Introduction

The explosion of knowledge about aerosol medicine since the early 1990s is impressive. Who would have thought 10-15 years ago that we would be investigating aerosols for use in such things as lung transplantation, gene therapy, treatment of respiratory failure, nicotine for smoking cessation, and many others, as well as adding new and valuable information to currently utilized therapeutic modalities such aerosol bronchodilators, aerosolized steroids, and, for CF, antibiotic aerosols. The potential for aerosol science to contribute to medical care has never been greater. The focus of this review is on three broad topics: (1) certain basic aspects of aerosol deposition, (2) new information about "old" aerosols, i.e., bronchodilators and their delivery, and (3) new horizons for aerosols in the treatment of human diseases.

As we recognize the progress in management of diseases by inhalational delivery of drugs as aerosols, it is necessary to acknowledge that many of the human conditions we treat are caused directly by inhaled particles. In the United

States alone, about 450,000 deaths a year are directly attributable to toxins inhaled via tobacco smoke. The increasing use of tobacco in developing nations is now bringing the epidemic of diseases caused by tobacco to the rest of the world. Occupational exposure to minerals such as asbestos and silica is now very much reduced in the industrialized West, but exposure continues to be a problem in the Third World. Inhaled antigens cause allergic lung diseases such as asthma, and inhaled microbes cause infections ranging from viral to tuberculosis. The importance of inhaled particles in the pathogenesis of lung disease cannot be overemphasized.

Some of the diseases caused by inhaled toxins and antigens are treated with inhaled medications. Inhalation therapy has been a mainstay of the treatment of lung disease for centuries [1]. Although most such early therapies were worthless, a few were effective. The inhalation of smoke from plants containing stramonium has been used since antiquity to treat asthma [2].

In 1974, the Sugarloaf Conference [3] underscored the empiric nature of many applications of inhalation therapy, as it was called at that time. The scientific basis for many treatments was very weak. Although there has been considerable progress since the early 1980s, there are today still many uncertainties about inhaled drug delivery and many variations of delivery equipment and methods. A more recent consensus statement reviews some advances and describes continuing needs for investigation [4].

Given the current rising interest in aerosol treatment modalities, it is especially remarkable that nothing of consequence is taught in medical schools about particle generation or deposition in the lung. The vast majority of physicians who order aerosol treatments of any type for their patients know next to nothing about this process. This is not to say they are uninformed about the medications they prescribe, only the delivery method. Graduates of schools of pharmacy are probably similarly devoid of adequate teaching about inhaled medications. The changing knowledge about best delivery practices is not well disseminated.

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