Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthma<i>versus</i>controls

Yick, Ching Yong; Zwinderman, Aeilko H.; Kunst, Peter W.A.; Grünberg, Katrien; Mauad, Thaís; Dijkhuis, Annemiek; Bel, Elisabeth H.; Baas, Frank; Lutter, René; Sterk, Peter J.

doi:10.1183/09031936.00115412

Cited by 74 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, while PDE4 is found in human airway smooth muscle, it is now clear from a number of clinical studies with a variety of PDE4 inhibitors administered either orally [52,53] or by inhalation [54], that this drug class is not able to induce acute bronchodilation [38]. In contrast, a number of selective PDE3 inhibitors have been shown to be bronchodilators in man [55,56] and, indeed, recently, PDE3 has been documented to be upregulated in airway smooth muscle obtained from patients with asthma [57].…”

Section: Bifunctional Bronchodilator/anti-inflammatory Drugsmentioning

confidence: 99%

Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease

Page

Cazzola

2014

Eur Respir J

View full text Add to dashboard Cite

Over the last decade, there has been a steady increase in the use of fixed-dose combinations of drugs for the treatment of a range of diseases, including hypertension, cancer, AIDS, tuberculosis and other infectious diseases. It is now evident that patients with asthma or chronic obstructive pulmonary disease (COPD) can also benefit from the use of fixed-dose combinations, including combinations of a long-acting b 2 -agonist and an inhaled corticosteroid, and combinations of long-acting b 2 -agonists and long-acting muscarinic receptor antagonists. In fact, there are now a number of ''triple-inhaler'' fixed-dose combinations under development, with the first such triple combination having been approved in India. This use of combinations containing drugs with complementary pharmacological actions in the treatment of patients with asthma or COPD has also led to the discovery and development of drugs having two different primary pharmacological actions in the same molecule, which we have called ''bifunctional drugs''. In this review, we discuss the state of the art of these new bifunctional drugs as novel treatments for asthma and COPD that can be categorised as bifunctional bronchodilators, bifunctional bronchodilator/antiinflammatory drugs and bifunctional anti-inflammatory drugs. @ERSpublications Bifunctional drugs offer an exciting new approach to the treatment of asthma and COPD

show abstract

Section: Bifunctional Bronchodilator/anti-inflammatory Drugsmentioning

confidence: 99%

Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease

Page

Cazzola

2014

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Pendrin up-regulation is seen in: 1) airway epithelial cultures chronically exposed to cytokines, including IL-4, IL-13, and IL-17A; 2) rodent models of inflammatory lung disease, including allergen (ovalbumin)-induced asthma, chronic obstructive pulmonary disease, infection, and industrial toxin exposure; and 3) humans with rhinovirus infection, asthma, cystic fibrosis (CF), rhinitis, and chronic rhinosinusitis (10,11,(17)(18)(19)(20)(21)(22)(23)(24)(25). Pendrin knockout is also associated with reduced lung inflammation in a murine model of Bordetella pertussis lung infection (26).…”

mentioning

confidence: 99%

Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

Haggie

Phuan²,

Tan³

et al. 2016

FASEB j.

View full text Add to dashboard Cite

Pendrin (SLC26A4) is a Cl 2 /anion exchanger expressed in the epithelium of inflamed airways where it is thought to facilitate Cl 2 absorption and HCO 3 2 secretion. Studies using pendrin knockout mice and airway epithelial cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic fibrosis (CF), perhaps by regulation of airway surface liquid (ASL) volume. Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in increasing ASL volume. A cell-based, functional high-throughput screen of ∼36,000 synthetic small molecules produced 3 chemical classes of inhibitors of human pendrin. After structure-activity studies, tetrahydropyrazolopyridine and pyrazolothiophenesulfonamide compounds reversibly inhibited pendrin-facilitated Cl 2 exchange with SCN 2 , I 2 , NO 3 2 , and HCO 3 2 with drug concentration causing 50% inhibition down to ∼2.5 mM. In well-differentiated primary cultures of human airway epithelial cells from non-CF and CF subjects, treatment with IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl 2 /HCO 3 2 exchange and the increase was blocked by pendrin inhibition. Pendrin inhibition significantly increased ASL depth (by ∼8 mm) in IL-13-treated non-CF and CF cells but not in untreated cells. These studies implicate the involvement of pendrin-facilitated Cl 2 / HCO 3 2 in the regulation of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, including CF

show abstract

“…Finally, Nicholas Carbonetti (University of Maryland, Baltimore, MD, USA) described the upregulation of pendrin in the lungs of B. pertussis-infected mice and baboons. An epithelial HCO 3 Ϫ /Cl Ϫ exchanger, pendrin is involved in asthma pathology in humans (17). B. pertussis-infected pendrin knockout mice showed reduced inflammatory pathology but higher bacterial loads in the lungs.…”

Section: Virulence Factors and Pathogenesismentioning

confidence: 99%

Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development

Carbonetti

König

Lan

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals.

show abstract

Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthmaversuscontrols

Cited by 74 publications

References 36 publications

Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease

Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease

Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development

Contact Info

Product

Resources

About