Respiratory Tract


The reader should be aware that the description of the deposition of inhaled materials in the human airways and alveoli is based almost entirely on indirect information and is colored to a large extent by theoretical ideas. For experimental reasons, the respiratory tract is conventionally divided into three regions: the head (or extrathoracic region), tracheobronchial tree (airways, bronchial region), and alveoli (sometimes also referred to as the peripheral region or the "deep lung") [31,32]. The first region is characterized spatially and also by its short mucociliary clearance half-life (of the order of minutes). The last two regions are named after the corresponding anatomical spaces, but, in fact, they are defined experimentally in terms of clearance: the fraction of the dose retained after 24 hours has been thought to be deposited in the nonciliated parts of the lung, that is, the alveoli. The remaining fraction of the dose that is cleared in normal subjects within 24 hours is then the "tracheobronchial deposition."

In several disease states, the mucociliary clearance is impaired, and in such subjects the clearance from the trachcobronchial tree almost certainly exceeds 24 hours [33,34], making the concept of alveolar deposition in terms of retention in excess of 24hours invalid. The slowly cleared material in normal subjects has been, however, regarded by most investigators as a true reflection of alveolar deposition. More recently, this assumption was seriously questioned [34] as a result of some problems with interpretation of experiments in which attempts were made to deposit materials selectively in the bronchial airways. In these investigations, despite the supposedly exclusive airway deposition that should be subject to mucociliary clearance, a slow phase of clearance was found in normal volunteers. The most plausible explanation of these observations was suggested to be a slow component of clearance from the tracheobronchial tree [35]. Although the classification of the regions in the respiratory tract in terms of clearance rates creates some difficulties with spatial targeting, it is, in fact, the relevant way for the understanding and design of optimal temporal patterns of drug action in the lung [36,37]. Duration of residence in the designated areas can be analyzed and modeled on the basis of this kinetic information, despite the uncertainty of the exact anatomical location of these compartments.

Two-dimensional anterior and posterior images (by gamma scintigraphy), or their geometric averages, of radiolabeled aerosol that are deposited in the respiratory tract should in principle provide an improved understanding of the spatial distribution of the deposited therapeutic and diagnostic aerosols. These studies customarily divide the respiratory tract into the oropharynx (or "extrathoracic deposition," which should include the radiolabeled aerosol swallowed into the stomach) and the pulmonary region. It is not unreasonable to expect that the oropharyngeal deposition should correspond to the head region and that the pulmonary deposition should correspond to the combined tracheobron-chial and alveolar fractions as defined in the techniques described previously.

The pulmonary region of the two-dimensional images is sometimes subdivided into the central and peripheral regions. A measure of regional distribution, the penetration index [38,39], is calculated by taking the ratio of the radioactivity in these two regions, with the intention that this reflects the distribution of radioactivity between the central (large) airways and the small airways combined with the alveoli. However, it has been suspected for some time that the radiolabeled material deposited in the latter region is superimposed over the radioactivity residing in the large (central) airways [40]. This was confirmed in a single-photon emission computerized tomography (SPECT) study [39,41]. Therefore, the interpretation of two-dimensional gamma-scintigraphic images, or the use of the clearance data obtained by techniques with poor spatial resolution, requires some care. Morphometric analysis after SPECT studies may facilitate even more detailed spatial interpretations of the tomographic images [42].

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