March 19, 2013

All that wheezes is not asthma

J Emerg Trauma Shock. 2013 Jan-Mar; 6(1): 61–62.

PMCID: PMC3589865

All that wheezes is not asthma

Girish Narayan, G K Narayana,¹ and K Prabhakar²

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Sir,

A 50-year-old female recently diagnosed with bronchial asthma presented with acute dyspnoea and wheeze. She did not respond to conventional treatment and progressed to acute respiratory failure requiring ventilation. The initial chest radiograph [Figure 1] was unremarkable. Two days later the patient developed left lung atelectasis [Figure 2], fiber optic bronchoscopy revealed a foreign body [Video 1], a betel nut in the left main bronchus. The betel nut [Figure 3] was removed and the patient was extubated five days later. The patient was a betel nut chewer and had aspirated it. Wheeze would have been heard due to a check-valve mechanism of airflow past the foreign body, and eventually a stop-valve mechanism, resulted in atelectasis [Figure 4].

Figure 1

Chest radiograph on day 1 immediately after intubation unremarkable

Figure 2

Chest radiograph on day 3, patient on ventilator, showing left ling atelectasis

Figure 3

Emergency bronchoscopy revealed a foreign body in left main bronchus

Figure 4

Pathogenesis of wheeze heard would have been due to a bypass/check-valve mechanism of airflow past the foreign body initially, and eventually a stop-valve mechanism, resulting in atelectasis

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Airflow through a narrow airway generates a coarse whistling sound, which is known as wheeze and is often equated with asthma. Chevalier Jackson recognized “all that wheezes is not asthma” and described the above mentioned mechanism of bronchial obstruction by a foreign body.[1,2] Another cause of wheeze that is at time misdiagnosed as asthma is pulmonary edema. Described as “cardiac asthma”, wheeze is heard due to bronchial wall and intraluminal edema fluid cause narrowing of the small airways.[3] Other processes that narrow the diameter of an airway inducing wheezing include chronic obstructive pulmonary disease, endobronchial or endotracheal stenosis, buildup of airway secretions, endobronchial obstruction, upper airway obstruction, and allergic reactions.[]

Establishing that wheezing is not due to asthma requires attention to the patient's history, physical examination results, and response to therapy.

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Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy

Original Research

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Authors: Gomes PJ, Ousler GW, Welch DL, Smith LM, Coderre J, Abelson MB

Published Date January 2013 Volume 2013:7 Pages 157 - 165
DOI: http://dx.doi.org/10.2147/OPTH.S38732

Received:	02 October 2012
Accepted:	09 November 2012
Published:	20 January 2013

Paulo J Gomes,¹ George W Ousler,¹ Donna L Welch,¹ Lisa M Smith,¹ Jeffrey Coderre,¹ Mark B Abelson^1,2
¹Ora Inc, Andover, MA; ²Harvard Medical School, Schepens Eye Research Institute, Boston, MA, USA

Background: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye.
Methods: Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3. Those who met the ocular redness and itching criteria were randomized to receive either the controlled adverse environment (CAE) challenge (group A, n = 9) or no challenge (group B, n = 8) at day 6. Thirty minutes after CAE/no-CAE, subjects were challenged with allergen and their signs and symptoms graded. Exploratory confocal microscopy was carried out in a subset of subjects at hourly intervals for 5 hours post-CAC on days 3 and 6.
Results: Seven minutes post-CAC, subjects exposed to the CAE had significantly greater itching (difference between groups, 0.55 ± 0.25, P = 0.028), conjunctival redness (0.59 ± 0.19, P = 0.002), episcleral redness (0.56 ± 0.19, P = 0.003) and mean overall redness (mean of conjunctival, episcleral, and ciliary redness, 0.59 ± 0.14, P < 0.001). The mean score at 7, 15, and 20 minutes post-CAC for conjunctival redness (0.43 ± 0.17, P = 0.012), episcleral redness (0.49 ± 0.15, P = 0.001), mean overall redness in all regions (0.43 ± 0.15, P = 0.005), and mean chemosis (0.20 ± 0.08, P = 0.017) were also all significantly greater in CAE-treated subjects. Confocal microscopic images of conjunctival vessels after CAC showed more inflammation in CAE-treated subjects.
Conclusion: In subjects with both dry eye and allergic conjunctivitis, exposure to adverse environmental conditions causes an ocular surface perturbation that can intensify allergic reactions.

