Category: U.S. National Library of Medicine (NIH)

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[Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma].

[Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Jun;32(6):730-733

Authors: Zhang M, Nong G, Jiang M, Zhan W

Abstract
Objective To observe the effect of lipid derivative of benzylidene malononitrile AG490 on the airway inflammation in a mouse model of neutrophilic asthma (NA). Methods Fifty-four specific pathogen-free (SPF) female C57BL/6 mice were randomly divided into 3 groups: NA group, AG490-treated NA (NAAG) group, and normal control (NC) group, 18 mice in each group. The NA group and the NAAG group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS) on day 0, 6 and 13. The NAAG group was injected with AG490 (500 ?g/mouse, i.p.) three times a week, from day 0 after the first sensitization, for 3 weeks. Mice were challenged on day 21, 22 for 1 hour/time with an aerosol of 10 g/L OVA. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected. The total number and differential counts of nucleated cells and the percentage of each type were determined. HE staining and PAS staining was employed for observing the lung pathological changes. The percentages of Th17 cells and regulatory T cells (Treg) in the lung issue were determined by flow cytometry. The level of interleukin-17 (IL-17) in BALF was measured using ELISA. Results Compared with the NA group, the total number of nucleated cells, the percentage of neutrophils and the percentage of eosinophils in BALF in the NAAG group were obviously reduced; lung tissue pathologic changes were improved in the NAAG group; goblet cell hyperplasia and the level of IL-17 in BALF in the NAAG group were significantly down-regulated; the proportion of Treg in the lung increased and the proportion of Th17 cells in the lung decreased in the NAAG group. Conclusion After NA mice are treated with AG490 during the sensitization phase, the proportion of Treg in the lung would increase and the proportion of Th17 cells in the lung would decrease. AG490 could attenuate the airway inflammation in the mouse model of NA.

PMID: 27371836 [PubMed – as supplied by publisher]

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Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model.

Int Immunopharmacol. 2016 Jun 16;38:261-266

Authors: Gao Y, Zhaoyu L, Xiangming F, Chunyi L, Jiayu P, Lu S, Jitao C, Liangcai C, Jifang L

Abstract
Abietic acid (AA), one of the terpenoids isolated from Pimenta racemosa var. grissea, has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-allergic effects of AA remain unclear. The aim of this study was to investigate the anti-allergic effects of AA in an ovalbumin (OVA)-induced asthma murine model. The model of mouse asthma was established by induction of OVA. AA (10, 20, 40mg/kg) was administered by oral gavage 1h after the OVA treatment on days 21 to 23. At 24h after the last challenge, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to assess pathological changes, cytokines production, and NF-?B expression. The results showed that AA attenuated lung histopathologic changes, inflammatory cells infiltration, and bronchial hyper-responsiveness. AA also inhibited OVA-induced the nitric oxide (NO), IL-4, IL-5, IL-13, and OVA-specific IgE production, as well as NF-?B activation. In conclusion, the current study demonstrated that AA exhibited protective effects against OVA-induced allergic asthma in mice and the possible mechanism was involved in inhibiting NF-?B activation.

PMID: 27318791 [PubMed – as supplied by publisher]

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Differential respiratory health effects from the 2008 northern California wildfires: A spatiotemporal approach.

Differential respiratory health effects from the 2008 northern California wildfires: A spatiotemporal approach.

Environ Res. 2016 Jun 15;150:227-235

Authors: Reid CE, Jerrett M, Tager IB, Petersen ML, Mann JK, Balmes JR

Abstract
We investigated health effects associated with fine particulate matter during a long-lived, large wildfire complex in northern California in the summer of 2008. We estimated exposure to PM2.5 for each day using an exposure prediction model created through data-adaptive machine learning methods from a large set of spatiotemporal data sets. We then used Poisson generalized estimating equations to calculate the effect of exposure to 24-hour average PM2.5 on cardiovascular and respiratory hospitalizations and ED visits. We further assessed effect modification by sex, age, and area-level socioeconomic status (SES). We observed a linear increase in risk for asthma hospitalizations (RR=1.07, 95% CI=(1.05, 1.10) per 5µg/m(3) increase) and asthma ED visits (RR=1.06, 95% CI=(1.05, 1.07) per 5µg/m(3) increase) with increasing PM2.5 during the wildfires. ED visits for chronic obstructive pulmonary disease (COPD) were associated with PM2.5 during the fires (RR=1.02 (95% CI=(1.01, 1.04) per 5µg/m(3) increase) and this effect was significantly different from that found before the fires but not after. We did not find consistent effects of wildfire smoke on other health outcomes. The effect of PM2.5 during the wildfire period was more pronounced in women compared to men and in adults, ages 20-64, compared to children and adults 65 or older. We also found some effect modification by area-level median income for respiratory ED visits during the wildfires, with the highest effects observed in the ZIP codes with the lowest median income. Using a novel spatiotemporal exposure model, we found some evidence of differential susceptibility to exposure to wildfire smoke.

