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Roflumilast partially reverses smoke-induced mucociliary dysfunction

Overview of attention for article published in Respiratory Research, January 2015
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (59th percentile)

Mentioned by

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4 tweeters
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1 Google+ user

Citations

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26 Dimensions

Readers on

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46 Mendeley
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Title
Roflumilast partially reverses smoke-induced mucociliary dysfunction
Published in
Respiratory Research, January 2015
DOI 10.1186/s12931-015-0294-3
Pubmed ID
Authors

Andreas Schmid, Nathalie Baumlin, Pedro Ivonnet, John S Dennis, Michael Campos, Stefanie Krick, Matthias Salathe, Schmid, Andreas, Baumlin, Nathalie, Ivonnet, Pedro, Dennis, John S, Campos, Michael, Krick, Stefanie, Salathe, Matthias

Abstract

Phosphodiesterases (PDEs) break down cAMP, thereby regulating intracellular cAMP concentrations and diffusion. Since PDE4 predominates in airway epithelial cells, PDE4 inhibitors can stimulate Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by increasing cAMP. Tobacco smoking and COPD are associated with decreased CFTR function and impaired mucociliary clearance (MCC). However, the effects of the PDE4 inhibitor roflumilast on smoke-induced mucociliary dysfunction have not been fully explored. Primary normal human bronchial epithelial cells (NHBE) from non-smokers, cultured at the air-liquid interface (ALI) were used for most experiments. Cultures were exposed to cigarette smoke in a Vitrocell VC-10 smoking robot. To evaluate the effect of roflumilast on intracellular cAMP concentrations, fluorescence resonance energy transfer (FRET) between CFP- and YFP-tagged protein kinase A (PKA) subunits was recorded. Airway surface liquid (ASL) was measured using light refraction scanning and ciliary beat frequency (CBF) employing infrared differential interference contrast microscopy. Chloride conductance was measured in Ussing chambers and CFTR expression was quantified with qPCR. While treatment with 100 nM roflumilast had little effect alone, it increased intracellular cAMP upon stimulation with forskolin and albuterol in cultures exposed to cigarette smoke and in control conditions. cAMP baselines were lower in smoke-exposed cells. Roflumilast prolonged cAMP increases in smoke-exposed and control cultures. Smoke-induced reduction in functional, albuterol-mediated chloride conductance through CFTR was improved by roflumilast. ASL volumes also increased in smoke-exposed cultures in the presence of roflumilast while it did not in its absence. Cigarette smoke exposure decreased CBF, an effect rescued with roflumilast, particularly when used together with the long-acting ß-mimetic formoterol. Roflumilast also enhanced forskolin-induced CBF stimulation in ASL volume supplemented smoked and control cells, confirming the direct stimulatory effect of rising cAMP on ciliary function. In active smokers, CFTR mRNA expression was increased compared to non-smokers and ex-smokers. Roflumilast also increased CFTR mRNA levels in cigarette-smoke exposed cell cultures. Our results show that roflumilast can rescue smoke-induced mucociliary dysfunction by reversing decreased CFTR activity, augmenting ASL volume, and stimulating CBF, the latter particularly in combination with formoterol. As expected, CFTR mRNA expression was not indicative of apical CFTR function.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 28%
Student > Ph. D. Student 9 20%
Student > Doctoral Student 6 13%
Student > Bachelor 4 9%
Student > Master 4 9%
Other 6 13%
Unknown 4 9%
Readers by discipline Count As %
Medicine and Dentistry 10 22%
Agricultural and Biological Sciences 8 17%
Biochemistry, Genetics and Molecular Biology 7 15%
Nursing and Health Professions 3 7%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Other 10 22%
Unknown 5 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 November 2015.
All research outputs
#5,204,386
of 10,677,937 outputs
Outputs from Respiratory Research
#526
of 1,236 outputs
Outputs of similar age
#87,099
of 249,897 outputs
Outputs of similar age from Respiratory Research
#16
of 44 outputs
Altmetric has tracked 10,677,937 research outputs across all sources so far. This one has received more attention than most of these and is in the 50th percentile.
So far Altmetric has tracked 1,236 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 249,897 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.