SUMMARY 1. Glucocorticoids are an effective treatment in the amelioration of chronic lung disease in neonates. However, systemic administration of glucocorticoids to neonates is associated with significant side‐effects that preclude them as an early intervention to prevent onset of the condition. Conversely, local intratracheal administration of glucocorticoids may prevent inflammatory insult to the lungs without the development of systemic side‐effects. We therefore investigated whether local intratracheal delivery of corticosteroids could be facilitated using surfactant as a vehicle. 2. Addition of dexamethasone to either diluted or commercial artificial surfactant, Survanta (Abbott Industries, Sydney, NSW, Australia), did not alter the surface properties of the surfactant. 3. After intratracheal instillation to rats, radiolabelled dexamethasone in Survanta was well distributed throughout all four lobes of the lungs. A concentration gradient of the steroid was observed between the root and the peripheral sections of all lobes. 4. Our results suggest that surfactant is an effective vehicle for intratracheal delivery of glucocorticoids. Moreover, we propose that prophylactic intratracheal administration of glucocorticoids administered shortly after birth may prevent inflammatory insult to the lungs and thereby reduce the likelihood of chronic lung disease developing.
Alveolar proteinosis (AP) is an idiopathic condition characterized by excess alveolar surfactant. Although the surfactant proteins (SP) are known to be aberrant, little is known of their variation between patients or their abundance relative to the lipids. We have examined surfactant composition in lavage fluid from 16 normal subjects and 13 patients with AP, one of whom was lavaged on 11 occasions over approximately 13 mo. In this patient we have examined composition on each occasion and in each sequential lavage aliquot. Composition was constant between right and left lung, but it differed markedly between patients. The cholesterol/disaturated phospholipid ratios (CHOL/DSP) were invariably elevated, on average by approximately 7-fold, whereas the SP-A/DSP and SP-B/DSP ratios were generally elevated, in some cases by as much as approximately 40- and approximately 100-fold, respectively. Although AP lavage generally contained more non-thiol-dependent SP-A aggregates and low Mr isoforms, the two-dimensional immunochemical staining patterns varied between patients and right and left lung. In the patient lavaged on multiple occasions, the SP-A/DSP and SP-B/DSP ratios progressively decreased as the patient's condition resolved. Because the SP-B/SP-A ratio was normal in all cases, we suggest that structural changes to the proteins occurred secondarily and that caution must be used in comparing functional data derived using SP-A obtained from patients with AP.
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