PMID: 27318255 [PubMed – as supplied by publisher]

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Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber.

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Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber.

Ann Allergy Asthma Immunol. 2016 Jun 1;

Authors: Okuma Y, Okamoto Y, Yonekura S, Iinuma T, Sakurai T, Hamasaki S, Ohki Y, Yamamoto H, Sakurai D

Abstract
BACKGROUND: Immediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis.
OBJECTIVE: To examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC).
METHODS: Fifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m(3) for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored.
RESULTS: The severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased.
CONCLUSION: Various mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.

PMID: 27263086 [PubMed – as supplied by publisher]

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[Biomarkers in asthma].

[Biomarkers in asthma].

Presse Med. 2016 May 25;

Authors: Taillé C, Bourdin A, Garcia G

Abstract
Identifying new biomarkers in asthma is attractive but requires assessing their relevance and their reliability to clinical practice. Beyond fashion, the improvement in identification of new candidate biomarkers benefited of scientific and biologic progresses, biobanks and platforms robustly backed on longitudinal cohorts and registries. Paradoxically, the main issue is now to stress up the good question, in other words to correctly characterize the unmet needs in asthma that might benefit of a biomarker. Chronicity, variability, weakness of diagnostic tools and the heterogeneity of the disease are features of asthma claiming for identifying new biomarkers. Unmet needs in asthma encompass areas such as diagnosis, prognosis, management and follow-up, therapeutic guidance and phenotypic/endotypic identification. FEV1 is an available biomarker largely tested in asthma worth in most of these areas. Albeit, mandatory features required for a new biomarker to emerge, pro/con debates on those already existing and currently used methods for identifying new ones are worth explorations. We reviewed and summarized the current literature focusing biomarkers in asthma.

PMID: 27236617 [PubMed – as supplied by publisher]

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Where does current and future pediatric asthma treatment stand? Remodeling and inflammation: Bird’s eye view.

Where does current and future pediatric asthma treatment stand? Remodeling and inflammation: Bird’s eye view.

Pediatr Pulmonol. 2016 May 27;

Authors: Yilmaz O, Yuksel H

Abstract
Airway remodeling is the chronic outcome of inflammation in asthma and a point of intervention between pediatric and adult ages. Pediatric asthma has been of great interest in the efforts to find a valuable time to interrupt remodeling. Various experimental and clinical research have assessed the effect of current therapeutic modalities on airway remodeling in asthma and many new agents are being developed with promising results. The heterogeneity in the results of these studies may lie in the heterogeneity of pathogenesis leading to asthma and remodeling; underlying the need for individualized treatment of the unique pathogenetic characteristics of each child’s asthma. The aim of this review is to summarize the evidence about the influence of current and future therapeutic modalities in the concept of inflammation and remodeling in pediatric asthma. Pediatr Pulmonol. 2016; 9999:1-9. © 2016 Wiley Periodicals, Inc.

PMID: 27233079 [PubMed – as supplied by publisher]

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Should Epinephrine Autoinjectors Be Prescribed to All Patients on Subcutaneous Immunotherapy?

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Should Epinephrine Autoinjectors Be Prescribed to All Patients on Subcutaneous Immunotherapy?

J Allergy Clin Immunol Pract. 2016 May 18;

Authors: Fitzhugh DJ, Bernstein DI

Abstract
Subcutaneous allergen immunotherapy (SCIT) clearly benefits appropriately selected patients with allergic rhinitis, asthma and anaphylaxis to stinging insects. Since inception of SCIT, systemic allergic reactions (SRs) and severe anaphylaxis have been risk management challenges facing the practicing allergist. Recently it has estimated that 14% of reported SRs begin at least 30 minutes after injection administration or after the 30 minute recommended clinic observation period. Faced with the possibility that SRs could occur after the patient leaves the clinic, some practicing allergists routinely prescribe epinephrine auto-injectors to all injection patients. This article summarizes the key arguments for and against routine prescription of epinephrine auto-injectors for all allergen injection patients, discussed in a PRO/CON debate at the 2015 AAAAI meeting. Currently, there is insufficient clinical evidence to make a strong recommendation for or against this practice.

PMID: 27209596 [PubMed – as supplied by publisher]

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