Abstract
BackgroundHaemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.MethodsA cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared.ResultsSputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test). Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).ConclusionsClinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.
Highlights
Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa
The protection of bronchial mucosa from H. influenzae is partly mediated by immune exclusion [12], an essentially mechanical process in which secretory IgA agglutinates bacteria allowing the entrapment of the created bacterial complexes in mucus, which are expelled through mucociliary clearance
Sputum quality One hundred thirty-three participants in the PAC-COPD Study produced good quality sputum samples which showed a low proportion of squamous cells (2 [0.5-6]) and high cell viability (79 [64-90]), which were considered as representative of bronchial secretions
Summary
Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa. H. influenzae is the most common colonizing bacteria isolated from these patients, and is frequently recovered when exacerbation symptoms appear [2] This PPM is able to adapt to changing environments through gene expression changes [3,4,5], some of which modify its virulence [6,7]. Under certain conditions H. influenzae may produce specific enzymes that cleave human IgA1, a subclass of bronchial IgA, separating the antigen recognition fragments of the immunoglobulin from its constant region and inactivating its protective role [13,14,15] This direct effect of the proteases produced by H. influenzae on the levels of IgA may be clinically significant in the pathogenesis of COPD in colonized and infected patients
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