In chiefly patients.

In chiefly patients, the deposition of aerosolized pentamidine (AP) is les in the apex of the lung relative to the base. As the apex of the lung is relatively les ventilated than the base, it is possible that reduc regional ventilation may explain the inhomogeneity in regional medicine deposition. The purpose of this inquiry was to measure the relationship between regional deposition of AP and regional ventilation, and the influence of particle size and airway caliber in succession this relationship. Ten exposes with HIV infection who were receiving prophylaxis with AP were recruited. Using krypton ([sup81m]Kr) we measured regional ventilation during treatment with AP, labeled with [sup99m]Tc pair nebulizers were used (Respirgard II and Fisoneb) that produc particles of different size. In addition, patients were studied with and without a bronchodilator because changes in airway geometry can affect sites of particle deposition. There was no significant correlation between regional ventilation and regional particle deposition (r = 000 linear regression). Particle deposition in the upper lobes relative to the lower lobes was les than would be predicted from regional ventilation, by a ratio of 084 [+ or -] 003 (mean [+ or -] SE) Using two-way analysis of variance (ANOVA), the upper to lower region deposition pattern was not affected on either nebulizer or by the use of albuterol. The Fisoneb had significantly more central deposition relative to the jet nebulizer (mean [+ or -] SE [Ssubk] C/P: Fisoneb 13 [+ or -] 01 Respirgard 11 [+ or -] 01 p = 0005 two-way ANOVA). The use of a bronchodilator did not significantly affect the central/peripheral deposition pattern. We infer that differences in deposition between upper and lower lung regions are not accounted for simply through differences in regional ventilation in patients undergoing prophylaxis with AP. In assessing the cause of regional inhomogeneities of pharmaceutical aerosol deposition (and in devising strategies to achieve more uniform distribution), regional ventilation should be measured directly rather than be inferred from the deposition pattern of the aerosol.

Aerosolized pentamidine (AP) is used as prophylaxis of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus (HIV) infection.[1] However, in addition to its part in preventing P carinii, AP may oblige as a paradigm for a modern generation of aerosolized therapies. In contrast to chiefly preexisting nebulized medications, it was intended for delivery to the alveoli, rather than to the airways. Furthermore, its delivery and efficacy could not be judg through simple clinical criteria, in contrast to bronchodilators, which are generally the most commonly administered aerosolized remedys Efforts to optimize AP therapy have yielded fresh techniques of administering therapeutic aerosols and a greater understanding of the principles governing the measurement of their deposition and clinical efficacy, increases that are likely to influence the what may occur hereafter design and assessment of other aerosolized medications.[2-11]

An issue that has stimulated a great deal of discussion during the evaluation of AP has been its regional distribution. Les aerosol is deposited in the upper lobes relative to the lower lobes[5-7] and it has been give an inkling ofed that this may contribute to localized recurrence[1213] Regional variation in ventilation between the upper and lower lung regions has been propos as a possible mechanism for the observ inhomogeneities in deposition.[6,12] This hypothesis alerted some investigators to suggest ways of improving upper lobe distribution: for example, administering therapy with the patient in a supine position or modifying the aerosol delivery system[5-7] Although these maneuvers undoubtably improve upper lobe deposition, it is not clear if the improvements are appropriate to a change in regional ventilation or to a change in a certain quantity of other factor (eg, the caliber of airspaces in a particular region). The uncertainty through the whole extent of the relationship between ventilation and deposition has implications for to come efforts to regionally target aerosolized medicines For example, if regional ventilation is the alone determinant of regional deposition of small pharmaceutical aerosols (mass median aerodynamic diameter [MMAD] = 1 [micro]m), then optimization of regional ventilation would spring in optimization of regional put drugs into deposition. However, if regional ventilation is not the solitary determinant of regional deposition, then more entangled strategies may be needed to optimize deposition.

In this contemplation we decided to measure regional ventilation using krypton ([sup81m]Kr) contemporaneously with the deposition of AP and papal court if they correlated. Further, because the choice of aerosol delivery method has been shown to influence regional deposition of AP,[5,7,13] we administered AP to each enslave using two types of nebulizer--an ultrasonic device (Fisoneb, Fisons, Rochester, NY) and a jet nebulizer (Respirgard II, Marquest, Englewood Colo) These are the sum of two units most commonly used devices for the administration of AP in North America. Because these devices bring forth aerosols of different sizes,[2] we can assess the result of changing particle size upon the relationship between regional ventilation and deposition. The Fisoneb causes larger particles and was the device used in an important clinical cogitation that reported increased upper lobe relapse.[12] In addition, we decided to assess the efficiencys of routinely administering an aerosolized [beta]-agonist with each of these nebulizers onward regional deposition and ventilation in HIV-infected patients.

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