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

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Abstract

PURPOSE: 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.

SUBJECTS AND METHODS: We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha1-antitrypsin levels, 62 with COPD and severe alpha1-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 106 to 107 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 105 to 106 colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 106 to 107 colony-forming units per milliliter (P <0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 107 to 108 colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 108 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.

Section snippets

Study sample and design

We recruited three groups of patients with stable chronic bronchitis (1) who were treated in specialist outpatient clinics between 1996 and 1999. The first group consisted of subjects with chronic obstructive pulmonary disease (COPD) related to smoking. The second group was recruited from an alpha1-antitrypsin deficiency clinic; these patients had COPD with serum alpha1-antitrypsin concentrations less than 11 μM (10) and the PiZ alpha1-antitrypsin phenotype (11). The remaining group of subjects

Results

The participants in the three study samples represented a wide spectrum of patients with chronic bronchitis (Table 1). Those with COPD (with or without alpha1-antitrypsin deficiency) had substantially worse pulmonary function than patients with bronchiectasis.

We analyzed 336 sputum samples from patients while they were clinically stable (72 samples from the 55 patients with COPD and normal alpha1-antitrypsin levels, 179 samples from the 62 patients with COPD and alpha1-antitrypsin deficiency,

Discussion

We used quantitative bacterial cultures to demonstrate that airway bacterial load varies greatly among several groups of patients with chronic sputum production. Although our sample does not reflect the usual spectrum of patients with COPD, excluding the patients with alpha1-antitrypsin deficiency or bronchiectasis did not influence the overall relation between colonizing load and airway inflammation. Increasing airway bacterial load was strongly related to several markers of inflammation in

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    Supported by an unrestricted research grant from Bayer as part of the ADAPT Programme.

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