Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung

Landon W Locke, Michael M Myerburg, Daniel J Weiner, Matthew R Markovetz, Robert S Parker, Ashok Muthukrishnan, Lawrence Weber, Michael R Czachowski, Ryan T Lacy, Joseph M Pilewski, Timothy E Corcoran, Landon W Locke, Michael M Myerburg, Daniel J Weiner, Matthew R Markovetz, Robert S Parker, Ashok Muthukrishnan, Lawrence Weber, Michael R Czachowski, Ryan T Lacy, Joseph M Pilewski, Timothy E Corcoran

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.

Trial registration: ClinicalTrials.gov NCT01486199 NCT01887197 NCT00541190 NCT01223183.

Copyright ©ERS 2016.

Figures

FIGURE 1
FIGURE 1
Measurement repeatability of (A) MCC and (B) ABS in 10 CF subjects. Unfilled circles are subjects who had a >5% change in FEV1%p between testing days.
FIGURE 1
FIGURE 1
Measurement repeatability of (A) MCC and (B) ABS in 10 CF subjects. Unfilled circles are subjects who had a >5% change in FEV1%p between testing days.
FIGURE 2
FIGURE 2
Comparing central lung deposition percentage to measurements of (A) MCC and (B) ABS
FIGURE 2
FIGURE 2
Comparing central lung deposition percentage to measurements of (A) MCC and (B) ABS
FIGURE 3
FIGURE 3
Multi-study comparison of measurements of ABS and MCC in CF and non-CF subjects (p-values by Mann-Whitney).
FIGURE 4
FIGURE 4
Mucociliary clearance (MCC) in healthy controls and CF subjects with or without PA infection. CF PA = positive sputum or throat culture in the last 2 years.
FIGURE 5
FIGURE 5
ABS in healthy controls and CF subjects with or without PA infection. CF PA = positive throat or sputum culture in the last 2 years.
FIGURE 6
FIGURE 6
Longitudinal measures of (A) MCC and (B) ABS in pediatric CF patients over a two-year period. Previous data from adult CF and adult control subjects is included for comparison (Ref. 12) All ± SD. For paired symbols gray fill represents an increase and white fill a decrease.
FIGURE 6
FIGURE 6
Longitudinal measures of (A) MCC and (B) ABS in pediatric CF patients over a two-year period. Previous data from adult CF and adult control subjects is included for comparison (Ref. 12) All ± SD. For paired symbols gray fill represents an increase and white fill a decrease.

Source: PubMed

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