Nebulization of Poractant alfa via a vibrating membrane nebulizer in spontaneously breathing preterm lambs with binasal continuous positive pressure ventilation

Hütten, Matthias C.; Kuypers, Elke; Ophelders, Daan; Nikiforou, Maria; Jellema, Reint K.; Niemarkt, Hendrik J.; Fuchs, Carola; Tservistas, Markus; Razetti, Roberta; Bianco, Federico; Kramer, Boris W.

doi:10.1038/pr.2015.165

Cited by 32 publications

(19 citation statements)

References 48 publications

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“…For instance, aerosol delivery of surfactant has been shown to improve lung function in animal models and it has been attempted in combination with non-invasive ventilation in clinical studies[16, 39, 40]. The clinical results of these studies did not find a clear advantage of aerosolized surfactant so far and this delivery method remains under active preclinical development[28, 41, 42]. The InSurE technique was successfully introduced by Verder et al .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the majority of these studies were performed during tracheal intubation and mechanical ventilation with full control of the airway. Managing preterm lambs in CPAP has been shown to be feasible in lambs with mild to moderate RDS, although pulmonary outcomes after surfactant treatment in combination with non-invasive ventilation are difficult to interpret due to the high variability in the response to CPAP and surfactant, and to the low sample size of lamb studies[28, 29]. BAL-based in vivo models of respiratory distress have also been managed in CPAP with conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, in the era of non-invasive surfactant, in order to be clinically relevant, the ventilation strategy of in vivo models must switch from the traditional use of invasive ventilation through a tracheal tube, towards the use of non-invasive support such as CPAP. In this regard, although feasible to some extent, managing preterm lambs in CPAP is complicated and the pulmonary outcomes after surfactant treatment are difficult to interpret due to the high variability in the response, and to the low sample size[28, 29]. In the case of BAL-based lung injury models the transition from invasive ventilation after the BAL procedure to non-invasive ventilation is certainly challenging and will depend, to a large extent, on the number of BALs performed to induce the lung injury[19, 20].…”

Section: Introductionmentioning

confidence: 99%

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Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

et al. 2017

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Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

et al. 2017

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“…A more high-tech approach that is now being tested in the NICU is surfactant administration through aerosolization, nebulization, or atomization (60–67). It has proven technically challenging to achieve sufficient delivery of surfactant in the distal lung compared to bolus administration of surfactant, although the recent development of vibrating membrane nebulizers seems promising (67).…”

Section: Bpd In 2017mentioning

confidence: 99%

The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment

Collins¹,

Tibboel²,

Kleer³

et al. 2017

Front. Med.

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Yearly more than 15 million babies are born premature (<37 weeks gestational age), accounting for more than 1 in 10 births worldwide. Lung injury caused by maternal chorioamnionitis or preeclampsia, postnatal ventilation, hyperoxia, or inflammation can lead to the development of bronchopulmonary dysplasia (BPD), one of the most common adverse outcomes in these preterm neonates. BPD patients have an arrest in alveolar and microvascular development and more frequently develop asthma and early-onset emphysema as they age. Understanding how the alveoli develop, and repair, and regenerate after injury is critical for the development of therapies, as unfortunately there is still no cure for BPD. In this review, we aim to provide an overview of emerging new concepts in the understanding of perinatal lung development and injury from a molecular and cellular point of view and how this is paving the way for new therapeutic options to prevent or treat BPD, as well as a reflection on current treatment procedures.

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“…Longer nebulization of higher doses of surfactant in humidified air improved oxygenation and lung mechanics. Surfactant was delivered to all lung lobes, with a preference to the lower lobes when given at high doses [64]. However, the yield of the nebulized surfactant into the lungs was very poor.…”

Section: New Techniques Of Surfactant Administrationmentioning

confidence: 99%

Surfactant for Respiratory Distress Syndrome: New Ideas on a Familiar Drug with Innovative Applications

Niemarkt¹,

Hütten²,

Kramer³

2017

Neonatology

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In the last 4 decades, advances in neonatology have led to a significant increase in the survival of preterm infants. One of the biggest advances was the introduction of surfactant replacement therapy for the treatment of respiratory distress syndrome. This is the main cause of respiratory insufficiency in preterm infants and is one of the major causes of perinatal morbidity and mortality. Surfactant replacement therapy is already a well-investigated and established therapy in neonatology. However, surfactant replacement therapy has progressed and been refined over recent decades, especially with the increasing care for preterm infants born before 26 weeks' gestational age and the recent clinical focus on avoiding mechanical ventilation. Clinical evidence is evolving on new types of surfactant, surfactant dosages, co-medication given before, with, or after surfactant replacement, and new technical advances regarding the mode of administration.

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Nebulization of Poractant alfa via a vibrating membrane nebulizer in spontaneously breathing preterm lambs with binasal continuous positive pressure ventilation

Cited by 32 publications

References 48 publications

Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome

The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment

Surfactant for Respiratory Distress Syndrome: New Ideas on a Familiar Drug with Innovative Applications

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