New Study Proves Useful in the Diagnosis and Treatment of COPD and Asthma
A research study recently published in the International Journal of Chronic Obstructive Pulmonary Disease entitled "The search for common pathways underlying asthma and COPD" identifies biological pathways and processes critical to asthma and International Journal of Chronic Obstructive Pulmonary Disease (COPD) and genetic similarities between the two diseases by constructing interaction networks among those pathways.
According to author Professor Nobuyuki Hizawa, "A common pathogenetic basis for asthma and COPD is implied by overlapping clinical characteristics, epidemiologic studies, and association of genes common to both asthma and COPD. Our study identified biological pathways and processes critical to asthma and COPD and genetic similarities between the two diseases by constructing interaction networks among those pathways. Identification of networks shared by asthma and COPD implies a polygenetic variation affecting the same pathway and the alteration of a functional network as a common root for increased risk for asthma and COPD, which may prove useful in the diagnosis and treatment of these two diseases."
The research provides a clear exposition of a very complex and vital area of research, says journal editor-in-chief Dr Richard Russell. "The linkages between disease phenotype and genetic susceptibility are poorly understood. However, as we discover more and clarify these links then new therapeutic targets will be identified.”
Recently, several genes and genetic loci associated with both asthma and COPD have been described as common susceptibility factors for the two diseases. In complex diseases such as asthma and COPD, a large number of molecular and cellular components may interact through complex networks involving gene–gene and gene–environment interactions. This study sought to understand the functional and regulatory pathways that play central roles in the pathobiology of asthma and COPD and to understand the overlap between these pathways.
The study authors searched the PubMed database up to September 2012 to identify genes found to be associated with asthma, COPD, tuberculosis, or essential hypertension in at least two independent reports of candidate-gene associations or in genome-wide studies. To learn how the identified genes interact with each other and other cellular proteins, we conducted pathway-based analysis using Ingenuity Pathway Analysis software.
They identified 108 genes and 58 genes that were significantly associated with asthma and COPD in at least two independent studies, respectively. These susceptibility genes were grouped into networks based on functional annotation: 12 (for asthma) and eleven (for COPD) networks were identified.
Analysis of the networks for overlap between the two diseases revealed that the networks form a single complex network with 229 overlapping molecules. These overlapping molecules are significantly involved in canonical pathways including the “aryl hydrocarbon receptor signaling,” “role of cytokines in mediating communication between immune cells,” “glucocorticoid receptor signaling,” and “IL-12 signaling and production in macrophages” pathways. The Jaccard similarity index for the comparison between asthma and COPD was 0.81 for the network-level comparison, and the odds ratio was 3.62 (P < 0.0001) for the asthma/COPD pair in comparison with the tuberculosis/essential hypertension pair.
In conclusion, although the identification of asthma and COPD networks is still far from complete, these networks may be used as frameworks for integrating other genome-scale information including expression profiling and phenotypic analysis. Network overlap between asthma and COPD may indicate significant overlap between the pathobiology of these two diseases, which are thought to be genetically related.
"This paper is of great importance for not only the Chest disease world but also the wider medical community. Our current understanding of disease is often based upon the results of the disease and what we see, which physiological or biochemical changes occur. This has led to treatments that are often directed at symptoms and not the underlying disease mechanisms. This needs to change. In a resource limited world we need to be much smarter with treatments and identify which patients with which specific types of a disease, such s types of asthma or COPD, will respond to which drugs. Thus, we give the right drugs to the right patients and not waste them on patients who are unlikely to get benefit and not put them at risk of unnecessary side effects," explains Dr. Russell.
"Understanding the genetic basis of disease and an individuals genetic response to disease is extremely complex and requires special expertise, but the benefits are potentially enormous. This paper is one of the first in this field to successfully analyze the links between disease phenotype and genetics in asthma and COPD. This work will directly lead to new avenues for research, potential for new therapies and a better use of our existing therapies."
The authors of the article are as follows: Yoshiko Kaneko, Yohei Yatagai, Hideyasu Yamada, Hiroki Iijima, Hironori Masuko, Tohru Sakamoto, Nobuyuki Hizawa, Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Japan.
Clinical Oncology in Adolescents and Young Adults is an international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus will be given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is directed at specialists and healthcare professionals.
Dove Medical Press Ltd is a privately held company specializing in the publication of Open Access peer-reviewed journals across the broad spectrum of science, technology and especially medicine.
Updated 23 July 2014