Toward an optimized strategy of using various airway mucus clearance techniques to treat critically ill COVID-19 patients

Muco-obstructive lung diseases (MOLDs), like cystic fibrosis and chronic obstructive pulmonary disease, affect a spectrum of subjects globally. In MOLDs, the airway mucus becomes hyperconcentrated, increasing osmotic and viscoelastic moduli and impairing mucus clearance. MOLD research requires relevant sources of healthy airway mucus for experimental manipulation and analysis. Mucus collected from endotracheal tubes (ETT) may represent such a source with benefits, e.g., in vivo production, over canonical sample types such as sputum or human bronchial epithelial (HBE) mucus. Ionic and biochemical compositions of ETT mucus from healthy human subjects were characterized and a stock of pooled ETT samples generated. Pooled ETT mucus exhibited concentration-dependent rheologic properties that agreed across spatial scales with reported individual ETT samples and HBE mucus. We suggest that the practical benefits compared with other sample types make ETT mucus potentially useful for MOLD research.

Download Full-text

Rehydration Of Surface Liquid And Restoration Of Mucociliary Clearance In A Fluid-depleted Airway Mucus Clearance Model

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6239 ◽

2010 ◽

Author(s):

Darryl W. O'Brien ◽

Ming C.J. Chiang ◽

Gustavo Zayas ◽

Malcolm King

Keyword(s):

Mucociliary Clearance ◽

Mucus Clearance ◽

Surface Liquid ◽

Airway Mucus ◽

Clearance Model

Download Full-text

Effects Of Mechanical In-Exsufflation On Mucus Clearance In Critically Ill Patients On Invasive Mechanical Ventilation

10.21203/rs.3.rs-52429/v1 ◽

2020 ◽

Author(s):

Roberto Martinez-Alejos ◽

Joan-Daniel Martí ◽

Gianluigi Li Bassi ◽

Daniel Gonzalez-Anton ◽

Xabier Pilar-Diaz ◽

...

Keyword(s):

Mechanical Ventilation ◽

Critically Ill ◽

Critically Ill Patients ◽

Invasive Mechanical Ventilation ◽

Invasive Technique ◽

Pulmonary Mechanics ◽

Post Intervention ◽

Mucus Clearance ◽

Registration Number ◽

Clinically Significant

Abstract Background: Mechanical insufflation-exsufflation (MI-E) is a non-invasive technique performed through the CoughAssist In-Exsufflator to simulate cough and remove mucus from proximal airways. To date, the effects of MI-E on critically ill patients on invasive mechanical ventilation (MV) are not fully elucidated. The purpose of this study was to compare the efficacy and safety of MI-E combined or not to manual chest physiotherapy (CPT) in these patients.Methods: This cross-over clinical study enrolled consecutive patients who were sedated, intubated and on MV > 48h with expected maintenance of these criteria > 24h. Over a 24-hour period, patients randomly performed two sessions of manual CPT with or without additional MI-E before tracheal suctioning. Following each procedure, volume of retrieved mucus (ml) was assessed to evaluate efficacy. We evaluated respiratory flows, pulmonary mechanics and hemodynamics before, during, and after treatment. In addition, safety of MI-E was also appraised.Results: 26 patients were included. In comparison to CPT, mucus volume retrieved was significantly higher during CPT+MI-E (0.42 [0; 1.39] ml vs 2.29 [1; 4.67] ml; p < 0.001). The respiratory system compliance immediately improved from pre and post Crs values in CPT+MI-E group (55.7 ml/cmH2O [38.3; 67.4] vs. 68.6ml/cmH2O [47.8;94.9]; p<0.001). Although, such increase was not significantly different between CPT and CPT+MI-E group (p=0.057). Heart rate significantly increased in both groups (p < 0.005) immediately after each intervention. Additionally, a significant impact on oxygenation was observed in the CPT+MI-E group when comparing the baseline values with the values one-hour post-intervention (p<0.05). Finally, several transitory hemodynamic variations occurred during both interventions, but these were non-significant and considered clinically irrelevant.Conclusion: In mechanically ventilated patients, MI-E increases the amount of secretions that can be retrieved post-CPT, without causing clinically significant adverse events.Clinical Trials Registration Number: NCT03316079 (24/11/2015; retrospectively registered)

Download Full-text

Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH

European Respiratory Journal ◽

10.1183/13993003.01297-2018 ◽

2018 ◽

Vol 52 (6) ◽

pp. 1801297 ◽

Cited By ~ 28

Author(s):

David B. Hill ◽

Robert F. Long ◽

William J. Kissner ◽

Eyad Atieh ◽

Ian C. Garbarine ◽

...

Keyword(s):

Cystic Fibrosis ◽

Disulfide Bonds ◽

Chemical Reduction ◽

Length Scales ◽

Mucus Clearance ◽

Alternative Hypotheses ◽

Series Of Experiments ◽

Airway Mucus ◽

Water Secretion ◽

Airway Acidification

Cystic fibrosis (CF) is a recessive genetic disease that is characterised by airway mucus plugging and reduced mucus clearance. There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.A series of experiments was conducted to determine the contributions of mucus concentration versus pH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.For length scales greater than the nanoscopic, i.e. those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.

Download Full-text