HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

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HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

J Immunol. 2016 Jan 29;

Authors: Wang Q, Li H, Yao Y, Lu G, Wang Y, Xia D, Zhou J

Abstract
The airway smooth muscle (ASM) cells’ proliferation, migration, and their progenitor’s migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling.

PMID: 26826248 [PubMed – as supplied by publisher]

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Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy.

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Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy.

Environ Int. 2016 Jan 27;89-90:71-80

Authors: Gabriel MF, Postigo I, Tomaz CT, Martínez J

Abstract
Alternaria alternata spores are considered a well-known biological contaminant and a very common potent aeroallergen source that is found in environmental samples. The most intense exposure to A. alternata allergens is likely to occur outdoors; however, Alternaria and other allergenic fungi can colonize in indoor environments and thereby increase the fungal aeroallergen exposure levels. A consequence of human exposure to fungal aeroallergens, sensitization to A. alternata, has been unequivocally associated with increased asthma severity. Among allergenic proteins described in this fungal specie, the major allergen, Alt a 1, has been reported as the main elicitor of airborne allergies in patients affected by a mold allergy and considered a marker of primary sensitization to A. alternata. Moreover, A. alternata sensitization seems to be a triggering factor in the development of poly-sensitization, most likely because of the capability of A. alternata to produce, in addition to Alt a 1, a broad and complex array of cross-reactive allergens that present homologs in several other allergenic sources. The study and understanding of A. alternata allergen information may be the key to explaining why sensitization to A. alternata is a risk factor for asthma and also why the severity of asthma is associated to this mold. Compared to other common environmental allergenic sources, such as pollens and dust mites, fungi are reported to be neglected and underestimated. The rise of the A. alternata allergy has enabled more research into the role of this fungal specie and its allergenic components in the induction of IgE-mediated respiratory diseases. Indeed, recent research on the identification and characterization of A. alternata allergens has allowed for the consideration of new perspectives in the categorization of allergenic molds, assessment of exposure and diagnosis of fungi-induced allergies.

PMID: 26826364 [PubMed – as supplied by publisher]

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Heavy metals in PM2.5 and in blood, and children’s respiratory symptoms and asthma from an e-waste recycling area.

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Heavy metals in PM2.5 and in blood, and children’s respiratory symptoms and asthma from an e-waste recycling area.

Environ Pollut. 2016 Jan 21;210:346-353

Authors: Zeng X, Xu X, Zheng X, Reponen T, Chen A, Huo X

Abstract
This study was to investigate the levels of heavy metals in PM2.5 and in blood, the prevalence of respiratory symptoms and asthma, and the related factors to them. Lead and cadmium in both PM2.5 and blood were significant higher in Guiyu (exposed area) than Haojiang (reference area) (p < 0.05), however, no significant difference was found for chromium and manganese in PM2.5 and in blood. The prevalence of cough, phlegm, dyspnea, and wheeze of children was higher in Guiyu compared to Haojiang (p < 0.05). No significant difference was found for the prevalence of asthma in children between Guiyu and Haojiang. Living in Guiyu was positively associated with blood lead (B = 0.196, p < 0.001), blood cadmium (B = 0.148, p < 0.05) and cough (OR, 2.37; 95% CI, 1.30-4.32; p < 0.01). Blood lead>5 ?g/dL was significantly associated with asthma (OR, 9.50; 95% CI, 1.16-77.49). Higher blood chromium and blood manganese were associated with more cough and wheeze, respectively. Our data suggest that living in e-waste exposed area may lead to increased levels of heavy metals, and accelerated prevalence of respiratory symptoms and asthma.

PMID: 26803791 [PubMed – as supplied by publisher]

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Respiratory disease in the Asia-Pacific region: Cough as a key symptom.

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Respiratory disease in the Asia-Pacific region: Cough as a key symptom.

Allergy Asthma Proc. 2016 Jan 21;

Authors: Cho SH, Ghoshal AG, Lin HC, Muttalif AR, Thanaviratananich S, Bagga S, Faruqi R, Sajjan S, Brnabic AJ, Dehle FC, Wang DY

