CRC PART-LUNG INTRACTN PDF

PREFACE

The atmospheric environment is composed of a number of gases in which particles are suspended. As a consequence, millions of particles are inhaled with every breath. A surface area the size of a tennis court is available in the lungs for the deposition of these particles. This huge surface area is in direct contact with the atmospheric environment, and is thus the primary target for inhaled particles. Usually particles in the diameter range of 0.01–10 mm are deposited in the lungs and are therefore available for interactions with pulmonary surfaces. Unfortunately, however, different definitions of particle size ranges are in use so that data are often not comparable. We were not able to cope with this problem, but we hope that Table 1 will help in the interpretation of the presented data.

The deeper a particle is deposited in the lungs the thinner is the barrier separating the lumen from blood vessels. In airways, it can be as thick as 20 mm; in peripheral airspaces, as thin as 0.5 mm, as illustrated in Figure 1. It is, therefore, most likely that the vulnerability of the epithelium to deposited particles depends on its location within the lungs.

The residence time of the particles on the epithelial surface is rather short. The particles may 1) be readily soluble in the fluid covering the epithelium; 2) be cleared by the mucociliary escalator; 3) be taken up by macrophages or epithelial or dendritic cells; or 4) penetrate into the interstitium. Depending on their disposition, they can activate cells, alter cell function, and interfere with cellto- cell communication. These responses, on the cellular and molecular level, to deposited particles can often be compensated for by the physiological defense capacity of the lungs, such that respiratory and nonrespiratory lung functions are not affected. However, they can also stimulate processes with which the lungs are unable to cope and thereby initiate cascades of pathophysiological events that can result in altered respiratory and nonrespiratory lung functions.

This all depends on the number of particles deposited in the lungs and on the mass of chemicals they carry into the lungs. Because the concentration and composition of particles in the indoor and outdoor environments vary considerably in space and time, the lungs are exposed to an ever-changing level and mixture of particles. Current research focuses on the question of which levels and mixtures should be considered a health risk. Many epidemiological studies, clinical studies with human volunteers and experimental animals, and studies on cell and tissue cultures are being carried out worldwide in attempts to answer this question.

On the other hand, particles can be used to carry drugs into the lungs for topical or systemic therapy. This field still has many controversial aspects: technical aspects regarding drug formulation and particle generation and the question of how drugs might interfere with pathogenic processes of pulmonary or systemic diseases.

Every human being experiences lifelong exposure to environmental particles, some also experience exposure to particles generated by occupational activities, and others are purposely exposed to therapeutic particles. Therefore, the characteristics of environmental, occupational, and medicinal particles are discussed at the beginning of the book. Their deposition and disposition in the respiratory tract are considered in the next chapter, before the discussion turns toward biological responses initiated by deposited particles. These responses are often physiological responses, without pathophysiological consequences. However, some of them are considered adverse responses. Therefore, health consequences associated with the inhalation of particles are discussed in the last chapter.

Since this monograph first took shape, the field of particle–lung interactions has expanded considerably. The ‘‘bad'' particles are currently ultrafine particles released into the environment from combustion processes. The ‘‘good'' particles are those carrying insulin into the lungs. The treatment of diabetes via the inhalation route will most likely become the first approved aerosol treatment for a systemic disease. Nevertheless, we both hope that established knowledge and controversial issues are sufficiently reflected in this volume on particle–lung interactions.

We are honored to have been asked to edit this monograph and grateful for the support of all the colleagues who contributed to the book. Now that the work is done, we must confess that—once in a while—we went through times of irritation, but the overwhelming sensation remaining is the enjoyment of the stimulating interactions with the executive editor, Claude Lenfant, all the authors, and the publisher while this book was formed. We are very pleased and grateful that this book is now available to the scientific and professional community. We certainly hope that it will serve its purpose and will take its place among the well-received monographs in the Lung Biology in Health and Disease series.