”2 This definition remains broad, describing an “airflow limitation” that, in reality, is caused by distinct features of small-airway disease, chronic bronchitis, and emphysema that may be highly variable among patients despite identical measures of airflow limitation measured by the forced expiratory volume in 1 second (FEV1)/forced vital capacity Veliparib ratio. Research during the past few decades has begun to reveal a new understanding of the pathophysiology, public health impact, and overall complexity of COPD. This

issue of Translational Research contains an in-depth review of COPD that includes 4 articles that serve as illustrative examples of how our understanding of COPD is shifting from a physiologically defined obstructive lung disease caused by cigarette smoking to a complex systemic 17-AAG manufacturer disease with risk that is modified by multiple factors (including genetics and the environment), has variable manifestations in different populations, is characterized by multiple disease phenotypes, and occurs, not in a vacuum, but in the context of

other common comorbid conditions ( Fig 1). COPD is the third leading cause of death in the United States and is the only leading cause of death that is increasing in prevalence.3 Between 1970 and 2002, death rates secondary to stroke and heart disease decreased by 63% and 52%, respectively, whereas death rates resulting from COPD increased by 100%.4 Currently, approximately 14 million Americans have been diagnosed with COPD, although it has been estimated that an additional 12 million individuals remain undiagnosed.5 By 2030, it is estimated that approximately 9 million people will die annually from COPD.6 COPD is also a source of significant health expenditure and societal ADP ribosylation factor costs. Until recently, patients, clinicians, and researchers undervalued the overwhelming impact of this disease on individuals’ quality of life and society’s economic stability. In 2008, it was estimated that the cost to the United States for COPD and asthma was approximately

$68 billion, including $14.3 billion in direct costs and $53.7 billion in mortality costs.5 In a 2001 international study, it was found that 45.3% of COPD patients younger than 65 years of age had missed at least 1 day of work within the previous year secondary to COPD. In that same study, patients with COPD often minimized their own symptoms; 60.3% of patients who ranked their disease as mild or moderate reported severe breathlessness.7 In recognition of the increasing prevalence and costs associated with COPD, during the past decade there has been great progress in our understanding of the pathogenesis, manifestations, and clinical outcomes of this common disease. In this in-depth review issue, we explore and celebrate the strides made while also identifying areas that require further investigation to expand our understanding of COPD.