Drug Delivery to the Lung PDF

PREFACE

Aerosolized delivery of drugs to the lungs has dramatically improved the treatment of a variety of respiratory diseases. For example, bronchodilator and antiinflammatory aerosol medications are the cornerstone of asthma treatment; antibiotics, DNase, and hypertonic saline are established treatment options in cystic fibrosis; and nebulized adrenaline and steroids have been used to treat croup. There is great interest in using the lungs as a portal of entry for systemic drug therapy. Measles vaccination has been successfully administered via the inhaled route and the possibility of diabetics inhaling as opposed to injecting insulin is becoming a reality.

Aerosol drug delivery allows treatment to be targeted to the lower airways and total systemic exposure to be reduced. The device chosen has a major impact on aerosol delivery, and it should be considered an integral part of any prescription or drug approval. To date, this is rarely reflected in treatment guidelines for conditions such as asthma and cystic fibrosis, nor in day-to-day clinical practice or drug labeling. Inconsistent terminology, variations in study methodology and design, and the absence of guidelines have all led to confusion among practitioners.

Device development and documentation are driven by many different needs. For patients, important factors include device size, simplicity, irritants, taste and odors, and interactive features. Such factors impact on compliance, which is the main hindrance for effectiveness of aerosol treatment. The needs of the patient change significantly with age. On the other hand, clinicians require knowledge of the fraction of drug likely to reach the lungs when different delivery devices are used for patients of different ages. Finally, health regulators tend to emphasize only in vitro reproducibility. The choice of drug defines the need for accurate estimation of drug delivery; for example, less accurate dosing of ß2-agonists is acceptable due to their wide therapeutic index. Steroids and insulin, with narrower therapeutic indices, require more accurate drug delivery. Impact on the environment is an important concern, and risk of exposure of caregivers should be considered. Efficient devices may be a priority since they reduce the loss of drug, which improves safety of treatment as well as cost effectiveness. Such a multitude of needs determines the development, documentation, and, eventually, choice of device.

Aerosol treatment is maturing technically with recent advances in the understanding of lung dose and major innovations in device technology. If the important knowledge gained within this area is to have an impact on the management of our patients, it is mandatory that aerosol standards and principles be clearly communicated to the health professional. With this aim, a group of leading experts joined together to develop a milestone publication on the stateof- the-art knowledge in the area of aerosol treatment. This volume has compiled their very comprehensive knowledge into an easily readable text with an emphasis on clinical implications.

This book is intended for clinicians, nurses, and respiratory therapists interested in the role of aerosol delivery for optimal management of lung diseases. The content was inspired by a debate between the authors, with the editors serving as referees. This process was fertilized by a workshop in the spring of 1999, which defined the general principles and emphasized clinical relevance to the practitioner. The practical implications of the issues communicated have been strongly emphasized. Therefore, we hope this book will act as a bridge between basic aerosol science and good clinical practice in the treatment of lung diseases.

This meeting and the resulting book have been made possible through an educational grant from AstraZeneca. We wish to express our gratitude to the editor of this series, Dr. Claude Lenfant, for his interest and support.