca Bascom, Scott Beegle, Nitin Bhatt, Sangeeta Bhorade, Sachin Chaudhary, Daniel A. Culver, Rick Enelow, Leo C. Ginns, Nishant Gupta, Amy Hajari Case, Mark Hamblin, Gary M. Hunninghake, Robert J. Kaner, Christopher S. King, Michelle Kopfinger, Matthew Kottmann, Lisa Lancaster, David J. Lederer, Tracy Luckhardt, Aditi Mathur, Teng Moua, Justin M. Oldham, Rishi Raj, Shelley L. Schmidt, Mary E. Strek, Varsha Taskar, Rade Tomic, Ayodeji Adegunsoye, Kareem Ahmad, Rifat Ahmed, Timothy Albertson, Martha Alemayehu, Theresa Altherr, Maura Alvarez, Sergio Alvarez-Mulett, Michaela R. Anderson, Boleyn R. Andrist, Adeeb Ansari, Abbas Arastu, Shambhu Aryal, Deelan Ayhan, Ken Baker, Misbah Baqir, Edwinia Battle, Stacy Beasley, B. Bemiss, Joanna Beros, Maneesh Bhargava, Jason Biehl, Reba Blissell, Valerie Bloss, Luigi Boccardi, Melissa Boerman, A.M. Bowser, Kelsey Brait, Linda Briggs, Jenna Brinker, Anne Brown, Cameron Brown, Cathy A. Brown, Sean J. Callahan, Jennifer Cannestra, Brenna Cannon, María G. Castro, Atif Choudhury, Sarah Chu, Chelsea Chung, Karen Clark, Michelle Clark, Michele Cohen, Bridget F. Collins, Ashley Collins, Molly Cope, Josefina Corral, Rebecca Cote, A. G. O. Crowther, D. Dacosta, Shannon Daley, Vijaya Dandamudi, Priscilla Dauphin, Lianne De La Cruz, Mandi DeGrote, Jim Del Greco, Maria del Pilar Acosta Lara, Kristina Delaney, Genecelle B. Delossantos, Jane E. Dematte, Tushar Desai, Vickie Desarro, Kathy Dickie, A.E.F. Dimmock, Maria DiSanto‐Rose, Tracy J. Doyle, Sakshi Dua, Puja Dubal, Rosemarie Beckford Dudenhofer, Patricia Durán Bravo, Soheil El-Chemaly, Alana English, Heidi L. Erickson, Mary Rose Evans, Candace Flaherty, Elaine Fletcher, Elena Foster, Grace Gallagher, Semir Garabin, Christy Getty, Ghoncheh Ghiasian, Alex H. Gifford, Penny Gingrich, Jessica Glennie, Hilary J. Goldberg, T. Campbell Goodwin, Chessa Goss, Carla Grabianowski, Sheila Greene, Stephanie M. Greer, Donna Griffiths, Kit Guinan, Swati Gulati, Rohit Gupta, Robert W. Hallowell, Laura L. Hammel, Richart W. Harper, Wanda L Haynes, Margaret Hegarty, Craig A. Henke, Anna Hernandez, Lawrence Ho, Samantha Hughes, Shaelah Huntington, Rebecca Ingledue, Leslie F. Jackson, Susan E Jacobs, James W. Jefferson, Monique D. Johnson, Thyrza Johnson, Maya Juarez, Marc A. Judson, Paige Kallenberger, David Kanarek, John Kim, Mamary Kone, Stephanie Koo, Tejaswini Kulkami, Loseph Lambert, Casssie Larsen, Merte Lemma, Nicole Lewis, Lloyd L. Liang, Daniel M. Libby, Wendy Long, Kimberly M. Lovell, Jim Loyd, Alexandria Lucas, Elizabeth Lyda, Shwu‐Fan Ma, Spring Maleckar, Numaan Malik, Adrija Mamidipalli, Kamesha Mangadi, Matthew Marcelino, Nathaniel Marchetti, Ethan Marrow, Susan Martin, Karen Martin, J Cifrián Martínez, José Luís Martínez, Melina Masihi, Wendi R. Mason, Emiri Matsuda, Karl McCloskey, Francine McGonagle, Tonja Meadows, Mory Mehrtash, Yatin Mehta, Debra Mercy, Lauren E. Miller, Sydney B. Montesi, Joshua J. Mooney, Sasha Moores, Karen Morris, Alicia Morris, Jenna Murray, David J. Nagel, Erin Narewski, Steven D. Nathan, Bhupinder Natt, Deb Nesler, Margaret Nielson, Roseline Nundo-Asari, Onumarekwu Opara, Sarah Owusu, Connie Pace, María Padilla, Aman Pande, Nina Patel, Tessy Paul, D. Perlman, A. Peters, Elizabeth Peters, Maria Planchart, Jennifer Pluhacek, Anna J. Podolanczuk, Mary Pollock, Jaya Prakash Sugunaraj, Katelynn Prodoehl, Sana Quaddus, Luisa Quesada, L.M. Rahimi, Susan Rauch, Luis Felipe Reyes, Manuel Ribeiro-Neto, Richard Rice, Andrea J. Rice, Tammy Roads, Juan Vincente Rodriguez, Iván O. Rosas, Sana Sajjad, Margaret L. Salisbury, Christie Schaeffer, Irma Scholler, Lindsey Schoon, Kelly Shaffer, Timothy Sheehan, Oksana A. Shlobin, Elzard Sikkema, Patricia J. Sime, Silvia E. Smith, Eric T. Smith, Brian D. Southern, Maahika Srinivasan, Shubhra Srivastava-Malhotra, M.K. STEWART, Cheryl Stibbe, Brenda S. Stofan, Scott Sweeten, Linda Tanner-Jones, Chelsea Thompson, Catherine Temme, Leslie Tolle, Diana Valerio, Rachel Vancavage, D. Delgado Vega, D. Venuto, Rekha Vij, Mary Vogt, Rosemary Vojnik, Lindsey Waddoups, James A. Waldron, Alice Wang, Lisa Weaver, Ron Wehrmann, Melessia Wells, Eric S. White, Maxfield Whitehead-Zimmers, F Wilk, Elizabeth Wilkins, Mona Wojtas, Taylor Wong, Xiaoping Wu, Marisol Zarate, Joseph D. Zibrak, Serina Zorilla, Julie Barndad, Katie Kavounis, Antonello Punturieri, Lora A. Reineck, Lisa Viviano, Gail Weinmann, Amanda Baucom, Heather Eng, Chad Karoleski, Vicky Palombizio, Jennifer C. Stevenson, Robert C. Wilson, Joan Albright, Emily Clausen, Joanna Cole, Dahlia Cowhig, Coleen Crespo, Jerry Kirchner, Heather Kuehn, Jay Rao, Qinghong Yang, Michael T. Durheim, Brett Ley, Deborah R. Barnbaum, Gordon R. Bernard, Joao deAndrade, Daren L. Knoell, Andrew H. Limper, Peter K. Lindenauer, André Rogatko, Marinella Temprosa · 发表于：JAMA · 年份：2021 · DOI：10.1001/jama.2021.4956 · 被引用次数：78 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Respiratory and Cough-Related Research、Sarcoidosis and Beryllium Toxicity Research

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective: To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020). Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group. Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care gro...