Keywords: allergic conjunctivitis, dry eye, conjunctival allergen challenge, controlled adverse environment, comorbidity

March 18, 2013

How Bitter Medicine Could Clear Up Asthma

SYNOPSIS

How Bitter Medicine Could Clear Up Asthma

Janelle Weaver

Citation: Weaver J (2013) How Bitter Medicine Could Clear Up Asthma. PLoS Biol 11(3): e1001500. doi:10.1371/journal.pbio.1001500

Published: March 5, 2013

Copyright: © 2013 Janelle Weaver. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing interests: The author has declared that no competing interests exist.

Airway obstructive diseases, such as asthma and chronic obstructive pulmonary disease, cause the airways to narrow and make it difficult to breathe. Broncodilators are used to treat these conditions, but they often don't work in severe cases and can cause serious side effects, such as abnormal heart rhythms and increased blood pressure. Recently, scientists discovered a potential alternative to currently available bronchodilators. These compounds act on bitter taste receptors in the airways called TAS2Rs, a class of proteins long thought to be restricted to taste buds on the tongue for the purpose of detecting and avoiding harmful toxins. Bitter substances are more effective than existing bronchodilators at causing the relaxation of smooth muscle cells—which control the diameter of the airways—and opening up the airways in a mouse model of asthma. But the mechanism of action of these promising compounds has been under dispute, limiting the potential of developing them into a new class of drugs for patients.

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Bitter tasting compounds, synthesized or natively present in plants such as bitter melon, act on bitter taste receptors (TAS2R) in airway smooth muscle cells, which can inhibit L-type calcium channels and lead to muscle cell relaxation.

This action may help in the treatment of asthma. Image credit: Qi Xiao, Nanjing University.

doi:10.1371/journal.pbio.1001500.g001

In this issue of PLOS Biology, a team led by Ronghua ZhuGe of the University of Massachusetts Medical School has uncovered how bitter compounds open up the airways. They found that these substances stimulate TAS2Rs to affect calcium signaling and contraction in smooth muscle cells. The study reveals a new cell-based screening method for quickly identifying bitter compounds that have the potential of becoming powerful broncodilators for the treatment of airway obstructive diseases.

ZhuGe and his team used freshly dissected smooth muscle cells and tissues, which should more accurately reflect calcium signaling and cell contraction than the cultured cells used in another recent study. Similar to the previous study, ZhuGe and his collaborators found that bitter compounds produced a counterintuitive effect: they stimulated TAS2Rs to cause a rise in calcium levels in smooth muscle cells, which might be expected to cause these cells to contract because broncoconstrictors also increase calcium levels in these cells. But unlike the previous study, the researchers discovered that the rise in calcium was not sufficient to cause the cells to contract.

Moreover, bitter compounds actually reversed the effects of broncoconstrictors by inhibiting L-type voltage-dependent calcium channels, thereby blocking calcium influx into smooth muscle cells and causing them to relax. Thus, bitter substances stimulate TAS2Rs to activate two opposing calcium signaling pathways, depending on the circumstances. Under normal conditions, the compounds can modestly raise calcium levels in smooth muscle cells without causing contraction, but they reverse the rise in calcium levels caused by broncoconstrictors. Together, these findings resolve the paradox about how bitter substances can cause airway dilation even though they raise calcium levels in smooth muscle cells.

