Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma - 05/11/19
Doi : 10.1016/j.jaci.2019.05.035
Kathryn McCauley, MPH a, Juliana Durack, PhD a, Ricardo Valladares, PhD a, ∗, Douglas W. Fadrosh, MS a, Din L. Lin, PhD a, Agustin Calatroni, PhD b, Petra K. LeBeau, ScD b, Hoang T. Tran, PhD b, Kei E. Fujimura, PhD a, Brandon LaMere, MPH a, Geil Merana, BS a, Kole Lynch, BS a, Robyn T. Cohen, MD c, Jacqueline Pongracic, MD d, Gurjit K. Khurana Hershey, MD, PhD e, Carolyn M. Kercsmar, MD e, Michelle Gill, MD, PhD f, g, Andrew H. Liu, MD h, i, Haejin Kim, MD j, Meyer Kattan, MD k, Stephen J. Teach, MD, MPH l, Alkis Togias, MD m, Homer A. Boushey, MD a, James E. Gern, MD n, Daniel J. Jackson, MD n, ⁎ 
, Susan V. Lynch, PhD a, ⁎
for the
, Susan V. Lynch, PhD a, ⁎ for the
National Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma Consortium
a Department of Medicine, University of California, San Francisco, Calif
b Rho Federal Systems Division, Chapel Hill, NC
c Boston University School of Medicine, Boston, Mass
d Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
e Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio
f Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Tex
g Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Tex
h Department of Pedatrics and Pulmonology Medicine, National Jewish Health, Denver, Colo
i Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colo
j Department of Internal Medicine, Division of Allergy and Immunology, Henry Ford Health System, Detroit, Mich
k College of Physicians and Surgeons, Columbia University, New York, NY
l Children's National Health System, Washington, DC
m National Institute of Allergy and Infectious Diseases, Bethesda, Md
n Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis
∗Corresponding authors: Susan V. Lynch, PhD, Division of Gastroenterology, Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, San Francisco, CA 94143.Division of GastroenterologyDepartment of MedicineUniversity of California San Francisco513 Parnassus Ave, S357DSan FranciscoCA94143∗Daniel J. Jackson, MD, Division of Allergy, Immunology & Rheumatology, Department of Pediatrics, University of Wisconsin Madison, 600 Highland Ave, K4/936 CSC, Madison, WI 53792.Division of Allergy, Immunology & RheumatologyDepartment of PediatricsUniversity of Wisconsin Madison600 Highland Ave, K4/936 CSCMadisonWI53792
Abstract |
Background |
In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.
Objective |
We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.
Methods |
Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses.
Results |
Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species–dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species–dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species–dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested.
Conclusion |
Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Microbiota, Moraxella species, Staphylococcus species, 16S rRNA, airway, asthma, exacerbation, rhinovirus
Abbreviations used : ECP, PROSE, RR, V4
Mappa
| Supported in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under contract and grant numbers HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01, and UM2AI117870. Additional support was provided by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, under grants NIH/NIAID 5R01AI098077; National Center for Advancing Translational Sciences (NCATS)/NIH UL1TR000150; and National Center for Research Resources (NCRR)/NCATS/NIH UL1TR000077-04, UL1TR000451, UL1TR001105, UL1TR000040, UM1AI109565, UL1TR000075, 1UL1RR025780, UL1TR000154 and UL1TR001082. The following were donated: omalizumab and matching placebo by Novartis and fluticasone and matching placebo by GlaxoSmithKline under a clinical trial agreement with the University of Wisconsin–Madison; EpiPens by Mylan; and Ayr nasal rinse by B.F. Ascher & Company. None of these companies had a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit for publication. |
|
| Disclosure of potential conflict of interest: All authors, with the exception of A. Togias, report grants from the National Institutes of Health (NIH) during the conduct of study. R. Valladares reports personal fees for employment with Siolta Therapeutics outside the submitted work. H. T. Tran reports personal fees from GlaxoSmithKline outside the submitted work. J. Pongracic reports provision of study drug for other asthma and allergy studies from GlaxoSmithKline, Boehringer Ingelheim, and Genentech/Novartis outside the submitted work. C. M. Kercsmar reports personal fees from GlaxoSmithKline for service on a DSMB and royalties from UpToDate outside the submitted work. M. Gill reports honoraria and support for travel from the American Academy of Allergy, Asthma & Immunology (AAAAI), as well as payment for lectures from the American Academy of Pediatrics outside the submitted work. A. H. Liu reports personal fees from Merck Sharp & Dohme and Phadia Thermo-Fisher and membership on a Data Monitoring Committee for GlaxoSmithKline outside the submitted work. M. Kattan reports personal feed from Novartis Pharma and Regeneron for service on advisory boards outside the submitted work. S. J. Teach reports grants from Patient-Centered Outcomes Research Institute (PCORI), EJF, and the NIH/National Heart, Lung, and Blood Institute (NHLBI) outside the submitted work and personal fees from UpToDate outside the submitted work. H. A. Boushey serves as a compensated member of a Scientific Advisory Committee for Siolta Therapeutics. J. E. Gern reports personal fees from PREP Biopharm, Regeneron, Meissa Vaccines, MedImmune, and Ena Pharmaceuticals, as well as stock options from Meissa Vaccines outside the submitted work and has a patent “Methods of Propagating Rhinovirus C in Previously Unsusceptible Cell Lines” issued and a patent “Adapted Rhinovirus C” pending outside the submitted work. D. J. Jackson reports personal fees from Novartis, Boehringer Ingelheim, Pfizer, Commense, and Sanofi/Genzyme outside the submitted work, as well as grants from GlaxoSmithKline and the NIH/NHLBI. S.V. Lynch reports grants from the NIH/National Institute of Allergy and Infectious Diseases (NIAID), NIH/National Institute on Drug Abuse (NIDA), NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH/Office of the Director, and the Crohn's and Colitis Foundation of America; reports personal fees from Siolta Therapeutics outside the submitted work; has a patent “Reductive prodrug cancer chemotherapy (Stan449-PRV)" issued, a patent “Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection (WO2010091189A1)" with royalties paid by KaloBios, a patent “Therapeutic microbial consortium for induction of immune tolerance” licensed to Siolta Therapeutics, a patent “Systems and methods for detecting antibiotic resistance (WO2012027302A3)" issued, a patent “Nitroreductase enzymes (US7687474B2)" issued, a patent “Sinusitis diagnostics and treatments (WO2013155370A1)" licensed by Reflourish, and a patent “Methods and systems for phylogenetic analysis (US20120264637A1)" issued; and is a cofounder of Siolta Therapeutics, a startup developing a mixed-species microbial oral therapeutic for induction of immune tolerance. The rest of the authors declare that they have no relevant conflicts of interest. |
© 2019
Pubblicato da Elsevier Masson SAS.
