title: Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.
abstract: Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.
authors.affiliation: Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Landon W
authors.initials: LW
authors.lastname: Locke
authors.affiliation: Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Myerburg
authors.affiliation: Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiner
authors.affiliation: Dept of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Markovetz
authors.affiliation: Dept of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA Dept of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA Dept of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Parker
authors.affiliation: Dept of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Muthukrishnan
authors.affiliation: Dept of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Weber
authors.affiliation: Dept of Radiology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Czachowski
authors.affiliation: Dept of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Lacy
authors.affiliation: Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA Dept of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.affiliation: Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA Dept of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA Dept of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA corcorante@upmc.edu.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Corcoran
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance; D009093:Mucus / Q000382:microbiology; D011552:Pseudomonas Infections / Q000150:complications / Q000473:pathology*; D011550:Pseudomonas aeruginosa; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012137:Respiratory System / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000336:Aerosols; D019275:Radiopharmaceuticals