title: Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.
abstract: BACKGROUND
  Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.
  
  
  OBJECTIVE
  We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.
  
  
  METHODS
  In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.
  
  
  RESULTS
  Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.
  
  
  CONCLUSIONS
  The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, Calif, USA.
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Huang
authors.forename: Craig E
authors.initials: CE
authors.lastname: Nelson
authors.forename: Eoin L
authors.initials: EL
authors.lastname: Brodie
authors.forename: Todd Z
authors.initials: TZ
authors.lastname: Desantis
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Baek
authors.forename: Jane
authors.initials: J
authors.lastname: Liu
authors.forename: Tanja
authors.initials: T
authors.lastname: Woyke
authors.forename: Martin
authors.initials: M
authors.lastname: Allgaier
authors.forename: Jim
authors.initials: J
authors.lastname: Bristow
authors.forename: Jeanine P
authors.initials: JP
authors.lastname: Wiener-Kronish
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.forename: Tonya S
authors.initials: TS
authors.lastname: King
authors.forename: Nikolina
authors.initials: N
authors.lastname: Icitovic
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.forename: Emily
authors.initials: E
authors.lastname: Dimango
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Wasserman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000382:microbiology; D001419:Bacteria / Q000302:isolation & purification*; D001980:Bronchi / Q000382:microbiology*; D016535:Bronchial Hyperreactivity / Q000382:microbiology*; D017291:Clarithromycin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D010865:Pilot Projects; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S; D017291:Clarithromycin