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Monday, 01. April 2019

The In Vitro effect of nebulized hypertonic saline on human bronchial epithelium (HBE)

Nebulized hypertonic saline (HS) is an effective approach in patients with CF in improving mucociliary clearance, lung function and quality of life.

The proposed mode of action of hyperosmolar agents such as HS is the restoration of the airway surface liquid layer in patients with high mucus content like in CF. But exact mechanism of action of HS remains to be elucidated.

In this study, Goralski et al.1 evaluated the effects of  7% HS on human bronchial epithelial HBE cells  that exhibit a range of mucus concentration, spanning „normal” (2%) to muco-obstructive conditions (12%) like in CF. Considering the diversity of nebulizers on the market, the authors mimicked the clinically-relevant delivery rates of a jet nebulizer.

Aim of this study:

Studying the kinetics of HS on the airway surface liquid (ASL): comparing the effect of repeated doses and different delivery rates.

Neue Erkenntnisse zur Wirkung von hypertoner Salzlösung am Modell der menschlichen Lungenzellen (Human Bronchial Epithelium, HBE)
Fig.1: Change in airway surface liquid (ASL) height following 7% HS nebulization.
ASL height was 7-fold increased in hyperconcentrate, CF-like (12%) mucus compared to a 3-fold increase in normal (2%) mucus above baseline
Neue Erkenntnisse zur Wirkung von hypertoner Salzlösung am Modell der menschlichen Lungenzellen (Human Bronchial Epithelium, HBE)
Fig.2:Two sequential doses of HS administered to hyperconcentrated cultures. ASL height difference favors the second dose (p<0.001).

HS effect in epithelial cells with normal mucus content (2%)

  • rapid 3-fold increase in ASL volume compared to baseline.
  • ASL height returned to baseline within 40 min
  • The effect of a second nebulization of HS on ASL was blunted

 

HS effect in epithelial cells with high mucus content (12%):

  • 7- fold increase in ASL weight compared to baseline.
  • Prolonged ASL reabsorption rate, ASL height returned to baseline within 80 min.
  • A second nebulization generates an ALS response similar to the first administration

Tab. 1. HS was delivered to HBE cultures for 15 min at a rate of 8µg NaCl/cm2/min to mimic standard jet nebulizer delivery rate for human subjects

Conclusion:

  • Higher increase in ASL volume and prolonged clinical response to 7% hypertonic saline in high concentrated mucus than in thinned mucus.
  • Repetitive HS dosing that is currently used in CF patients can be confirmed to be an efficient strategy in patients with highly concentrated mucus contents
  • The used HBE model allows to transfer the results also to other chronic airway diseases with mucus hypersecretion like bronchiectasis or COPD
     

1. Goralski JL, Wu D, Thelin WR, Boucher RC, Button B. The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J. 2018;51(5):1702652.

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