Association of Allergic Rhinitis and Sinusitis with Childhood Asthma.

Association of Allergic Rhinitis and Sinusitis with Childhood Asthma.

Indian Pediatr. 2016 Nov 5;:

Authors: Kumar S, Singh M, Das RR, Mathew JL, Saxena AK

Abstract
BACKGROUND: To study the point prevalence of allergic rhinitis and sinusitis in childhood asthma and to examine the relationships among them.
METHODS: In 250 children (age <13 y) with mild-to-moderte asthma, allergic rhinitis was diagnosed by clinical plus nasal eosinophilia criteria, and sinusitis was diagnosed clinically plus confirmation by computerized tomography scan.
RESULTS: The point prevalence of allergic rhinitis was 13.6%, and of sinusitis was 2%. On multivariate analysis, allergic rhinitis, sinusitis, and family history were significantly associated with asthma severity.
CONCLUSION: Allergic rhinitis is common in childhood, but sinusitis is rare.

PMID: 27889716 [PubMed – as supplied by publisher]

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Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma.

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Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma.

Inflammation. 2016 Nov 19;

Authors: Chauhan PS, Dash D, Singh R

Abstract
Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week). Curcumin (intranasal) was administered during the OVA aerosol challenge. Mice exposed to OVA developed inflammation dominated by eosinophils which lead to fibrosis and airway remodeling. Intranasal administration of curcumin significantly inhibited airway inflammation and pulmonary fibrosis, where MMP-9 activities were decreased along with ?-smooth muscle actin (?-SMA), MMP-9, TIMP-1, and eotaxin expressions. These results suggest that intranasal curcumin regulates airway inflammation and remodeling in chronic asthma.

PMID: 27866296 [PubMed – as supplied by publisher]

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Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Design.

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Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Design.

Handb Exp Pharmacol. 2016 Nov 13;

Authors: Singh D

Abstract
There remains a considerable need to develop novel therapies for patients with asthma and chronic obstructive pulmonary disease (COPD). The greatest challenge at the moment is measuring the effects of novel anti-inflammatory drugs, as these drugs often cause only small effects on lung function. Measurements that demonstrate the pharmacological and clinical effects of these drugs are needed. Furthermore, we now recognise that only subgroups of patients are likely to respond to these novel drugs, so using biomarkers to determine the clinical phenotype most suitable for such therapies is important. An endotype is a subtype of a (clinical) condition defined by a distinct pathophysiological mechanism. An endotype-driven approach may be more helpful in drug development, enabling drugs to be targeted specifically towards specific biological mechanisms rather than clinical characteristics. This requires the development of biomarkers to define endotypes and/or to measure drug effects. This newer approach should continue alongside efforts to optimise the measurement of clinical endpoints, including patient-reported outcome measurements, required by drug regulatory authorities.

PMID: 27838852 [PubMed – as supplied by publisher]

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[Medical Diagnostics for Mold Exposure Indoors].

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[Medical Diagnostics for Mold Exposure Indoors].

Pneumologie. 2016 Nov;70(11):699-741

Authors: Wiesmüller GA, Heinzow B, Aurbach U, Bergmann KC, Bufe A, Buzina W, Cornely OA, Engelhart S, Fischer G, Gabrio T, Heinz W, Herr CE, Kleine-Tebbe J, Klimek L, Köberle M, Lichtnecker H, Lob-Corzilius T, Merget R, Mülleneisen N, Nowak D, Rabe U, Raulf M, Seidl HP, Steiß JO, Szewszyk R, Thomas P, Valtanen K, Hurraß J

PMID: 27829254 [PubMed – in process]

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

Pulm Pharmacol Ther. 2016 Nov 2;:

Authors: Baldissera L, Squebola-Cola DM, Calixto MC, Lima-Barbosa AP, Rennó AL, Anhê GF, Condino-Neto A, De Nucci G, Antunes E

Abstract
OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis.
METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis.
RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (?1 and ?1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 ?M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 ?M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis.
CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

PMID: 27816773 [PubMed – as supplied by publisher]

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Exposure to Community Violence and Physical Health Outcomes in Youth: A Systematic Review.

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Exposure to Community Violence and Physical Health Outcomes in Youth: A Systematic Review.

J Pediatr Psychol. 2016 Oct 28;:

Authors: Wright AW, Austin M, Booth C, Kliewer W

Abstract
OBJECTIVE?: To systematically review the evidence for associations between exposure to community violence and physical health outcomes in children and adolescents. METHODS?: A thorough search of multiple online databases and careful consideration of inclusion and exclusion criteria yielded a final 28 studies for detailed review. In addition to review of findings, studies were rated on overall quality based on study design. RESULTS?: Seven categories of physical health outcomes emerged, including asthma/respiratory health, cardiovascular health, immune functioning, hypothalamic-pituitary-adrenal axis functioning, sleep problems, weight, and a general health category. There were mixed findings across these categories. Evidence for a positive association between community violence exposure and health problems was strongest in the cardiovascular health and sleep categories. CONCLUSION?: There is reason to believe that community violence exposure has an effect on some areas of physical health. Additional well-designed research that focuses on mechanisms as well as outcomes is warranted.

