title: Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.
abstract: BACKGROUND
  Pulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.
  
  
  OBJECTIVE
  To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.
  
  
  METHODS
  Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.
  
  
  RESULTS
  Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = -0.67, p<0.001), decreased FEV(1%) predicted (r = 0.49, p = 0.03) and increased CRP (r = -0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.
  
  
  CONCLUSIONS
  Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States of America. edith.zemanick@childrenscolorado.org
authors: Edith T
authors: ET
authors: Zemanick
authors: J Kirk
authors: JK
authors: Harris
authors: Brandie D
authors: BD
authors: Wagner
authors: Charles E
authors: CE
authors: Robertson
authors: Scott D
authors: SD
authors: Sagel
authors: Mark J
authors: MJ
authors: Stevens
authors: Frank J
authors: FJ
authors: Accurso
authors: Theresa A
authors: TA
authors: Laguna
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000235:genetics; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000382:microbiology* / Q000503:physiopathology; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents
references: Appl Environ Microbiol. 2010 Jun;76(12):3863-8
references: 20418443
references: Respir Res. 2010 Oct 06;11:137
references: 20925941
references: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13769-74
references: 22872870
references: Appl Environ Microbiol. 2007 Aug;73(16):5261-7
references: 17586664
references: Clin Microbiol Infect. 2009 May;15(5):454-60
references: 19196263
references: J Clin Microbiol. 2004 Nov;42(11):5238-44
references: 15528720
references: Appl Environ Microbiol. 2007 Jan;73(1):32-9
references: 17071791
references: Am J Respir Crit Care Med. 2003 Dec 15;168(12):1471-5
references: 12969869
references: PLoS One. 2010 Jun 23;5(6):e11044
references: 20585638
references: Clin Infect Dis. 1998 Jul;27(1):158-63
references: 9675470
references: BMC Bioinformatics. 2009 Oct 29;10:362
references: 19874596
references: Clin Microbiol Infect. 2010 Nov;16(11):1656-8
references: 20148918
references: Bioinformatics. 2009 May 15;25(10):1335-7
references: 19307242
references: J Mol Biol. 1990 Oct 5;215(3):403-10
references: 2231712
references: Pediatr Pulmonol. 2010 Jun;45(6):569-77
references: 20503282
references: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20529-33
references: 18077362
references: PLoS One. 2011 Feb 22;6(2):e16384
references: 21364979
references: J Cyst Fibros. 2013 Jan;12(1):22-8
references: 22717533
references: Thorax. 2007 Apr;62(4):360-7
references: 17387214
references: Thorax. 2011 Jul;66(7):579-84
references: 21270069
references: Am J Respir Crit Care Med. 2010 Sep 1;182(5):627-32
references: 20463179
references: PLoS One. 2012;7(9):e45001
references: 23049765
references: Pediatr Pulmonol. 2005 Jul;40(1):15-21
references: 15858808
references: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5809-14
references: 22451929
references: Pediatr Pulmonol. 2012 Sep;47(9):856-63
references: 22431382
references: Thorax. 2010 Nov;65(11):978-84
references: 20880875
references: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15070-5
references: 18812504
references: Genome Res. 2011 Mar;21(3):494-504
references: 21212162
references: J Clin Microbiol. 2006 Jul;44(7):2601-4
references: 16825392
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D13-21
references: 18045790
references: Nucleic Acids Res. 2007;35(21):7188-96
references: 17947321
references: Nat Methods. 2008 Mar;5(3):235-7
references: 18264105
references: Pediatr Pulmonol. 2011 Apr;46(4):393-400
references: 20967845
references: Eur Respir J. 2005 Aug;26(2):319-38
references: 16055882
references: Am J Epidemiol. 2001 Feb 15;153(4):345-52
references: 11207152
references: Pediatr Pulmonol. 2008 May;43(5):490-7
references: 18383109
references: Future Microbiol. 2006 Jun;1(1):53-61
references: 17661685
references: Chest. 2009 Dec;136(6):1561-1568
references: 19567495
references: PLoS One. 2008 Aug 06;3(8):e2908
references: 18682840
references: PLoS One. 2010 Nov 30;5(11):e15101
references: 21152087
references: Am J Respir Crit Care Med. 2010 Nov 1;182(9):1137-43
references: 20581166
references: Environ Microbiol. 2010 May;12(5):1293-303
references: 20192960
references: J Clin Microbiol. 2004 Nov;42(11):5176-83
references: 15528712
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D141-5
references: 19004872
references: PLoS One. 2010 Jan 05;5(1):e8578
references: 20052417
references: Am J Respir Crit Care Med. 2003 Oct 15;168(8):918-51
references: 14555458
references: Am J Respir Crit Care Med. 2008 May 1;177(9):995-1001
references: 18263800
references: Clin Microbiol Infect. 2010 Jul;16(7):809-20
references: 20880410
references: PLoS One. 2009 Aug 20;4(8):e6669
references: 19693277
references: Anaerobe. 2008 Jun;14(3):131-7
references: 18539056
references: Respir Med. 2009 Mar;103(3):407-13
references: 19027279