Elsevier

Journal of Proteomics

Volume 75, Issue 1, 10 December 2011, Pages 192-201
Journal of Proteomics

Review
Proteomics in asthma and COPD phenotypes and endotypes for biomarker discovery and improved understanding of disease entities

https://doi.org/10.1016/j.jprot.2011.10.008Get rights and content

Abstract

The application of proteomics to respiratory diseases, such as asthma and COPD, has been limited compared to other fields, like cancer. Both asthma and COPD are recognised to be multi-factorial and complex diseases, both consisting of clusters of multiple disease phenotypes. The complexity of these diseases combined with the inaccessibility and invasiveness of disease relevant samples have provided a hurdle to the progress of respiratory proteomics. Advances in proteomic instrumentation and methodology have led to the possibility to identify proteomes in much smaller quantities of biological material. This review focuses on the efforts in respiratory proteomics in relation to asthma and COPD, and the importance of identifying subgroups of disease entities to establish appropriate biomarkers, and to enhance the understanding of underlying mechanisms in each subgroup. Careful phenotype characterisation of patient subpopulations is required to make improvement in the field of heterogeneous diseases such as asthma and COPD, and the clusters of phenotypes are likely to encompass subgroups of disease with distinct molecular mechanisms; endotypes. The utilisation of modern advanced proteomics in endotypes of asthma and COPD will likely contribute to the increased understanding of disease mechanisms, establishment of biomarkers for these endotypes and improved patient care.

Graphical abstract

Highlights

► Asthma and COPD are diseases comprising of multiple phenotypes. ► The complexity of asthma and COPD is challenging to study by proteomics. ► Improved phenotyping may improve future proteomic studies. ► Proteomic studies of disease phenotypes may reveal pathobiological mechanisms.

Introduction

From the clinic to the bench and back again, respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) pose multiple challenges in understanding their respective mechanisms. Despite being two of the most common chronic diseases in the world, their exact molecular mechanisms have yet to be elucidated. The challenge of analysing mechanisms is further confounded by the presence of multiple phenotypically specific subgroups within each disease and the overlapping symptoms between diseases.

A combination of challenges may have led to the relatively slow pace of asthma and COPD proteomics in relation to other respiratory proteomic studies (Fig. 1). The relative inaccessibility of relevant biological samples, combined with the heterogeneity of asthma and COPD diseases, and methodological difficulties, poses many problems to be overcome. The increase in asthma and COPD proteomics studies may reflect the improvement in technology, which can address some methodological difficulties (Fig. 1). Despite efforts and the identification of some biomarker candidates, translation of these to clinical applicability is rare. Careful selection of patient phenotypes, in combination with clinically relevant patient samples (i.e. bronchial/lung tissue) will have the potential to contribute to a substantially improved understanding of the different mechanisms of the endotypes of each disease, using global proteomic studies.

This article reviews the recent efforts in the respiratory proteomics field and the importance of selecting samples from distinct disease subgroups, to assist in improving the understanding of the underlying mechanisms of disease entities.

Section snippets

Asthma and COPD

Asthma and COPD are complex diseases which affect millions of people worldwide and constitute a huge burden for sufferers and society. The global prevalence of both diseases is predicted to increase substantially in the decades to come. Both asthma and COPD are diagnosed by specific medical history, spirometry and other physiological measurements, but few molecular markers currently exist to assist in diagnosis. Currently, only markers of eosinophilic disease (ECP; eosinophil cationic protein

Clinical respiratory proteomics

Proteomic studies of clinical samples; clinical proteomics, face more challenges than the proteomics of genetically identical mice or cell cultures. The natural variation of the human proteome can be compounded by variations in external factors like sample collection, storage, handling and processing [14].

In addition to the difficulties faced by clinical proteomics in general, respiratory proteomics faces further challenges. As the biological samples and methods used in respiratory proteomics

Proteomics of asthma and COPD

In comparison to other fields, the use of proteomics in the field of respiratory proteomics, in particular asthma and COPD, has not been as extensive. To improve the understanding of respiratory diseases, research has moved from the detailed analyses of individual proteins to the global proteomic analyses in an attempt to identify mechanisms of disease and use it as a hypothesis generating or screening tool.

Phenotypes of asthma and COPD

The heterogeneity of asthma and COPD is due to the existence of multiple phenotypes within the diseases and overlapping symptoms. In addition, each disease has multiple phenotypes with vastly different underlying mechanisms. As well as distinguishing asthma from COPD, distinguishing the multiple phenotypes within each disease and the underlying mechanisms, is crucial for appropriate patient care.

“Phenotypes”, defined as “the visible characteristics of an organism resulting from the interaction

Conclusions

The existence of phenotypes and endotypes in respiratory diseases, especially asthma and COPD, has been known for a while. Immunological and clinical studies will continue to contribute to the understanding of the underlying mechanisms of asthma and COPD in general, but specifically in disease endotypes. As proteins are the functional molecules in the body, determining the proteomic differences in patients, and changes induced by disease progression, disease severity and treatments, will also

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