1502 decreased only tracheal reactivity with no effect on lung tissue [50, 51]. Nevertheless, in the above-mentioned clinical studies [4, 77, 78], no differences between the methylprednisolone- and budesonide-treated groups were found. Similarly, inhaled GCs (beclomethasone) showed no priority to intravenous GCs (dexamethasone) in ventilator- dependent preterm newborns [72]. We may speculate that the absence of superior action of locally administered GCs to systemic GCs may be related to the method of administration used—nebulization. Consider- ing high extrapulmonal losses (>80%) of nebulized material [61], other ways of administration, such as slow administra- tion directly into the trachea, should be considered. In our study, budesonide administered via inpulsion effect of HFJV effectively improved the lung functions with minimum losses of the drug and negligible side effects [49, 51]. Intratracheal administration of GCs may be further mitigated by the use of suitable vehicle, e.g. saline or exogenous surfactant [22]. In experimental conditions, an addition of GCs to exogenous surfactant did not alter the surface properties of the surfactant and GCs were well distributed throughout the lungs with 30–60% of the delivered material detected in the lung tissue [58]. In preterm infants, intra- tracheal instillation of a mixture of budesonide (0.25 mg/kg) and beractant (100 mg/kg) every 8 h decreased the mean airway pressure, oxygenation index and PCO2 and reduced deaths and chronic lung disease at 36th week of postconcep- tional age compared to the group treated solely by Survanta (100 mg/kg, every 8 h) [90]. Combinations of GCs with other drugs Regarding the results of experimental and clinical studies, GCs may show some benefit in the treatment of MAS. However, due to the complex and multifactorial pathophys- iology of the disease, other drugs (e.g. exogenous surfactant) should be included in the therapeutic scheme, too. In newborns with MAS, intravenous dexamethasone at a single dose of 0.5 mg/kg was administered within the first 5 h of life prior to a bronchoalveolar lavage using beractant (5 mg/ml) in a volume of 15 ml/kg in four aliquots [62]. The authors found that the surfactant lung lavage in combination with dexa- methasone pretreatment may improve the status of the newborns with MAS more effectively than the surfactant lavage alone [62]. Similarly, in animal models of acute lung injury, the combination of dexamethasone with exogenous surfactant showed an additional improvement to the surfac- tant treatment alone [13, 26]. By utilization of their synergic or additive effects, GCs may be well combined also with other medicaments, e.g. with methylxanthine derivatives such as theophylline [32], with antioxidants such as N-acetylcysteine [33] or with β2- agonists such as terbutaline [84]. In the experimental model Eur J Pediatr (2011) 170:1495–1505 of MAS, intratracheal budesonide followed by the intrave- nous administration of aminophylline improved the lung functions more effectively than aminophylline alone [53]. Concluding remarks Despite the increasing number of trials with GCs in experimental models and newborns with MAS, their administration is still missing in the generally accepted therapeutic protocol of MAS. However, favourable results from the studies indicate that GCs may be beneficial, particularly in severe forms of MAS with apparent lung edema, pulmonary vasoconstriction and inflammation. Summarizing all mentioned data, in the future, the research activities should be focused on an appropriate dosing, timing and ways of administration of GCs considering their individual properties and possible acute and long-term side effects. Since the causal treatment of MAS should consist of several agents, it is necessary to also verify the promising combinations of GCs with other drugs, particularly with exogenous surfactant, anti- inflammatory drugs and pulmonary vasodilators. Acknowledgement This work was supported by “Center of Excel- lence for Perinatology Research” Project No. 26220120016 co- financed by EU sources and by Ministry of Education VEGA Project Nos. 1/0061/08, 1/0057/11 and 1/0030/11. Conflicts of interest The authors have no financial relationship with the organization that sponsored the research. 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