July 15, 2013

Allergic inflammation: focus on eosinophils



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Allergic inflammation: focus on eosinophils

  1. Hans-Uwe Simon
Article first published online: 15 JUL 2013
DOI: 10.1111/all.12231
Allergy

Allergy

Volume 68Issue 7pages 823–824July 2013



In allergic diseases, such as atopic dermatitis [1], bronchial asthma [2, 3], rhinosinusitis [4], or eosinophilic esophagitis [5], eosinophil numbers are usually increased. Therefore, the physiological and pathological roles of eosinophils remain a hot research topic. Recent progress in the understanding of eosinophil biology includes recognizing the capacity of eosinophils to generate different functional subsets under in vivo inflammatory conditions [6], as well as extracellular DNA-containing structures able to bind and kill bacteria [7, 8]. Furthermore, new pathogenetic insights reveal a molecular link between organismal metabolism and eosinophilic inflammation [9].
The molecular interactions between mast cells and eosinophils in allergic inflammatory responses have evoked an increasing research interest [10, 11]. The activation of eosinophils may result in tissue damage; therefore, inhibition of eosinophil effector functions is an important therapeutic strategy in eosinophilic disorders [12]. Interestingly, CRTH2 antagonists have been demonstrated to exhibit anti-eosinophilic activities in allergic rhinitis [13] and eosinophilic esophagitis [14]. But how can the anti-eosinophilic activity of a given drug be monitored? The results of a recent study suggest that, although reduced blood eosinophil numbers may reflect an anti-eosinophilic efficacy, they do not necessarily indicate a reduced eosinophilic inflammation [15]. Thus, the search for and testing of eosinophil biomarkers remain subjects of intense investigation [16].
In this issue of Allergy, several original articles report interesting new findings with implications for the diagnosis and treatment of eosinophilic diseases. Simon et al. demonstrate that adult patients suffering from eosinophilic esophagitis are frequently sensitized towardCandida albicans [17]. It is possible that such patients would benefit from antimycotic therapy. Muniz-Junqueira et al. describe morphological changes in eosinophils that correlate with the severity of asthma exacerbations in children [18]. Ueki et al. observed that retinoic acids increase the functional expression of eotaxin receptors, suggesting that vitamin A derivatives could play an important role in the tissue accumulation of eosinophils [19]. Moreover, the molecular events of the eotaxin receptor-mediated signaling pathway have been investigated by Shamri et al., and the reported data are likely relevant for both host defense and immunopathology [20]. Gleich et al. reviewed the current opinion with respect to the consequences of eosinophil-depleting treatments [21], and the data collected appear to be of great interest, particularly, because several anti-eosinophilic therapies are still in development.
Taken together, research in the field of eosinophilic diseases continues to be promising. Indeed, several new therapeutic approaches to different allergic conditions have also recently been reported in the Journal [22-24]. In spite of this progress, the role of the eosinophil in physiology and disease remains a subject for further research.

Acknowledgement

Work in the laboratory of HUS is supported by the Swiss National Science Foundation and Allergie-Stiftung Ulrich Müller-Gierok, Bern, Switzerland.

Conflict of interest

The author declares no conflict of interest.

