Changing Patient Mindsets About Non-Life-Threatening Symptoms During Oral Immunotherapy: A Randomized Clinical Trial

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Lauren C. Howe, Kari A. Leibowitz, Margaret A. Perry, Julie M. Bitler, Whitney Block, Ted J. Kaptchuk, Kari C. Nadeau, Alia J. Crum

Abstract

Background

Oral immunotherapy (OIT) can lead to desensitization to food allergens, but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout. Interventions to improve OIT for patients are needed.

Objective

To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes.

Methods

In a randomized, blinded, controlled phase II study, 50 children/adolescents (28% girls, aged 7-17, M=10.82, SD=3.01) completed six-month OIT for peanut allergies. Patients and their parent(s) had monthly clinic visits at the Sean N. Parker Center for Allergy & Asthma Research between 1/5/2017-8/3/2017. All families received identical symptom management training. In a 1:1 approach, 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment, and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization. Families participated in activities to reinforce these symptom mindsets.

Results

Compared to families informed that symptoms are side effects, families informed that symptoms can signal desensitization were less anxious (B=-0.46, 95% CI (-0.76 to -0.16), p=0.003), less likely to contact staff about symptoms (5/24[9.4%] vs. 27/154[17.5%] instances, p=0.036), experienced fewer non-life-threatening symptoms as doses increased (B_Interaction=-0.54(-0.83 to -0.27), p<0.001), less likely to skip/reduce doses (1/26[4%] vs. 5/24[21%] patients, p=0.065), and showed greater increase in patient peanut-specific blood IgG4 levels (B_Interaction=0.76(0.36 to 1.17), p<0.001).

Conclusion

Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes. Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2T4d9Zc

Surgical management of nasal dermoid lesions

Publication date: Available online 23 January 2019

Source: Operative Techniques in Otolaryngology-Head and Neck Surgery

Author(s): Craig Miller, Scott Manning, Randall Bly

Nasal dermoids are the most common congenital midline nasal lesions. They often present as a midline pit or nasal mass and arise from incomplete or failed regression of the dural diverticulum during embryogenesis. Management requires complete resection of the tract and an appropriate surgical approach is based on location, extent, and presence and/or degree of intracranial extension. Classically requiring an open craniotomy for resection, newer strategies employ a minimally disruptive approach to fully excise the lesion and the tract to prevent recurrence. This article presents details on embryology, imaging work up, and surgical technique for resection of these lesions either via an open approach or with an endoscopic-assisted method.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R9drML

Information for Readers

Publication date: February 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 2

Author(s):

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Wfbbr9

Society Page

Publication date: February 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 2

Author(s):

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R6STEE

Editorial Board

Publication date: February 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 2

Author(s):

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2WebamX

Table of Contents

Publication date: February 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 127, Issue 2

Author(s):

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R8GKPh

Vaccine Allergy? Skin testing and challenge at a tertiary pediatric hospital in Melbourne, Australia

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Abigail Cheung, Sharon Choo, Kirsten P. Perrett

Abstract

Background

The rate of true vaccine allergy is unknown. Children with potential IgE-mediated Adverse Events Following Immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all; a practice not evidence based, technically difficult and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with history of anaphylaxis.

Objective

We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. Secondary aims were to identify any significant risk factors for vaccine allergy.

Methods

A retrospective review of all children (< 18 years), who underwent vaccine skin testing (skin prick test (SPT) or intradermal (IDT)) or challenge over a 5-year period (May 1, 2011 to April 30, 2016) at the Royal Children's Hospital Melbourne.

Results

There were 109 admissions in 74 children. 8% (6/74) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to suspect vaccine but challenge negative to alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. Children with an AEFI < 15 minutes post vaccination or with grade 1 anaphylaxis at any time post vaccination had higher rate of true vaccine allergy (9.6% vs 4.5%).

Conclusion

The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with suspect vaccine if negative testing or previous non-anaphylactic potential IgE mediated AEFI.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2B0rn6y

Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE: SAHARA Randomized Study

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): William R. Lumry, Inmaculada Martinez-Saguer, William H. Yang, Jonathan A. Bernstein, Joshua Jacobs, Dumitru Moldovan, Marc A. Riedl, Douglas T. Johnston, H.Henry Li, Yongqiang Tang, Jennifer Schranz, Peng Lu, Moshe Vardi, Henriette Farkas, SAHARA study group

Abstract

Background

Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues.

Objective

To evaluate efficacy/ safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959).

Methods

Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre–long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. Primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety.

Results

75 patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH–treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively).

Conclusion

Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2T9EOrJ

Specific antibody deficiencies in clinical practice

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Ricardo U. Sorensen, David Edgar

Abstract

Specific antibody deficiency (SAD) is defined as the inability to mount an antibody response to purified S. pneumoniae capsular polysaccharide antigens in presence of normal immunoglobulin concentrations and normal antibody responses to protein antigens. In this review we discuss the difficulties in using presently available testing methods to adequately define SAD. The fact that there are different forms of specific antibody deficiencies to pneumococcal surface polysaccharides is detailed. The diagnostic and therapeutic implications of recognizing that in addition to SAD, there are other forms of specific antibody deficiency in the response to S. pneumoniae polysaccharides is described in detail. The conclusion of this review is that assessment of immunity and therapeutic actions to deal with specific antibody deficiencies need to be based on clinical evidence rather than solely on arbitrarily defined antibody responses.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2AYU7fX

Changing Patient Mindsets About Non-Life-Threatening Symptoms During Oral Immunotherapy: A Randomized Clinical Trial

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Lauren C. Howe, Kari A. Leibowitz, Margaret A. Perry, Julie M. Bitler, Whitney Block, Ted J. Kaptchuk, Kari C. Nadeau, Alia J. Crum

Abstract

Background

Oral immunotherapy (OIT) can lead to desensitization to food allergens, but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout. Interventions to improve OIT for patients are needed.

Objective

To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes.

Methods

In a randomized, blinded, controlled phase II study, 50 children/adolescents (28% girls, aged 7-17, M=10.82, SD=3.01) completed six-month OIT for peanut allergies. Patients and their parent(s) had monthly clinic visits at the Sean N. Parker Center for Allergy & Asthma Research between 1/5/2017-8/3/2017. All families received identical symptom management training. In a 1:1 approach, 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment, and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization. Families participated in activities to reinforce these symptom mindsets.

Results

Compared to families informed that symptoms are side effects, families informed that symptoms can signal desensitization were less anxious (B=-0.46, 95% CI (-0.76 to -0.16), p=0.003), less likely to contact staff about symptoms (5/24[9.4%] vs. 27/154[17.5%] instances, p=0.036), experienced fewer non-life-threatening symptoms as doses increased (B_Interaction=-0.54(-0.83 to -0.27), p<0.001), less likely to skip/reduce doses (1/26[4%] vs. 5/24[21%] patients, p=0.065), and showed greater increase in patient peanut-specific blood IgG4 levels (B_Interaction=0.76(0.36 to 1.17), p<0.001).