PMID: 27794530 [PubMed – as supplied by publisher]

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Th1/Th2 Immune Balance and Other T Helper Subsets in IgG4-Related Disease.

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Th1/Th2 Immune Balance and Other T Helper Subsets in IgG4-Related Disease.

Curr Top Microbiol Immunol. 2016 Oct 16;

Authors: Moriyama M, Nakamura S

Abstract
IgG4-related disease (IgG4-RD) is a systemic disease characterized by elevated serum IgG4 levels and a strong infiltration of IgG4-positive plasma cells in various organs. IgG4-RD patients also frequently suffer from allergic diseases, including asthma and atopic dermatitis. It is well known that T helper type 2 (Th2) cells have an important role in the initiation of allergic diseases, and Th2 cytokines such as interleukin (IL)-4 and IL-13 promote class switching to IgG4. Therefore, IgG4-RD is considered to be a Th2-predominant disease. However, other Th subsets, including regulatory T cells and T follicular helper cells, have recently received increasing attention with regard to the pathogenesis of IgG4-RD. Exploring the interconnected network of Th subsets in IgG4-RD is a highly promising field of investigation. In this review, we focus on the localization and functions of individual Th subsets to clarify the involvement of these cells in the pathogenesis of IgG4-RD.

PMID: 27744510 [PubMed – as supplied by publisher]

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European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a Real-Life Clinical Assessment.

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European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a Real-Life Clinical Assessment.

Allergy. 2016 Oct 8;:

Authors: Calderón MA, Vidal C, Rodríguez Del Río P, Just J, Pfaar O, Tabar AI, Sánchez-Machín I, Bubel P, Borja J, Eberle P, Reiber R, Bouvier M, Lepelliez A, Klimek L, Demoly P, EASSI Doctors’ Group

Abstract
BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce.
METHODS: A prospective, longitudinal, web-based survey of “real-life” respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified.
RESULTS: A total of 4,316 patients (corresponding to 4,363 ongoing courses of AIT) were included. 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n=97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were: the use of natural extracts (odds ratio (OR) [95% confidence interval (CI)]=2.74 [1.61-4.87]; p=0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], p=0.047), asthma diagnosis (1.74 [1.05-2.88], p=0.03), sensitization to animal dander (1.93 [1.21-3.09]; p=0.006) or pollen (1.16 [1.03-1.30]; p=0.012), and cluster regimens (vs. rush) (4.18 [1.21-14.37]; p=0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95%CI]=17.35 [1.91-157.28]; p=0.01).
CONCLUSION: AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs. This article is protected by copyright. All rights reserved.

PMID: 27718250 [PubMed – as supplied by publisher]

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A 12-week, Randomized, Parallel-Group, Proof-of-Concept Study of Tulobuterol Patch and Salmeterol Inhaler as Add-on Therapy in Adult-Onset Mild-to-Moderate Asthma.

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A 12-week, Randomized, Parallel-Group, Proof-of-Concept Study of Tulobuterol Patch and Salmeterol Inhaler as Add-on Therapy in Adult-Onset Mild-to-Moderate Asthma.

Clin Exp Pharmacol Physiol. 2016 Oct 8;:

Authors: Inoue H, Niimi A, Matsumoto H, Ito I, Oguma T, Otsuka K, Takeda T, Nakaji H, Tajiri T, Iwata T, Nagasaki T, Mishima M

Abstract
Patch formulation of tulobuterol has been used in asthma treatment as a long-acting ?2 -agonist (LABA) through sustained skin absorption. Its treatment efficacy, especially in small airways, remains poorly understood. The study aim was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol inhaler (SA) on pulmonary function, asthma control, and health status. Patients who had adult-onset under-controlled asthma, despite taking inhaled corticosteroids, were enrolled in a randomized, open-label, parallel-group, proof-of-concept study of 12-week add-on treatment with TP (n = 16) or SA (n = 17). Spirometry, impulse oscillometry (IOS), exhaled nitric oxide levels, and clinical questionnaires of asthma control, health status (St. George’s Respiratory Questionnaire: SGRQ), and symptoms were evaluated every 4 weeks. Add-on treatment of SA significantly improved the spirometric indices of small airway obstruction (forced expiratory flow between 25% and 75% of FVC: FEF25-75 , and maximum expiratory flow at 25% of FVC: MEF25 ) and IOS indices of whole respiratory resistance (resistance at 5 Hz) as compared to TP. In intra-group comparisons, add-on treatment of TP improved the scores of the asthma control test and the total SGRQ, as well as the symptom and impact components of the SGRQ. SA add-on treatment improved FEV1 and IOS parameters of resistance at 20 Hz and reactance at 5 Hz. Neither of the treatments improved exhaled nitric oxide levels. In conclusion, add-on treatment of TP improved asthma control and health status, whereas SA improved pulmonary function measures associated with large and small airway involvement among patients with adult-onset mild-to-moderate asthma. This article is protected by copyright. All rights reserved.

PMID: 27718262 [PubMed – as supplied by publisher]

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