Influence of the Surfactant Tyloxapol on Mucociliary Clearance in Human Respiratory Cystic Fibrosis Cells

Beubler, Eckhard; Fischer, Rainald; Untersteiner, Gerald; Strohmaier, Wolfgang

doi:10.1159/000444589

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Both models are well characterised in terms of structure, barrier properties, expression of tissue -relevant markers and in vivo-like behaviour (Balogh Sivars et al, 2018;Baxter et al, 2015;Huang et al, 2017;Iskandar et al, 2013;Zavala et al, 2016). In addition to tissue inserts derived from healthy donors, MucilAir™ and EpiAir-way™ tissues are also available from donors with airway diseases such as cystic fibrosis (Beubler et al, 2016), asthma (Chortarea et al, 2017) and COPD. This may be beneficial in the development of new treatments for these conditions, or for risk assessments relevant to these particularly vulnerable groups.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro

Welch

Wallace

Lansley

et al. 2021

Regulatory Toxicology and Pharmacology

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The aim of the study was to use multiple in vitro assays to assess the effects of a model irritant, sodium dodecyl sulphate (SDS) (≤10 mM (0.29 %, w/v)), on an in vitro model of the airway, MucilAir™. The use of MucilAir™ in recovery studies was also explored.A 24 h exposure increased IL-8 release at an SDS concentration ≥0.63 mM (0.018 %, w/v). Mucin secretion increased and transepithelial electrical resistance (TEER) decreased at SDS concentrations ≥1.25 mM (0.04 %, w/v). Cytotoxicity (lactate dehydrogenase (LDH) release into basolateral chamber) was observed at SDS concentrations of ≥2.5 mM (0.07 %, w/v). The sensitivity of the assays was IL-8 release > TEER = mucin secretion > LDH release.After 7 days, full or partial recovery was observed for intermediate concentrations of SDS using all assays but not at 5 and 10 mM SDS. Morphologically, erosion and cell loss were observed at these concentrations. Resazurin metabolism at 7 days tended to decrease in a dose-dependent manner at SDS concentrations above 2.5 mM (0.07 %, w/v).Together, these data support a No Observable Effect Level of 0.31 mM (0.009 % w/v) SDS and the use of MucilAir™ as a relevant model for airway toxicity studies.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro

Welch

Wallace

Lansley

et al. 2021

Regulatory Toxicology and Pharmacology

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“…According to the reported effect on the airways, elevated tracheal IL-6 levels, a proinflammatory cytokine and an important mediator of the acute phase response, have been measured in patients with tracheostomy compared to controls [ 18 ]. The influence of a substitution of surfactant on the limited mucociliary clearance has already been described for different types of applications in different situations [ 19 , 20 ]. In addition to a restoration of mucociliary clearance, a decrease of the IL-6 levels in tracheal fluid following surfactant therapy was observed, indicating its ability to modulate levels of inflammatory cytokines in the airways [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Liposomal Inhalation after Tracheostomy—A Randomized Controlled Trial

Hofauer

Straßen

Chaker

et al. 2021

JCM

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Background: Tracheostomy is a common procedure in critical care. The aim of this study was to evaluate the application of a liposomal inhalation compared to standard physiologic saline (SPS) inhalation on basis of objective and subjective parameters of airway inflammation. Methods: We evaluated in this two-armed, double-blinded and randomized control group study the effect of liposomal compared with SPS inhalation in newly tracheotomized patients. The primary endpoint was defined as trend of tracheobronchial IL-6 secretion at day 1 compared to day 10. Further objective and subjective parameter were evaluated. Results: Fifty patients were randomized in each arm. Tracheal IL-6 levels decreased significantly only after liposomal inhalation. Both inhalative agents seem to have an effect on the respiratory impairment after tracheostomy. Subjective patient impairment was reduced significantly from day 1 to day 10 after tracheostomy with liposomal inhalation. Conclusions: Liposomal inhalation demonstrated an advantage over SPS inhalation in newly tracheotomized patients.

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“…These parameters are all of relevance to both infectious disease and chronic disease progression. 33,[56][57][58][59][60][61] Specifically considering SARS-CoV-2 studies, a recent paper by Pizzorno and coworkers 62 applied two commercially available ALI nasal and bronchial epithelial models to assess the host response to the virus, as well as to investigate potential therapeutic options. The in vitro models employed in the study successfully addressed several disease hallmarks, including: virus replication kinetics; epithelial barrier function; ultrastructural tissue alterations; differential inflammatory response of epithelial cells from nasal and bronchial compartments; and the antiviral activity of remdesivir/diltiazem in combination.…”

Section: Air-liquid Interface (Ali) Modelsmentioning

confidence: 99%

“…These parameters are all of relevance to both infectious disease and chronic disease progression. 33,56–61…”

Section: Air–liquid Interface (Ali) Modelsmentioning

confidence: 99%

The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside

Silva

Valadares

2023

Altern Lab Anim

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The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.

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Influence of the Surfactant Tyloxapol on Mucociliary Clearance in Human Respiratory Cystic Fibrosis Cells

Cited by 5 publications

References 13 publications

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro

Liposomal Inhalation after Tracheostomy—A Randomized Controlled Trial

The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside

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