Although the airway has traditionally been considered sterile, nowadays, due to the new culture-independent microbiological techniques, it is known that the airway presents a characteristic microbiota, which may be altered in pathological processes. Moreover, bronchial colonization by potentially pathogenic microorganisms (PPMs) in patients with Chronic Obstructive Pulmonary Disease (COPD) has been recognized for years, but its effect is not defined. The studies that form this thesis aim to investigate the effect of the microorganisms on COPD. In the first study, the effect of bronchial colonization by Haemophilus influenzae on the immune response mediated by IgA, and on the levels of metaloproteinase 9 (MMP-9) and its inhibitor, tissue inhibitor of metaloproteinases 1 (TIMP-1) was analyzed, in patients with stable COPD. Analysis of the immune response against this microorganism showed a deficiency that may favor the persistence of colonization. The levels of MMP-9 and its molar ratio with TIMP-1 were significantly higher in colonized patients, which may promote airway remodeling in COPD patients. Therefore, defects in the immune system may facilitate bronchial colonization by H. influenzae. This colonization also seems to stimulate the activity of MMP-9, which could be associated with structural damage. The second study examined the differences between bronchial microbiome of patients with severe COPD in stability and during exacerbation, depending on the presence of bronchial colonization by Pseudomonas aeruginosa. Colonized patients had similar biodiversity than non-colonized patients, despite the higher relative abundance of Pseudomonas genus and, in both groups of patients, exacerbations had the same causative bacterial spectrum. Therefore, in severe COPD patients colonized by P. aeruginosa and non-colonized patients, the same MPPs may cause exacerbation, independently of previous colonization. In the third study we evaluated the changes in bronchial microbiota in severe COPD patients compared to patients with moderate disease. A loss of microbial diversity in the severe stage of the disease was seen, with a greater abundance of genera that include the most important pathogens related to the disease. These works show the effect of the microorganisms on COPD in either stable or exacerbated states.
|Date of Award||30 May 2014|
|Supervisor||Eduard Monso Molas (Director) & Miquel Sabria Leal (Tutor)|