The behavior of terminal lung units (alveoli) with changes in lung volume is controversial. For example, different investigators using similar techniques have suggested that alveoli expand homogeneously or, conversely, get smaller with increases in lung volume. We studied this problem by filling excised dog lobes with monodisperse aerosol and observing deposition at zero airflow. Under these conditions, the deposition of particles is inversely proportional to a mean alveolar linear dimension (ALD). With this technique, changes in ALD were assessed as the lung ventilated along its pressure-volume (PV) curve. PV curves were generated using a rapid cycling technique that minimized trapping and allowed reversible regulation of inflation-deflation hysteresis. Irreversible changes in PV hysteresis were assessed by rinsing the lung with Tween. With significant PV hysteresis, the ALD progressively decreased with inflation to total lung capacity (TLC). With deflation from TLC, the ALD was unchanged until low volumes were reached, when it decreased markedly. When PV hysteresis was minimized (reversibly or irreversibly), inflation and deflation ALD were superimposed. These data are consistent with progressive alveolar recruitment with inflation to TLC and derecruitment with deflation. The correlation between alveolar dimensions and PV hysteresis suggests that shifts in the PV curve can be accounted for by changes in the population of units. The number open at any given point is determined by the dynamic history of inflation.

D De ep po os si it ti io on n o of f a am mp ph ho ot te er ri ic ci in n B B a ae er ro os so ol ls s i in n p pu ul lm mo on na ar ry y a as sp pe er rg gi il ll lo om ma a ABSTRACT: The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99m Tc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb® or DP100® (ultrasonic) or Respirgard II® (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed.Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II®; 26.5 and 28.3% with Fisoneb®; 5.9 and 6.3% for DP100®. Mass median aerodynamic diameter (mean±SD) results were: 0.28±0.04 µm with Respirgard II®; 4.82±0.78 µm with Fisoneb®; and 2.27±1.14 µm with DP100®. Because of larger particles and significantly greater inhaled mass, Fisoneb® delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng·mL -1 . No untoward effects were reported by the patients during the 4 week trial.This study demonstrates that amphotericin B suspension can be accurately radiolabelled, is effectively nebulized by a variety of nebulizers, and is well-tolerated by human subjects.

Using intrabronchial lateral pressure catheters, we determined the precise location and movement of the flow-limiting segment (FLS) in excised dog and human lungs; under maximal flow conditions, profiles of resistance and transmural pressure from the "mouth" to segmental bronchi were also obtained. In the same lungs, using the interrupter technique, IVFP curves were constructed; with these curves and lung compliance, the relationship between Vmax and Pel was studied using the analysis of Pride et al. The FLS consisted of well-demarcated short lengths (2-3 cm) of the trachea at large lung volumes which moved to lobar or semental bronchi at small volumes (10-20% TLC). These relationships, coupled with observations of the movement of the equal pressure point (EPP), support the idea that in the excised lung the location of the FLS is determined by both the location of the EPP and the compliance of the downstream airway wall; thus FLS MAY NOT FOLLOW UPSTREAM MOVEMENTS OF EPP until EPP reaches a more compliant segment of the bronchial tree (lobar and proximal segmental bronchi). Upstream resistance (Rs) and transmural pressure of collapse (Ptm') calculated indirectly from the slope and intercept of the Vmax vs. Pel relationship accurately predicted values of resistance and transmural pressure measured directly in the same lungs at a point just upstream to FLS.

A new technique using a monodispersed aerosol of histamine delivered to sublobar bronchi through a flexible fiber-optic bronchoscope was used to study the role of the vagus nerve and the effect of anesthesia in the response of collateral channels to exogenous histamine. Studies were performed in paralyzed dogs anesthetized with pentobarbital sodium or alpha-chloralose. Challenges with histamine aerosol were delivered to separate bronchi in each animal before and after bilateral cervical vagotomy. Resistance through collateral channels increased in a reproducible manner following histamine challenge. Vagotomy resulted in no significant change in base-line resistance through collateral channels. The response of collateral channels to exogenous histamine aerosol was not significantly affected by vagotomy or the type of anesthesia used. We conclude that vagal reflexes do not play a significant role in the response of collateral channels to exogenous histamine.

We tested the hypothesis that voluntary changes of thoraco-abdominal shape can influence regional ventilation via altering regional pleural pressure swings (Ppl). Regional ventilation was measured simultaneously with regional Ppl during tidal volume breathing maneuvers in five normal subjects while they were performing one of three thoracoabdominal patterns of breathing: normal, preferential intercostal (IC), or preferential diaphragmatic (DIA). In every subject, the lower lung region's 133Xe washout rate was faster than the upper region's, regardless of the pattern of thoracoabdominal breathing adopted. Although IC breathing tended to make regional ventilation more homogeneous, DIA breathing tended to augment regional ventilation inhomogenities. On the average, the Ppl values were greatest in the lower lung region, regardless of the thoracoabdominal pattern adopted; however, IC breathing reduced and DIA breathing increased regional Ppl inhomogenities. When the ratios of the Ppl (lower/upper) were plotted vs. the ratios of the regional 133Xe washout decay constants (lower/upper), a significant positive correlation was found. These data suggest that a causal relation between regional tidal Ppl and regional ventilation exist, thus supporting the concept that thoracoabdominal shape changes can influence regional ventilation.