Vol 144 - N° 5
P. 1187-1197 - novembre 2019 Ritorno al numero
Articolo precedente
- Symptoms and perception of airway obstruction in asthmatic patients: Clinical implications for use of reliever medications
- Peter J. Barnes, Stanley J. Szefler, Helen K. Reddel, Bradley E. Chipps
- IL-17–high asthma with features of a psoriasis immunophenotype
- Jörgen Östling, Marleen van Geest, James P.R. Schofield, Zala Jevnikar, Susan Wilson, Jonathan Ward, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Sven-Erik Dahlen, Stephen J. Fowler, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Ana R. Sousa, Yike Guo, Ian M. Adcock, Peter Howarth, Kian Fan Chung, Jeanette Bigler, Peter J. Sterk, Paul J. Skipp, Ratko Djukanovi?, Outi Vaarala, U-BIOPRED Study Group, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, K.F. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, A.J. Knox, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powell, G. Praticò, M. Puig N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Antonios Aliprantis, David Allen, Kjell Alving, P. Badorrek, David Balgoma, S. Ballereau, Clair Barber, Manohara Kanangana Batuwitage, A. Bautmans, A. Bedding, A.F. Behndig, Jorge Beleta, A. Berglind, A. Berton, Grazyna Bochenek, Armin Braun, D. Campagna, Leon Carayannopoulos, C. Casaulta, Romanas Chaleckis, B. Dahlén, imothy Davison, Jorge De Alba, Inge De Lepeleire, Tamara Dekker, Ingrid Delin, P. Dennison, Annemiek Dijkhuis, Paul Dodson, Aleksandra Draper, K. Dyson, Jessica Edwards, L. El Hadjam, Rosalia Emma, Magnus Ericsson, C. Faulenbach, Breda Flood, G. Galffy, Hector Gallart, D. Garissi, J. Gent, M. Gerhardsson de Verdier, D. Gibeon, Cristina Gomez, Kerry Gove, Neil Gozzard, E. Guillmant-Farry, E. Henriksson, Lorraine Hewitt, U. Hoda, Richard Hu, Sile Hu, X. Hu, E. Jeyasingham, K. Johnson, N. Jullian, Juliette Kamphuis, Erika J. Kennington, Dyson Kerry, G. Kerry, M. Klüglich, Hugo Knobel, Johan Kolmert, J.R. Konradsen, Maxim Kots, Kosmas Kretsos, L. Krueger, Scott Kuo, Maciej Kupczyk, Bart Lambrecht, A.-S. Lantz, Christopher Larminie, L.X. Larsson, P. Latzin, N. Lazarinis, N. Lemonnier, Saeeda Lone-Latif, L.A. Lowe, Alexander Manta, Lisa Marouzet, Jane Martin, Caroline Mathon, L. McEvoy, Sally Meah, A. Menzies-Gow, Leanne Metcalf, Maria Mikus, Philip Monk, Shama Naz, K. Nething, Ben Nicholas, U. Nihlén, Peter Nilsson, R. Niven, B. Nordlund, S. Nsubuga, Antonio Pacino, Susanna Palkonen, J. Pellet, Giorgio Pennazza, Anne Petrén, Sandy Pink, C. Pison, Anthony Postle, Malayka Rahman-Amin, Lara Ravanetti, Emma Ray, Stacey Reinke, Leanne Reynolds, K. Riemann, Martine Robberechts, J.P. Rocha, C. Rossios, Kirsty Russell, Michael Rutgers, G. Santini, Marco Santoninco, M. Saqi, Corinna Schoelch, James P.R. Schofield, S. Scott, N. Sehgal, Marcus Sjödin, Barbara Smids, Caroline Smith, Jessica Smith, Katherine M. Smith, P. Söderman, A. Sogbessan, F. Spycher, Doroteya Staykova, S. Stephan, J. Stokholm, K. Strandberg, M. Sunther, M. Szentkereszty, L. Tamasi, K. Tariq, John-Olof Thörngren, Jonathan Thorsen, S. Valente, Marianne van de Pol, C.M. van Drunen, Jonathan Van Eyll, Jenny Versnel, Anton Vink, C. von Garnier, A. Vyas, Frans Wald, Samantha Walker, Jonathan Ward, Kristiane Wetzel, Coen Wiegman, Siân Williams, Xian Yang, Elizabeth Yeyasingham, W. Yu Amgen, W. Zetterquist, Z. Zolkipli, A.H. Zwinderman
Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.
Già abbonato a @@106933@@ rivista ?