Therapeutic Targets in Airway Inflammation PDF

PREFACE

Asthma has many etiological aspects and should be treated according to the various causes that bring it about . . . , the success of relieving the patient from asthma depends largely on an intimate knowledge of the total patient . . . , the physician should not treat the disease but the patient who is suffering from it . . . , I have no magic cure to report.

These words of wisdom, uttered almost a thousand years ago, still ring true today. Moshe ben Maimon, a physician, philosopher, and rabbi, practiced in Cairo in the court of Saladin, Sultan of Egypt, whose nephew suffered from asthma. The prince, who lived in Alexandria, found he could tide over an asthmatic attack more quickly by going to Cairo. Maimon attributed this favorable response to the cleaner environment in Cairo as opposed to the contaminated air of Alexandria. He emphasized understanding the patient and the balance between him and his environment (1).

This lack of balance has been linked to asthma over centuries and across civilizations. The ancient Egyptians used the hieroglyphics to mean asthma several millennia ago. The lizard was used as a reference to the wheezing noise a chameleon makes when it deflates its lungs in anger (2). Chinese healers understood that xiao-chuan, or "wheezy breathing," was a symptom of imbalance in the life force. The ancient Greco-Roman physicians' treatment for "gasping" was tailor-made for an individual's unique balance of the four "humors": yellow bile, black bile, blood, and phlegm. Native Americans recognized the effect of the environment on the disease and designated the rain god Tla´loc as the god of asthma (3).

It seems educational to recall these earlier perspectives on asthma at a time when an increase in both asthma incidence and its severity has reached epidemic proportions. One cannot help wondering what sort of imbalance is propagating this epidemic and, more importantly, what specific therapies can target this imbalance. Over the last two decades, airway inflammation has become recognized as a cornerstone in asthma pathogenesis. In a philosophical sense, inflammation can be recognized as a sort of imbalance between the host and its environment. However, inflammation or imbalance encompasses many underlying pathways and mechanisms. If we are to make a serious leap—one that is badly needed—in our understanding and treatment of asthma, we have to dissect the wide variety of complex pathways that contribute to airway inflammation. Only by doing so can we identify potential therapeutic targets. This book attempts to meet this challenge. It should not be perceived not as a prescription for asthma, but rather as a springboard from which future asthma medicine will evolve.

In producing this book, we have assembled a group of physicians and scientists who are considered leaders in their respective fields. The list of contributors is truly a "dream team" of asthma experts. In spite of the length of the book, justified by the vast subject matter, we chose not to divide it into parts because biological processes often defy our arbitrary classification. Instead, we have organized it into rather invisible domains. The emphasis in the early chapters is on the pathophysiology of the disease. Throughout the book, as different mediators are discussed, clear links to therapeutic targets are envisioned. The latter chapters emphasize therapeutic strategies that are in a more advanced stage of development. The book is a state-of-theart assessment of our understanding of the biology and therapeutic targets in airway inflammation.

We would like to thank all of the authors for contributing their time and expertise and, quite often, their prepublication data, which were vital for the book's success. We are also indebted to Dr. Claude Lenfant for his unwavering enthusiasm and support during the production of this book.