Conclusion

Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes. Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2T4d9Zc

Surgical management of nasal dermoid lesions

Publication date: Available online 23 January 2019

Source: Operative Techniques in Otolaryngology-Head and Neck Surgery

Author(s): Craig Miller, Scott Manning, Randall Bly

Nasal dermoids are the most common congenital midline nasal lesions. They often present as a midline pit or nasal mass and arise from incomplete or failed regression of the dural diverticulum during embryogenesis. Management requires complete resection of the tract and an appropriate surgical approach is based on location, extent, and presence and/or degree of intracranial extension. Classically requiring an open craniotomy for resection, newer strategies employ a minimally disruptive approach to fully excise the lesion and the tract to prevent recurrence. This article presents details on embryology, imaging work up, and surgical technique for resection of these lesions either via an open approach or with an endoscopic-assisted method.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R9drML

Introduction

Publication date: Available online 23 January 2019

Source: Operative Techniques in Otolaryngology-Head and Neck Surgery

Author(s): Meghan N. Wilson

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2WcFE9a

Frequency following responses to tone glides: effects of frequency extent, direction, and electrode montage

Publication date: Available online 23 January 2019

Source: Hearing Research

Author(s): Curtis J. Billings, William J. Bologna, Ramesh Muralimanohar, Brandon M. Madsen, Michelle R. Molis

Abstract

The spectral (frequency) and amplitude cues in speech change rapidly over time. Study of the neural encoding of these dynamic features may help to improve diagnosis and treatment of speech-perception difficulties. This study uses tone glides as a simple approximation of dynamic speech sounds to better our understanding of the underlying neural representation of speech. The frequency following response (FFR) was recorded from 10 young normal-hearing adults using six signals varying in glide direction (rising and falling) and extent of frequency change (13, 23, and 1 octave). In addition, the FFR was simultaneously recorded using two different electrode montages (vertical and horizontal). These factors were analyzed across three time windows using a measure of response strength (signal-to-noise ratio) and a measure of temporal coherence (stimulus-to-response correlation coefficient). Results demonstrated effects of extent, montage, and a montage-by-window interaction. SNR and stimulus-to-response correlation measures differed in their sensitivity to these factors. These results suggest that the FFR reflects dynamic acoustic characteristics of simple tonal stimuli very well. Additional research is needed to determine how neural encoding may differ for more natural dynamic speech signals and populations with impaired auditory processing.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FIAA7g

Assessment of Interleukin – 18 gene polymorphism and serum levels in Oral Lichen Planus in an Indian population

Abstract

Background

Oral Lichen Planus (OLP) is a chronic, inflammatory disease with uncertain aetiology. The aim of this study was to assess Interleukin‐18 (IL‐18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background.

Methods

Assessment of single nucleotide polymorphisms (SNPs) of IL‐18 gene at promoter regions 137(G/C) and 607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence specific primer‐polymerase chain reaction (SSP‐PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL‐18 levels were assessed using enzyme linked immunosorbent assay (ELISA).

Results

Mean serum levels of IL‐18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL‐18 at position 137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL‐18 at position 607(C/A) showed no significant differences.

Conclusions

Gene polymorphism at ‐137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas 137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL‐18 genetic polymorphisms in OLP development.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FRkUy2

Frequency following responses to tone glides: effects of frequency extent, direction, and electrode montage

Publication date: Available online 23 January 2019

Source: Hearing Research

Author(s): Curtis J. Billings, William J. Bologna, Ramesh Muralimanohar, Brandon M. Madsen, Michelle R. Molis

Abstract

The spectral (frequency) and amplitude cues in speech change rapidly over time. Study of the neural encoding of these dynamic features may help to improve diagnosis and treatment of speech-perception difficulties. This study uses tone glides as a simple approximation of dynamic speech sounds to better our understanding of the underlying neural representation of speech. The frequency following response (FFR) was recorded from 10 young normal-hearing adults using six signals varying in glide direction (rising and falling) and extent of frequency change (13, 23, and 1 octave). In addition, the FFR was simultaneously recorded using two different electrode montages (vertical and horizontal). These factors were analyzed across three time windows using a measure of response strength (signal-to-noise ratio) and a measure of temporal coherence (stimulus-to-response correlation coefficient). Results demonstrated effects of extent, montage, and a montage-by-window interaction. SNR and stimulus-to-response correlation measures differed in their sensitivity to these factors. These results suggest that the FFR reflects dynamic acoustic characteristics of simple tonal stimuli very well. Additional research is needed to determine how neural encoding may differ for more natural dynamic speech signals and populations with impaired auditory processing.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FIAA7g

Assessment of Interleukin – 18 gene polymorphism and serum levels in Oral Lichen Planus in an Indian population

Abstract

Background

Oral Lichen Planus (OLP) is a chronic, inflammatory disease with uncertain aetiology. The aim of this study was to assess Interleukin‐18 (IL‐18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background.

Methods

Assessment of single nucleotide polymorphisms (SNPs) of IL‐18 gene at promoter regions 137(G/C) and 607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence specific primer‐polymerase chain reaction (SSP‐PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL‐18 levels were assessed using enzyme linked immunosorbent assay (ELISA).

Results

Mean serum levels of IL‐18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL‐18 at position 137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL‐18 at position 607(C/A) showed no significant differences.

Conclusions

Gene polymorphism at ‐137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas 137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL‐18 genetic polymorphisms in OLP development.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2FRkUy2

Comparison of Whole Heart Computed Tomography Scanners for Image Quality Lower Radiation Dosing in Coronary Computed Tomography Angiography: The CONVERGE Registry

Publication date: Available online 23 January 2019

Source: Academic Radiology

Author(s): Nirali Patel, Dong Li, Rine Nakanishi, Badiha Fatima, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Rachael O'Rourke, Eranthi Jayawardena, Christian Hamilton-Craig, Manojna Nimmagadda, Matthew J. Budoff

Rationale and Objectives

Novel technology in coronary computed tomographic angiography allows assessment of coronary artery disease with high image quality (IQ). There are currently two wide detector "whole heart" coverage scanners available, which avoid misregistration artifacts. However, there are no data directly comparing IQ between the two scanners. The aim of the current study is to investigate if IQ is different between the most current scanners of GE and Toshiba broad detector scanners.

Materials and Methods

Prospective, observational, multicenter international cohort study comparing 236 consecutive patients who underwent coronary computed tomographic angiography using whole-heart scanners; 126 patients on scanner S1 (Aquilion ONE, Toshiba), and 110 patients on scanner S2 (Revolution CT, GE Healthcare). Hounsfield units were measured using regions of interest in the descending aorta at 6 points (cranial slice, level of the visualized first, second, third, and fourth spines, and the caudal slice). We also compared the coverage length (z-axis) of the full width field of view between a single rotation of the two scanners.

Results

Evaluating mean CT attenuation values Hounsfield units through the scan range, are progressively reduced across the descending aorta in the S1 group, resulting in the larger difference of contrast brightness between the cranial and caudal slices compared to the S2 group (absolute difference: S2 13.0 ± 4.4 vs S1 141.9 ± 16.4, p < 0.0001; Percent difference: 19.3 ± 2.1 vs −3.4 ± 1.2, <0.0001). The standard deviation (SD) is similar at the cranial slice between the two scanners, however, the S1 group demonstrated higher SD-differential from cranial to caudal than S2 group. Median radiation exposure was significantly lower for the S2 scanner 1.50 ± 0.75 mSv vs the S1 system 1.9 mSv (IQR 1.7–2.7 mSv) (p = 0.01). Z-axis coverage was larger for the S2 scanner 152.5 mm (244 slices × 0.625 mm/slice) than 133 mm for S1 (266 slices × 0.5 mm/slice).

Conclusion

Although both "volume" scanners cover the whole heart z-axis with one beat, scans using the S1 scanner have a larger variability in attenuation values throughout the scan range, resulting in 20% increase in nonuniformity from cranial to caudal slice. Additionally, SD variation across the field of view, a metric of noise, is larger when using the S1 scanner vs the S2 scanner. These results indicate that the GE Revolution CT has more uniform contrast enhancement and more coverage, lower radiation and lower image noise compared to the current Toshiba Aquilion ONE system.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UalpXW

Detection of Pulmonary Embolism Based on Reduced Changes in Radiographic Lung Density During Cardiac Beating Using Dynamic Flat-panel Detector: An Animal-based Study

Publication date: Available online 23 January 2019

Source: Academic Radiology

Author(s): Rie Tanaka, Tohru Tani, Norihisa Nitta, Takahisa Tabata, Noritsugu Matsutani, Shintaro Muraoka, Tsutomu Yoneyama, Shigeru Sanada

Rationale and Objectives

To assess the capacity of dynamic flat-panel detector imaging without the use of contrast media to detect pulmonary embolism (PE) based on temporal changes in radiographic lung density during cardiac beating.

Materials and Methods

Sequential chest radiographs of six pigs were acquired using a dynamic flat-panel detector system. A porcine model of PE was developed, and temporal changes in pixel values in the imaged lungs were analyzed during a whole cardiac cycle. Mean differences in temporal changes in pixel values between affected and unaffected lobes were assessed using the paired t test. To facilitate visual evaluation, temporal changes in pixel values were depicted using a colorimetric scale and were compared to the findings of contrast-enhanced images.

