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Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences

Emily K. Cope, Andrew N. Goldberg, Steven D. Pletcher and 1 more

Microbiome · 2017

doi:10.1186/s40168-017-0266-6

Abstract

Background. Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients.

Results. Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, TH1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher’s exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045).

Conclusions. A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response—features which may inform strategies for tailored therapy in this patient population.

Electronic supplementary material. The online version of this article (doi:10.1186/s40168-017-0266-6) contains supplementary material, which is available to authorized users.

References 73

  1. 1.

    Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, Woyke T, Allgaier M, Bristow J, Wiener-Kronish JP, et al. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol. 2011;127(2):372-381.

    Not in our library10.1016/j.jaci.2010.10.048

  2. 2.
    Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment · 2012
    No notice
  3. 3.

    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222-227.

    Not in our library10.1038/nature11053

  4. 4.

    Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, Holt BJ, Hales BJ, Walker ML, Hollams E, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17(5):704-715.

    Not in our library10.1016/j.chom.2015.03.008

  5. 5.

    Abreu NA, Nagalingam NA, Song Y, Roediger FC, Pletcher SD, Goldberg AN, Lynch SV. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012;4(151):151ra124.

    Not in our library10.1126/scitranslmed.3003783

  6. 6.

    Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, Bushman FD, Collman RG. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med. 2011;184(8):957-963.

    Not in our library10.1164/rccm.201104-0655oc

  7. 7.

    Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol. 2015;136(4):874-884.

    Not in our library10.1016/j.jaci.2015.05.044

  8. 8.

    Simpson JL, Daly J, Baines KJ, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, Hugenholtz P, Willner D, et al. Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma. Eur Respir J. 2016;47(3):792-800.

    Not in our library10.1183/13993003.00405-2015

  9. 9.

    Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;23(3):1–298.

    Not in our library

  10. 10.

    Caulley L, Thavorn K, Rudmik L, Cameron C, Kilty SJ. Direct costs of adult chronic rhinosinusitis by using 4 methods of estimation: results of the US Medical Expenditure anel Survey. J Allergy Clin Immunol. 2015;136(6):1517-1522.

    Not in our library10.1016/j.jaci.2015.08.037

  11. 11.

    Kim RJ, Biswas K, Hoggard M, Taylor MW, Douglas RG. Paired analysis of the microbiota of surface mucus and whole-tissue specimens in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2015;5(10):877-883.

    Not in our library10.1002/alr.21600

  12. 12.
    The nasal microbiota in health and disease: variation within and between subjects · 2015
    No notice
  13. 13.

    Ramakrishnan VR, Hauser LJ, Feazel LM, Ir D, Robertson CE, Frank DN. Sinus microbiota varies among chronic rhinosinusitis phenotypes and predicts surgical outcome. J Allergy Clin Immunol. 2015;136(2):334-342.

    Not in our library10.1016/j.jaci.2015.02.008

  14. 14.

    Bendouah Z, Barbeau J, Hamad WA, Desrosiers M. Biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa is associated with an unfavorable evolution after surgery for chronic sinusitis and nasal polyposis. Otolaryngol Head Neck Surg. 2006;134(6):991-996.

    Not in our library10.1016/j.otohns.2006.03.001

  15. 15.

    Divekar R, Patel N, Jin J, Hagan J, Rank M, Lal D, Kita H, O'Brien E. Symptom-based clustering in chronic rhinosinusitis relates to history of aspirin sensitivity and postsurgical outcomes. J Allergy Clin Immunol Pract. 2015;3(6):934-940.

    Not in our library10.1016/j.jaip.2015.06.018

  16. 16.

    Lal D, Rounds AB, Rank MA, Divekar R. Clinical and 22-item sino-nasal outcome test symptom patterns in primary headache disorder patients presenting to otolaryngologists with “sinus” headaches, pain or pressure. Int Forum Allergy Rhinol. 2015;5(5):408-416.

    Not in our library10.1002/alr.21502

  17. 17.

    Derycke L, Eyerich S, Van Crombruggen K, Perez-Novo C, Holtappels G, Deruyck N, Gevaert P, Bachert C. Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps. PLoS One. 2014;9(6):e97581.

    Not in our library10.1371/journal.pone.0097581

  18. 18.

    Yang Y, Zhang N, Crombruggen KV, Lan F, Hu G, Hong S, Bachert C. Differential expression and release of activin a and follistatin in chronic rhinosinusitis with and without nasal polyps. PLoS One. 2015;10(6):e0128564.

