CRC BIOTHER APPR ASTH PDF

PREFACE

Despite the current multiple therapeutic options for asthma, in the United States more than 5000 patients annually succumb to asthma. A major proportion of these patients with asthma live with chronic limitation of activity, intermittent exacerbations, decreased quality of life, and progressively declining respiratory function. Elucidating the role of inflammation in the pathogenesis of asthma has led to acceptance of corticosteroids as the requisite controller therapy. However, patients remain reluctant to use inhaled corticosteroids because of concern about the adverse side effects of such therapy. Poor compliance with preventive (controller) therapy only emphasizes the need for improved therapeutic options.

Recent discoveries and our enhanced appreciation of the epidemiological, genetic, and immunological mechanisms that contribute to the pathogenesis of asthma now provide insight into newer approaches for the prevention and treatment of asthma. Clinical trials of the newer therapeutic modalities available as a result of DNA and monoclonal antibody technology have provided clarification of the relative roles of the participating various inflammatory pathways. This volume links such scientific appreciation of asthma to the newer effective asthma therapies.

The book is divided into 9 parts, including 15 chapters, which address the current status of asthma therapy with regard to some of the promising new interventions derived from the enhanced appreciation of the various immunobiological mechanisms participating in the genesis of this disorder.

Part One addresses the inhibition of allergen sensitization. Chapter 1 introduces the hygiene hypothesis and the pertubation of IFN-γ. Chapter 2 presents the current epidemiological understanding of the role of aeroallergens and their primary avoidance in asthma causation.

Part Two discusses the role of anti-IgE therapy in asthma (Chapter 3).

Part Three pertains to the role of mast-cell-mediator inhibition in asthma therapy. Chapter 4 addresses the role of immunoreceptor tyrosine-based inhibitory motifs (ITIM) and Chapter 5 the mast-cell-mediated immune responses in the lung, particularly those mediated by proteases and tryptases.

Part Four focuses on targeting the proallergic cytokines. Chapter 6 covers interleukin-4 inhibition and Chapter 7 covers anti-interleukin-5, anti-interleukin-9, and interleukin-10 for the treatment of asthma. Chapters 8 and 9 discuss therapeutic targeting of chemokines and chemokine receptors, as well as interleukin-13, as therapeutic strategies in asthma therapy. Tumor necrosis factor and interleukin-1 asthma inhibitory therapies are reviewed in Chapter 10.

In Part Five, the development and inhibition of the Th2 response is addressed in Chapter 11.

Part Six addresses cell adhesion molecule blocker/modulators in Chapter 12.

Part Seven relates to allergen-specific immunotherapy (Chapter 13).

Part Eight addresses the glucocorticoid effects on mediator modulation/ inhibition (Chapter 14).

Finally, Part Nine is devoted to future asthma therapies. Despite the development of many promising modalities to treat asthma, Chapter 15 enumerates some of the limitations to such therapies and the necessity for focusing on the newer formulations of current pharmacological interventions.

This book assembles information regarding drugs that may soon reach human clinical trials. Newer, more specifically targeted pharmacological interventions may present safe and effective therapeutic modalities that may enhance compliance and, hopefully, reduce asthma morbidity and mortality.