Preface

Cystic Fibrosis (CF) is the most common autosomal recessive inherited disease. The inci‐ dence of CF in the UK is around 1 in 2,500 live births with 1 in 25 carrying a CF gene muta‐ tion. CF is a multisystem disorder and is characterised by chronic suppurative lung disease and by exocrine pancreatic insufficiency, which affects gastrointestinal function and causes restricted growth and maturation. CF also causes obstructive azoospermia and thus male infertility. It is an autosomal recessive disorder and is accounted for by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The main function of CFTR in many tissues is to regulate and participate in the transport of chloride ions across epithelial cell membranes. Thus far, more than 1,900 mutations have been described in this gene, but the most common mutation worldwide is caused by the deletion of phenylalanine at position 508 (Delta F508) of the CFTR.

The existing therapeutic modalities for CF lung disease are predominantly reliant on the me‐ chanical clearance of airway secretions, treatment of infection with novel antibiotics and in‐ tense nutritional support and care delivered by dedicated specialist CF centres. All these have contributed to the improved life expectancy and quality of life in recent decades. How‐ ever, antibiotic treatments are at times fraught with difficulties of bacterial resistance and cumulative toxicity, and they are also cumbersome and time consuming for patients and families. Eventual respiratory failure is the main cause of mortality in CF. Hence, there is a pressing need for the development of newer treatment approaches.

This book has attracted leading experts in this field, covering a variety of topics regarding this fascinating condition ranging from microbiology, immunologic aspects, therapeutic op‐ tions and the exciting genetic management of this condition.

It is well recognised that *Pseudomonas aeruginosa* is the major infective organism in adult CF lungs; there is a dedicated chapter that defines some of the niches which enable this organ‐ ism to thrive in the CF lung and the available therapeutic options.

Another chapter presents an overview on the impact of respiratory viruses in CF, providing an insight on the interaction between viruses and bacteria as well as the preventative and therapeutic measures that are currently available for the management of viral lung infection in CF.

There is also a chapter that outlines how the prognosis of this life-limiting illness has changed in the last decade and some co-morbidities in CF that may influence its long-term outcomes. It also outlines some useful clinical measurements which may enable clinicians to make predictions on CF prognosis.

#### X Preface

CF-related diabetes is an emerging area. This book recounts the difficulties in securing this diagnosis and the advantages of continuous glucose monitoring rather than the traditional oral glucose tolerance test as a diagnostic tool for this condition. It also explains how some lifestyle changes may potentially improve glycaemic control.

As CF prognosis improves, this poses a question about fertility in patients with CF. This subject also poses challenges to clinicians when addressing fertility issues with CF patients. This book provides some advanced treatment options for infertility in CF and the subse‐ quent impact of pregnancy on lung function progression, diabetes control and nutritional status.

Oxidative stress has been implicated as a causative factor in the etiology of progressive lung damage in CF. Supplementation with antioxidant micronutrients might therefore be helpful in rendering progression of CF lung disease. A section is this book is dedicated to looking at the main pathways of oxidative stress in CF and the role of new antioxidant treatments.

Despite advances in our understanding of the molecular and cellular bases of CF, there per‐ sists an enigma as to why recruited neutrophils fail to eradicate bacterial infections in the lung. This books provides an overview of neutrophil functions in CF as well as the altera‐ tions of cellular activities that lead to the pathogenesis of this disease.

Genetic treatment is a hot topic in CF. This book encompasses a collection of chapters that provide an overview of the therapies that are designed to enhance CFTR protein activity. The book also presents some theoretical possibilities and primary data in preclinical models using genome editing and technologies that support in vivo gene correction of CFTR. All these aspects provide hope to enhance the overall prognosis of this condition. This is a book aimed for clinicians, scientists and researchers with specialist interest in CF. I hope that they will gain a greater insight into this fascinating condition, as I have done. Through the inter‐ esting ideas expressed by the authors, I hope this will generate future research ideologies and innovations which may have significant impacts on this life-limiting illness.

I would like to use this opportunity to thank all the authors who have contributed to this book; without their effort, this book would not have materialised. I would also like to thank INTECH for appointing me as the Editor and providing me with guidance throughout the development of this book.

Finally, I would like to thank my wife, Pauline, and my three lovely children, Lucinda, Har‐ rison and Edison, for sacrificing their precious family time for the preparation of this book.

> **Dr Dennis Wat** Consultant Chest Physician Liverpool Heart and Chest Hospital, United Kingdom

**Basic Science for the Clinician**

CF-related diabetes is an emerging area. This book recounts the difficulties in securing this diagnosis and the advantages of continuous glucose monitoring rather than the traditional oral glucose tolerance test as a diagnostic tool for this condition. It also explains how some

As CF prognosis improves, this poses a question about fertility in patients with CF. This subject also poses challenges to clinicians when addressing fertility issues with CF patients. This book provides some advanced treatment options for infertility in CF and the subse‐ quent impact of pregnancy on lung function progression, diabetes control and nutritional

Oxidative stress has been implicated as a causative factor in the etiology of progressive lung damage in CF. Supplementation with antioxidant micronutrients might therefore be helpful in rendering progression of CF lung disease. A section is this book is dedicated to looking at the main pathways of oxidative stress in CF and the role of new antioxidant treatments.

Despite advances in our understanding of the molecular and cellular bases of CF, there per‐ sists an enigma as to why recruited neutrophils fail to eradicate bacterial infections in the lung. This books provides an overview of neutrophil functions in CF as well as the altera‐

Genetic treatment is a hot topic in CF. This book encompasses a collection of chapters that provide an overview of the therapies that are designed to enhance CFTR protein activity. The book also presents some theoretical possibilities and primary data in preclinical models using genome editing and technologies that support in vivo gene correction of CFTR. All these aspects provide hope to enhance the overall prognosis of this condition. This is a book aimed for clinicians, scientists and researchers with specialist interest in CF. I hope that they will gain a greater insight into this fascinating condition, as I have done. Through the inter‐ esting ideas expressed by the authors, I hope this will generate future research ideologies

I would like to use this opportunity to thank all the authors who have contributed to this book; without their effort, this book would not have materialised. I would also like to thank INTECH for appointing me as the Editor and providing me with guidance throughout the

Finally, I would like to thank my wife, Pauline, and my three lovely children, Lucinda, Har‐ rison and Edison, for sacrificing their precious family time for the preparation of this book.

**Dr Dennis Wat**

Consultant Chest Physician

Liverpool Heart and Chest Hospital, United Kingdom

lifestyle changes may potentially improve glycaemic control.

tions of cellular activities that lead to the pathogenesis of this disease.

and innovations which may have significant impacts on this life-limiting illness.

status.

X Preface

development of this book.
