Particle-Lung Interactions [ Active ]

Preface

Leonardo da Vinci (1452–1519), prototype of the universal genius, was a painter, musician, architect, and an engineer. He was also a sculptor and an anatomist. In his Anatomical Atlas he added the short comment above the trachea, "dust is harmful." Today we know that Leonardo da Vinci was right. During the past decades, a growing body of epidemiological and experimental literature has provided evidence that inhalation of "dust," that is, airborne particles in the widest sense, substantially contributes to creating adverse health effects. The characteristics of the particles that may be inhaled with every breath depend on many factors, like season, climate, and environment. Similarly diverse are the health effects of particles, ranging from respiratory to cardiovascular diseases, from asthma over increased susceptibility to viral infections to myocardial infarction. In recent years, there has been evidence that the fraction of nano-sized particles, that is, particles smaller than 100 nm (0.1 mm) are of particular concern.

When the first edition of this book entered the market, the editors anticipated that the field of particle-lung interactions was about to enter a new era. Cautiously, the editors mentioned the likely changes in the preface:

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 the volume on particle-lung interactions.

In 2007, Joachim Heyder and Peter Gehr were asked by the publisher of Claude Lenfant's series on Lung Biology in Health and Disease, Informa Healthcare, whether they would be interested in publishing a second edition of their volume, number 143, on Particle-Lung Interactions. Due to various circumstances Joachim Heyder was not able to work on the second edition. Therefore, Peter Gehr asked three young researchers around him to co-edit the next edition. This gave rise to the new editor team for this second edition on Particle-Lung Interactions. Although Joachim Heyder's wisdom, editorial skills and fundamental and comprehensive knowledge cannot be overrated, the composition of the new editorial team provided different advantages.

Throughout all the work of editing, we experienced a very close and respectful collaboration.

Two things have changed, since the appearance of the last book. Whereas nano-sized particles were briefly mentioned by only a few authors earlier, nanomaterials are now a major aspect in this second edition. A totally new field dealt with in many chapters, which is rapidly gaining significance, is manufactured nanoparticles. Publications in this field are still rather sparse but rapidly growing in number. A lot of experimental work is still needed, and this is particularly true for the good particles as they were called in the preface of the first edition. The hope expressed almost 10 years ago that the treatment of diabetes via the inhalation route will most likely become the first approved aerosol treatment for a systemic disease was abruptly destroyed when Pfizer stopped the production of insulin, apparently due to poor sales. Since then, Lilly and Novo Nordisk have also dropped their plans to produce inhalable insulin.

The lung is a major target of ambient air pollution. The relationship between increased concentrations of air pollution and adverse health effects in children, subjects with asthma and COPD, and vulnerable adults is well documented. Major adverse health effects include not only increased respiratory symptoms, decreased lung function, and increased hospitalization but also altered mucociliary clearance, COPD, asthma, and increased mortality. Several chapters in this book deal with the various diseases associated with particle inhalation.

A number of in vitro studies have been performed to investigate how fine and nano-sized particles enter tissues and cells of the lungs and to determine what effect they may have. In contrast to fine particles that are taken up by cells by phagocytosis, nanoparticles may enter cells by an endocytic or by another, yet to be defined mechanism. This circumstance could be a major cause for the enhanced adverse health effects of nano-sized particles. Many publications have shown that the main cellular effect of exposure to combustion-derived nanoparticles is the production of reactive oxygen species, which is a major factor in inflammation and toxicity. There is increasing evidence that these nanoparticles may pose a particular danger because of their high content of organic chemicals and the pro-oxidative potential. The key properties associated with these particles are their large surface area and the presence of metals and organics, all of which have the potential to produce oxidative stress. Moreover, the same particles may also have genotoxic effects. These aspects are discussed in this book.

Studies investigating the interactions of the lungs with these minute particles have also been stimulated by advances in nanotechnology. This technological branch has been overwhelming us with newly designed materials that due to different physicochemical behaviors offer great advantages in many applications, ranging from antibacterial clothing to car lacquers and to medicinal particles. The latter have the potential not only of drug delivery via inhalation for systemic treatment but also of targeting drugs to specific cell types and even organelles. This might significantly reduce the side effects of current therapeutics or lead to new developments in diagnostics and therapy. However, due to their minute size, potential toxicity should be considered for manufactured nanoparticles as well. In most studies, investigators found that these artificially produced nanoparticles were associated with the generation of reactive oxygen species by cells exposed to the particles. A lot of work is still needed to determine whether the conclusions drawn for combustion-derived particles can be extrapolated to manufactured nanoparticles. Since both nanotechnology in its widest sense and nanotoxicology have been recognized to have a great future impact, governmental programs in the whole world are supporting both research fields financially.

The concern about possible hazardous effects of manufactured nanoparticles crosses the borders of scientific curiosity quickly and enters broad public awareness. Some of the fears associated with nanoparticles are related to the lessons learned from the deleterious effects of inhaled asbestos particles. This time particle researchers are working hard to assess the risks associated with manufactured nanoparticles well in advance to avoid the health consequences and financial burdens that may follow after exposure. While the exposure of combustion-derived nanoparticles affects everyone, it is obvious that the exposure to manufactured nanoparticles may primarily affect people working in the production of nanoparticles, their processing, or application. These important concerns have caused the development of a whole new scientific field known as "nanotoxicology." In January 2006, the first international congress on nanotoxicology took place in Miami and a second one was held in September 2008 in Zurich. Both journals and books entirely devoted to the subject have entered the market. Nevertheless, a great amount of work still needs to be done.

In the light of the new developments, the second edition of this book has to face the dilemma that the established knowledge from the first edition needs to be combined with the vastly growing knowledge gained during the past few years, a process that will surely continue. This dilemma is aggravated by the publishers' request to shorten the book compared to the first edition. Therefore, the second edition of this book has been rearranged completely. Fundamental aspects on pulmonary structure and function as well as different kinds of particles have been shifted into the first and second part of this book to avoid repetition of these aspects in different chapters. The third part deals with the inhalation of particles, their deposition and retention in the respiratory tract as well as their clearance and translocation. The two following parts are devoted to the interaction of particles with biological structures, starting at the systemic and organ level (part 4) and finishing with the cellular and molecular effects inhalation of particles may have (part 5). We provide the reader with a combination of both established knowledge and, hopefully, exciting new observations.

We are well pleased with the result of the second edition and we warmly thank our colleagues for their extraordinary support. Without their special effort, it would have never been possible to finish this publication. We are grateful to the staff of Informa Healthcare for their invaluable and professional assistance in editing this book. The interactions with the authors as well as with the publisher were always stimulating. We do hope that the result will serve its purpose and that this book will take its place among the well-received monographs in the series in Lung Biology in Health and Disease.