Introduction: The Burden of Respiratory Disease

Respiratory disease refers to the broad category of illnesses affecting the upper and lower airways, the lung parenchyma, and the pulmonary vasculature. To date, however, studies focusing on the pharmacogenetics of respiratory disease have been largely concentrated in the areas of lung cancer and obstructive lung disease. This is primarily due to the relative rarity of many pulmonary diseases, providing insufficient sample size for pharmacogenetic studies. In addition, for many respiratory diseases, there is a relative paucity of available therapies, providing no current alternatives even if a priori prediction of poor response to therapies was available. For many of these diseases (e.g., interstitial pulmonary fibrosis, chronic hypersensitivity pneumonitis, and primary pulmonary hypertension), multicenter studies and/or industry collaborations are warranted. This chapter focuses on the genetics of drug treatment response in obstructive lung disease, with an emphasis on the pharmacogenetics of asthma. Although lung cancer is the leading cause of cancer deaths in both males and females in America and clearly of great importance, the pharmacogenetics of oncologic disorders has been covered separately in Chapter 10. We will review how the respiratory pharmacogenetics fits within the context of the four major categories of pharmacogenetic response and detail approaches to defining respiratory pharmacogenetic phenotypes. The chapter continues with a review of the literature on the pharmacogenetic associations that have been characterized in relation to asthma and chronic obstructive pulmonary disease (COPD). We conclude with some thoughts on the future of pharmacogenetics in these two diseases. However, we first provide an overview of the burden of obstructive respiratory disease.

Chronic obstructive respiratory disease, including COPD and asthma, is currently the fourth leading cause of death in the United States and is projected to move into third place nationwide by 2020 (1). Although mortality rates for the top two leading causes of death in the United States, heart disease and cancer, respectively, are decreasing, deaths from chronic lung disease continue to rise. According to the National Center for Health Statistics, more than 16 million people in the United States have been diagnosed with COPD, and it is estimated that another 16 million cases are undiagnosed (2). COPD cost the nation more than $30 billion in 2000, $14.7 billion in direct health care costs and $15.7 billion in indirect costs. In 2007, there were 22.9 million Americans with asthma, with an estimated annual cost of $19.7 billion ($14 billion in direct costs, of which the largest component was medication costs). Whereas COPD is a leading cause of morbidity and mortality in the elderly, asthma remains the leading cause of hospitalizations and school absences in children.