February 14, 2013

Inflammation signals airway smooth muscle cell proliferation in asthma pathogenesis

Review

Inflammation signals airway smooth muscle cell proliferation in asthma pathogenesis

Mohammad Afzal Khan

Correspondence: Mohammad Afzal Khan afzal@stanford.edu

Department of Medicine, Stanford University, VAPAHCS, 3801 Miranda Avenue, Building 101, Room B4-105, Palo Alto, California, 94304, USA

Multidisciplinary Respiratory Medicine 2013, 8:11 doi:10.1186/2049-6958-8-11

The electronic version of this article is the complete one and can be found online at:http://www.mrmjournal.com/content/8/1/11

Received:	21 November 2012
Accepted:	3 January 2013
Published:	6 February 2013

licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Airway inflammation stimulates proliferation of airway smooth muscle cell, which contributes to the development of hyperplasia and hypertrophy of smooth muscle cell. The increase in airway smooth muscle cell mass is believed to be due to an up-regulation of inflammatory mediators in the airway. It is now well recognized that chronic inflammation as well as airway hyper-responsiveness and remodeling of airway during inflammation, are crucial to asthma. Airway hyper-responsiveness is caused by increased cell proliferation or by hypertrophy of airway smooth muscle cell depending on the nature of the inflammatory stimulation. Airway smooth muscle cell proliferation in asthma is regulated by the proinflammatory cytokines including IL-1β and TNF-α. These proinflammatory cytokines have been shown to influence human airway smooth muscle cell proliferation in vitro, which is due to cyclooxygenase-2 expression, production of prostaglandin E2, and increased cAMP levels.

Conclusions

This review highlights the role of different proinflammatory cytokines in regulating airway smooth muscle cell growth and also focuses on regulation of differential gene expression in airway smooth muscle cell by growth factors and cytokines, also to bestow unique insight into the effects of conventional asthma therapies on airway smooth muscle cell proliferation and development of new therapeutic strategies to control asthma.

Keywords:

Airway inflammation; Airway smooth muscle cells; Asthma

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The impact of pre- and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care

Research article

The impact of pre- and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care

Christian Kvikne Dotterud, Ola Storrø, Melanie Rae Simpson, Roar Johnsen and Torbjørn Øien

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BMC Public Health 2013, 13:123 doi:10.1186/1471-2458-13-123

Published: 8 February 2013

Abstract (provisional)

Background

Environmental factors such as tobacco exposure, indoor climate and diet are known to be involved in the development of allergy related diseases. The aim was to determine the impact of altered exposure to these factors during pregnancy and infancy on the incidence of allergy related diseases at 2 years of age.

Methods

Children from a non-selected population of mothers were recruited to a controlled, multicenter intervention study in primary health care. The interventions were an increased maternal and infant intake of n-3 PUFAs and oily fish, reduced parental smoking, and reduced indoor dampness during pregnancy and the children's first 2 years of life. Questionnaires on baseline data and exposures, and health were collected at 2 years of age.

Results

The prevalence of smoking amongst the mothers and fathers was approximately halved at 2 years of age in the intervention cohort compared to the control cohort. The intake of n-3 PUFA supplement and oily fish among the children in the intervention cohort was increased. There was no significant change for indoor dampness. The odds ratio for the incidence of asthma was 0.72 (95% CI, 0.55-0.93; NNTb 53), and 0.75 for the use of asthma medication (95% CI, 0.58-0.96). The odds ratio for asthma among girls was 0.41 (95% CI 0.24-0.70; NNTb 32), and for boys 0.93 (95% CI 0.68-1.26). There were no significant change for wheeze and atopic dermatitis.

Conclusion

Reduced tobacco exposure and increased intake of oily fish during pregnancy and early childhood may be effective in reducing the incidence of asthma at 2 years of age. The differential impact in boys and girls indicates that the pathophysiology of asthma may depend on the sex of the children.

Trial registration: Current Controlled Trials ISRCTN28090297.

