title: Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis.
abstract: OBJECTIVE
  Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation.
  
  
  METHODS
  We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation.
  
  
  RESULTS
  Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.
  
  
  CONCLUSIONS
  The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.
authors.affiliation: Department of Medicine, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Hill
authors.forename: E J
authors.initials: EJ
authors.lastname: Campbell
authors.forename: S L
authors.initials: SL
authors.lastname: Hill
authors.forename: D L
authors.initials: DL
authors.lastname: Bayley
authors.forename: R A
authors.initials: RA
authors.lastname: Stockley
mesh_terms: D000368:Aged; D001419:Bacteria / Q000201:enzymology / Q000302:isolation & purification*; D015415:Biomarkers / Q000032:analysis; D001991:Bronchitis / Q000175:diagnosis / Q000382:microbiology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016009:Chi-Square Distribution; D002908:Chronic Disease; D015169:Colony Count, Microbial; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D016209:Interleukin-8 / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis; D008173:Lung Diseases, Obstructive / Q000175:diagnosis / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000032:analysis; D011379:Prognosis; D012016:Reference Values; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry / Q000166:cytology / Q000382:microbiology*; D018709:Statistics, Nonparametric; D013234:Stem Cells
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D016209:Interleukin-8; D007975:Leukotriene B4; D009195:Peroxidase