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

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.

Conflict of interest statement

The authors declare that no competing financial interests exist.

Figures

FIG. 1.

Schematic drawing showing the randomized treatment schedule for roflumilast, or placebo, × 4 weeks, followed by a 4-week washout phase and a second 4-week period of the other treatment (V1–V4, Visits 1–4).

FIG. 2.

(A) Nine regions of interest as determined on the transmission scan of the right lung of a representative subject. The inner zone (indicated by arrow) included ∼11% of the total right lung region. The outer zone included all other regions combined. (B) Nine regions of interest superimposed on the aerosol scan of the representative subject immediately following inhalation. A significant proportion of radioactivity (bright region), appears in the inner lung region.

FIG. 3.

Lines of identity for baseline MCC30 measurements (A), MCC60 measurements (B) and MCC90 measurements (C) (all N = 9 pairs). Pearson correlations for these baseline measurements were significant, with r = 0.87; p < 0.01 (MCC30); r = 0.84; p < 0.01 (MCC60); and r = 0.88; p < 0.01 (MCC90). MCC30, mucociliary clearance measures through 30 minutes; MCC60, mucociliary clearance measures through 60 minutes; MCC90, mucociliary clearance measures through 90 minutes.

FIG. 4.

Mean percent MCC at each time point between 0 and 90 minutes for all four study visits in the roflumilast trial for the eight subjects who completed the trial. MCC, mucociliary clearance.