Pharmacogenetics and the development of personalized approaches for combination therapy in asthma.

Asthma is a common, chronic disease of the airways that is treated with a combination of different therapies. The combination of LABA and ICS therapy results in a synergistic interaction that is efficacious in improving asthma symptom control; however, genetic variation has the potential to alter therapeutic efficacy. Both agents mediate complex molecular pathways consisting of gene variation that has been investigated with the analysis of candidate genes in the ß2-adrenergic receptor and glucocorticoid pathway. These pharmacogenetic studies have been limited to retrospective analyses of clinical trial cohorts and a small number of prospective, genotype-stratified trials. More recently, genome-wide association studies in combination with replication in additional cohorts and in vitro cell-based models have been used to identify novel pathway-related pharmacogenetic variations. This review of the pharmacogenetics of the ß2-adrenergic receptor and glucocorticoid pathways highlights the genotypic effects of variation in multiple genes from interacting pathways which may contribute to differential responses to inhaled beta agonists and glucocorticoids. As our understanding of these genetic mechanisms improves, panels of biomarkers may be developed to determine which combination therapies are the most effective with the least risk to an individual asthma patient. Before we can usher in an era of personalized medicine for asthma, it is first important to improve our ability to analyze large volumes of genetic data in large clinical trial cohorts using a combination of study designs, analytical methods, and in vitro functional studies.

Argon plasma coagulation and electrosurgery for benign endobronchial tumors.

BACKGROUND: Benign endobronchial tumors are a rare entity capable of causing significant symptoms. Endobronchial tumor destruction has the potential for relieving symptoms while sparing the patient from invasive surgical resection. Although Nd:YAG laser has been successfully used, other less costly approaches such as argon plasma coagulation (APC) and electrocautery, may be effective alternatives for the bronchoscopic treatment of benign endobronchial tumors. METHODS: A retrospective medical chart review was conducted at a single academic center in the United States from the period of January 2005 through December 2011 to collect a minimum of 10 cases for review. Eligibility criteria included diagnosis of a benign endobronchial tumor and age over 18 years. Our institution's pathology database was searched by specific benign tumor and the results were further refined based on an endobronchial location. The bronchoscopic procedure log was also searched and identified procedures were cross referenced with the medical record to confirm eligibility. RESULTS: Ten patients with pathologically confirmed benign endobronchial tumors were identified. All patients achieved tumor regression with APC in combination with electrocautery or cryotherapy. Majority of the procedures (75%) were performed with flexible bronchoscopy and 55% were performed under moderate sedation. CONCLUSIONS: APC is an effective method for tumor devitalization and reduction in tumor size, making it a viable and less costly therapeutic option for the treatment of benign endobronchial tumors.