Mucociliary Clearance in Former Tobacco Smokers with Both Chronic Obstructive Pulmonary Disease and Chronic Bronchitis and the Effect of Roflumilast

J Aerosol Med Pulm Drug Deliv. 2019 Aug;32(4):189-199. doi: 10.1089/jamp.2018.1459. Epub 2019 Apr 8.

Abstract

Background: Little is known of the repeatability and reliability of mucociliary clearance (MCC) in former tobacco smokers who have both chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB). Less is known of the effect of roflumilast, a selective inhibitor of PDE4, on MCC in these patients. Methods: Former tobacco smokers with COPD and CB were treated for 4 weeks with either roflumilast, or placebo, in a randomized, crossover trial. The following were measured on two baseline and two posttreatment visits: MCC values through 90 minutes, following inhalation of 99mtechnetium sulfur colloid and gamma camera imaging; outer:inner (O:I) deposition ratio; forced expiratory volume in 1 second (FEV1); and symptom scores. Comparisons included: MCC measures through 30 minutes (MCC30), 60 minutes (MCC60), and 90 minutes (MCC90) on the two baseline visits (n = 9) and mean change [(roflumilast - baseline)-(placebo - baseline)] for MCC30, MCC60, MCC90, and FEV1 (n = 8). Associations between MCC measurements, FEV1 and O:I ratio with symptom scores were also examined. Results: Pearson correlation tests indicated good repeatability for baseline measures of MCC30, MCC60, and MCC90 and intraclass correlation coefficients indicated good reliability. Only FEV1 (percent predicted) improved significantly following roflumilast treatment. There were no statistically significant correlations between MCC measures and symptom scores. Lower FEV1 values were significantly associated with increased shortness of breath (dyspnea), and lower O:I ratios (more inner region deposition) were significantly associated with increased cough and sputum. Conclusions: Measurements of MCC30, MCC60, and MCC90 are repeatable and reliable in former tobacco smokers with both COPD and CB. One month of treatment with roflumilast did not improve MCC in this limited study. Airway narrowing in the larger, central airways of these subjects could lead to decreased FEV1, increased inner region deposition of the radiolabeled particles, and the associated increase in symptoms of dyspnea, cough, and sputum.

Keywords: chronic obstructive pulmonary disease (COPD) and chronic bronchitis; former tobacco smokers; mucociliary clearance; roflumilast; scintigraphy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aminopyridines / administration & dosage*
  • Aminopyridines / pharmacology
  • Benzamides / administration & dosage*
  • Benzamides / pharmacology
  • Bronchitis, Chronic / drug therapy*
  • Bronchitis, Chronic / physiopathology
  • Cross-Over Studies
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / pharmacology
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Mucociliary Clearance / drug effects
  • Phosphodiesterase 4 Inhibitors / administration & dosage*
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Reproducibility of Results
  • Tobacco Smoking / physiopathology

Substances

  • Aminopyridines
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast