Page 33 - MemoriaES-Eng

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terms of readmission rate and mortality within 90 days is alarming, and several

factors have been identified. To study fragile patients cohorts in which these fac-
tors are present is required.

Infection and colonization of the tracheobronchial tree may be related to biolo-

gical activity of the disease. Strong evidence implicates bacterial infection in the

course and pathogenesis of COPD: (i) changes in the respiratory microbiome of
COPD patients compared to healthy individuals have been reported; (ii) chronic

and recurrent infection is associated to chronic bronchitis, to increased risk of
exacerbation, and to accelerated loss of lung function, which may be translating

into activity.; (iii) COPD infectious exacerbation is a frequent cause of death.

In this context, we hypothesize that COPD has different levels of activity that lead

to different natural histories of the disease, ranging from the asymptomatic pa-
tient with preserved lung function along time with little or no exacerbations to the

fragile symptomatic patient with accelerated loss of lung function and frequent

exacerbations. The more fragile patients will show the most prominent markers
of COPD activity that can be later applied to a cohort of early COPD patients in

order to predict the type of progression. Markers of activity can be identified in
the clinical, biopathology, microbiology and imaging domains.

The main aim of this project is to demonstrate and define properly the concept of
Aims and
biologic activity in COPD as the undergoing mechanism that leads to differential
objectives
evolution of disease, ranging from the low activity with low impact and low progres-
sion of disease to the high activity with high impact and rapid progression. As start-

ing point, it is assumed that the fragile patients with more severe disease are those
in which the disease is-or has been-more active. For that reason, this project plans

to explore the concept of activity in a fragile COPD population from the clinical, mi-

crobiologic and experimental point of view as a first step, and subsequently apply
the information obtained from them into a population at early stages of disease.

Mechanistic studies in animal models of fragile, early COPD and microbial infection

will help to probe the hypothesis generated from the clinical studies. To achieve this
general goal, the following specific objectives will be pursued:

1- To validate frailty criteria in relation to prognosis and evaluate the im-

pact of different Health Care approaches to management on disease activity by
generating a fragile COPD cohort.

analyse clinical, imaging and biological markers of activity
2- To as determi-
nants of disease progression and severity in fragile COPD patients.

3- To identify microbiology patterns or changes within the pathogen or the 13
20
host associated to disease progression in Fragile COPD patients.
T
OR
4- To investigate potential markers of activity in animal models.
P
RE
5- To integrate the previously identified markers of activity in fragile patients into a L
A
cohort of early COPD patients in order to identify the patients with more ac- NU
tive disease and faster progression.
N
A
S /
E
ER
B
CI

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