References

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    Straumann AAceves SSBlanchard CCollins MHFuruta GTHirano I et al. Pediatric and adult eosinophilic esophagitis: similarities and differencesAllergy 2012;67:477490.
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    Roth NStädtler SLemann MHösli SSimon HUSimon DDistinct eosinophil cytokine expression patterns in skin diseases – the possible existence of functionally different eosinophil subpopulationsAllergy 2011;66:14771486.
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    Morshed MYousefi SStöckle CSimon HUSimon DThymic stromal lymphopoietin stimulates the formation of eosinophil extracellular trapsAllergy 2012;67:11271137.
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    Simon DSimon HUYousefi SExtracellular DNA traps in allergic, infectious, and autoimmune diseasesAllergy2013;68:409416.
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    Dietze JBöcking CHeverhagen JTVoelker MNRenz HObesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthmaAllergy 2012;67:15191529.
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    Elishmereni MAlenius HTBradding PMizrahi SShikotra AMinai-Fleminger Y et al. Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitroAllergy 2011;66:376385.
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    Elishmereni MBachelet INissim Ben Efraim AHMankuta DLevi-Schaffer FInteracting mast cells and eosinophils acquire an enhanced activation state in vitroAllergy 2013;68:171179.
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    Nissim Ben Efraim AHKarra LBen-Zimra MLevi-Schaffer FThe inhibitory receptor CD300a is up-regulated by hypoxia and GM-CSF in human peripheral blood eosinophilsAllergy 2013;68:397401.
  • 13
    Horak FZieglmayer PZieglmayer RLemell PCollins LPHunter MG et al. The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trialAllergy2012;67:15721579.
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    Straumann AHoesli SBussmann ChStuck MPerkins MCollins LP et al. Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitisAllergy 2013;68:375385.
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    Ullmann NBossley CJFleming LSilvestri MBush ASaglani SBlood eosinophil counts rarely reflect airway eosinophilia in children with severe asthmaAllergy 2013;68:402406.
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    Khoury PZagallo PTalar-Williams CSantos CSDinerman EHolland NC et al. Serum biomarkers are similar in Churg-Strauss syndrome and hypereosinophilic syndromeAllergy 2012;67:11491156.
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    Simon DStraumann ADahinden CSimon H-UFrequent sensitization to Candida albicans and profilins in adult eosinophilic esophagitisAllergy 2013;68:945948.
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    Muniz-Junqueira MIBarbosa-Marques SMJunqueira LF JrMorphological changes in eosinophils are reliable markers of the severity of an acute asthma exacerbation in childrenAllergy 2013;68:911920.
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    Ueki SNishikawa JYamauchi YKonno YTamaki MItoga M et al. Retinoid acids up-regulate functional eosinophil-driving receptor CCR3Allergy 2013;68:953956.
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    Shamri RYoung KMWeller PFPI3K, ERK, p38 MAPK and integrins regulate CCR-mediated secretion of mouse and human eosinophil-associated RNasesAllergy 2013;68:880889.
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    Sharma SKAlmeida FAKierstein SHortobagyi LLin TLarkin A et al. Systemic FasL neutralization increases eosinophilic inflammation in a mouse model of asthmaAllergy 2012;67:328335.
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    Sandell JHedman JSaarinen KHaahtela TSalt chamber treatment is ineffective in treating eosinophilic inflammation in asthma.Allergy 2013;68:125127.

July 14, 2013

Etiologic Aspect of Sarcoidosis as an Allergic Endogenous Infection Caused by Propionibacterium acnes

BioMed Research International
Volume 2013 (2013), Article ID 935289, 18 pages
http://dx.doi.org/10.1155/2013/935289
Review Article

Etiologic Aspect of Sarcoidosis as an Allergic Endogenous Infection Caused by Propionibacterium acnes

Department of Human Pathology, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Received 12 January 2013; Accepted 7 May 2013
Academic Editor: Peter A. Lambert
Copyright © 2013 Yoshinobu Eishi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Propionibacterium acnes is the only microorganism that has been isolated from sarcoid lesions. Many P. acnes have been detected in sarcoid lymph nodes using quantitative PCR and in sarcoid granulomas by in situ hybridization. P. acnes trigger factor protein causes a cellular immune response only in sarcoid patients and induces pulmonary granulomas in mice sensitized with the protein and adjuvant, but only those with latent P. acnes infection in their lungs. Eradication of P. acnes by antibiotics prevents the development of granulomas in this experimental model. Although P. acnes is the most common commensal bacterium in the lungs and lymph nodes, P. acnes-specific antibody detected the bacterium within sarcoid granulomas of these organs. P. acnes can cause latent infection in the lung and lymph node and persist in a cell-wall-deficient form. The dormant form is activated endogenously under certain conditions and proliferates at the site of latent infection. In patients with P. acnes hypersensitivity, granulomatous inflammation is triggered by intracellular proliferation of the bacterium. Proliferating bacteria may escape granulomatous isolation, spreading to other organs. Latent P. acnes infection in systemic organs can be reactivated by another triggering event, leading to systemic sarcoidosis.

Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

Logo of jresmedsci
J Res Med Sci. 2012 November; 17(11): 1086–1088.
PMCID: PMC3702094

Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

Abstract

Helicobacter pylori (H. pylori) are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP), chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pyloriinfection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP.
Keywords: Eradication therapy, helicobacter pylori, schonlein-henoch purpura

Formats:

A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis

A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis

Authors: Meadows A, Kaambwa B, Novielli N, Huissoon A, Fry-Smith A, Meads C, Barton P, Dretzke J
Journal: Health Technology Assessment Volume: 17 Issue: 27
Publication date: July 2013
DOI: 10.3310/hta17270
Citation: 
Meadows A, Kaambwa B, Novielli N, Huissoon A, Fry-Smith A, Meads C, et al.A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis.Health Technol Assess 2013;17(27)

  • Abstract

Background

Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life. Immunotherapy involves administering increasing doses of a specific allergen, with the aim of reducing sensitivity and symptomatic reactions. Recent meta-analyses have concluded that both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are more effective than placebo in reducing symptoms. It is uncertain which route of administration is more effective and whether or not treatment is cost-effective.

