title: Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.
abstract: BACKGROUND
  Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches.
  
  
  OBJECTIVE
  We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers.
  
  
  METHODS
  Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis.
  
  
  RESULTS
  In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count.
  
  
  CONCLUSIONS
  Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors: Benjamin J
authors: BJ
authors: Green
authors: Molecular Microbiology Research Laboratory, Pharmaceutical Science Division, King's College London, London, United Kingdom.
authors: Surasa
authors: S
authors: Wiriyachaiporn
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom; Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
authors: Christopher
authors: C
authors: Grainge
authors: Molecular Microbiology Research Laboratory, Pharmaceutical Science Division, King's College London, London, United Kingdom; SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia.
authors: Geraint B
authors: GB
authors: Rogers
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors: Valia
authors: V
authors: Kehagia
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors: Laurie
authors: L
authors: Lau
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors: Mary P
authors: MP
authors: Carroll
authors: Molecular Microbiology Research Laboratory, Pharmaceutical Science Division, King's College London, London, United Kingdom.
authors: Kenneth D
authors: KD
authors: Bruce
authors: Academic Unit of Clinical and Experimental Sciences; NIHR Respiratory Biomedical Research Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors: Peter H
authors: PH
authors: Howarth
mesh_terms: D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000209:etiology / Q000473:pathology; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D001419:Bacteria / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology*; D013183:Sputum / Q000276:immunology / Q000382:microbiology*