    Not in our library10.1371/journal.pone.0128564

  19. 19.

    Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, Schleimer RP, Ledford D. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131(6):1479-1490.

    Not in our library10.1016/j.jaci.2013.02.036

  20. 20.

    Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, Forster-Ruhrmann U, Kowalski ML, Olszewska-Ziaber A, Holtappels G, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449-1456.

    Not in our library10.1016/j.jaci.2015.12.1324

  21. 21.

    Tan NC, Cooksley CM, Roscioli E, Drilling AJ, Douglas R, Wormald PJ, Vreugde S. Small-colony variants and phenotype switching of intracellular Staphylococcus aureus in chronic rhinosinusitis. Allergy. 2014;69(10):1364-1371.

    Not in our library10.1111/all.12457

  22. 22.

    Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E et al. Immune response and mortality risk relate to distinct lung microbiomes in HIV-pneumonia patients. Am J Respir Crit Care Med. 2017;195(1):104–14.

    Not in our library10.1164/rccm.201603-0523oc

  23. 23.

    Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, Panzer AR, LaMere B, Rackaityte E, Lukacs NW, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016;22(10):1187-1191.

    Not in our library10.1038/nm.4176

  24. 24.

    Rosenfeld RM. Clinical practice guideline on adult sinusitis. Otolaryngol Head Neck Surg. 2007;137(3):365-377.

    Not in our library10.1016/j.otohns.2007.07.021

  25. 25.

    Roediger FC, Slusher NA, Allgaier S, Cox MJ, Pletcher SD, Goldberg AN, Lynch SV. Nucleic acid extraction efficiency and bacterial recovery from maxillary sinus mucosal samples obtained by brushing or biopsy. Am J Rhinol Allergy. 2010;24(4):263-265.

    Not in our library10.2500/ajra.2010.24.3472

  26. 26.

    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6(8):1621-1624.

    Not in our library10.1038/ismej.2012.8

  27. 27.

    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Lozupone CA, Turnbaugh PJ, Fierer N, Knight R. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4516-4522.

    Not in our library10.1073/pnas.1000080107

  28. 28.

    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335-336.

    Not in our library10.1038/nmeth.f.303

  29. 29.
    EMPeror: a tool for visualizing high-throughput microbial community data · 2013
    No notice
  30. 30.

    Oksanen J, Blanchet, F.G., Kindt, R., Legendre, P., Minchin, P.R., O’Hara, R.B., Simpson, G.L., Solymos, P., Stevens, H.H., Wagner, H. Vegan: community ecology package. R package version 20-10 2013.

    Not in our library

  31. 31.

    Anderson MJ. A new method for non-parametric multivariate analysis of variance. Austral Ecol. 2001;26:32-46.

    Not in our library

  32. 32.

    Storey JD. A direct approach to false discovery rates. J R Stat Soc B. 2002;64:479-498.

    Not in our library10.1111/1467-9868.00346

  33. 33.
    Dirichlet Multinomial Mixtures: Generative Models for Microbial Metagenomics · 2012
    No notice
  34. 34.

    Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31(9):814–21.

    Not in our library10.1038/nbt.2676

  35. 35.

    Foreman A, Psaltis AJ, Tan LW, Wormald PJ. Characterization of bacterial and fungal biofilms in chronic rhinosinusitis. Am J Rhinol Allergy. 2009;23(6):556-561.

    Not in our library10.2500/ajra.2009.23.3413

  36. 36.

    Lina G, Boutite F, Tristan A, Bes M, Etienne J, Vandenesch F. Bacterial competition for human nasal cavity colonization: role of Staphylococcal agr alleles. Appl Environ Microbiol. 2003;69(1):18-23.

    Not in our library10.1128/aem.69.1.18-23.2003

  37. 37.

    Yan M, Pamp SJ, Fukuyama J, Hwang PH, Cho DY, Holmes S, Relman DA. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe. 2013;14(6):631-640.

    Not in our library10.1016/j.chom.2013.11.005

  38. 38.

    Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity. 2015;42(4):756-766.

    Not in our library10.1016/j.immuni.2015.03.014

  39. 39.
    Lung microbiota across age and disease stage in cystic fibrosis · 2015
    No notice
  40. 40.

    Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin ML et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio. 2012;3(4).

    Not in our library10.1128/mbio.00251-12

  41. 41.

    Evans SE, Goult BT, Fairall L, Jamieson AG, Ko Ferrigno P, Ford R, Schwabe JW, Wagner SD. The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain. PLoS One. 2014;9(3):e90889.