By revealing the mechanisms by which bitter compounds open up the airways, the study paves the way for developing safer and more effective therapies for airway obstructive diseases. For one, the results suggest that bitter compounds should be explored as a more effective asthma treatment than currently available L-type calcium channel blockers, which don't work very well. And by simultaneously measuring calcium signaling and cell contraction, scientists will be able to efficiently identify the most promising bitter compounds. Because there are thousands of available bitter substances, some of which can stimulate TAS2Rs at extremely low concentrations, it is likely that very strong bronchodilators can be identified in future studies.

Zhang C-H, Lifshitz LM, Uy KF, Ikebe M, Fogarty KE, et al. (2013) The Cellular and Molecular Basis of Bitter Tastant-Induced Bronchodilation. doi:10.1371/journal.pbio.1001501

Heart Rate Variability Analysis in Patients with Allergic Rhinitis

The Scientific World Journal
Volume 2013 (2013), Article ID 947385, 4 pages
http://dx.doi.org/10.1155/2013/947385

Clinical Study

Heart Rate Variability Analysis in Patients with Allergic Rhinitis

Ming-Ying Lan,^1,2,3 Guo-She Lee,^3,4 An-Suey Shiao,^1,3 Jen-Hung Ko,^3,4 and Chih-Hung Shu^1,3

¹Department of Otolaryngology, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou District, Taipei 11217, Taiwan
²Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
³School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
⁴Department of Otolaryngology, Taipei City Hospital, Taipei 103, Taiwan

Received 18 December 2012; Accepted 28 January 2013

Academic Editors: M. Armengot and M. Schloss

Copyright © 2013 Ming-Ying Lan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Very few studies investigate the role of the autonomic nervous system in allergic rhinitis. In this study, we evaluated the autonomic nervous system in allergic rhinitis patients using heart rate variability (HRV) analysis. Methods. Eleven patients with allergic rhinitis and 13 healthy controls, aged between 19 and 40 years old, were enrolled in the study. Diagnosis of allergic rhinitis was based on clinical history, symptoms, and positive Phadiatop test. Electrocardiographic recordings on the sitting and supine positions were obtained for HRV analysis. Results. In the supine position, there were no significant statistical differences in very-low-frequency power (VLF, ≤0.04 Hz), low-frequency power (LF, 0.04–0.15 Hz), high-frequency power (HF, 0.15–0.40 Hz), and the ratio of LF to HF (LF/HF) between the patient and control groups. The mean RR intervals significantly increased, while LF% and LF/HF significantly decreased in the patient group in the sitting position. Moreover, mean RR intervals, LF, and LF/HF, which were significantly different between the two positions in the control group, did not show a significant change with the posture change in the patient group. Conclusion. These suggest that patients with allergic rhinitis may have poor sympathetic modulation in the sitting position. Autonomic dysfunction may therefore play a role in the pathophysiology of allergic rhinitis.

March 15, 2013

Blomia tropicalis Blo t 5 and Blo t 21 recombinant allergens might confer higher specificity to serodiagnostic assays than whole mite extract

Kellyanne Anjos dos Carvalho, Oswaldo Pompílio de Melo-Neto, Franklin Barbalho Magalhães, João Carlos Ponte, Filipe Adriano Felipe, Mariese Conceição dos Santos, Givaneide dos Santos Lima, Álvaro Augusto Cruz, Carina Silva Pinheiro,Lain Carlos de Pontes Carvalho and Neuza Maria Alcântara Neves

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BMC Immunology 2013, 14:11 doi:10.1186/1471-2172-14-11

Published: 27 February 2013

Abstract (provisional)

Background

Blomia tropicalis is a dust mite and an important source of allergens in tropical regions. Up to now, the assays to diagnose atopy to this mite use whole body extract as antigens. However, anti-B. tropicalis IgE antibodies cross-react with Ascaris lumbricoides antigens, hindering the diagnosis of allergy to this mite. In this study, B. tropicalis recombinant allergens were evaluated with the purpose of developing an immunodiagnostic assay for allergy to this mite with greater specificity than those commercially available.

