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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Coordinator
Dr. Borja G. Cosío
Defining biologic activity in copd: from the fragile patient to the
early stage of the disease
It is necessary to study patients with early COPD for the understanding of the natural history of the disease and for the design of therapeutic interventions with potential to modify its prognosis . COPD is a highly prevalent disease affecting about 44 million people in Europe . In contrast to other major causes of death, its prevalence has been increasing in the past three decades . However, the natural history
of COPD is still poorly understood, which limits the targets for intervention . The heterogeneous nature of COPD has led to the proposal that there might be different natural histories with different pathogenetic mechanisms in COPD . Indeed, the ECLIPSE study has shown that this accelerated loss of lung function is not present in 40% of patients diagnosed and treated for COPD . There are many questions about the natural history of the disease unresolved, such as the effect of lung development during childhood and adolescence on the future risk of COPD, the progression or activity of the disease from early stages, the role of bronchial hyperresponsiveness, the role of infection, among others . The lack of a reliable animal model has contributed to maintain this problem. Also, little is known about the early stages of COPD because most patients are either never diagnosed or diagnosed at the age of sixty when they already have moderate to severe disease . Furthermore the diagnosis of COPD is associated with a poorer quality of life and to a greater use of health resources .
There is a need for biomarkers of disease progression even in animal models . A number of attempts have been made in the last decade to obtain suitable biomarkers of COPD and its different associated conditions . However, only a general approach to this objective, with no really wide clinical applicability, has been achieved . The fact that only a limited number of molecules have been explored so far, especially in the area of inflammatory activity, may account for such a shortcoming . Despite these considerations, there are still interesting new possibilities such as those concerning lung injury, and the structure and metabolism of vascular and muscular tissues, among others . It is therefore necessary to identify biological markers of progression and of upmost importance to define and validate the concept of disease activity in COPD .
The role of COPD exacerbations and airway infection on disease activity is unknown.
COPD exacerbations are intermittent events occurring in the course of this disease . They speed the progression of the disease, reduce health-related quality of life and are associated with significant mortality, which can all translate into disease activity . The role of treatment on disease activity is unknown . A recent European audit showed that delivery of care based on the differences of resources revealed a huge inequality of care throughout Europe . As a consequence the outcome of COPD in 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 factors are present is required .
Infection and colonization of the tracheobronchial tree may be related to biological 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 patient with preserved lung function along time with little or no exacerbations to the fragile symptomatic patient with accelerated loss of lung function
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