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Roflumilast reverses CFTR-mediated ion transport dysfunction in cigarette smoke-exposed mice

Overview of attention for article published in Respiratory Research, September 2017
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6 X users

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27 Dimensions

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Title
Roflumilast reverses CFTR-mediated ion transport dysfunction in cigarette smoke-exposed mice
Published in
Respiratory Research, September 2017
DOI 10.1186/s12931-017-0656-0
Pubmed ID
Authors

S. Vamsee Raju, Lawrence Rasmussen, Peter A. Sloane, Li Ping Tang, Emily Falk Libby, Steven M. Rowe

Abstract

Dysfunction in cystic fibrosis transmembrane conductance regulator (CFTR) can be elicited by cigarette smoke and is observed in patients with chronic bronchitis. We have previously demonstrated in human airway epithelial cell monolayers that roflumilast, a clinically approved phosphodiesterase 4 inhibitor that reduces the risk of exacerbations in chronic obstructive pulmonary disease patients with chronic bronchitis and a history of exacerbations, activates CFTR-dependent chloride secretion via a cAMP-mediated pathway, partially restores the detrimental effects of cigarette smoke on CFTR-mediated ion transport, and increases CFTR-dependent gastrointestinal fluid secretion in isolated murine intestine segments. Based on these findings, we hypothesized that roflumilast could improve CFTR-mediated chloride transport and induce secretory diarrhea in mice exhibiting cigarette smoke-induced CFTR dysfunction. A/J mice expressing wild type CFTR (+/+) were exposed to cigarette smoke or air with or without roflumilast and the effect of treatment on CFTR-dependent chloride transport was quantified using nasal potential difference (NPD) measurements in vivo and short-circuit current (Isc) analysis of trachea ex vivo. Stool specimen were collected and the wet/dry ratio measured to assess the effect of roflumilast on secretory diarrhea. Acute roflumilast treatment increased CFTR-dependent chloride transport in both smoke- and air-exposed mice (smoke, -2.0 ± 0.4 mV, 131.3 ± 29.3 μA/cm(2), P < 0.01 and air, 3.9 ± 0.8 mV, 147.7 ± 38.0 μA/cm(2), P < 0.01 vs. vehicle -0.3 ± 0.7 mV, 10.4 ± 7.0 μA/cm(2)). Oral administration of roflumilast over five weeks completely reversed the deleterious effects of cigarette smoke on CFTR function in smoke-exposed animals, in which CFTR-dependent chloride transport was 64% that of air controls (roflumilast, -15.22 ± 2.7 mV vs. air, -14.45 ± 1.4 mV, P < 0.05). Smoke exposure increased the wet/dry ratio of stool specimen to a level beyond which roflumilast had little additional effect. Roflumilast effectively rescues CFTR-mediated chloride transport in vivo, further implicating CFTR activation as a mechanism through which roflumilast benefits patients with bronchitis.

X Demographics

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The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 17%
Student > Master 5 17%
Student > Bachelor 4 14%
Professor 3 10%
Student > Doctoral Student 1 3%
Other 4 14%
Unknown 7 24%
Readers by discipline Count As %
Medicine and Dentistry 6 21%
Pharmacology, Toxicology and Pharmaceutical Science 4 14%
Biochemistry, Genetics and Molecular Biology 3 10%
Agricultural and Biological Sciences 1 3%
Computer Science 1 3%
Other 4 14%
Unknown 10 34%
Attention Score in Context

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 22 December 2018.
All research outputs
#14,605,790
of 25,382,440 outputs
Outputs from Respiratory Research
#1,416
of 3,062 outputs
Outputs of similar age
#159,251
of 325,430 outputs
Outputs of similar age from Respiratory Research
#18
of 35 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,062 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 51% 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 325,430 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 50% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.