Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved Following Ivacaftor Treatment in Cystic Fibrosis

William D. Bennett, Kirby L. Zeman, Beth L Laube, Jihong Wu, Gail Sharpless, Peter Mogayzel, Scott H. Donaldson

Research output: Contribution to journalArticle

Abstract

Background: Using planar gamma scintigraphy of inhaled radioaerosols, we have developed new analytical methods for assessing homogeneity of aerosol deposition and time-dependent particle clearance on a pixel-by-pixel basis, and applied them to a therapeutic cystic fibrosis (CF) study. Methods: At baseline and 1 month after beginning treatment with ivacaftor, a cystic fibrosis transmembrane regulator modulator for CF patients with at least one copy of the G551D mutation (n = 13), initial deposition and subsequent mucociliary clearance (MCC) of radiolabeled particles (99mTechnetium-sulfur colloid, 5 μm mass median aerodynamic diameter) inhaled under controlled breathing conditions were measured. Results: Improved homogeneity of deposition, that is, decreased areas of higher and lower particle deposition in the lungs, was observed following ivacaftor treatment. The mean number ratio (NR) of pixels with higher deposition, relative to lung size, decreased from 0.14 to 0.09 (p = 0.003) and mean NR of colder pixels decreased from 0.23 to 0.19 (p = 0.004). Particle clearance was also improved following treatment, with mean MCC through 60 minutes equal to 12% versus 24%, without and with treatment, respectively (p = 0.010). Pixel-level analysis of MCC showed that (1) the fraction of pixels clearing >30% at 60 minutes was increased from 0.13 to 0.32 (p = 0.007); and (2) the fraction of pixels clearing <5% at 60 minutes was decreased from 0.54 to 0.37 (p = 0.014), indicating an overall recruitment of more fast-clearing lung regions with ivacaftor treatment. Conclusion: These detailed pixel analyses of deposition and clearance homogeneity may supplement traditional methods that use large regions of interest for assessing efficacy and mechanisms of therapeutic intervention in patients with airways disease.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Volume31
Issue number4
DOIs
StatePublished - Aug 1 2018

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Mucociliary Clearance
Aerosols
Cystic Fibrosis
Lung
Therapeutics
Colloids
ivacaftor
Sulfur
Radionuclide Imaging
Respiration
Mutation

Keywords

  • gamma scintigraphy
  • mucociliary clearance
  • particle deposition

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved Following Ivacaftor Treatment in Cystic Fibrosis. / Bennett, William D.; Zeman, Kirby L.; Laube, Beth L; Wu, Jihong; Sharpless, Gail; Mogayzel, Peter; Donaldson, Scott H.

In: Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 31, No. 4, 01.08.2018, p. 204-211.

Research output: Contribution to journalArticle

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AU - Bennett, William D.

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AU - Laube, Beth L

AU - Wu, Jihong

AU - Sharpless, Gail

AU - Mogayzel, Peter

AU - Donaldson, Scott H.

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AB - Background: Using planar gamma scintigraphy of inhaled radioaerosols, we have developed new analytical methods for assessing homogeneity of aerosol deposition and time-dependent particle clearance on a pixel-by-pixel basis, and applied them to a therapeutic cystic fibrosis (CF) study. Methods: At baseline and 1 month after beginning treatment with ivacaftor, a cystic fibrosis transmembrane regulator modulator for CF patients with at least one copy of the G551D mutation (n = 13), initial deposition and subsequent mucociliary clearance (MCC) of radiolabeled particles (99mTechnetium-sulfur colloid, 5 μm mass median aerodynamic diameter) inhaled under controlled breathing conditions were measured. Results: Improved homogeneity of deposition, that is, decreased areas of higher and lower particle deposition in the lungs, was observed following ivacaftor treatment. The mean number ratio (NR) of pixels with higher deposition, relative to lung size, decreased from 0.14 to 0.09 (p = 0.003) and mean NR of colder pixels decreased from 0.23 to 0.19 (p = 0.004). Particle clearance was also improved following treatment, with mean MCC through 60 minutes equal to 12% versus 24%, without and with treatment, respectively (p = 0.010). Pixel-level analysis of MCC showed that (1) the fraction of pixels clearing >30% at 60 minutes was increased from 0.13 to 0.32 (p = 0.007); and (2) the fraction of pixels clearing <5% at 60 minutes was decreased from 0.54 to 0.37 (p = 0.014), indicating an overall recruitment of more fast-clearing lung regions with ivacaftor treatment. Conclusion: These detailed pixel analyses of deposition and clearance homogeneity may supplement traditional methods that use large regions of interest for assessing efficacy and mechanisms of therapeutic intervention in patients with airways disease.

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