Abstract
BACKGROUND: Respiratory diseases represent a significant impact on health care. A cross-sectional, multicountry (India, Korea, Malaysia, Singapore, Taiwan, and Thailand) observational study was conducted to investigate the proportion of adult patients who received care for a primary diagnosis of asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), or rhinosinusitis.
OBJECTIVE: To determine the proportion of patients who received care for asthma, AR, COPD, and rhinosinusitis, and the frequency and main symptoms reported.
METHODS: Patients ages greater than or equal to 18 years, who presented to a physician with symptoms that met the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Patients and physicians completed a survey that contained questions related to demographics and respiratory symptoms.
RESULTS: A total of 13,902 patients with a respiratory disorder were screened, of whom 7030 were eligible and 5250 enrolled. The highest percentage of patients who received care had a primary diagnosis of AR (14.0% [95% confidence interval {CI}, 13.4 -14.6%]), followed by asthma (13.5% [95% CI, 12.9 -14.1%]), rhinosinusitis (5.4% [95% CI, 4.6 -5.3%]), and COPD (4.9% [95% CI, 5.0 -5.7%]). Patients with a primary diagnosis of COPD (73%), followed by asthma (61%), rhinosinusitis (59%), and AR (47%) most frequently reported cough as a symptom. Cough was the main reason for seeking medical care among patients with a primary diagnosis of COPD (43%), asthma (33%), rhinosinusitis (13%), and AR (11%).
CONCLUSION: Asthma, AR, COPD, and rhinosinusitis represent a significant proportion of respiratory disorders in patients who presented to health care professionals in the Asia-Pacific region, many with concomitant disease. Cough was a prominent symptom and the major reason for patients with respiratory diseases to seek medical care.

PMID: 26802834 [PubMed – as supplied by publisher]

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Allergy to hedgehog with carboxypeptidase and chitinase-like and chymotrypsin-like elastase family members as the relevant allergens.

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Allergy to hedgehog with carboxypeptidase and chitinase-like and chymotrypsin-like elastase family members as the relevant allergens.

Ann Allergy Asthma Immunol. 2016 Jan 7;

Authors: González-de-Olano D, Muñoz-García E, Haroun-Díaz E, Bartolomé B, Pastor-Vargas C

PMID: 26774975 [PubMed – as supplied by publisher]

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Sex differences in the association between neck circumference and asthma.

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Sex differences in the association between neck circumference and asthma.

Pediatr Pulmonol. 2016 Jan 15;

Authors: Maltz L, Matz EL, Gordish-Dressman H, Pillai DK, Teach SJ, Camargo CA, Hubal MJ, Behniwal S, Prosper GD, Certner N, Marwah R, Mansell DM, Nwachukwu F, Lazaroff R, Tsegaye Y, Freishtat RJ

Abstract
INTRODUCTION: The association between obesity and asthma control/quality of life commonly relies on body mass index (BMI) as the anthropomorphic measure. Due to limitations of BMI and the existence of alternative measures, such as neck circumference (NC), we examined the association between NC and asthma control/quality of life, with particular attention to male-female differences.
MATERIALS AND METHODS: The AsthMaP-2 Project is an observational study of youth with physician-diagnosed asthma. NC was stratified according to age- and sex-specific cutoffs and associated with asthma control (via Asthma Control Test [ACT]) and quality of life (via Integrated Therapeutics Group [ITG]-Asthma Short Form).
RESULTS: The mean?±?SD age was 11.9?±?3.6 years, and 53% were male (N?=?116). The mean BMI percentile was at the 71?±?28 percentile. Thirty-one participants (27%) met criteria for high NC. Males with high NC had significantly worse asthma control (P?=?0.02) and lower quality of life than those with low NC. No similar association was found for females and the proportion of variability in ACT and ITG was best explained by BMI percentile. Conversely, for males, the proportion of variability in these scores explained by NC was larger than BMI percentile alone (Cohen’s f(2) ?=?0.04-0.09, a small to medium effect size).
DISCUSSION: Among male youth with asthma, combined use of NC and BMI percentile explained asthma control and quality of life better than BMI alone. Future studies of asthma should include measurement of NC and other anthropogenic measures of regional adiposity to clarify sex differences in asthma. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

PMID: 26774073 [PubMed – as supplied by publisher]

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Weakness in an Elderly Woman With Asthma and Chronic Sinusitis.

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Weakness in an Elderly Woman With Asthma and Chronic Sinusitis.

Neurohospitalist. 2016 Jan;6(1):36-40

Authors: Kannan M, Greene JG

Abstract
Weakness and sensory changes are common complaints in both the inpatient and the outpatient setting. However, this presentation remains a diagnostic challenge to clinicians due to the many possible underlying etiologies. The initial evaluation of weakness and sensory changes starts a thorough history and physical examination to guide the diagnostic process. In this article, we present the case of an elderly woman with complaints of weakness and sensory changes to highlight a step-wise approach to diagnosis and management.

PMID: 26753055 [PubMed]

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Medical care and treatment of allergic rhinitis. A population-based cohort study based on routine healthcare utilization data.

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Medical care and treatment of allergic rhinitis. A population-based cohort study based on routine healthcare utilization data.