Results

Affected lobes exhibited a mean reduction of 49.6% in temporal changes in pixel values compared to unaffected lobes within the same animals, and a mean reduction of 41.3% compared to that before vessel blockage in the same lobe. All unaffected lobes exhibited significantly-increased changes in pixel values after vessel blockage (p < 0.01). In all PE models, there were color-deficient areas with shapes and locations that matched well with the perfusion defects confirmed in the corresponding contrast-enhanced images.

Conclusion

Dynamic chest radiography enables the detection of perfusion defects in the lobe unit based on temporal changes in image density, even without the use of contrast media. Quantification and visualization techniques provide a better understanding of the circulation-induced changes depicted in dynamic chest radiographs.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dvfuat

Fast myocardial T1 mapping using shortened inversion recovery based schemes

Background

Myocardial T₁ mapping shows promise for assessment of cardiomyopathies. Most myocardial T₁ mapping techniques, such as modified Look–Locker inversion recovery (MOLLI), generate one T₁ map per breath‐held acquisition (9–17 heartbeats), which prolongs multislice protocols and may be unsuitable for patients with breath‐holding difficulties.

Purpose

To develop and characterize novel shortened inversion recovery based T₁ mapping schemes of 2–5 heartbeats.

Study Type

Prospective.

Population/Phantom

Numerical simulations, agarose/NiCl₂ phantom, 16 healthy volunteers, and 24 patients.

Field Strength/Sequence

1.5T/MOLLI.

Assessment

All shortened T₁ mapping schemes were characterized and compared with a conventional MOLLI scheme (5‐(3)‐3) in terms of accuracy, precision, spatial variability, and repeatability.

Statistical Tests

Kruskal–Wallis, Wilcoxon rank sum tests, analysis of variance, Student's t‐tests, Bland–Altman analysis, and Pearson correlation analysis.

Results

All shortened schemes provided limited T₁ time variations (≤2% for T₁ times ≤1200 msec) and limited penalty of precision (by a factor of ~1.4–1.5) when compared with MOLLI in numerical simulations. In phantom, differences between all schemes in terms of accuracy, spatial variability, and repeatability did not reach statistical significance (P > 0.71). In healthy volunteers, there were no statistically significant differences between all schemes in terms of native T₁ times and repeatability for myocardium (P = 0.21 and P = 0.87, respectively) and blood (P = 0.79 and P = 0.41, respectively). All shortened schemes led to a limited increase of spatial variability for native myocardial T₁ mapping with respect to MOLLI (by a factor of 1.2) (P < 0.0001). In both healthy volunteers and patients, the two‐heartbeat scheme and MOLLI led to highly linearly correlated T₁ times (correlation coefficients ≥0.83).

Data Conclusion

The proposed two‐heartbeat T₁ mapping scheme yields a 5‐fold acceleration compared with MOLLI, with highly linearly correlated T₁ times, no significant difference of repeatability, and limited spatial variability penalty at 1.5T. This approach may enable myocardial T₁ mapping in patients with severe breath‐holding difficulties and reduce the examination time of multislice protocols.

Level of Evidence: 1

Technical Efficacy Stage: 3

J. Magn. Reson. Imaging 2019.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UcZorw

Comparison of Whole Heart Computed Tomography Scanners for Image Quality Lower Radiation Dosing in Coronary Computed Tomography Angiography: The CONVERGE Registry

Publication date: Available online 23 January 2019

Source: Academic Radiology

Author(s): Nirali Patel, Dong Li, Rine Nakanishi, Badiha Fatima, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Rachael O'Rourke, Eranthi Jayawardena, Christian Hamilton-Craig, Manojna Nimmagadda, Matthew J. Budoff

Rationale and Objectives

Novel technology in coronary computed tomographic angiography allows assessment of coronary artery disease with high image quality (IQ). There are currently two wide detector "whole heart" coverage scanners available, which avoid misregistration artifacts. However, there are no data directly comparing IQ between the two scanners. The aim of the current study is to investigate if IQ is different between the most current scanners of GE and Toshiba broad detector scanners.

Materials and Methods

Prospective, observational, multicenter international cohort study comparing 236 consecutive patients who underwent coronary computed tomographic angiography using whole-heart scanners; 126 patients on scanner S1 (Aquilion ONE, Toshiba), and 110 patients on scanner S2 (Revolution CT, GE Healthcare). Hounsfield units were measured using regions of interest in the descending aorta at 6 points (cranial slice, level of the visualized first, second, third, and fourth spines, and the caudal slice). We also compared the coverage length (z-axis) of the full width field of view between a single rotation of the two scanners.

Results

Evaluating mean CT attenuation values Hounsfield units through the scan range, are progressively reduced across the descending aorta in the S1 group, resulting in the larger difference of contrast brightness between the cranial and caudal slices compared to the S2 group (absolute difference: S2 13.0 ± 4.4 vs S1 141.9 ± 16.4, p < 0.0001; Percent difference: 19.3 ± 2.1 vs −3.4 ± 1.2, <0.0001). The standard deviation (SD) is similar at the cranial slice between the two scanners, however, the S1 group demonstrated higher SD-differential from cranial to caudal than S2 group. Median radiation exposure was significantly lower for the S2 scanner 1.50 ± 0.75 mSv vs the S1 system 1.9 mSv (IQR 1.7–2.7 mSv) (p = 0.01). Z-axis coverage was larger for the S2 scanner 152.5 mm (244 slices × 0.625 mm/slice) than 133 mm for S1 (266 slices × 0.5 mm/slice).

Conclusion

Although both "volume" scanners cover the whole heart z-axis with one beat, scans using the S1 scanner have a larger variability in attenuation values throughout the scan range, resulting in 20% increase in nonuniformity from cranial to caudal slice. Additionally, SD variation across the field of view, a metric of noise, is larger when using the S1 scanner vs the S2 scanner. These results indicate that the GE Revolution CT has more uniform contrast enhancement and more coverage, lower radiation and lower image noise compared to the current Toshiba Aquilion ONE system.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UalpXW

Detection of Pulmonary Embolism Based on Reduced Changes in Radiographic Lung Density During Cardiac Beating Using Dynamic Flat-panel Detector: An Animal-based Study

Publication date: Available online 23 January 2019

Source: Academic Radiology

Author(s): Rie Tanaka, Tohru Tani, Norihisa Nitta, Takahisa Tabata, Noritsugu Matsutani, Shintaro Muraoka, Tsutomu Yoneyama, Shigeru Sanada

Rationale and Objectives

To assess the capacity of dynamic flat-panel detector imaging without the use of contrast media to detect pulmonary embolism (PE) based on temporal changes in radiographic lung density during cardiac beating.

Materials and Methods

Sequential chest radiographs of six pigs were acquired using a dynamic flat-panel detector system. A porcine model of PE was developed, and temporal changes in pixel values in the imaged lungs were analyzed during a whole cardiac cycle. Mean differences in temporal changes in pixel values between affected and unaffected lobes were assessed using the paired t test. To facilitate visual evaluation, temporal changes in pixel values were depicted using a colorimetric scale and were compared to the findings of contrast-enhanced images.

Results

Affected lobes exhibited a mean reduction of 49.6% in temporal changes in pixel values compared to unaffected lobes within the same animals, and a mean reduction of 41.3% compared to that before vessel blockage in the same lobe. All unaffected lobes exhibited significantly-increased changes in pixel values after vessel blockage (p < 0.01). In all PE models, there were color-deficient areas with shapes and locations that matched well with the perfusion defects confirmed in the corresponding contrast-enhanced images.

Conclusion

Dynamic chest radiography enables the detection of perfusion defects in the lobe unit based on temporal changes in image density, even without the use of contrast media. Quantification and visualization techniques provide a better understanding of the circulation-induced changes depicted in dynamic chest radiographs.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dvfuat

Fast myocardial T1 mapping using shortened inversion recovery based schemes

Background

Myocardial T₁ mapping shows promise for assessment of cardiomyopathies. Most myocardial T₁ mapping techniques, such as modified Look–Locker inversion recovery (MOLLI), generate one T₁ map per breath‐held acquisition (9–17 heartbeats), which prolongs multislice protocols and may be unsuitable for patients with breath‐holding difficulties.