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

February 12, 2013

Interleukin-13 Genetic Variants, Household Carpet Use and Childhood Asthma

OPEN ACCESS PEER-REVIEWED

RESEARCH ARTICLE

Interleukin-13 Genetic Variants, Household Carpet Use and Childhood Asthma

Ching-Hui Tsai,
Kuan-Yen Tung,
Ming-Wei Su,
Bor-Luen Chiang,
Fook Tim Chew,
Nai-Wei Kuo,
Yungling Leo Lee

Abstract

Interleukin (IL)-13 genetic polymorphisms have shown adverse effects on respiratory health. However, few studies have explored the interactive effects between IL-13 haplotypes and environmental exposures on childhood asthma. The aims of our study are to evaluate the effects of IL-13 genetic variants on asthma phenotypes, and explore the potential interaction between IL-13 and household environmental exposures among Taiwanese children. We investigated 3,577 children in the Taiwan Children Health Study from 14 Taiwanese communities. Data regarding children's exposure and disease status were obtained from parents using a structured questionnaire. Four SNPs were tagged accounting for 100% of the variations in IL-13. Multiple logistic regression models with false-discovery rate (FDR) adjustments were fitted to estimate the effects of IL-13 variants on asthma phenotypes. SNP rs1800925, SNP rs20541 and SNP rs848 were significantly associated with increased risks on childhood wheeze with FDR of 0.03, 0.04 and 0.04, respectively. Children carrying two copies of h1011 haplotype showed increased susceptibility to wheeze. Compared to those without carpet use and h1011 haplotype, children carrying h1011 haplotype and using carpet at home had significantly synergistic risks of wheeze (OR, 2.5; 95% CI, 1.4–4.4; p for interaction, 0.01) and late-onset asthma (OR, 4.7; 95% CI, 2.0–10.9; p for interaction, 0.02). In conclusions, IL-13 genetic variants showed significant adverse effects on asthma phenotypes among children. The results also suggested that asthma pathogenesis might be mediated by household carpet use.

Citation: Tsai C-H, Tung K-Y, Su M-W, Chiang B-L, Chew FT, et al. (2013) Interleukin-13 Genetic Variants, Household Carpet Use and Childhood Asthma. PLoS ONE 8(1): e51970. doi:10.1371/journal.pone.0051970

Editor: Guoying Wang, John Hopkins Bloomberg School of Public Health, United States of America

Received: August 1, 2011; Accepted: November 13, 2012; Published: January 30, 2013

Copyright: © 2013 Tsai et al. 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.

Funding: This study was supported by the National Science Council (Grant #96-2314-B-006-053, #98-2314-B-002-138-MY3 and #101-2314-B-002-113-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Mould Sensitisation among Bakers and Farmers with Work-related Respiratory Symptoms

Industrial Health
Article ID: 2012-0051

Language:

http://dx.doi.org/10.2486/indhealth.2012-0051

DN/JST.JSTAGE/indhealth/2012-0051

Advance Publication

Mould Sensitisation among Bakers and Farmers with Work-related Respiratory Symptoms

Marta WISZNIEWSKA¹⁾, Diana TYMOSZUK¹⁾, Ewa NOWAKOWSKA-SWIRTA¹⁾, Cezary PALCZYNSKI¹⁾, Jolanta WALUSIAK-SKORUPA¹⁾

1) Department of Occupational Diseases, Nofer Institute of Occupational Medicine

[Advance Publication] Released: 2013/02/04

Keywords: bakers, farmers, mould allergy, work-related symptoms

Full Text PDF [213K]

Abstracts

Fungi belong to common allergens, which can be found both in occupational and non-occupational environment. The aim of the study was to determine the frequency and factors associated with mould allergy among bakers and farmers reporting work-related respiratory symptoms. The study group comprised 117 bakers and 83 farmers reporting work-related respiratory symptoms. Skin prick tests (SPT) with common, fungal and occupational allergens, estimation of serum total IgE level, spirometry, histamine test and specific inhalative challenge test with occupational allergens were performed in all subjects. The prevalence of hypersensitivity to fungal species was higher among farmers (32.5%) than bakers (16.2%). Positive SPT with mould allergens were found among 10.8% farmers and 6.8% bakers with occupational allergy. The fungi allergens giving positive SPT results most frequently were Candida albicans, Levures mélanges, Aspergillus mix, and Charbons cerealiers in both groups. Among mould allergens, hypersensitivity to Aspergillus genus was the most common in farmers and bakers group, while among Saccharomyces - Candida albicans sensitization was the most frequently detected. Mould hypersensitivity is related to occupational respiratory allergy, especially to asthma and rhinitis in farmers, and occupational asthma in bakers. Although sensitization to Saccharomyces was more frequent, similar correlation was not observed.

