A physiologically-motivated compartment-based model of the effect of inhaled hypertonic saline on mucociliary clearance and liquid transport in cystic fibrosis.
BACKGROUND
Cystic Fibrosis (CF) lung disease is characterized by liquid hyperabsorption, airway surface dehydration, and impaired mucociliary clearance (MCC). Herein, we present a compartment-based mathematical model of the airway that extends the resolution of functional imaging data.


METHODS
Using functional imaging data to inform our model, we developed a system of mechanism-motivated ordinary differential equations to describe the mucociliary clearance and absorption of aerosolized radiolabeled particle and small molecules probes from human subjects with and without CF. We also utilized a novel imaging metric in vitro to gauge the fraction of airway epithelial cells that have functional ciliary activity.


RESULTS
This model, and its incorporated kinetic rate parameters, captures the MCC and liquid dynamics of the hyperabsorptive state in CF airways and the mitigation of that state by hypertonic saline treatment.


CONCLUSIONS
We postulate, based on the model structure and its ability to capture clinical patient data, that patients with CF have regions of airway with diminished MCC function that can be recruited with hypertonic saline treatment. In so doing, this model structure not only makes a case for durable osmotic agents used in lung-region specific treatments, but also may provide a possible clinical endpoint, the fraction of functional ciliated airway.
Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
Matthew R
MR
Markovetz
Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States of America; Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
Timothy E
TE
Corcoran
Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
Landon W
LW
Locke
Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
Michael M
MM
Myerburg
Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America.
Joseph M
JM
Pilewski
Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States of America; McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America; Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratories, University of Pittsburgh, Pittsburgh, PA, United States of America; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, United States of America.
Robert S
RS
Parker
D000280:Administration, Inhalation; D001692:Biological Transport / Q000187:drug effects; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D057446:Hydrodynamics; D008954:Models, Biological; D009079:Mucociliary Clearance / Q000187:drug effects*; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology
D012462:Saline Solution, Hypertonic