Allergy. 2016 Jan 8;

Authors: Schmitt J, Stadler E, Küster D, Wüstenberg EG

Abstract
BACKGROUND: Health services research on medical care and treatment of allergic rhinitis (AR) is scarce.
OBJECTIVES: To investigate the prevalence, incidence, comorbidities, and treatment of AR in a realistic setting.
METHODS: A cohort of 1,811,094 German National Health Insurance beneficiaries in 2005 was followed until 2011. To avoid misclassification, the ICD-10-code for AR (J30) had to be documented at least twice to classify patients as having AR. Descriptive statistics and logistic regression models were used to describe the burden, comorbidities, and treatment of AR.
RESULTS: A total of 111,394 patients (6.2%) had prevalent AR in 2005/2006. In another 60,145 individuals (3.3%) AR was newly diagnosed in 2007 to 2011 (incident cases). Patients with prevalent AR were three times more likely to develop asthma compared to patients without AR (age and sex-adjusted risk ratio (RR) 3.04; 95% confidence interval (95%CI) 2.98 – 3.10). Newly diagnosed recurrent depressive disorder (RR 1.61; 95%CI 1.55 – 1.68), anxiety disorder (RR 1.52; 95%CI 1.48 – 1.56) and ADHD (RR 1.21; 95%CI 1.13 – 1.29) were also related to prevalent AR. Approximately 20% of children and 36% of adults with AR were exclusively treated by general practitioners. Allergy immunotherapy (AIT) was prescribed for 16.4% of AR patients. Subcutaneous immunotherapy was most frequently used (80% of AIT).
CONCLUSIONS: This study highlights the significant burden of AR. Despite the established benefits of AIT to treat AR and prevent asthma this study suggests significant undertreatment. Future research is necessary to develop and implement adequate measures to increase guideline adherence. This article is protected by copyright. All rights reserved.

PMID: 26749452 [PubMed – as supplied by publisher]

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MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.

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MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.

Mol Immunol. 2015 Dec 31;70:84-93

Authors: Chen M, Huang L, Zhang W, Shi J, Lin X, Lv Z, Zhang W, Liang R, Jiang S

Abstract
BACKGROUND: Abnormal proliferation of ASM (airway smooth muscle) directly contributes to the airway remodeling during development of lung diseases such as asthma. Here we report that a specific microRNA (miR-23b) controls ASMCs proliferation through directly inhibiting TGF?R2/p-Smad3 pathway.
METHODS: The expression of miR-23b in ASMCs was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and apoptosis of ASMCs were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.
RESULTS: Overexpression of miR-23b significantly inhibited TGF-?1-induced ASMCs proliferation and promoted apoptosis. RT-PCR and Western blotting analysis showed miR-23b negatively regulates the expression of TGF?R2 and p-Smad3 in ASMCs. Subsequent analyses demonstrated that TGF?R2 was a direct and functional target of miR-23b, which was validated by the dual luciferase reporter assay.
CONCLUSIONS: MiR-23b may function as an inhibitor of airway smooth muscle cells proliferation through inactivation of TGF?R2/p-Smad3 pathway.

PMID: 26748386 [PubMed – as supplied by publisher]

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Nuclear factor-?B mediates the phenotype switching of airway smooth muscle cells in a murine asthma model.

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Nuclear factor-?B mediates the phenotype switching of airway smooth muscle cells in a murine asthma model.

Int J Clin Exp Pathol. 2015;8(10):12115-28

Authors: Qiu C, Zhang J, Su M, Fan X

Abstract
Airway smooth muscle cells (ASMCs) phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to airway proliferative diseases such as allergic asthma. Nuclear Factor-?B (NF-?B) has been reported as a key regulator for the occurrence and development of asthma. However, little is known regarding its role in ASM cell phenotypic modulation. To elucidate the role of NF-?B in regulating ASM cells phenotypic modulation, we investigated the effects of NF-?B on ASM cells contractile marker protein expression, and its impact on proliferation and apoptosis. We found that chronic asthma increased the activation of NF-?B in the primary murine ASM cells with a concomitant marked decrease in the expression of contractile phenotypic marker protein including smooth muscle alpha-actin (?-SMA). Additionally, we used the normal ASM cells under different processing to build the phenotype switching when we found the activation of NF-?B. Meanwhile, the expression of ?-SMA in asthma was significantly increased by the NF-?B blocker. NF-?B blocker also suppressed asthma mouse ASM cell proliferation and promoted apoptosis. These findings highlight a novel role for the NF-?B in murine ASM cell phenotypic modulation and provide a potential target for therapeutic intervention for asthma.

PMID: 26722396 [PubMed – in process]

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