Inducible nitric oxide synthase (iNOS): role in asthma pathogenesis.

Asthma is one of the most common chronic inflammatory disorder of the airways of the lungs, affecting more than 300 million people all over the world. Nitric oxide (NO) is endogenously produced in mammalian airways by nitric oxide synthase (NOS) and is known to regulate many aspects of human asthma, including the modulation of airway and vascular smooth muscle tone and the inflammation. Asthmatic patients show an increased expression of inducible nitric oxide synthase (iNOS) in airway epithelial cells and an increased level of NO in exhaled air. Using various NO inhibitors (non-specific or iNOS-specific) and gene knock-out experiments, controversial results have been obtained regarding iNOS's beneficial and deleterious effects in the disease. In the present review, we have attempted to summarize the results of these experiments and also the genetic studies being undertaken to understand the role of iNOS in asthma. It is argued that extensive biochemical, clinical and genetic studies will be required to assess the precise role of NO in the asthma. This may help in designing selective and more potent iNOS inhibitors and NO donors for developing novel therapeutics for the asthma patients.

Genetics of asthma: current research paving the way for development of personalized drugs.

Asthma is a complex genetic disorder involving the interplay between various environmental and genetic factors. In this review, efforts have been made to provide information on the recent advances in these areas and to discuss the future perspective of research in the area of developing personalized drugs using pharmacogenomic approach. Atopic asthma is found to be strongly familial, however the mode of inheritance is controversial. A large number of studies have been carried out and a number of candidate genes have been identified. In addition, a number of chromosomal regions have been identified using genome-wide scans, which might contain important unknown genes. It has been shown in studies carried out in different populations that the genetic predisposition varies with ethnicity. In other words, genes that are associated with asthma in one population may not be associated with asthma in another population. In addition to the involvement of multiple genes, gene-gene interactions play a significant role in asthma. The importance of environmental factors in asthma is beyond doubt. However, it remains controversial whether a cleaner environment or increased pollution is a trigger for asthma. Despite the increasing prevalence of the disorder, only a limited number of therapeutic modalities are available for the treatment. A number of novel therapeutic targets have been identified and drugs are being developed for better efficacy with less side-effects. With the rapid progress in the identification of genes involved in various ethnic populations combined with the availability in future of well-targeted drugs, it will be possible to have appropriate medicine as per the genetic make-up of an individual.