Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as highthroughput surface plasmon resonance (SPR), that we also describe.

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

“…Alkanes are cleared either by diffusion through the lungs, or by further oxidation to alcohols by cytochrome P450 enzymes [41], which are also known to play a role in the pathogenesis of COPD [42]. Therefore, the complex nature of the inflammation in COPD probably makes metabolomic assessment of biomarkers a suitable approach, as a single marker that is representative of the airway inflammation in COPD has not been identified [13,43,44].…”

“…However, it is a time consuming procedure and patients may find it unpleasant. The different clinical, immunological and oxidative mechanisms of COPD emphasise the need to provide composite profiles of biomarkers of the disease [13]. Integrative metabolomic assessment of molecular signatures by high-dimensional diagnostic techniques can provide fingerprints of disease.…”

“…Integrative metabolomic assessment of molecular signatures by high-dimensional diagnostic techniques can provide fingerprints of disease. In COPD, this has been done at the gene expression and protein level using blood and bronchoalveolar lavage fluid [13,14].…”

Survey of the 2009 commercial optical biosensor literature

“…Full references for the 316 papers that were given the thumbs up are provided in the reference section. To make this list useful as a tool for identifying examples of the various assay formats, the citations are subgrouped by reviews/protocols dedicated to biosensor studies, kinetic, equilibrium/competition, or concentration analyses, qualitative formats (e.g., yes/no, screening, epitope mapping),…”

Analysis of cardiovascular system responses to forced vital capacity in COPD

“…Besides pulmonary involvement, cardiovascular events are commonly observed in this population 2 , although the mechanisms responsible for these manifestations have not yet been fully elucidated. It is postulated that chronic systemic inflammation and/or cardiovascular autonomic neuropathy may be involved [3][4][5][6] , since there is evidence that COPD patients present dysautonomia, sympathetic hyperactivity, reduced vagal tone and heart rate variability (HRV). These phenomena are highly associated with the appearance of arrhythmias and a risk of sudden death in this population [7][8][9][10][11][12][13] .…”