Purpose

To develop and characterize novel shortened inversion recovery based T₁ mapping schemes of 2–5 heartbeats.

Study Type

Prospective.

Population/Phantom

Numerical simulations, agarose/NiCl₂ phantom, 16 healthy volunteers, and 24 patients.

Field Strength/Sequence

1.5T/MOLLI.

Assessment

All shortened T₁ mapping schemes were characterized and compared with a conventional MOLLI scheme (5‐(3)‐3) in terms of accuracy, precision, spatial variability, and repeatability.

Statistical Tests

Kruskal–Wallis, Wilcoxon rank sum tests, analysis of variance, Student's t‐tests, Bland–Altman analysis, and Pearson correlation analysis.

Results

All shortened schemes provided limited T₁ time variations (≤2% for T₁ times ≤1200 msec) and limited penalty of precision (by a factor of ~1.4–1.5) when compared with MOLLI in numerical simulations. In phantom, differences between all schemes in terms of accuracy, spatial variability, and repeatability did not reach statistical significance (P > 0.71). In healthy volunteers, there were no statistically significant differences between all schemes in terms of native T₁ times and repeatability for myocardium (P = 0.21 and P = 0.87, respectively) and blood (P = 0.79 and P = 0.41, respectively). All shortened schemes led to a limited increase of spatial variability for native myocardial T₁ mapping with respect to MOLLI (by a factor of 1.2) (P < 0.0001). In both healthy volunteers and patients, the two‐heartbeat scheme and MOLLI led to highly linearly correlated T₁ times (correlation coefficients ≥0.83).

Data Conclusion

The proposed two‐heartbeat T₁ mapping scheme yields a 5‐fold acceleration compared with MOLLI, with highly linearly correlated T₁ times, no significant difference of repeatability, and limited spatial variability penalty at 1.5T. This approach may enable myocardial T₁ mapping in patients with severe breath‐holding difficulties and reduce the examination time of multislice protocols.

Level of Evidence: 1

Technical Efficacy Stage: 3

J. Magn. Reson. Imaging 2019.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UcZorw

Association of distant recurrence‐free survival with algorithmically extracted MRI characteristics in breast cancer

Background

While important in diagnosis of breast cancer, the scientific assessment of the role of imaging in prognosis of outcomes and treatment planning is limited.

Purpose: To evaluate the potential of using quantitative imaging variables for stratifying risk of distant recurrence in breast cancer patients.

Study Type

Retrospective.

Population

In all, 892 female invasive breast cancer patients.

Sequence

Dynamic contrast‐enhanced MRI with field strength 1.5 T and 3 T.

Assessment

Computer vision algorithms were applied to extract a comprehensive set of 529 imaging features quantifying size, shape, enhancement patterns, and heterogeneity of the tumors and the surrounding tissue. Using a development set with 446 cases, we selected 20 imaging features with high prognostic value.

Statistical Tests

We evaluated the imaging features using an independent test set with 446 cases. The principal statistical measure was a concordance index between individual imaging features and patient distant recurrence‐free survival (DRFS).

Results

The strongest association with DRFS that persisted after controlling for known prognostic clinical and pathology variables was found for signal enhancement ratio (SER) partial tumor volume (concordance index [C] = 0.768, 95% confidence interval [CI]: 0.679–0.856), tumor major axis length (C = 0.742, 95% CI: 0.650–0.834), kurtosis of the SER map within tumor (C = 0.640, 95% CI: 0.521–0.760), tumor cluster shade (C = 0.313, 95% CI: 0.216–0.410), and washin rate information measure of correlation (C = 0.702, 95% CI: 0.601–0.803).

Data Conclusion

Quantitative assessment of breast cancer features seen in a routine breast MRI might be able to be used for assessment of risk of distant recurrence.

Level of Evidence: 4

Technical Efficacy: Stage 6

J. Magn. Reson. Imaging 2019.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DuYqkJ

Somatosensory evoked potential: Preventing brachial plexus injury in transaxillary robotic surgery

Objectives/Hypothesis

The potential for brachial plexopathy due to arm positioning is a major concern regarding the robotic transaxillary approach. Intraoperative nerve monitoring via somatosensory evoked potential (SSEP) has been suggested to prevent such injury. In this study, we examined the use of SSEP in detecting imminent brachial plexus traction during robotic transaxillary thyroid and parathyroid surgery.

Study Design

Retrospective case series.

Methods

A analysis was performed for all patients undergoing robotic transaxillary surgery with continuous intraoperative SSEP monitoring at a North American institution between 2015 and 2017. A significant intraoperative SSEP change was defined as a decrease in signal amplitude of >50% or an increase in latency of >10% from baseline established during preoperative positioning.

Results

One hundred thirty‐seven robotic transaxillary surgeries using SSEP monitoring were performed on 123 patients. Seven patients (5.1%) developed significant changes, with an average SSEP amplitude reduction of 73% ± 12% recorded at the signals' nadir. Immediate arm repositioning resulted in recovery of signals and complete return to baseline parameters in 14.3 ± 9.2 minutes. There was no difference in age (40.4 ± 9.4 years vs. 44.5 ± 13.4 years; P = .31) or body mass index (27.3 ± 3.7 kg/m² vs. 26.9 ± 6.1 kg/m²; P = .79) between cases with and without SSEP change. Operative time was shorter for patients with significant SSEP change (131.6 ± 14.7 minutes vs. 146.5 ± 46.7 minutes; P = .048). There were no postoperative positional brachial plexus injuries.

Conclusions

SSEP is a novel, safe, and reliable tool in detection of position‐related brachial plexus neuropathy. Intraoperative monitoring using SSEP can play a vital role in early recognition and prevention of injury during robotic transaxillary thyroid and parathyroid surgery.

Level of Evidence

4 Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RFEZ1n

Comparative Assessment of Drug‐Induced Sleep Endoscopy Scoring Systems in Pediatric Sleep Apnea

Objectives/Hypothesis

A wide variety of drug‐induced sleep endoscopy (DISE) scoring systems has been used to evaluate sites of upper airway obstruction in children and adults; however, a universally accepted DISE scoring system dedicated to children has not been developed. We evaluated the utility of DISE scoring systems in the assessment of obstructive sleep apnea (OSA) using a single cohort of pediatric patients.

Study Design

Retrospective chart review.

Methods

The medical records of surgically naïve–healthy children with OSA who had undergone DISE were reviewed. Information about demographics, past medical history, and severity of OSA were obtained. A literature review was conducted to identify DISE scoring systems used in children with OSA. Recordings of DISE were analyzed without knowledge of patient information and severity of OSA. The effect of age, obesity, severity of OSA, and oxygen nadir on DISE score was assessed.

Results

Sixty‐eight patients (46 male, 22 female, age range: 19 months–18 years) were included. Forty‐three patients were obese and 25 were nonobese. The severity of OSA was mild in 12 patients, moderate in 13 patients, and severe in 43 patients. DISE scoring systems did not document differences among the groups of patients with mild OSA, moderate OSA, and severe OSA (P > .05). DISE scores were not different among the studied age and weight categories (P > .05).

Conclusions

The DISE scoring systems did not show differences in DISE scores in surgically naïve–healthy children with varying age, weight, and OSA severity categories. Our findings provide preliminary evidence for the need of a universally applicable pediatric DISE scoring system for OSA.

Level of Evidence

4 Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CISGlE

Pediatric dysphagia: Is interarytenoid mucosal height significant?

Objectives

The clinical significance of the interarytenoid mucosal height (IAMH) in pediatric dysphagia, ranging from normal anatomy to a laryngeal cleft, is unknown. This study seeks to evaluate a cohort of patients who underwent evaluation of their IAMH during microdirect laryngoscopy (MDL) for associations between IAMH and dysphagia as diagnosed on preoperative videofluoroscopic swallow study (VFSS).

