BACKGROUND: The present study tested a novel nebulizer and circuit that use breath enhancement and breath actuation to minimize ventilator influences. The unique circuit design incorporates "wetside" jet nebulization (the nebulizer connected to the humidifier outlet port) to prevent unpredictable aerosol losses with active humidification. The system was studied using several ventilator brands over a wide range of settings, with and without humidification. METHODS: During treatment, a 2-position valve directed all ventilator flow to the nebulizer, providing breath enhancement during inspiration. Aerosol was generated by air 50 psi 3.5 L/m triggered during inspiration by a pressure-sensitive circuit. Particles were captured on an inhaled mass filter. Testing was performed by using active humidification or bypassable valved heat and moisture exchanger (HME) over a range of breathing patterns, ventilator modes, and bias flows (0.5-5.0 L/m). The nebulizer was charged with 6 mL of radiolabeled saline solution. Mass balance was performed by using a gamma camera. Tidal volume was monitored by ventilator volume (exhaled V T) and test lung volume. The Mann-Whitney test was used. RESULTS: A total of 6 mL was nebulized within 1 h. Inhaled mass (% neb charge): mean 6 SD (all data) 31.1% 6 6.45; no. 5 83. Small significant differences were seen with humidification for all modes (humidified 36.1% 6 5.60, no. 5 26; bypassable valved HME 28.8% 6 5.51, no. 5 57 [P < .001]), continuous mandatory ventilation modes [P < .001], and pressure support airway pressure release ventilation modes [P < .001]. Mass median aerodynamic diameter ranged from 1.04 to 1.34 lm. The V T was unaffected (exhaled V T-5.0 6 12.9 mL; P 5 .75) and test lung (test lung volume 25 6 14.5 mL; P 5 .13). Bias flow and PEEP had no effect. CONCLUSIONS: Breath enhancement with breath actuation provided a predictable dose at any ventilator setting or type of humidification. Preservation of drug delivery during active humidification is a new finding, compared with previous studies. The use of wall gases and stand alone breath actuation standardizes conditions that drive the nebulizer independent of ventilator design. Wet-side nebulizer placement at the humidifier outlet allows delivery without introducing aerosol into the humidification chamber.

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BRITISH certain of these changes occurred to a lesser degree in stress involution. The stress-involuted thymuses in our study showed the well-known change of cortical atrophy (Hammar, 1921), cystic Hassall's corpuscles, which have been observed in the involuted thymuses of guinea-pigs given cortisone or x-irradiation (Blau, 1965), and an increased percentage area of epithelial cell aggregates, these also being regarded by Lattes (1962) as associated with stress. The nature of these epithelial aggregates remains uncertain. Their appearances may be due simply to loss of lymphocytes with condensation of reticuloepithelial cells, or they may represent hyperplasia of reticuloepithelial cells, perhaps as a reaction to stress. The fact that these epithelial aggregates are seen to some degree in stressed thymuses makes it unlikely that they have any unique relation to systemic lupus erythematosus.The finding that certain of the thymic changes in systemic lupus erythematosus are an exaggeration, albeit gross, of those present in stress involution is in keeping with the prolonged and often debilitating course of the disease, the long terminal stages, and intense treatment with "thymolytic " drugs such as corticosteroids and mercaptopurines. However, we would emphasize that our series contained three surgically resected thymuses, two of which were from patients who had not received " thymolytic " drugs, yet both showed changes as pronounced as others in the series. On the other hand, the greatly increased numbers of plasma cells in the thymus in systemic lupus erythematosus and the presence of germinal centres in the medulla in two of the cases could not be accounted for by stress involution, and point rather to an immune (probably autoimmune) reaction within the thymus (Goldstein, 1966).C jr interpretation is that the thymus in systemic lupus erythematosus is a target organ. There is histological evidence of extreme stress involution and of an autoimmune reaction which could augment changes usually associated with stress involution. SummayStructural changes in the thymus were assessed by a quantitative method in 13 patients with systemic lupus erythematosus and in two groups of control cases representing minimal stress (94 cases) and stress involution (104 cases).The changes of stress involution included reduction of cortex, epithelial cell aggregates in the medulla, and cystic Hassall's corpuscles. In systemic lupus erythematosus there was pronounced lymphocytic depletion resulting in complete cortical atrophy and disorganization of the medulla. A large proportion of the medulla (mean 36%) was occupied by epithelial cell aggregates, and there was a high proportion (89%) of cystic Hassall's corpuscles; moreover, there were greatly increased numbers of plasma cells, and germinal centres were present in two cases.Our interpretation is that the thymus in systemic lupus erythematosus is a target organ. There is histological evidence of extreme stress involution and of an autoimmune reaction which could augment changes usually...

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