Full Text PDF [213K]

Air pollution exposure in early pregnancy and adverse pregnancy outcomes

BMJ Open

2013;3:e001955 doi:10.1136/bmjopen-2012-001955

Occupational and environmental medicine

Air pollution exposure in early pregnancy and adverse pregnancy outcomes: a register-based cohort study

¹Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden
²Department of Clinical Science, Obstetrics and Gynaecology, Umeå University, Umeå, Sweden

Correspondence toDavid Olsson; david.olsson{at}envmed.umu.se

Received 2 October 2012
Revised 3 December 2012
Accepted 3 January 2013
Published 5 February 2013

Abstract

Objectives Our aim was to study the possible associations between exposure to elevated levels of air pollution, ozone (O₃) and vehicle exhaust (NO_x), during early gestation, and adverse pregnancy outcomes such as pre-eclampsia, preterm birth and small for gestational age.

Design Prospective register-based cohort study.

Setting The Swedish Medical Birth Register includes data on all deliveries during 1998 to 2006 in Greater Stockholm, Sweden. The national Patient Register and the Prescribed Drug Register were used to collect information on maternal asthma.

Participants All singleton pregnancies, conceived at the earliest in August 1997 and at the latest in February 2006, were included, n=120 755.

Outcome measures We studied preterm birth, small for gestational age and pre-eclampsia.

Results 4.4% of pregnancies resulted in a preterm birth. The prevalence of pre-eclampsia was 2.7%. We observed an association between first trimester O₃ and preterm birth (OR 1.04, 95% CI 1.01 to 1.08) as well as an association with pre-eclampsia (OR 1.04, 95% CI 1.01 to 1.08), per 10 µg/m³ increase in O₃. We observed no association between first trimester NO_xand adverse pregnancy outcomes. No associations were observed between any of the air pollutants and small for gestational age.

Conclusions Increased levels of O₃ during the first trimester increased the risk of pre-eclampsia and preterm birth. Air pollutants did not exhibit any effects on fetal growth restriction. We estimated 1 in every 20 cases of pre-eclampsia to be associated with O₃exposure.

ARTICLE SUMMARY

Article focus

Does early gestation air pollution exposure, in particular ozone (O₃), affect the risk of adverse birth outcomes (ie, pre-eclampsia, preterm birth and small for gestational age)?

Key messages

This large European study adds to the evidence that preterm birth may be caused by O₃exposure, and that the effect may be greater among asthmatic mothers.
This is one of the first studies to show an association between O₃ and pre-eclampsia.
Health impact assessment of O₃ exposure should include also effects on pregnancy outcomes.

Strengths and limitations of this study

Temporal fluctuations in air pollution exposure are unlikely correlated to individual level risk factors, however still accounted for in order to improve the model performance.
This study uses valid estimates of temporal variation in O₃ exposure, adjusts for seasonality, but does not take into account any spatial variation in the traffic pollutants.

Eosinophil-derived neurotoxin: a novel biomarker for diagnosis and monitoring of asthma

Review Article

Korean J Pediatr 2013 January;56(1) :8-12.
Published online 2012 August 09.
doi:http://dx.doi.org/10.3345/kjp.2013.56.1.8

Eosinophil-derived neurotoxin: a novel biomarker for diagnosis and monitoring of asthma

Chang-Keun Kim (Kim CK)

Department of Pediatrics, Asthma & Allergy Center, Inje University Sanggye Paik Hospital, Seoul, Korea

Corresponding Author: Chang-Keun Kim ,Tel: +82-2-950-8832, Fax: +82-2-950-1662, Email: kimck@paik.ac.kr

ABSTRACT

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

Keywords: Eosinophil-derived neurotoxin | Biological markers | Diagnosis | Monitoring of asthma | Child

Allergy, Asthma and Immunology

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February 14, 2013

Inflammation signals airway smooth muscle cell proliferation in asthma pathogenesis