Preface

Cough is one of the most frequent complaints for which patients seek medical attention. Acute cough has massive health economic consequences and yet available treatments are at best of limited efficacy. Chronic cough is a common and debilitating symptom that in the past has frequently been poorly managed. Our perception of cough as a symptom is now changing. Progress has been made in defining the range of conditions responsible for persistent cough and scientific advances in understanding the biology of the cough reflex should in time lead to improved therapeutic strategies. In this volume, we have drawn on the expertise of a body of international opinion to present the current state of knowledge concerning the pathogenesis and treatment of acute and chronic cough.

The opening chapters address the basic science of the cough reflex. Dr. Hwang discusses the molecular biology of the putative cough receptor TRPV1, activation of this receptor by endogenous ligands, and molecular mechanisms that may operate to upregulate its function in the setting of pathologic cough. Dr. Canning and Dr. Mazzone discuss the conflicting work on afferent nerve pathways mediating cough and present evidence that a distinct and previously unrecognized subtype of afferent neuron may play a primary role in regulation of the cough reflex. Dr. Shannon and colleagues review central neuronal networks involved in generating the motor pattern of the cough reflex and present recent novel observations from their own laboratory. In chapter 4, Dr. Advenier and colleagues consider the evidence to support a role for tachykinins as important mediators of cough. They discuss the antitussive effects of tachykinin receptor antagonists in animal models, including recent work from their own laboratory, and consider their relevance to human disease. Angiotensin converting enzyme (ACE) inhibitors represent an important cause of chronic cough. In chapter 5, Dr. Morishima and colleagues review animal studies that provide insights into the mechanisms of ACE inhibitor-induced cough and also discuss the clinical management of this condition.

There is a need for more effective antitussive medications and the next chapters focus on recent developments in the pharmacology of cough. Dr. Geppetti and colleagues concentrate on the pharmacology of TRPV1 and other putative cough receptors: selective TRPV1 antagonists are now becoming available and it is likely these will play an important role in dissecting cough pathways in various settings. Dr. Chung appraises other agents that are under investigation as potential novel therapies in cough.

The third section concerns experimental methodologies. Dr. Earis and Dr. Smith describe their work on the acoustic properties of the cough sound and the development of automated cough recognition algorithms, studies that will be integral to the development of a robust, accurate, and clinically useful cough recorder. The remaining chapters in this section deal with the various sorts of inhalation cough challenge. The authors of these chapters critically appraise the various approaches that have been taken, make specific recommendations about how factors such as reproducibility can be improved, and consider the way forward in terms of increasing co-operation and standardization between different centers.

The final section addresses the more clinical aspects of cough in both the acute and chronic settings. The emphasis here is on helpful advice on appropriate investigation, avoiding pitfalls in diagnosis, and providing practical strategies for successful management. Prof. Eccles reviews the mechanisms of cough associated with acute upper respiratory tract infection and highlights the lack of evidence to support the various treatments that are widely used in this condition. Dr. Everett and Prof. Morice review the strategies that can be taken to investigate and manage patients with chronic cough and consider the relative merits of the different approaches. Chapters 14–19 are devoted to the major specific causes of chronic cough. The first two of these chapters are devoted to cough associated with gastroesophageal reflux disease (GERD). Dr. Ing discusses the pathogenesis of this condition in terms of a self-perpetuating cough-reflux cycle and also includes important recent information about hereditary autonomic neuropathies associated with cough. Dr. Allen concentrates on the effective management of GERD-related chronic cough, including assessment of nonacid reflux and the role of laparoscopic fundoplication. In chapter 16, Dr. Redington examines the epidemiology, pathophysiology, and pathology of cough-variant asthma with emphasis on how this differs from more typical asthma. Eosinophilic bronchitis has emerged as an important cause of chronic cough in some populations and Dr. Brightling and colleagues discuss the diagnosis, pathophysiology and management of this condition. Dr. Bartter and colleagues discuss the definition, differential diagnosis, and treatment of postnasal drip. Psychogenic cough is covered by Dr. Greenberger who offers practical advice on the diagnosis and management of this difficult condition. Prof. Morice discusses possible mechanisms that may be responsible for hypersensitivity of the cough reflex in disease states and speculates how this knowledge will allow rational drug design to normalize cough. In chapter 21, Dr. Fujimura reviews the evidence that chronic cough is more frequent in females and discusses possible mechanisms underlying this difference. Assessment of quality-of-life/health status is increasingly becoming an important outcome measure in many clinical studies. In chapter 22, Dr. Birring and Dr. Pavord describe the development of a validated cough-specific quality-of-life instrument, the Leicester Cough Questionnaire, and its use in clinical and research settings. Chronic cough in children differs in many aspects from that in adults. In the final chapter, Dr. Marchant and Dr. Chang describe the different approach that is necessary to diagnose and manage cough in children.

Our intention in co-editing this volume has been to produce a timely, comprehensive, and authoritative summary of current understanding, to suggest likely future developments, and to identify areas where knowledge is deficient and further research is required. We hope that this will be of interest to investigators, clinicians, and students.