Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis

PURPOSE: Viable bacteria are often isolated from airway secretions in clini cally stable patients with chronic bronchitis. We hypothesized that the num ber of organisms and bacterial species might be important modulators of air way inflammation. SUBJECTS AND METHODS: We performed quantitative sputum cultures in 160 stab le patients [55 with chronic obstructive pulmonary disease (COPD) and norma l serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antit rypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The result s were related to several indicators of the mechanisms and severity of airw ay inflammation. RESULTS: Airway bacterial load correlated with sputum myeloperoxidase level , an indirect measure of neutrophil activation and number (r = 0.50, P <0.0 01); sputum neutrophil chemoattractants [interleukin-8 level (r = 0.68, P < 0.001) and leukotriene B4 level (r = 0.53, P <0.001)]; sputum leukocyte ela stase activity (r = 0.55, P <0.001); and albumin leakage from serum to sput um (r = 0.26, P <0.01). Markers of inflammation increased at bacterial load s of 10(6) to 10(7) colony-forming units per milliliter, and increased prog ressively with increasing bacterial load. For example, the median (interqua rtile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) fo r patients who were not colonized or who had mixed normal oropharyngeal flo ra alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colon y-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for p atients 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 patient s with 108 or greater colony-forming units per milliliter (P <0.0001). The bacterial species influenced airway inflammation; for example, sputum myelo peroxidase activity was greater (P <0.005) in patients colonized with Pseud omonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] tha n 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 rela tion between bacterial load and lung function. CONCLUSIONS: The bacterial load and species contribute to airway inflammati on in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidi ty and decline in lung function. Am J Med. 2000;109:288-295. (C) 2000 by Ex cerpta Medica, Inc.