Methods

A retrospective case series of 1,351 patients who underwent MDL between 2011 and 2016 were reviewed for intraoperative evaluation of IAMH using our interarytenoid assessment protocol. After exclusions, 182 patients were divided into three groups: 1) thickened diet: VFSS with recommendation for thickened liquids (n = 82 of 182; 45.1%), 2) normal diet: VFSS with allowance of thin liquids (n = 19 of 182; 10.4%), and 3) control: no VFSS performed (n = 81 of 182; 44.5%).

Results

There was no difference in IAMH between groups (P = 0.35). Power analysis was able to achieve > 80% power to detect an effect size of ≥ 0.5 (1–5 mucosal height scale). The majority of patients in each group had an IAMH above the false vocal folds (thickened diet: 57.3%, normal diet: 57.9%, control: 64.2%). There were similar percentages of patients in each group with an IAMH at or below the true vocal folds (thickened diet: 4.9%, normal diet: 5.3%, control: 6.1%).

Conclusion

There was no significant association between IAMH and preoperative thickened liquid recommendation in this cohort. This data fails to support the hypothesis that the IAMH is an independent etiological factor for pediatric pharyngeal dysphagia. Further studies comparing IAMH with outcomes after feeding therapy and surgery may better clarify this relationship between anatomy and physiology.

Level of Evidence

4. Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RGpPJ2

Masthead

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CGhhrl

Somatosensory evoked potential: Preventing brachial plexus injury in transaxillary robotic surgery

Objectives/Hypothesis

The potential for brachial plexopathy due to arm positioning is a major concern regarding the robotic transaxillary approach. Intraoperative nerve monitoring via somatosensory evoked potential (SSEP) has been suggested to prevent such injury. In this study, we examined the use of SSEP in detecting imminent brachial plexus traction during robotic transaxillary thyroid and parathyroid surgery.

Study Design

Retrospective case series.

Methods

A analysis was performed for all patients undergoing robotic transaxillary surgery with continuous intraoperative SSEP monitoring at a North American institution between 2015 and 2017. A significant intraoperative SSEP change was defined as a decrease in signal amplitude of >50% or an increase in latency of >10% from baseline established during preoperative positioning.

Results

One hundred thirty‐seven robotic transaxillary surgeries using SSEP monitoring were performed on 123 patients. Seven patients (5.1%) developed significant changes, with an average SSEP amplitude reduction of 73% ± 12% recorded at the signals' nadir. Immediate arm repositioning resulted in recovery of signals and complete return to baseline parameters in 14.3 ± 9.2 minutes. There was no difference in age (40.4 ± 9.4 years vs. 44.5 ± 13.4 years; P = .31) or body mass index (27.3 ± 3.7 kg/m² vs. 26.9 ± 6.1 kg/m²; P = .79) between cases with and without SSEP change. Operative time was shorter for patients with significant SSEP change (131.6 ± 14.7 minutes vs. 146.5 ± 46.7 minutes; P = .048). There were no postoperative positional brachial plexus injuries.

Conclusions

SSEP is a novel, safe, and reliable tool in detection of position‐related brachial plexus neuropathy. Intraoperative monitoring using SSEP can play a vital role in early recognition and prevention of injury during robotic transaxillary thyroid and parathyroid surgery.

Level of Evidence

4 Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RFEZ1n

Pediatric dysphagia: Is interarytenoid mucosal height significant?

Objectives

The clinical significance of the interarytenoid mucosal height (IAMH) in pediatric dysphagia, ranging from normal anatomy to a laryngeal cleft, is unknown. This study seeks to evaluate a cohort of patients who underwent evaluation of their IAMH during microdirect laryngoscopy (MDL) for associations between IAMH and dysphagia as diagnosed on preoperative videofluoroscopic swallow study (VFSS).

Methods

A retrospective case series of 1,351 patients who underwent MDL between 2011 and 2016 were reviewed for intraoperative evaluation of IAMH using our interarytenoid assessment protocol. After exclusions, 182 patients were divided into three groups: 1) thickened diet: VFSS with recommendation for thickened liquids (n = 82 of 182; 45.1%), 2) normal diet: VFSS with allowance of thin liquids (n = 19 of 182; 10.4%), and 3) control: no VFSS performed (n = 81 of 182; 44.5%).

Results

There was no difference in IAMH between groups (P = 0.35). Power analysis was able to achieve > 80% power to detect an effect size of ≥ 0.5 (1–5 mucosal height scale). The majority of patients in each group had an IAMH above the false vocal folds (thickened diet: 57.3%, normal diet: 57.9%, control: 64.2%). There were similar percentages of patients in each group with an IAMH at or below the true vocal folds (thickened diet: 4.9%, normal diet: 5.3%, control: 6.1%).

Conclusion

There was no significant association between IAMH and preoperative thickened liquid recommendation in this cohort. This data fails to support the hypothesis that the IAMH is an independent etiological factor for pediatric pharyngeal dysphagia. Further studies comparing IAMH with outcomes after feeding therapy and surgery may better clarify this relationship between anatomy and physiology.

Level of Evidence

4. Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RGpPJ2

Validation of the Chinese Velopharyngeal Insufficiency Effects on Life Outcomes Instrument

Objectives/Hypothesis

To translate the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) instrument into Chinese and test its psychometric properties.

Study Design

Quality of life instrument translation and validation.

Methods

The original English version of the VELO instrument was translated into Mandarin, back‐translated, and adapted among the Chinese population, based on the standardized guidelines for the cross‐culture adaption process. Velopharyngeal insufficiency (VPI) patients were identified by a professional speech and language pathologist. Internal reliability of the VELO instrument was assessed by the Cronbach's α coefficient. Discriminant validity was tested by the Mann‐Whitney U test. Construct validity was assessed by factor analysis.

Results

A total of 113 patients with VPI and 72 parents of the patients were enrolled. The mean age of the VPI patients was 14.8 years. Internal reliability was excellent; Cronbach's α coefficients were 0.92 and 0.94 for VPI patients and their parents, respectively. The Chinese VELO discriminated well between the VPI group and the controls, with a mean (standard deviation) score that was significantly lower for the VPI group (74.8 [25.7]) than the control group (98.0 [15.9]) (P < .001). The total scores and scores in the emotional domain or perception domain showed differences between VPI patients and their parents. Similar to the original study, the factor loading after rotation followed hypothesized domains largely, in spite of items from several domains loaded on the same factor.

Conclusions

The translated Chinese version of the VELO instrument demonstrated an acceptable reliability, discriminant validity, and construct validity. These psychometric properties suggested theoretical evidence for the further use of the VELO instrument among Chinese patients with VPI.

Level of Evidence

3b Laryngoscope, 2019

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CFKYIW

Table of contents

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RLc6ko

Masthead

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CGhhrl

Development Of Atopic Sensitization In Finnish And Estonian Children – A Latent Class Analysis In A Multicenter Cohort

In two countries differing fundamentally in environmental and socioeconomic determinants and sensitization rates, similar atopy classes were found regarding composition and disease relevance. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Uh4lQ7

Beta-defensins are pro-inflammatory pruritogens that activate Mrgprs

Beta-defensins increase vascular permeability in mouse skin through activation of Mrgprs expressed by mast cells. Defensins also activate Mrgprs expressed by neurons associated with itch, and induce itch themselves, establishing defensins as novel pro-inflammatory pruritogens. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Udl9r8

Acculturation is Associated with Asthma Burden and Pulmonary Function in Latino Youth: The GALA II Study

High acculturation increases likelihood of diagnosed asthma whereas low acculturation is associated with lower pulmonary function and increased bronchodilator response in Latinos; cultural and behavioral practices should be considered when determining risk and managing asthma. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dtbver

Functional Ct Imaging For Identification Of The Spatial Determinants Of Small Airways Disease In Adult Asthma

This study analyses spatially localised ventilation heterogeneity in adult asthma using CT imaging and modelling, and presents evidence of inferior to superior ventilation gradient reversal in the disease pathogenesis. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Udl9aC

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

This study shows a novel immune regulatory pathway that avoids excessive lung inflammation through conversion of ILC2s to ILCregs by retinoic acid that is synthesized by airway epithelial cells. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DswwpA

A sputum 6 gene signature predicts future exacerbations of poorly controlled asthma

In this AMAZES RCT sub-analysis, the sputum 6GS predicts exacerbation and airway inflammatory phenotype of uncontrolled, moderate-to-severe asthma. Azithromycin appears to exert a therapeutic effect independently of 6GS-related airway inflammatory factors. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UckndT

Atopic dermatitis and cardiovascular disease: what are the clinical implications?

(Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dua9Ac

Combined liver and hematopoietic stem cell transplantation in X-linked hyper IgM syndrome

Liver disease in X-linked hyper IgM syndrome (XHIGM) is an important predictor of mortality. In case liver transplantation (LT) is required, a survival benefit is observed when LT is combined with HSCT. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DrRV1V

Development Of Atopic Sensitization In Finnish And Estonian Children – A Latent Class Analysis In A Multicenter Cohort

In two countries differing fundamentally in environmental and socioeconomic determinants and sensitization rates, similar atopy classes were found regarding composition and disease relevance. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Uh4lQ7

Nanoallergen Platform for the Detection of Platin Drugs Allergies

In this study, we validated a novel nanoparticle based in vitro diagnostic technique for drug allergies to two common platinum-based chemotherapeutics, oxaliplatin and carboplatin. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DtqmFs

Allergen Specific CD8+ T cells in Peanut Allergic Individuals

CD8+ T cells are seldom considered in IgE mediated food allergy; we show that peanut specific CD8+ T cells are increased in peanut allergic human subjects. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2U4XN6O

ADRB2 p.Thr164Ile association with hospitalization depends upon asthma severity

In LABA-treated patients, the ADRB2 p.Thr164Ile only associate with asthma exacerbation risk in some patients with severe asthma but is not predictive of asthma exacerbation risk in all asthmatics. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dtqe8W

Beta-defensins are pro-inflammatory pruritogens that activate Mrgprs

Beta-defensins increase vascular permeability in mouse skin through activation of Mrgprs expressed by mast cells. Defensins also activate Mrgprs expressed by neurons associated with itch, and induce itch themselves, establishing defensins as novel pro-inflammatory pruritogens. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Udl9r8

Acculturation is Associated with Asthma Burden and Pulmonary Function in Latino Youth: The GALA II Study

High acculturation increases likelihood of diagnosed asthma whereas low acculturation is associated with lower pulmonary function and increased bronchodilator response in Latinos; cultural and behavioral practices should be considered when determining risk and managing asthma. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Dtbver

Functional Ct Imaging For Identification Of The Spatial Determinants Of Small Airways Disease In Adult Asthma

This study analyses spatially localised ventilation heterogeneity in adult asthma using CT imaging and modelling, and presents evidence of inferior to superior ventilation gradient reversal in the disease pathogenesis. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2Udl9aC

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

This study shows a novel immune regulatory pathway that avoids excessive lung inflammation through conversion of ILC2s to ILCregs by retinoic acid that is synthesized by airway epithelial cells. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2DswwpA

A sputum 6 gene signature predicts future exacerbations of poorly controlled asthma

In this AMAZES RCT sub-analysis, the sputum 6GS predicts exacerbation and airway inflammatory phenotype of uncontrolled, moderate-to-severe asthma. Azithromycin appears to exert a therapeutic effect independently of 6GS-related airway inflammatory factors. (Source: Journal of Allergy and Clinical Immunology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2UckndT

ADRB2 p.Thr164Ile association with hospitalization depends upon asthma severity

Publication date: Available online 23 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Lynn D. Condreay, Mathias N. Chiano, Li Li, Elizabeth Harris, Dana J. Fraser, Deborah A. Meyers, Eugene R. Bleecker, Courtney Crim, David Stempel, Steven W. Yancey, Soumitra Ghosh

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RJHvnh

Development Of Atopic Sensitization In Finnish And Estonian Children – A Latent Class Analysis In A Multicenter Cohort

Publication date: Available online 23 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Felicitas Schmidt, Alexander J. Hose, Susanne Mueller-Rompa, Tabea Brick, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Onni Niemelä, Heli Siljander, Mikael Knip, Juliane Weber, Erika von Mutius, Markus J. Ege, DIABIMMUNE Study Group

Abstract

Background

The prevalence of atopy is associated with a western lifestyle as illustrated by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors.

Objective

To define phenotypes of atopic sensitization in early childhood and to examine their association with allergic diseases and hereditary background in Finland and Estonia

Methods

The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4 and 5 respectively, and categorized into three CAP classes. Latent Class Analysis (LCA) was performed with the statistic software package poLCA in R.

Results

Both populations differed in terms of socioeconomic status and environmental determinants such as pet ownership, farm-related exposure, time of playing outdoors and prevalence of allergic diseases (all p-values <0.001). Nevertheless, we found similar latent classes (LC) in both populations: an unsensitized class, a food class, two inhalant classes differentiating between seasonal and perennial aero-allergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio 5.64 [3.07-10.52] and 4.56 [2.35-8.52]), allergic rhinitis (22.4 [11.67-44.54] and 13.97 [7.33-26.4]) and atopic eczema (9.39 [4.9-19.3] and 9.5 [5.2-17.5], for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland though composition of classes was comparable between countries.

Conclusion

Despite profound differences in environmental exposures there may exist genuine patterns of atopic sensitization. The distribution of these patterns may determine the contribution of atopic sensitization to disease onset.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RH6S9c

Combined liver and hematopoietic stem cell transplantation in X-linked hyper IgM syndrome

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Giorgia Bucciol, Sarah K. Nicholas, Pier Luigi Calvo, Andrew Cant, J.David M. Edgar, Teresa Español, Francesca Ferrua, Miguel Galicchio, Andrew R. Gennery, Nedim Hadzic, I.Celine Hanson, Gustavo Kusminsky, Andrzej Lange, Fanny Lanternier, Nizar Mahlaoui, Despina Moshous, Zohreh Nademi, Benedicte Neven, Matias Oleastro, Fulvio Porta

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CCeCiu

Functional Ct Imaging For Identification Of The Spatial Determinants Of Small Airways Disease In Adult Asthma

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Alex J. Bell, Brody H. Foy, Matthew Richardson, Amisha Singapuri, Evgeny Mirkes, Maarten van den Berge, David Kay, Chris Brightling, Alexander N. Gorban, Craig J. Galbán, Salman Siddiqui

abstract

Background

Asthma is a disease characterised by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived using impulse oscillometry (IOS) or multiple breath washout (MBW) are associated with key asthma patient related outcome measures and airways hyper responsiveness. However the topographical mechanisms of VH in the lung remain poorly understood.

Objectives

We hypothesised that specific regionalisation of topographical small airway disease would best account for IOS and MBW measured indices in patients.

METHODS

We evaluated paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n=41) and healthy volunteers (n=11) to understand the determinants of clinical VH indices commonly reported using IOS and MBW. Parametric response mapping (PRM) was utilised to calculate functional small airways disease marker PRM^fSAD and Hounsfield unit (HU) based density change from total lung capacity to functional residual capacity (ΔHU); gradients of ΔHU, in gravitationally perpendicular (parallel), inferior-superior (anterior-posterior) axes, were quantified.

Results

ΔHU gradient in the inferior-superior axis provided the highest level of discrimination of both S_acin and R5-20. Patients with a high inferior-superior ΔHU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRM^fSAD. A computational small airway tree model confirmed that constriction of gravitationally dependant lower zone small airway branches would promote the largest increases in R5-R20. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency.

Conclusions

Lower lobe predominant small airways disease is a major driver of clinically measured VH in adult asthma.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RNRGr6

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Hideaki Morita, Terufumi Kubo, Beate Rückert, Avinash Ravindran, Michael B. Soyka, Arturo Ottavio Rinaldi, Kazunari Sugita, Marcin Wawrzyniak, Paulina Wawrzyniak, Kenichiro Motomura, Masato Tamari, Keisuke Orimo, Naoko Okada, Ken Arae, Kyoko Saito, Can Altunbulakli, Francesc Castro-Giner, Ge Tan, Avidan Neumann, Katsuko Sudo

Abstract

Background

Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus, clarification of the mechanisms that underlie the regulation of ILC2 activation has received significant attention. Although ILCs are divided into three major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T (Treg) cells have not been well characterized.

