Effect of nebulised BromAc ® on rheology of artificial sputum: relevance to muco-obstructive respiratory diseases including COVID-19

  1. Krishna Pillai
  2. Ahmed H. Mekkawy
  3. Javed Akhter
  4. Sarah J. Valle
  5. David L. Morris

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Abstract

Respiratory diseases such as cystic fibrosis, COPD, bronchiectasis asthma and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Since earlier studies have shown success with BromAc ® as mucolytic agent for treating a rare disease known as pseudomyxoma peritonei (PMP), we tested the formulation on two gelatinous airway representative sputa models, in order to determine whether similar efficacy exist.

The sputum (1.5 ml) lodged in an endotracheal tube was treated to aerosolised N-acetylcysteine, bromelain, or their combination (BromAc ® ) using a nebuliser with 6.0 ml of the agents in phosphate buffer saline, over 25 min. Controls received phosphate buffer saline. The dynamic viscosity was measured before and after treatment using a capillary tube method, whilst the sputum flow (ml/sec) was assessed using a 0.5 ml pipette. Finally, the sequestered agents (concentration) in the sputa after treatment were quantified using standard bromelain and N-acetylcysteine chromogenic assays.

Results indicated that bromelain and N-acetylcysteine affected both the dynamic viscosities and pipette flow in the two sputa models, with changes in the former parameter having immense effect on the latter. BromAc ® showed a greater rheological effect on both the sputa models compared to individual agents. Further, correlation was found between the rheological effects and the concentration of agents in the sputa.

Hence, this study indicates that BromAc ® may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretion, however further studies with patient sputum samples using aerosol BromAc ® is warranted.

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    SciScore for 10.1101/2021.12.28.474344: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.12.28.474344v1 on bioRxiv