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Lipid- and protein-mediators critical in the pathological mechanisms underlying chronic obstructive pulmonary disease

Final Activity Report Summary - COPD PROTEOMICS (Lipid- and protein-mediators critical in the pathological mechanisms underlying Chronic Obstructive Pulmonary Disease)

Chronic obstructive pulmonary disease (COPD) is a global health problem of pandemic proportion and is expected to become a leading cause of global morbidity and mortality within 15 years. Furthermore, new evidence indicating that exposure to air pollutants increases the risk of developing the disease is shifting the perception of COPD as solemnly a smokers’ disease towards becoming a general health concern in urban areas. COPD is primarily an inflammatory disease of the peripheral airways. However, in contrast to other chronic airway inflammatory diseases, no efficacious treatments currently exist to prevent the inflammatory progression of COPD, which invariably leads to impaired lung function and premature death. The mechanisms underlying the disease progression are not well understood, yet very few resources have been allocated to the study of COPD.

The main objective of the proposed study was to profile the abundance of specific proteins in different compartments of the lung of patients with early stage COPD as compared to healthy smokers and never-smokers in order to identify protein-mediators that were critical in the development of COPD. Through the use of these so called ‘proteomics’ methods, in combination with bioinformatic applications and database construction, a global understanding of the cellular mechanisms underlying COPD could be achieved.

Over the two year tenure of this project, a large translational COPD study involving a total of 120 volunteer subjects of both genders was designed and initiated and sample collection was progressing well by the time of the fellowship completion. In addition, a range of novel methods, specifically optimised for clinical settings, were developed. These included standards for monitoring the acute smoking status of volunteer subjects through measuring the levels of carbon monoxide in exhaled air, novel internal standard methods for gel-based proteomics and, finally, the design of an innovative method for in-gel protein visualisation and quantification, which facilitated a drastic improvement in both the dynamic range and sensitivity of protein detection. The latter resulted in a patent. Upon completion of this project, which was expected to last about 5 years, the results were anticipated to have major effects upon the field of inflammation-associated diseases and would potentially develop new diagnostic techniques for early stage lung disease, enabling clinicians to apply intervention at earlier stages, thereby greatly reducing the costs to society and saving lives. A secondary accomplishment could be the identification of novel pharmaceutical targets for COPD.