Methods

Two B. tropicalis allergens (Blo t 5 and Blo t 21) were cloned into a plasmidial expression vector, expressed in Escherichia coli and purified by affinity chromatography. Sixty-three sera containing anti-B. tropicalis extract (BtE) IgE antibodies were used to investigate IgE reactivity to the recombinant Blot 5 and 21 allergens. Inhibition assays with 20 sera pre-adsorbed with A. lumbricoides extract were performed using rBlo t 5, rBlo t 21, and BtE as antigens. All the assays were carried using indirect ELISA.

Results

Eighty-two point nine percent and 80.0 % of the sera with anti-BtE antibodies from 35 children reacted with rBlo t 5 and rBlo t 21, respectively, whereas 92.8% and 89.3% of the 28 sera with anti-BtE antibodies from adult asthma patients reacted with the same allergens, and 96.4% of these sera reacted with a mixture of rBlo t 5 and rBlo t 21. In an inhibition ELISA, the absorption of sera by A. lumbricoides extract affected less the reaction with rBlo t 5 and rBlo t 21 than with BtE.

Conclusions

The rBlo t 5 and rBlo t 21 allergens contain important epitopes recognized by IgE antibodies of individuals allergic to B. tropicalis antigens. Moreover, the assays using the recombinant allergens had lower IgE cross-reactivity with A. lumbricoides antigens, a fact which would confers higher specificity to serodiagnostic assays than the crude mite extract. However, additional recombinant allergens should be evaluated in order to reach the same sensitivity of the commercially available assays based on mite extract.

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

Evaluation of Adipokines: Apelin, Visfatin, and Resistin in Children with Atopic Dermatitis

Mediators of Inflammation
Volume 2013 (2013), Article ID 760691, 8 pages
http://dx.doi.org/10.1155/2013/760691

Clinical Study

Evaluation of Adipokines: Apelin, Visfatin, and Resistin in Children with Atopic Dermatitis

Edyta Machura,¹ Maria Szczepanska,¹ Katarzyna Ziora,¹ Dariusz Ziora,² Elzbieta Swietochowska,³ Małgorzata Barc-Czarnecka,¹ and Alicja Kasperska-Zajac⁴

¹Department of Pediatrics, Medical University of Silesia, Ulica 3-go Maja 13-15, 41-800 Zabrze, Poland
²Department of Pneumonology and Tuberculosis, Medical University of Silesia, Ulica Koziołka 1, 41-803 Zabrze, Poland
³Department of Biochemistry, Medical University of Silesia, Ulica Jordana 19, 41-808 Zabrze, Poland
⁴Department of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia, Ulica Ceglana 35, 40-952 Katowice, Poland

Received 9 July 2012; Revised 27 December 2012; Accepted 28 December 2012

Academic Editor: Wilco de Jager

Copyright © 2013 Edyta Machura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Very little is known about the role of adipokines in atopic dermatitis (AD) in children. This study aimed at analyzing the serum levels of resistin, apelin, and visfatin in children with AD in relation to body weight, AD severity, and gender. Serum concentration of adipokines was measured in 27 children with AD and in 46 healthy subjects. Selected biochemical parameters were evaluated and skin prick test was performed. Serum levels of resistin and apelin were significantly higher, whereas serum visfatin concentration was significantly lower in children with AD versus healthy controls, although an increase in resistin levels was exclusively demonstrated in boys. In AD group, a significant increase in apelin levels in girls was documented. There was no relationship between adipokines levels and the degree of allergic sensitization. Receiver operating characteristic curve analysis demonstrated that the serum apelin cutoff value differentiating children with AD from those without was >137.8 pg/mL. Resistin and visfatin cutoff values were >3.8 ng/mL and ≤ 2.13 ng/mL, respectively. Apelin and visfatin can serve as excellent indicators to distinguish children with AD from those without disease.

Allergy, Asthma and Immunology

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March 19, 2013