Literature DB >> 30964381

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

Beth L Laube1, Kathryn A Carson2, Gail Sharpless1, Laura M Paulin3, Nadia N Hansel1.   

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.

Entities:  

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

Mesh:

Substances:

Year:  2019        PMID: 30964381      PMCID: PMC6685194          DOI: 10.1089/jamp.2018.1459

Source DB:  PubMed          Journal:  J Aerosol Med Pulm Drug Deliv        ISSN: 1941-2711            Impact factor:   2.849


  42 in total

1.  Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro.

Authors:  J Milara; M Armengot; P Bañuls; H Tenor; Rolf Beume; E Artigues; J Cortijo
Journal:  Br J Pharmacol       Date:  2012-08       Impact factor: 8.739

Review 2.  The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.

Authors:  Armin Hatzelmann; Esteban J Morcillo; Giuseppe Lungarella; Serge Adnot; Shahin Sanjar; Rolf Beume; Christian Schudt; Hermann Tenor
Journal:  Pulm Pharmacol Ther       Date:  2010-04-07       Impact factor: 3.410

3.  Deposition and clearance of 2 micron particles in the tracheobronchial tree of normal subjects--smokers and nonsmokers.

Authors:  R V Lourenço; M F Klimek; C J Borowski
Journal:  J Clin Invest       Date:  1971-07       Impact factor: 14.808

4.  Enhancement of particle deposition by flow-limiting segments in humans.

Authors:  G C Smaldone; M S Messina
Journal:  J Appl Physiol (1985)       Date:  1985-08

Review 5.  Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance.

Authors:  S Vamsee Raju; George M Solomon; Mark T Dransfield; Steven M Rowe
Journal:  Clin Chest Med       Date:  2015-12-24       Impact factor: 2.878

6.  Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells.

Authors:  M Mata; B Sarriá; A Buenestado; J Cortijo; M Cerdá; E J Morcillo
Journal:  Thorax       Date:  2005-02       Impact factor: 9.139

7.  Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration.

Authors:  Lucy A Clunes; Catrin M Davies; Raymond D Coakley; Andrei A Aleksandrov; Ashley G Henderson; Kirby L Zeman; Erin N Worthington; Martina Gentzsch; Silvia M Kreda; Deborah Cholon; William D Bennett; John R Riordan; Richard C Boucher; Robert Tarran
Journal:  FASEB J       Date:  2011-10-11       Impact factor: 5.191

8.  Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.

Authors:  Alberto Papi; Cinzia Maria Bellettato; Fausto Braccioni; Micaela Romagnoli; Paolo Casolari; Gaetano Caramori; Leonardo M Fabbri; Sebastian L Johnston
Journal:  Am J Respir Crit Care Med       Date:  2006-02-16       Impact factor: 21.405

9.  Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial (NCI-H292) cells.

Authors:  Matt X G Shao; Takashi Nakanaga; Jay A Nadel
Journal:  Am J Physiol Lung Cell Mol Physiol       Date:  2004-04-30       Impact factor: 5.464

Review 10.  The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD.

Authors:  Janice M Leung; Pei Yee Tiew; Micheál Mac Aogáin; Kurtis F Budden; Valerie Fei Lee Yong; Sangeeta S Thomas; Kevin Pethe; Philip M Hansbro; Sanjay H Chotirmall
Journal:  Respirology       Date:  2017-03-25       Impact factor: 6.424

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  1 in total

1.  Changes in mucociliary clearance over time in children with cystic fibrosis.

Authors:  Beth L Laube; Kathryn A Carson; Christopher M Evans; Vanessa L Richardson; Gail Sharpless; Pamela L Zeitlin; Peter J Mogayzel
Journal:  Pediatr Pulmonol       Date:  2020-05-29
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