Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis
Sachin Yende, Gina D'Angelo, John A Kellum, Lisa Weissfeld, Jonathan Fine, Robert D Welch, Lan Kong, Melinda Carter, Derek C Angus, GenIMS Investigators, Derek C Angus, John A Kellum, Vincent Arena, Gregory F Cooper, Russell L Delude, Eleanor Feingold, Robert Ferrell, Michael J Fine, David Finegold, Mitchell P Fink, Lan Kong, Alexander Krichevsky, Michael Martino, Michael R Pinsky, Malik Rahim, Mark S Roberts, Andrew Schaefer, Lisa A Weissfeld, Kelly A Wood, Donald M Yealy, Richard G Wunderink, Jonathan M Fine, Kevin J Tracey, Haichao Wang, LiHong Yang, Jason Christie, Richard Bucala, Michael Werdmann, Kathy Nunnink, Larry H Bernstein, Herbert Scherzer, Raymond Haddad, Robert Grant, Roseanne Papa, Caryn St Clair, Beverly Reynholds, Jay Walshon, Tina Null, Lloyd Friedman, Suri Pappu, Louis M Graff, Nancy Bennett, David Buono, Barry Jacobs, Michael McNamme, Stephen Wolf, Michael Carius, Christine Belden, Leonard Scinto, Saraswathi Nair, Steve Holland, Eleanor Flynn, Rose Riordan, Linda C Degutis, Nancy Olson, Peter Jatlow, Mark Siegel, Robert Welch, Denise Waselewsky, Robert Dunne, James Kruse, Kristen Bilicki, Emanuel Rivers, Kant Shah, Christopher Dooley, Jacqueline Anderson, David Laman, Mahapareh Mostoufi, Sandy Ergas, Karen Betcher, Antoinette Furman, Ed Rocker, Bruce MacLeod, Susan Rolniak, Dennis Borochovitz, Ken Greer, Pat Riley, Frank Gaudio, Greg Maggi, Mindy Hufnagel, Christopher DeLuca, Arlene Grogan, Stephen Basheda, Martha Clark, Thomas P Campbell, Diana Morrow, Paul C Fiehler, Stanley Geyer, Richard Heath, Sandra Casey, Emily Yee, Charles Krifcher, Jeffrey Moldovan, Janet Moldovan, Amy Pagano, Ed Castor, Rani K Kumar, Linda Hewitt, Linda Knestaut, Rahut Chaudhry, Ray Probst, William Kristan, Linda Campbell, Carol Hewlett, Mark Provenzano, Joe Kuzma, Ted Delbridge, Mary Ann Murcek, Alan Wells, Jerold Solot, Linda Waddell, Michael Becich, Joel Weinberg, Joel Rosenbloom, Carol Joyce, Sukamal Khasnabis, C Vaughn Strimlan, James Nicholas, Ann Morris, Nancy Gorsha, Mitchell Patti, Jagjit Singh, Meredith Naples, Richard Wunderink, Carol Jones, Lori Kessler, Tammy L Young, Margaret V Bowman, Melinda Carter, Jodi Gigler, Thomas E Auble, Angela Darnley, Karen Greenwald, Lynda J Guzik, Susan Hebda, Tracy Hoteck, Marcia McCaw, Lee Anne Mandich, Tricia A Powell, Angel Shaufl, Heather Sterling, Heather Woods, Javier Martinez, Xia Tang, Dara Greenhouse, Shui He, Jennifer Kreke, Gorkem Saka, Shyam Visweswaran, Xing Yuan, Sachin Yende, Gina D'Angelo, John A Kellum, Lisa Weissfeld, Jonathan Fine, Robert D Welch, Lan Kong, Melinda Carter, Derek C Angus, GenIMS Investigators, Derek C Angus, John A Kellum, Vincent Arena, Gregory F Cooper, Russell L Delude, Eleanor Feingold, Robert Ferrell, Michael J Fine, David Finegold, Mitchell P Fink, Lan Kong, Alexander Krichevsky, Michael Martino, Michael R Pinsky, Malik Rahim, Mark S Roberts, Andrew Schaefer, Lisa A Weissfeld, Kelly A Wood, Donald M Yealy, Richard G Wunderink, Jonathan M Fine, Kevin J Tracey, Haichao Wang, LiHong Yang, Jason Christie, Richard Bucala, Michael Werdmann, Kathy Nunnink, Larry H Bernstein, Herbert Scherzer, Raymond Haddad, Robert Grant, Roseanne Papa, Caryn St Clair, Beverly Reynholds, Jay Walshon, Tina Null, Lloyd Friedman, Suri Pappu, Louis M Graff, Nancy Bennett, David Buono, Barry Jacobs, Michael McNamme, Stephen Wolf, Michael Carius, Christine Belden, Leonard Scinto, Saraswathi Nair, Steve Holland, Eleanor Flynn, Rose Riordan, Linda C Degutis, Nancy Olson, Peter Jatlow, Mark Siegel, Robert Welch, Denise Waselewsky, Robert Dunne, James Kruse, Kristen Bilicki, Emanuel Rivers, Kant Shah, Christopher Dooley, Jacqueline Anderson, David Laman, Mahapareh Mostoufi, Sandy Ergas, Karen Betcher, Antoinette Furman, Ed Rocker, Bruce MacLeod, Susan Rolniak, Dennis Borochovitz, Ken Greer, Pat Riley, Frank Gaudio, Greg Maggi, Mindy Hufnagel, Christopher DeLuca, Arlene Grogan, Stephen Basheda, Martha Clark, Thomas P Campbell, Diana Morrow, Paul C Fiehler, Stanley Geyer, Richard Heath, Sandra Casey, Emily Yee, Charles Krifcher, Jeffrey Moldovan, Janet Moldovan, Amy Pagano, Ed Castor, Rani K Kumar, Linda Hewitt, Linda Knestaut, Rahut Chaudhry, Ray Probst, William Kristan, Linda Campbell, Carol Hewlett, Mark Provenzano, Joe Kuzma, Ted Delbridge, Mary Ann Murcek, Alan Wells, Jerold Solot, Linda Waddell, Michael Becich, Joel Weinberg, Joel Rosenbloom, Carol Joyce, Sukamal Khasnabis, C Vaughn Strimlan, James Nicholas, Ann Morris, Nancy Gorsha, Mitchell Patti, Jagjit Singh, Meredith Naples, Richard Wunderink, Carol Jones, Lori Kessler, Tammy L Young, Margaret V Bowman, Melinda Carter, Jodi Gigler, Thomas E Auble, Angela Darnley, Karen Greenwald, Lynda J Guzik, Susan Hebda, Tracy Hoteck, Marcia McCaw, Lee Anne Mandich, Tricia A Powell, Angel Shaufl, Heather Sterling, Heather Woods, Javier Martinez, Xia Tang, Dara Greenhouse, Shui He, Jennifer Kreke, Gorkem Saka, Shyam Visweswaran, Xing Yuan
Abstract
Rationale: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown.
Objectives: To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes.
Methods: Prospective cohort study at 28 sites.
Measurements and main results: We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008).
Conclusions: Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.
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Source: PubMed