    Not in our library10.1371/journal.pone.0090889

  42. 42.

    Asaka C, Honda K, Ito E, Fukui N, Chihara J, Ishikawa K. Peroxisome proliferator-activated receptor-gamma is expressed in eosinophils in nasal polyps. Int Arch Allergy Immunol. 2011;155(Suppl 1):57-63.

    Not in our library10.1159/000327294

  43. 43.

    Bogefors J, Kvarnhammar AM, Latif L, Petterson T, Uddman R, Cardell LO. Retinoic acid-inducible gene 1-like receptors in the upper respiratory tract. Am J Rhinol Allergy. 2011;25(6):e262-e267.

    Not in our library10.2500/ajra.2011.25.3712

  44. 44.

    Bachert C, Wagenmann M, Hauser U, Rudack C. IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol. 1997;99(6 Pt 1):837-842.

    Not in our library10.1016/s0091-6749(97)80019-x

  45. 45.

    Cho KS, Kim CS, Lee HS, Seo SK, Park HY, Roh HJ. Role of interferon-gamma-producing T cells in the pathogenesis of chronic rhinosinusitis with nasal polyps associated with staphylococcal superantigen. J Otolaryngol Head Neck Surg. 2010;39(5):600-605.

    Not in our library

  46. 46.

    Joss TV, Burke CM, Hudson BJ, Darling AE, Forer M, Alber DG, Charles IG, Stow NW. Bacterial communities vary between sinuses in chronic rhinosinusitis patients. Front Microbiol. 2015;6:1532.

    Not in our library10.3389/fmicb.2015.01532

  47. 47.

    Hoggard M, Biswas K, Zoing M, Wagner Mackenzie B, Taylor MW, Douglas RG. Evidence of microbiota dysbiosis in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2017;7(3):230–9.

    Not in our library10.1002/alr.21871

  48. 48.

    Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. MBio. 2016;7(1):e01725–15.

    Not in our library10.1128/mbio.01725-15

  49. 49.

    Qingzhen H, Jia T, Shengjun W, Yang Z, Yanfang L, Pei S, Essien BS, Zhaoliang S, Sheng X, Qixiang S, et al. Corynebacterium pyruviciproducens promotes the production of ovalbumin specific antibody via stimulating dendritic cell differentiation and up-regulating Th2 biased immune response. Vaccine. 2012;30(6):1115-1123.

    Not in our library10.1016/j.vaccine.2011.12.005

  50. 50.

    Mishra AK, Alves JE, Krumbach K, Nigou J, Castro AG, Geurtsen J, Eggeling L, Saraiva M, Besra GS. Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation. J Biol Chem. 2012;287(53):44173-44183.

    Not in our library10.1074/jbc.m112.402396

  51. 51.

    Lee KS, Park SJ, Hwang PH, Yi HK, Song CH, Chai OH, Kim JS, Lee MK, Lee YC. PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J. 2005;19(8):1033-1035.

    Not in our library10.1096/fj.04-3309fje

  52. 52.

    Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol. 2004;113(5):882-888.

    Not in our library10.1016/j.jaci.2004.02.036

  53. 53.

    Imaizumi T, Tanaka H, Tajima A, Tsuruga K, Oki E, Sashinami H, Matsumiya T, Yoshida H, Inoue I, Ito E. Retinoic acid-inducible gene-I (RIG-I) is induced by IFN-γ in human mesangial cells in culture: possible involvement of RIG-I in the inflammation in lupus nephritis. Lupus. 2010;19(7):830-836.

    Not in our library10.1177/0961203309360540

  54. 54.

    Harden JL, Lewis SM, Lish SR, Suarez-Farinas M, Gareau D, Lentini T, Johnson-Huang LM, Krueger JG, Lowes MA. The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases. J Allergy Clin Immunol. 2016;137(6):1830–40.

    Not in our library10.1016/j.jaci.2015.09.055

  55. 55.

    Favre D, Mold J, Hunt PW, Kanwar B, Loke P, Seu L, Barbour JD, Lowe MM, Jayawardene A, Aweeka F, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med. 2010;2(32):32ra36.

    Not in our library10.1126/scitranslmed.3000632

  56. 56.

    Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, Hernandez RD, Lederman MM, Huang Y, Somsouk M, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra191.

    Not in our library10.1126/scitranslmed.3006438

  57. 57.