Objective

We sought to determine the factors that induce regulatory ILCs (ILCregs).

Methods

IL-10⁺ ILCregs induced from ILC2s by retinoic acid (RA) were analyzed using RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissues from healthy individuals and patients with chronic rhinosinusitis with nasal polyp (CRSwNP), and in lung tissues from house dust mite (HDM)- or saline-treated mice.

Results

RA induced IL-10 secretion by human ILC2s, but not type-2 cytokines. IL-10⁺ ILCregs, converted from ILC2s by RA stimulation, expressed a Treg-like signature with the expression of IL-10, CTLA-4 and CD25, with down regulated effector type 2-related markers such as CRTH-2 and ST2, and suppressed activation of CD4⁺ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy individuals or lung tissues from saline-treated mice, but were increased in nasal tissues from patients with CRSwNP and in lung tissues from HDM-treated mice. Enzymes for RA synthesis were up-regulated in airway epithelial cells during type-2 inflammation in vivo and by IL-13 in vitro.

Conclusion

We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CDlVX3

Beta-defensins are pro-inflammatory pruritogens that activate Mrgprs

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Li Zhang, Benjamin D. McNeil

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RL2PsC

A sputum 6 gene signature predicts future exacerbations of poorly controlled asthma

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Michael Fricker, Peter G. Gibson, Heather Powell, Jodie L. Simpson, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Guy B. Marks, Melissa Baraket, Katherine J. Baines

Abstract:

Background

Improved diagnostic tools for predicting future exacerbation frequency in asthma are required. A sputum gene expression signature of 6 biomarkers (6GS - including CLC, CPA3, DNASE1L3, ALPL, CXCR2, IL1B) predicts inflammatory and treatment response phenotypes in stable asthma. We recently demonstrated that azithromycin (AZM) add-on treatment in uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial).

Objectives

To test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES. To test the impact of AZM therapy on 6GS expression and prognostic capacity.

Methods

142 patients (73 placebo-treated, 69 AZM-treated) had sputum stored for qPCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression, ROC and AUC were performed on baseline measures, and in an exploratory analysis the predictive value of 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes.

Results

The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for 6GS were significantly higher than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts and combined sputum eosinophils and neutrophil counts. 6GS AUCs were also were numerically, but not significantly, higher than FeNO and sputum eosinophil counts. AZM treatment neither altered the 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population.

Conclusion

We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CDlU5r

Acculturation is Associated with Asthma Burden and Pulmonary Function in Latino Youth: The GALA II Study

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Neeta Thakur, Luisa N. Borrell, Morgan Ye, Sam S. Oh, Celeste Eng, Kelley Meade, Pedro C. Avila, Harold J. Farber, Denise Serebrisky, Emerita Brigino-Buenaventura, William Rodriguez-Cintron, Rajesh Kumar, Kirsten Bibbins-Domingo, Shannon Thyne, Saunak Sen, Jose R. Rodriguez-Santana, Esteban G. Burchard

Abstract

Background

Acculturation is an important predictor of asthma in Latino youth, specifically, Mexican Americans. Less is known about acculturation and pulmonary function measures.

Objective

To estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups.

Methods

We included 1,849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1,136 Mexican Americans, 218 other Latino children) aged 8-21 years old from 4 urban regions in the U.S. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the U.S. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study) adjusting for demographic, socio-environmental, and clinical variables.

Results

For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the U.S.), higher levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (p=0.009 and 0.02, respectively). Similarly, high language acculturation was associated with increased FEV₁ compared with low language acculturation (p=0.02). There was insufficient evidence of heterogeneity for associations across Latino subgroups.

Conclusions

Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is important factor to consider in the management of Latino youth with asthma.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RH9wMn

Allergen Specific CD8+ T cells in Peanut Allergic Individuals

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Wong Yu, Xiaoying Zhou, Diane Dunham, Shu Chen Lyu, Monali Manohar, Wenming Zhang, Fan Zhao, Mark M. Davis, Kari Nadeau

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CGeu1l

ADRB2 p.Thr164Ile association with hospitalization depends upon asthma severity

Publication date: Available online 23 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Lynn D. Condreay, Mathias N. Chiano, Li Li, Elizabeth Harris, Dana J. Fraser, Deborah A. Meyers, Eugene R. Bleecker, Courtney Crim, David Stempel, Steven W. Yancey, Soumitra Ghosh

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RJHvnh

Nanoallergen Platform for the Detection of Platin Drugs Allergies

Publication date: Available online 23 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Peter E. Deak, Baksun Kim, Ather Adnan, Marina Labella, Leticia De las Vecillas, Mariana Castells, Basar Bilgicer

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2COf9Oz

Development Of Atopic Sensitization In Finnish And Estonian Children – A Latent Class Analysis In A Multicenter Cohort

Publication date: Available online 23 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Felicitas Schmidt, Alexander J. Hose, Susanne Mueller-Rompa, Tabea Brick, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Onni Niemelä, Heli Siljander, Mikael Knip, Juliane Weber, Erika von Mutius, Markus J. Ege, DIABIMMUNE Study Group

Abstract

Background

The prevalence of atopy is associated with a western lifestyle as illustrated by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors.

Objective

To define phenotypes of atopic sensitization in early childhood and to examine their association with allergic diseases and hereditary background in Finland and Estonia

Methods

The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4 and 5 respectively, and categorized into three CAP classes. Latent Class Analysis (LCA) was performed with the statistic software package poLCA in R.

Results

Both populations differed in terms of socioeconomic status and environmental determinants such as pet ownership, farm-related exposure, time of playing outdoors and prevalence of allergic diseases (all p-values <0.001). Nevertheless, we found similar latent classes (LC) in both populations: an unsensitized class, a food class, two inhalant classes differentiating between seasonal and perennial aero-allergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio 5.64 [3.07-10.52] and 4.56 [2.35-8.52]), allergic rhinitis (22.4 [11.67-44.54] and 13.97 [7.33-26.4]) and atopic eczema (9.39 [4.9-19.3] and 9.5 [5.2-17.5], for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland though composition of classes was comparable between countries.

Conclusion

Despite profound differences in environmental exposures there may exist genuine patterns of atopic sensitization. The distribution of these patterns may determine the contribution of atopic sensitization to disease onset.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RH6S9c

Combined liver and hematopoietic stem cell transplantation in X-linked hyper IgM syndrome

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Giorgia Bucciol, Sarah K. Nicholas, Pier Luigi Calvo, Andrew Cant, J.David M. Edgar, Teresa Español, Francesca Ferrua, Miguel Galicchio, Andrew R. Gennery, Nedim Hadzic, I.Celine Hanson, Gustavo Kusminsky, Andrzej Lange, Fanny Lanternier, Nizar Mahlaoui, Despina Moshous, Zohreh Nademi, Benedicte Neven, Matias Oleastro, Fulvio Porta

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CCeCiu

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Hideaki Morita, Terufumi Kubo, Beate Rückert, Avinash Ravindran, Michael B. Soyka, Arturo Ottavio Rinaldi, Kazunari Sugita, Marcin Wawrzyniak, Paulina Wawrzyniak, Kenichiro Motomura, Masato Tamari, Keisuke Orimo, Naoko Okada, Ken Arae, Kyoko Saito, Can Altunbulakli, Francesc Castro-Giner, Ge Tan, Avidan Neumann, Katsuko Sudo

Abstract

Background

Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus, clarification of the mechanisms that underlie the regulation of ILC2 activation has received significant attention. Although ILCs are divided into three major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T (Treg) cells have not been well characterized.

Objective

We sought to determine the factors that induce regulatory ILCs (ILCregs).

Methods

IL-10⁺ ILCregs induced from ILC2s by retinoic acid (RA) were analyzed using RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissues from healthy individuals and patients with chronic rhinosinusitis with nasal polyp (CRSwNP), and in lung tissues from house dust mite (HDM)- or saline-treated mice.

