Acute allergic contact dermatitis (ACD) has been previously linked to secreted osteopontin (sOPN), a glycoprotein with cytokine and chemokine functions. OPN is known to attract myeloid dendritic cells (mDCs) to activate naïve T cells in draining lymph nodes in the skin and induce a TH1 phenotype.
Seier et al. (Am J Path 2010, 176:246-258) follow up on their work identifying osteopontin as a principal player in acute ACD with investigations into the pathophysiology that leads to the chronic condition, which is associated with severe eczema. They discover that OPN attracts memory T cells, monocytes, macrophages, and DCs to the skin in acute exposure. Cytokine function of OPN specifically induces IL-12 secretion and suppresses IL-10 production in macrophages. Then, OPN-related IL-12 production establishes Th1 conditions by skewing mDCs toward IL-12 production, which in turn, augments further OPN secretion. The authors also find that IFN-γ from antigen-specific T cells is critical for activation of OPN production in keratinocytes. The Th1 environment in the epidermis is maintained through cybernetic mechanisms involving OPN, IL-12, and antigen-specific T cells, which support persistent, chronic inflammatory conditions in the skin.
Seier et al. also report that anti-OPN antibody treatment can suppress response in established chronic ACD, suggesting possible prevention and intervention possibilities.
Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
Monday, November 29, 2010
Monday, November 22, 2010
Inhaled corticosteroids do not increase pneumonia risk in asthma
Previous research has reported an increased risk of pneumonia in patients with COPD who are on inhaled corticosteroids (ICS). This finding was associated with use of fluticasone, but not with budesonide-treated COPD. O’Byrne et al. (Am J Respir Crit Care Med 2010, doi:10.1164/rccm.201005-0694OC) present results from their analyses on pneumonia adverse events [AEs] and serious adverse events [SAE] from budesonide and budesonide/formoterol clinical trials involving asthma subjects. AstraZeneca collected and analyzed the data, which was reviewed by an independent statistician for the purposes of this research.
O’Byrne and co-authors evaluate two datasets, one from studies in subjects 4 years of age and older comparing placebo to Pulmicort® or Symbicort®, and a second dataset from studies of similar design that also include comparative data on fluticasone and high- and low-dosing effects. Pneumonia AEs from the first dataset were 0.5% in the budesonide group and 1.2% in the placebo group. Pneumonia SAEs were lower in the budesonide and placebo groups.
Analyses of the second dataset show pneumonia AEs in the budesonide group were slightly higher, but still lower than in the placebo group from the first dataset. Pneumonia SAEs were similar between the two datasets. The authors note that the risk of pneumonia between high-dose subjects and low-dose subjects was nearly equivalent. In contrast to the findings in COPD, pneumonia risk was similar, low, and not significant between budesonide and fluticasone.
Wrapping up, O’Byrne et al. point out that subjects in the second dataset with the lowest FEV1 values had higher risk of pneumonia. They comment that, in general, COPD subjects have lower baseline FEV1 than asthma subjects, which could account for greater risk of pneumonia in COPD.
Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
O’Byrne and co-authors evaluate two datasets, one from studies in subjects 4 years of age and older comparing placebo to Pulmicort® or Symbicort®, and a second dataset from studies of similar design that also include comparative data on fluticasone and high- and low-dosing effects. Pneumonia AEs from the first dataset were 0.5% in the budesonide group and 1.2% in the placebo group. Pneumonia SAEs were lower in the budesonide and placebo groups.
Analyses of the second dataset show pneumonia AEs in the budesonide group were slightly higher, but still lower than in the placebo group from the first dataset. Pneumonia SAEs were similar between the two datasets. The authors note that the risk of pneumonia between high-dose subjects and low-dose subjects was nearly equivalent. In contrast to the findings in COPD, pneumonia risk was similar, low, and not significant between budesonide and fluticasone.
Wrapping up, O’Byrne et al. point out that subjects in the second dataset with the lowest FEV1 values had higher risk of pneumonia. They comment that, in general, COPD subjects have lower baseline FEV1 than asthma subjects, which could account for greater risk of pneumonia in COPD.
Tell us what you think. Please feel free to post your own comments and/or predictions below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
Wednesday, November 3, 2010
Simvastatin provides little help for reducing steroid use in asthma
Statins have shown anti-inflammatory properties in animal models and human tissues, reducing airway hyperreactivity, mast cell degranulation, and inhibition of airway smooth muscle proliferation. Great hopes have been placed in the treatment of asthma by statins, but only two clinical trials have been published, though, using statins in subjects with asthma.
A double-blind, placebo-controlled, crossover study by Cowan et al. (Thorax 2010, 65:891-896) examines whether simvastatin demonstrates steroid-sparing effects across a 6 month period in 43 subjects with stable persistent asthma. All subjects started on 500μg of fluticasone and simvastatin or placebo. Fluticasone was stepped down each month for 6 months or until loss of control (LOC). Subjects were stepped up at the point of LOC until “minimum necessary” ICS dose to achieve control.
Cowan et al report that subjects at the LOC point were not significantly different between simvastatin and placebo. Nevertheless, the authors note that sputum eosinophils were lower on simvastatin than placebo. They conclude that simvastatin did not produce clinically important steroid-sparing effects, though it was associated with improvements in Asthma Control Questionnaire score and FEV1 as well as mitigating eosinophilia.
Tell us what you think. Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
A double-blind, placebo-controlled, crossover study by Cowan et al. (Thorax 2010, 65:891-896) examines whether simvastatin demonstrates steroid-sparing effects across a 6 month period in 43 subjects with stable persistent asthma. All subjects started on 500μg of fluticasone and simvastatin or placebo. Fluticasone was stepped down each month for 6 months or until loss of control (LOC). Subjects were stepped up at the point of LOC until “minimum necessary” ICS dose to achieve control.
Cowan et al report that subjects at the LOC point were not significantly different between simvastatin and placebo. Nevertheless, the authors note that sputum eosinophils were lower on simvastatin than placebo. They conclude that simvastatin did not produce clinically important steroid-sparing effects, though it was associated with improvements in Asthma Control Questionnaire score and FEV1 as well as mitigating eosinophilia.
Tell us what you think. Please feel free to post your own comments below. Topics and articles that you think would be of interest in our NBOP section and/or this blog can be sent to the JACI Editorial Office at jaci@njhealth.org.
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