    Ujimaru T, Kakimoto T, Chibata I. l-Tryptophan production by Achromobacter liquidum. Appl Environ Microbiol. 1983;46(1):1-5.

    Not in our library10.1128/aem.46.1.1-5.1983

  58. 58.

    Sasaki-Imamura T, Yano A, Yoshida Y. Production of indole from L-tryptophan and effects of these compounds on biofilm formation by Fusobacterium nucleatum ATCC 25586. Appl Environ Microbiol. 2010;76(13):4260-4268.

    Not in our library10.1128/aem.00166-10

  59. 59.

    Lee J, Attila C, Cirillo SL, Cirillo JD, Wood TK. Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence. Microb Biotechnol. 2009;2(1):75-90.

    Not in our library10.1111/j.1751-7915.2008.00061.x

  60. 60.

    Anyanful A, Dolan-Livengood JM, Lewis T, Sheth S, Dezalia MN, Sherman MA, Kalman LV, Benian GM, Kalman D. Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene. Mol Microbiol. 2005;57(4):988-1007.

    Not in our library10.1111/j.1365-2958.2005.04739.x

  61. 61.

    Hirakawa H, Kodama T, Takumi-Kobayashi A, Honda T, Yamaguchi A. Secreted indole serves as a signal for expression of type III secretion system translocators in enterohaemorrhagic Escherichia coli O157:H7. Microbiology. 2009;155(Pt 2):541-550.

    Not in our library10.1099/mic.0.020420-0

  62. 62.

    Lubamba BA, Jones LC, O'Neal WK, Boucher RC, Ribeiro CM. X-box-binding protein 1 and innate immune responses of human cystic fibrosis alveolar macrophages. Am J Respir Crit Care Med. 2015;192(12):1449-1461.

    Not in our library10.1164/rccm.201504-0657oc

  63. 63.

    LaFayette SL, Houle D, Beaudoin T, Wojewodka G, Radzioch D, Hoffman LR, Burns JL, Dandekar AA, Smalley NE, Chandler JR et al. Cystic fibrosis-adapted quorum sensing mutants cause hyperinflammatory responses. Sci Adv. 2015;1(6).

    Not in our library10.1126/sciadv.1500199

  64. 64.

    Jones CL, Weiss DS. TLR2 signaling contributes to rapid inflammasome activation during F. novicida infection. PLoS One. 2011;6(6):e20609.

    Not in our library10.1371/journal.pone.0020609

  65. 65.

    Makowska JS, Burney P, Jarvis D, Keil T, Tomassen P, Bislimovska J, Brozek G, Bachert C, Baelum J, Bindslev-Jensen C et al. Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey. Allergy. 2016;71(11):1603–11.

    Not in our library10.1111/all.12941

  66. 66.

    Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4554-4561.

    Not in our library10.1073/pnas.1000087107

  67. 67.

    Theriot CM, Koenigsknecht MJ, Carlson PE, Hatton GE, Nelson AM, Li B, Huffnagle GB JZL, Young VB. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5:3114.

    Not in our library10.1038/ncomms4114

  68. 68.

    Liu CM, Soldanova K, Nordstrom L, Dwan MG, Moss OL, Contente-Cuomo TL, Keim P, Price LB, Lane AP. Medical therapy reduces microbiota diversity and evenness in surgically recalcitrant chronic rhinosinusitis. Int Forum Allergy Rhinol. 2013;3(10):775-781.

    Not in our library10.1002/alr.21195

  69. 69.

    Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med. 2015;373(13):1241-1249.

    Not in our library10.1056/nejmra1411863

  70. 70.

    Christenson SA, Steiling K, van den Berge M, Hijazi K, Hiemstra PS, Postma DS, Lenburg ME, Spira A, Woodruff PG. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;191(7):758-766.

    Not in our library10.1164/rccm.201408-1458oc

  71. 71.

    Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol. 2013;131(2):346-352.

    Not in our library10.1016/j.jaci.2012.11.013

  72. 72.

    Bacci G, Paganin P, Lopez L, Vanni C, Dalmastri C, Cantale C, Daddiego L, Perrotta G, Dolce D, Morelli P, et al. Pyrosequencing unveils cystic fibrosis lung microbiome differences associated with a severe lung function decline. PLoS One. 2016;11(6):e0156807.

    Not in our library10.1371/journal.pone.0156807

  73. 73.

    Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, Arron JR, Fahy JV. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388-395.

    Not in our library10.1164/rccm.200903-0392oc

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