Glucocorticoid-resistant asthma and novel anti-inflammatory drugs

Keenan, Christine R.; Salem, Saad; Fietz, Ebony R; Gualano, Rosa C.; Stewart, Alastair G.

doi:10.1016/j.drudis.2012.05.011

Cited by 50 publications

(42 citation statements)

References 64 publications

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“…Corticosteroids are generally the first line therapy in sarcoidosis and are often effective in the short term management of pulmonary sarcoidosis. In addition, there is little evidence that corticosteroids modify long term disease progression 3,4 and they are fraught with numerous and debilitating side effects 5 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of mycophenolate mofetil in sarcoidosis

Hamzeh

Voelker

Forssén

et al. 2014

Respiratory Medicine

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Background Immunosuppressive (IS) therapy is indicated to treat progressive sarcoidosis, but randomized controlled trials to guide physicians in the use of steroid sparing agents are lacking. The aim of this retrospective study was to examine the role of Mycophenolate Mofetil (MMF) as an alternative therapy in the treatment of sarcoidosis. Methods A retrospective chart review of all patients who had been prescribed MMF between January 2008 and October 2011 was conducted. Patients with insufficient data or who had another IS therapyinitiated concomitantly with MMF, including prednisone, were excluded. Physiological data obtained at the time MMF therapy was initiated as well as six and twelve months before and after therapy was extracted. Longitudinal analyses of the effect of MMF on changes in pulmonary function at MMF start, 6 months, 12 months pre and post MMF therapy were conducted. Results 37/76 patients met our inclusion/exclusion criteria. There were no statistically significant changes in PFT measurements pre and post MMF therapy. We did find a trend (p=0.07) towards improvement in DLCO 12 months pre and post MMF in patients who were started on MMF due to intolerance to previous IS therapy compared to those who were unresponsive to their previous IS therapy. We also noted a reduction in prednisone dose in those treated with MMF. Conclusion MMF appears to offer no extra benefit to sarcoidosis patients unresponsive to previous steroid-sparing agents, but may be beneficial in patients intolerant to their previous steroid-sparing agent. Additional studies investigating the efficacy of MMF as the initial steroid-sparing agent are needed to further clarify the role of MMF in sarcoidosis.

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Section: Introductionmentioning

confidence: 99%

Efficacy of mycophenolate mofetil in sarcoidosis

Hamzeh

Voelker

Forssén

et al. 2014

Respiratory Medicine

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“…In patients with asthma, many molecular mechanisms correlate with GC resistance, including impaired GR nuclear translocation, decreased GR levels, increased GRβ expression, or increased AP-1 expression, which is hypothesized to impair GR function [ 37 ]. In GC refractory asthma, reduced HDAC2 expression correlates with decreased recruitment of GR to DNA sites [ 31 ].…”

Section: Acquired Resistance To Gcsmentioning

confidence: 98%

The Clinical Pharmacology of Past, Present, and Future Glucocorticoids

Nocentini

Ronchetti

Bruscoli

et al. 2015

Systemic Corticosteroids for Inflammatory Disorders in Pediatrics

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“…In severe neutrophilic asthma, asthmatics who smoke, chronic obstructive pulmonary disease (COPD), and during exacerbations of asthma and chronic obstructive pulmonary disease, glucocorticoids may show reduced efficacy (3). Thus, pro-inflammatory cytokines, growth factors, viruses, double-stranded RNA, bacterial products, and oxidative stress reduce GR function, and terms such as glucocorticoid "resistance" or "insensitivity" are used to describe this clinical problem (4,5). As such patients are major healthcare utilizers, solving the problem of glucocorticoid resistance would be of immense societal benefit.…”

mentioning

confidence: 99%

“…As such patients are major healthcare utilizers, solving the problem of glucocorticoid resistance would be of immense societal benefit. For example, pharmacological targeting of signaling pathways, such as mitogen-activated protein kinase (MAPK) or phosphatidylinositol-3-kinase (PI3K) pathways, which are implicated in GR resistance, represents a logical approach to restore sensitivity (3)(4)(5).…”

mentioning

confidence: 99%

Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance

Newton

Shah

Altonsy

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillInflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNAdestabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-B (NF-B), may enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, provide feedforward control to limit expression of the transcription factor IRF1, and the chemokine, CXCL10. We propose that modulation of feedback and feedforward control can determine repression or resistance of inflammatory gene expression toglucocorticoid.

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Glucocorticoid-resistant asthma and novel anti-inflammatory drugs

Cited by 50 publications

References 64 publications

Efficacy of mycophenolate mofetil in sarcoidosis

Efficacy of mycophenolate mofetil in sarcoidosis

The Clinical Pharmacology of Past, Present, and Future Glucocorticoids

Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance

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