Results

RA induced IL-10 secretion by human ILC2s, but not type-2 cytokines. IL-10⁺ ILCregs, converted from ILC2s by RA stimulation, expressed a Treg-like signature with the expression of IL-10, CTLA-4 and CD25, with down regulated effector type 2-related markers such as CRTH-2 and ST2, and suppressed activation of CD4⁺ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy individuals or lung tissues from saline-treated mice, but were increased in nasal tissues from patients with CRSwNP and in lung tissues from HDM-treated mice. Enzymes for RA synthesis were up-regulated in airway epithelial cells during type-2 inflammation in vivo and by IL-13 in vitro.

Conclusion

We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CDlVX3

Beta-defensins are pro-inflammatory pruritogens that activate Mrgprs

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Li Zhang, Benjamin D. McNeil

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RL2PsC

A sputum 6 gene signature predicts future exacerbations of poorly controlled asthma

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Michael Fricker, Peter G. Gibson, Heather Powell, Jodie L. Simpson, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Guy B. Marks, Melissa Baraket, Katherine J. Baines

Abstract:

Background

Improved diagnostic tools for predicting future exacerbation frequency in asthma are required. A sputum gene expression signature of 6 biomarkers (6GS - including CLC, CPA3, DNASE1L3, ALPL, CXCR2, IL1B) predicts inflammatory and treatment response phenotypes in stable asthma. We recently demonstrated that azithromycin (AZM) add-on treatment in uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial).

Objectives

To test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES. To test the impact of AZM therapy on 6GS expression and prognostic capacity.

Methods

142 patients (73 placebo-treated, 69 AZM-treated) had sputum stored for qPCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression, ROC and AUC were performed on baseline measures, and in an exploratory analysis the predictive value of 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes.

Results

The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for 6GS were significantly higher than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts and combined sputum eosinophils and neutrophil counts. 6GS AUCs were also were numerically, but not significantly, higher than FeNO and sputum eosinophil counts. AZM treatment neither altered the 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population.

Conclusion

We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.

Graphical abstract

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CDlU5r

Acculturation is Associated with Asthma Burden and Pulmonary Function in Latino Youth: The GALA II Study

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Neeta Thakur, Luisa N. Borrell, Morgan Ye, Sam S. Oh, Celeste Eng, Kelley Meade, Pedro C. Avila, Harold J. Farber, Denise Serebrisky, Emerita Brigino-Buenaventura, William Rodriguez-Cintron, Rajesh Kumar, Kirsten Bibbins-Domingo, Shannon Thyne, Saunak Sen, Jose R. Rodriguez-Santana, Esteban G. Burchard

Abstract

Background

Acculturation is an important predictor of asthma in Latino youth, specifically, Mexican Americans. Less is known about acculturation and pulmonary function measures.

Objective

To estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups.

Methods

We included 1,849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1,136 Mexican Americans, 218 other Latino children) aged 8-21 years old from 4 urban regions in the U.S. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the U.S. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study) adjusting for demographic, socio-environmental, and clinical variables.

Results

For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the U.S.), higher levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (p=0.009 and 0.02, respectively). Similarly, high language acculturation was associated with increased FEV₁ compared with low language acculturation (p=0.02). There was insufficient evidence of heterogeneity for associations across Latino subgroups.

Conclusions

Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is important factor to consider in the management of Latino youth with asthma.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2RH9wMn

Allergen Specific CD8+ T cells in Peanut Allergic Individuals

Publication date: Available online 22 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Wong Yu, Xiaoying Zhou, Diane Dunham, Shu Chen Lyu, Monali Manohar, Wenming Zhang, Fan Zhao, Mark M. Davis, Kari Nadeau

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2CGeu1l

Safety and reproducibility of Nasal Allergen Challenge

Abstract

Background

The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR), and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility is scarce.

Objective

To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls.

Methods

A retrospective evaluation of the NACs conducted in our Unit for 2005‐2017 and monitored by acoustic rhinometry and nasal‐ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session (NAC‐S & NAC‐M)). The adverse events (AE), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC‐S performed at 1‐2‐month interval in AR, LAR and non‐allergic rhinitis patients, and in healthy controls.

Results

A total of 11499 NACs were performed in 518 children and 5830 adults. Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC‐S performed in 710 subjects were 97.32%, 100%, and 92.91% respectively. There were no false positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes.

Conclusion

The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R7NUmR

Contribution of airway eosinophils in airway wall remodeling in asthma: role of MMP‐10 and MET

Abstract

Background

Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma.

Methods

We analyzed the transcriptomic data from bronchial biopsies of 81 moderate‐to‐severe asthma patients of the U‐BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localisation of proteins was by immunohistochemistry.

Results

Using stringent false discovery rate analysis, MMP‐10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP‐10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less‐stringent conditions (raw p‐value <0.05, log2Fold Change>0.5), we defined a 73‐gene set characteristic of the HE compared to the LE group. 33/73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC‐chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organisation correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS‐1 and SOX family proteins that showed positive correlation with MMP10 and MET expression.

Conclusion

Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP‐10 likely play an important role in these processes.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2WaDpmy

Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis

Abstract

Background

Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood‐derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remains largely uncharacterized.

Methods

We established a method for isolating CD69^hi CCR3^low CXCR4^‐ siglec‐8^int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP‐EOS). Multi‐omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP‐EOS as compared with peripheral blood‐derived eosinophils from healthy subjects (PB‐EOS).

Results

Lipidomic analysis revealed impaired synthesis of prostaglandins and 15‐lipoxygenase (15‐LOX)‐derived mediators, and selective upregulation of leukotriene D₄ production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15‐LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB‐EOS with eosinophil activators IL‐5, GM‐CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.

Conclusion

Inflammatory tissue‐derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R88e7F

Safety and reproducibility of Nasal Allergen Challenge

Abstract

Background

The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR), and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility is scarce.

Objective

To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls.

Methods

A retrospective evaluation of the NACs conducted in our Unit for 2005‐2017 and monitored by acoustic rhinometry and nasal‐ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session (NAC‐S & NAC‐M)). The adverse events (AE), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC‐S performed at 1‐2‐month interval in AR, LAR and non‐allergic rhinitis patients, and in healthy controls.

Results

A total of 11499 NACs were performed in 518 children and 5830 adults. Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC‐S performed in 710 subjects were 97.32%, 100%, and 92.91% respectively. There were no false positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes.

Conclusion

The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R7NUmR

Contribution of airway eosinophils in airway wall remodeling in asthma: role of MMP‐10 and MET

Abstract

Background

Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma.

Methods

We analyzed the transcriptomic data from bronchial biopsies of 81 moderate‐to‐severe asthma patients of the U‐BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localisation of proteins was by immunohistochemistry.

Results

Using stringent false discovery rate analysis, MMP‐10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP‐10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less‐stringent conditions (raw p‐value <0.05, log2Fold Change>0.5), we defined a 73‐gene set characteristic of the HE compared to the LE group. 33/73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC‐chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organisation correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS‐1 and SOX family proteins that showed positive correlation with MMP10 and MET expression.

Conclusion

Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP‐10 likely play an important role in these processes.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2WaDpmy

Dysregulated fatty acid metabolism in nasal polyp‐derived eosinophils from patients with chronic rhinosinusitis

Abstract

Background

Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood‐derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remains largely uncharacterized.

Methods

We established a method for isolating CD69^hi CCR3^low CXCR4^‐ siglec‐8^int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP‐EOS). Multi‐omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP‐EOS as compared with peripheral blood‐derived eosinophils from healthy subjects (PB‐EOS).

Results

Lipidomic analysis revealed impaired synthesis of prostaglandins and 15‐lipoxygenase (15‐LOX)‐derived mediators, and selective upregulation of leukotriene D₄ production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15‐LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB‐EOS with eosinophil activators IL‐5, GM‐CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism.

Conclusion

Inflammatory tissue‐derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

This article is protected by copyright. All rights reserved.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2R88e7F