Objective

To determine the comparative clinical effectiveness and cost-effectiveness of SCIT and SLIT for seasonal allergic rhinitis in adults and children.

Data sources

Electronic databases {MEDLINE, EMBASE, The Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)], NHS Economic Evaluation Database (NHS EED)} and trial registries (from inception up to April 2011).

Review methods

Standard systematic review methods were used for study selection, data extraction and quality assessment. Double-blind randomised, placebo-controlled trials of SCIT or SLIT, or of SCIT compared with SLIT, and economic evaluations were included. Meta-analysis and indirect comparison meta-analysis and meta-regression were carried out. A new economic model was constructed to estimate cost-utility.

Results

Meta-analyses found statistically significant effects for SCIT and SLIT compared with placebo across a number of outcome measures and for the vast majority of subgroup analyses (type and amount of allergen, duration of treatment). There was less evidence for children, but some results in favour of SLIT were statistically significant. Indirect comparisons did not provide conclusive results in favour of either SCIT or SLIT. Economic modelling suggested that, when compared with symptomatic treatment (ST), both SCIT and SLIT may become cost-effective at a threshold of £20,000-30,000 per quality-adjusted life-year (QALY) from around 6 years, or 5 years for SCIT compared with SLIT (NHS and patient perspective).

Limitations

It is uncertain to what extent changes in the outcome measures used in the trials translate into clinically meaningful benefits. Cost-effectiveness estimates are based on a simple model, limited data and a number of assumptions, and should be seen as indicative only.

Conclusions

A benefit from both SCIT and SLIT compared with placebo has been consistently demonstrated, but the extent of this effectiveness in terms of clinical benefit is unclear. Both SCIT and SLIT may be cost-effective compared with ST from around 6 years (threshold of £20,000-30,000 per QALY). Further research is needed to establish the comparative effectiveness of SCIT compared with SLIT and to provide more robust cost-effectiveness estimates.

Funding

The National Institute for Health Research Health Technology Assessment programme.

July 13, 2013

Seasonal Changes in Endotoxin Exposure and Its Relationship to Exhaled Nitric Oxide and Exhaled Breath Condensate pH Levels in Atopic and Healthy Children.

RESEARCH ARTICLE

Seasonal Changes in Endotoxin Exposure and Its Relationship to Exhaled Nitric Oxide and Exhaled Breath Condensate pH Levels in Atopic and Healthy Children

  • Gwo-Hwa Wan equal contributor mail,
  •  
  • Dah-Chin Yan equal contributor,
  •  
  • Tao-Hsin Tung,
  •  
  • Chin-Sheng Tang,
  •  
  • Chiu-Hsin Liu
  • Abstract

    Endotoxin, a component of the cell walls of gram-negative bacteria, is a contaminant in organic dusts (house dust) and aerosols. In humans, small amounts of endotoxin may cause a local inflammatory response. Exhaled nitric oxide (eNO) levels, an inflammation indicator, are associated with the pH values of exhaled breath condensate (EBC). This study evaluated seasonal changes on indoor endotoxin concentrations in homes and the relationships between endotoxin exposure and eNO/EBC pH levels for healthy children and children with allergy-related respiratory diseases. In total, 34 children with allergy-related respiratory diseases and 24 healthy children were enrolled. Indoor air quality measurements and dust sample analysis for endotoxin were conducted once each season inside 58 surveyed homes. The eNO, EBC pH levels, and pulmonary function of the children were also determined. The highest endotoxin concentrations were on kitchen floors of homes of children with allergy-related respiratory diseases and healthy children, and on bedroom floors of homes of asthmatic children and healthy children. Seasonal changes existed in endotoxin concentrations in dust samples from homes of children with allergic rhinitis, with or without asthma, and in EBC pH values among healthy children and those with allergy-related respiratory diseases. Strong relationships existed between endotoxin exposure and EBC pH values in children with allergic rhinitis.

    Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    Open AccessResearch

    Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    Harold R CollardEric YowLuca RicheldiKevin J Anstrom and Craig Glazer
    For all author emails, please log on.
    Respiratory Research 2013, 14:73 doi:10.1186/1465-9921-14-73
    Published: 13 July 2013

    Abstract (provisional)

    Background

    Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure.

    Methods

    Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria.

    Results

    Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality.

    Conclusions

    In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures.

    The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.