scope:

PREFACE

As we enter the first decade of the 21st century, we can be proud of the big achievements in health care that characterized the last one hundred years. The lifespan of a human born in the early 1900s was 48 years; today we believe it is our right to reach our 70s and still contemplate another healthy decade or two. Indeed, vaccinations, water management, antisepsis and antibiotics, and greater understanding of the causes and therapy of many diseases have made longevity the rule rather than the exception.We have witnessed a decrease in the mortality rate from the major causes of death: heart attacks, strokes, and cancer. However, there is a silent killer, which looms menacingly as we begin this new millennium. This disease is chronic obstructive pulmonary disease (COPD), a forgotten chronic illness that has become the fourth major cause of death in the United States, and the world overall, and is projected to be the third most important one in the year 2020.

Unfortunately and undeservingly, COPD has been thought to be progressive and poorly responsive to therapy. This stems primarily from the basic belief that the airflow limitation used to diagnose the disease is largely irreversible. Indeed, if we have defined the disease using a single physiological variable that does not reverse with bronchodilators and we then show that the obstruction does not respond well to therapy, it is no wonder that the general belief is that the disease is progressive and relentless. This has been detrimental in that the general feeling, by patients and their caregivers, has been desperation, frustration, and lack of hope.

The reality is totally different. The last years have seen a dramatic influx of solid studies exploring many forms of therapy that have had great impact on the outcomes of these patients. Indeed, we now know that several forms of therapy improve survival: smoking cessation, oxygen therapy for hypoxemic patients, and lung volume reduction therapy in selected patients with inhomogeneous emphysema do increase survival rates. In addition, pulmonary rehabilitation improves dyspnea, exercise performance, and health status. Within this rich armamentarium, pharmacological therapy is central to the overall management. Indeed, if asked, most of us will think of medication as the first line of therapy for our patients.

This book addresses the major advances that have occurred in the area of pharmacological therapy for COPD over the last decades. It first provides the reader with a review of outcome measurements in order to increase awareness of the fact that airflow limitation, and, for that matter, lung function, as important as they may be, are not the only outcomes that reflect the impact of COPD. Indeed, we have begun to modify the way in which we think of COPD, from one in which the most important effect of any therapy is to modify the obstruction to one in which the therapy is evaluated in terms of its capacity to modify other equally important outcomes. I have often referred to the great advances that have been achieved in the treatment of hypertension, when the focus changed from the treatment of the high value of the blood pressure per se to the effect of the change on other outcomes such as strokes, congestive heart failure, and myocardial infarction. Indeed, the book concentrates not only on the classic physiological outcomes such as the spirometry and static lung volumes but also on the effect of pharmacotherapy on other physiological events, such as dynamic hyperinflation, that have been shown to provide important clues in the pathogenesis of exercise-induced dyspnea. The book also addresses the newer outcomes that have become tools to evaluate the effect of therapy. Indeed, the systematic evaluation of dyspnea and health status in many recent studies has provided a new dimension to our understanding of the management of patients with COPD. Further, the inclusion of exacerbation as an outcome that is crucial to modify has revolutionized how we view the comprehensive therapy of the disease.

The second part of the book centers on the actual effect of the different pharmacological agents on those outcomes. When we look back and see that we have gone from one single agent, theophylline, to several classes of agents, all of which are becoming more selective and potent, we begin to realize our need to better understand their effect and use. Although we all agree that the actual effect of the different medications on the degree of airflow obstruction is relatively modest, its magnitude is not different, percent-wise, from the magnitude of the effect of the antihypertensive agents in high blood pressure. Further, when we appreciate the effect of the different agents on other, more important outcomes, we begin to realize how much we have improved our capacity to help patients suffering from this disease.

In the last chapter I integrate all of the content of the book into one practical synthesis, aimed at the busy practitioner. However, I strongly recommend that the reader progressively enjoy the knowledge that the individual chapters provide. All the contributors are known for their expertise in their field and have made an effort to bring the most recent information to readers.

The evidence presented in this book supports our optimism. It is no longer justified to adopt a negative attitude toward COPD. Fortunately, the great advances we have witnessed pale in comparison with those that will come. The completion of the first two mega-trials-one comparing the effect of tiotropium with placebo on the baseline rate of decline of forced expiratory volume in one second and the other comparing the effect of inhaled fluticasone and salmeterol on survival-will represent a new level of evidence that may become the gold standard. In the meantime, we must make use of what is already a rich body of knowledge to complement the armamentarium currently available to us.

I do not want to close without expressing my gratitude to the contributors who have provided their time and knowledge; to Claude Lenfant,M.D., who had the foresight to begin this now legendary series of books and encouraged me to tackle this project; to the editors at Marcel Dekker, Inc., who know about bringing ideas to print; and to the pharmaceutical industry, which has made possible the testing and production of many agents that are invaluable to our patients. I trust that the future is bright, and that within our lifetime we will begin to see the decline of COPDas a major cause of death and disability.