TY - JOUR
AU - Fiore-Gartland, Andrew
AU - Panoskaltsis-Mortari, Angela
AU - Agan, Anna A.
AU - Mistry, Anushay J.
AU - Thomas, Paul G.
AU - Matthay, Michael A.
AU - , PALISI PICFlu Investigators
AU - Hertz, Tomer
AU - Randolph, Adrienne G.
AU - Sanders, Ronald C.
AU - Hefley, Glenda
AU - Tellez, David
AU - Bliss, Courtney
AU - Labell, Aimee
AU - Liss, Danielle
AU - Ortiz, Ashley L.
AU - Typpo, Katri
AU - Deschenes, Jen
AU - Markovitz, Barry
AU - Terry, Jeff
AU - Morzov, Rica Sharon P.
AU - Graciano, Ana Lia
AU - Baldwin, Melita
AU - Anas, Nick
AU - Schwarz, Adam
AU - Onwunyi, Chisom
AU - Osborne, Stephanie
AU - Patterson, Tiffany
AU - Vargas-Shiraishi, Ofelia
AU - Sapru, Anil
AU - Convery, Maureen
AU - Lo, Victoria
AU - Flori, Heidi
AU - Brumfield, Becky
AU - Simon, Julie
AU - Czaja, Angela
AU - Mourani, Peter
AU - Aymami, Valeri Batara
AU - Burr, Susanna
AU - Brocato, Megan
AU - Huston, Stephanie
AU - Jewett, Emily
AU - Loyola, Danielle
AU - Carroll, Christopher
AU - Sala, Kathleen
AU - Thornton-Thompson, Sherell
AU - Giuliano, John S.
AU - Tala, Joana
AU - McLaughlin, Gwenn
AU - Paden, Matthew
AU - Manghram, Chee-Chee
AU - Meisner, Stephanie
AU - Stone, Cheryl L.
AU - Wardenburg, Juliane Bubeck
AU - DeDent, Andrea
AU - Montgomery, Vicki
AU - Sullivan, Janice
AU - Evans, Tracy
AU - Richardson, Kara
AU - Thomas, Melissa
AU - Randolph, Adrienne
AU - Agan, Anna A.
AU - Mistry, Anushay J.
AU - Sullivan, Ryan M.
AU - Cobb, Stephanie
AU - Bembea, Melania
AU - White, Elizabeth D.
AU - Kurachek, Stephen
AU - Doucette, Angela A.
AU - Olson, Erin
AU - Hartman, Mary
AU - Jacobs, Rachel
AU - Truemper, Edward
AU - Dawson, Machelle
AU - Levin, Daniel L.
AU - Jarvis, J. Dean
AU - Katyal, Chhavi
AU - Ackerman, Kate
AU - Daugherty, L. Eugene
AU - Baglia, Laurel
AU - Hall, Mark W.
AU - Greathouse, Kristin
AU - Steele, Lisa
AU - Thomas, Neal
AU - Raymond, Jill
AU - Spear, Debra
AU - Fitzgerald, Julie
AU - Helfaer, Mark
AU - Weiss, Scott
AU - Bush, Jenny L.
AU - Diliberto, Mary Ann
AU - Park, Brooke B.
AU - Sisko, Martha
AU - Barr, Frederick E.
AU - Higgerson, Renee
AU - Christie, LeeAnn
AU - Darnell, Cindy
AU - Johnson, Shanda
AU - Loftis, Laura L.
AU - Jaimon, Nancy
AU - Kyle, Ursula
AU - Gedeit, Rainer
AU - Horn, Briana E.
AU - Luther, Kate
AU - Murkowski, Kathy
AU - Willson, Douglas F.
AU - Kelly, Robin L.
AU - Jouvet, Philippe A.
AU - Fontaine, Anne-Marie
AU - Dugas, Marc-André
PY - 2017
M3 - Original Research
TI - Cytokine Profiles of Severe Influenza Virus-Related Complications in Children
JO - Frontiers in Immunology
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2017.01423
VL - 8
SN - 1664-3224
N2 - RationaleEffective immunomodulatory therapies for children with life-threatening “cytokine storm” triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis.ObjectivesTo compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications.MethodsChildren with influenza-related critical illness were enrolled across 32 hospitals in development (N = 171) and validation (N = 73) cohorts (December 2008 through May 2016). Concentrations of 42 cytokines were measured in serum and endotracheal samples and clustered into modules of covarying cytokines. Relative concentrations of cytokines and cytokine modules were tested for associations with acute lung injury (ALI), shock requiring vasopressors, and death/ECMO.Measurements and main resultsModules of covarying cytokines were more significantly associated with disease severity than individual cytokines. In the development cohort, increased levels of a serum module containing IL6, IL8, IL10, IP10, GCSF, MCP1, and MIP1α [shock odds ratio (OR) = 3.37, family-wise error rate (FWER) p < 10−4], and decreased levels of a module containing EGF, FGF2, SCD40L, and PAI-1 (shock OR = 0.43, FWER p = 0.002), were both associated with ALI, shock, and death-ECMO independent of age and bacterial coinfection. Both of these associations were confirmed in the validation cohort. Endotracheal and serum cytokine associations differed markedly and were differentially associated with clinical outcomes.ConclusionWe identified strong positive and negative associations of cytokine modules with the most severe influenza-related complications in children, providing new insights into the pathogenesis of influenza-related critical illness in children. Effective therapies may need to target mediators of both inflammation and repair.
ER -