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Surfactant phosphatidylcholine composition during dexamethasone treatment in chronic lung disease
M R Ashton1, A D Postle, D E Smith
1Department of Neonatal Medicine, Southampton University Hospitals NHS Trust.
Insights
Dexamethasone did not mature the phosphatidylcholine (PC) composition in infants at high risk for neonatal chronic lung disease (CLD). The study found no significant increase in dipalmitoylphosphatidylcholine (DPPC) proportions or DPPC:POPC ratios, challenging the proposed mechanism of action.
Area of Science:
- Neonatal Medicine
- Pulmonology
- Pharmacology
Background:
- Neonatal chronic lung disease (CLD) is a significant concern in premature infants.
- Pulmonary surfactant phosphatidylcholine (PC) composition is crucial for lung function.
- Dexamethasone is used to manage neonatal CLD, but its mechanism is not fully understood.
Purpose of the Study:
- To investigate if dexamethasone enhances the maturation of bronchoalveolar fluid phosphatidylcholine (PC) in high-risk infants.
- To assess dexamethasone's effect on dipalmitoylphosphatidylcholine (DPPC) percentage and the DPPC:palmitoyloleoylphosphatidylcholine (POPC) ratio.
Main Methods:
- A double-blind, placebo-controlled study involving 16 infants (<32 weeks gestation, <1250g birth weight) requiring mechanical ventilation.
- Infants received either dexamethasone or placebo for two weeks, starting at 14 days of age.
- Bronchoalveolar lavage was performed serially, and PC composition was analyzed using high-performance liquid chromatography.
Main Results:
- The DPPC:POPC ratio was significantly lower in the dexamethasone group on days 1-3 compared to placebo.
- While some infants showed increased DPPC:POPC ratios later in treatment, overall changes were not statistically significant.
- Dexamethasone did not increase the proportion of DPPC as a percentage of total PC.
Conclusions:
- The study's findings do not support the hypothesis that dexamethasone improves neonatal CLD within 72 hours by 'maturing' pulmonary surfactant PC composition.
- The mechanism of dexamethasone's clinical benefit in neonatal CLD may not involve accelerated surfactant PC maturation.
- Further research is needed to elucidate the precise mechanisms of dexamethasone's therapeutic effects in neonatal CLD.
Objectives:
To determine whether dexamethasone 'matures' the phosphatidylcholine (PC) composition of broncheoalveolar fluid in infants at high risk of neonatal chronic lung disease (CLD), either by increasing the proportion of dipalmitoylphosphatidylcholine (DPPC), expressed as a percentage of total PC (%DPPC), or by increasing the ratio of DPPC to palmitoyloleoylphosphatidylcholine (DPPC:POPC ratio).
Design:
Double blind, placebo controlled.
Setting And Patients:
Sixteen infants < 32 weeks' gestation, < 1250 g birth weight who were dependent on mechanical ventilation and requiring a fractional inspired oxygen of > 0.30 at 12 days of chronological age.
Intervention:
Randomisation to receive a two week reducing course of dexamethasone base at an initial dose of 0.2 mg/kg three times a day, or equivalent volumes of normal saline, starting at 14 days. Eight infants were randomised into each group. Broncheoalveolar lavage was performed serially throughout the study period or until extubation. PC composition of the fluid was analysed by high performance liquid chromatography.
Outcome Measures:
The %DPPC and the DPPC:POPC ratios were calculated for individual infants for days -1 and 0 combined, days 1 and 3 combined, and days 5 and 7 combined. Analysis of covariance was used to analyse the results.
Results:
The DPPC:POPC ratio was significantly less in the treated group than the placebo group on days 1 and 3, and not greater as the hypothesis stated. Three out of five infants treated with dexamethasone and for whom data were available showed a substantial rise in DPPC:POPC ratio on days 5/7, compared with the placebo group, but overall these changes were not statistically significant.
Conclusions:
The data do not support the hypothesis that dexamethasone's action in producing a clinical improvement within the first 72 hours of treatment for neonatal CLD is by the 'maturation' of pulmonary surfactant PC.