Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

McCauley, Kathryn¹  Durack, Juliana¹  Valladares, Ricardo^1,16  Fadrosh, Douglas W.¹  Lin, Din L.¹  Calatroni, Agustin²  LeBeau, Petra K.²  Tran, Hoang T.²  Fujimura, Kei E.¹  LaMere, Brandon¹  Merana, Geil¹  Lynch, Kole¹  Cohen, Robyn T.³  Pongracic, Jacqueline⁴  Hershey, Gurjit K. Khurana⁵  Kercsmar, Carolyn M.⁵  Gill, Michelle^6,7  Liu, Andrew H.^8,9,10  Kim, Haejin¹¹  Kattan, Meyer¹²  Teach, Stephen J.¹³  Togias, Alkis¹⁴  Boushey, Homer A.¹  Gern, James E.¹⁵  Jackson, Daniel J.¹⁵  Lynch, Susan V.¹ 

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[2] Rho Fed Syst Div, Chapel Hill, NC USA

[3] Boston Univ, Sch Med, Boston, MA 02215 USA

[4] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA

[5] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA

[6] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA

[7] Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA

[8] Natl Jewish Hlth, Dept Pedatr & Pulmonol Med, Denver, CO USA

[9] Childrens Hosp Colorado, Aurora, CO USA

[10] Univ Colorado, Sch Med, Aurora, CO USA

[11] Henry Ford Hlth Syst, Div Allergy & Immunol, Dept Internal Med, Detroit, MI USA

[12] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA

[13] Childrens Natl Hlth Syst, Washington, DC USA

[14] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA

[15] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA

[16] Siolta Therapeut, San Francisco, CA USA

关键词: Microbiota;    Moraxella species;    Staphylococcus species;    16S rRNA;    airway;    asthma;    exacerbation;    rhinovirus;   

DOI  :  10.1016/j.jaci.2019.05.035

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free