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Researchers Link FDA Actions to Decrease in LABA Use in Asthma Treatment
Regulatory Focus A recent study finds an association between regulatory actions by the US Food and Drug Administration (FDA) and the use of long-acting ?2-agonists (LABA) commonly used to treat asthma. The study, published in the Journal of Allergy and Clinical … Simple asthma screening test could improve care for children |
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Teva's asthma candidates successful in three late-stage studies; regulatory …
Seeking Alpha Top-line results from three Phase 3 clinical trials assessing Teva Pharmaceutical Industries' (TEVA +0.4%) fluticasone propionate/salmeterol, a combination inhaled corticosteroid and long-acting beta agonist delivered via a multidose dry powder inhaler … |
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IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.
J Immunol. 2014 Dec 19;
Authors: Böhm L, Maxeiner J, Meyer-Martin H, Reuter S, Finotto S, Klein M, Schild H, Schmitt E, Bopp T, Taube C
Abstract
Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.
PMID: 25527785 [PubMed – as supplied by publisher]
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A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk.
Genes Immun. 2013 Aug 15;
Authors: Revez JA, Bain L, Chapman B, Powell JE, Jansen R, Duffy DL, Tung JY, AAGC Collaborators, Matheson MC, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Beilby J, Cheah F, Madden PA, Heath AC, Hopper JL, Musk B, Leeder SR, Walters EH, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Thompson PJ, Penninx BW, Visscher PM, De Geus EJ, Boomsma DI, Hinds DA, Martin NG, Montgomery GW, Ferreira MA
Abstract
The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ?20?ng?ml(-1) and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4?ng?ml(-1). Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16?705 asthmatics and 30?809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.Genes and Immunity advance online publication, 15 August 2013; doi:10.1038/gene.2013.38.
PMID: 23945879 [PubMed – as supplied by publisher]
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Multiple In Vitro and In Vivo Regulatory Effects of Budesonide in CD4+ T Lymphocyte Subpopulations of Allergic Asthmatics.
PLoS One. 2012;7(12):e48816
Authors: Pace E, Di Sano C, La Grutta S, Ferraro M, Albeggiani G, Liotta G, Di Vincenzo S, Uasuf CG, Bousquet J, Gjomarkaj M
Abstract
BACKGROUND: Increased activation and increased survival of T lymphocytes characterise bronchial asthma.
OBJECTIVES: In this study the effect of budesonide on T cell survival, on inducible co-stimulator T cells (ICOS), on Foxp3 and on IL-10 molecules in T lymphocyte sub-populations was assessed.
METHODS: Cell survival (by annexin V binding) and ICOS in total lymphocytes, in CD4+/CD25+ and in CD4+/CD25- and Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25-cells was evaluated, by cytofluorimetric analysis, in mild intermittent asthmatics (n?=?19) and in controls (n?=?15). Allergen induced T lymphocyte proliferation and the in vivo effects of budesonide in mild persistent asthmatics (n?=?6) were also explored.
RESULTS: Foxp3 was reduced in CD4+/CD25- and in CD4+/CD25+ cells and ICOS was reduced in CD4+/CD25+ cells but it was increased in CD4+CD25-in asthmatics when compared to controls. In asthmatics, in vitro, budesonide was able to: 1) increase annexin V binding and to reduce ICOS in total lymphocytes; 2) increase annexin V binding and Foxp3 and to reduce ICOS in CD4+/CD25- cells; 3) reduce annexin V binding and to increase IL-10 and ICOS in CD4+/CD25+ cells; 4) reduce cell allergen induced proliferation. In vivo, budesonide increased ICOS in CD4+/CD25+ while it increased Foxp3 and IL-10 in CD4+/CD25+ and in CD4+/CD25- cells.
CONCLUSIONS: Budesonide modulates T cell survival, ICOS, Foxp3 and IL-10 molecules differently in T lymphocyte sub-populations. The findings provided shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation.
PMID: 23251336 [PubMed – in process]
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GSK and Theravance Announce Regulatory Submissions for FF/VI in the US and …
MarketWatch (press release) Asthma (100/25mcg and 200/25mcg): The regular treatment of asthma in adults and adolescents aged 12 years and older, where use of a combination product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate. COPD (100/25mcg): The … GSK, Theravance unveil Regulatory Submissions for FF/VI in US, Europe GSK files key new lung drug for regulatory approval |
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Glaxo set to submit Relovair to regulatory authorities
ShareCast Additionally, all but one of the pivotal studies in patients with asthma have been completed. For COPD, Glaxo intends to submit regulatory applications in the US and Europe in mid-2012. For asthma, Glaxo plans to submit an application in Europe in … GSK and Theravance Announce Initial Outcomes From Pivotal Phase III Studies … |
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Regulatory pendulum has swung too far
Hernando Today The EPA says its new rules will cost about $10.6 billion by 2016 — but will save anywhere from $59 billion to $140 billion in health costs, forestall up to 17000 premature deaths and prevent up to 130000 cases of childhood asthma per year. … |
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Merck Withdraws Bid For EU Regulatory OK Of Asthma Medicine
Capital.gr (press release) (MRK) has withdrawn its application for European regulatory approval of an asthma treatment, citing outstanding questions by regulators. … |
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Merck Withdraws Bid For EU Regulatory OK Of Asthma Medicine
Wall Street Journal (MRK) has withdrawn its application for European regulatory approval of an asthma treatment, citing outstanding questions by regulators. … |
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