http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Thu, 23 May 2013 14:13:23 +0000 http://www.hindawi.com/journals/ja/2013/106781/ Gastroallergic anisakiasis (GAA) and Anisakis-sensitization-associated chronic urticaria (CU+) differ with respect to specific IgE levels. We hypothesised different immunoglobulin avidities in both entities as well as their dependence on TI and fish consumption. 16 patients with GAA and 17 patients with CU+ were included, and immunoglobulin levels were analysed by CAP (Phadia). IgE and IgG avidity indexes (AvIgE and AvIgG, resp.) were also determined. IgG avidity was higher in GAA than in CU+ (), whereas there was a tendency to lower IgE avidity in GAA (). When analysing all patients, AvIgG was positively correlated with specific IgE, IgG, and IgG4 as well as total IgE (Rho between 0.66 and 0.71; ), but AvIgE was negatively correlated with specific IgE (Rho −0.57; ), specific IgG4 (Rho −0.38; ), and total IgE (Rho 0.66; ). In GAA, weekly fish consumption was positively associated with AvIgE (Rho 0.51; ). A multivariate regression showed that time interval was the main explaining factor for AvIgE in GAA. We could show a differential behaviour of immunoglobulin isotype avidities in both entities and their dependence on fish-eating habits as well as on the time elapsed to the last parasitic episode. Carmen Cuéllar, Ana Valls, Consolación de Frutos, Marta Rodero, and Alvaro Daschner Copyright © 2013 Carmen Cuéllar et al. All rights reserved. Wed, 24 Apr 2013 08:09:35 +0000 http://www.hindawi.com/journals/ja/2013/538642/ Asthma is a disease with distinct phenotypes that have implications for both prognosis and therapy. Epidemiologic studies have demonstrated an association between asthma and obesity. Further studies have shown that obese asthmatics have poor asthma control and more severe asthma. This obese-asthma group may represent a unique phenotype. The mechanisms behind poor asthma control in obese subjects remain unclear, but recent research has focused on adipokines and their effects on the airways as well as the role of oxidative stress. Both surgical and nonsurgical weight loss therapy have shown promising results with improvements in asthma control and decreased asthma severity. Comorbid conditions such as gastroesophageal reflux disease and obstructive sleep apnea may also have a role in poor asthma control in obese asthmatics. Further research is needed to define the mechanisms behind this phenotype which will guide the development of targeted therapies. Shannon Novosad, Supriya Khan, Bruce Wolfe, and Akram Khan Copyright © 2013 Shannon Novosad et al. All rights reserved. Sun, 21 Apr 2013 11:08:09 +0000 http://www.hindawi.com/journals/ja/2013/714595/ Obesity is a comorbidity that adversely affects asthma severity and control by mechanisms that are not fully understood. This review will discuss evidence supporting a role for nitric oxide (NO) as a potential mechanistic link between obesity and late-onset asthma (>12 years). Several studies have shown that there is an inverse association between increasing body mass index (BMI) and reduced exhaled NO. Newer evidence suggests that a potential explanation for this paradoxical relationship is related to nitric oxide synthase (NOS) uncoupling, which occurs due to an imbalance between L-arginine (NOS substrate) and its endogenous inhibitor, asymmetric di-methyl arginine (ADMA). The review will propose a theoretical framework to understand the relevance of this pathway and how it may differ between early and late-onset obese asthmatics. Finally, the paper will discuss potential new therapeutic approaches, based on these paradigms, for improving the respiratory health of obese subjects with asthma. Fernando Holguin Copyright © 2013 Fernando Holguin. All rights reserved. Thu, 11 Apr 2013 11:58:09 +0000 http://www.hindawi.com/journals/ja/2013/635695/ Food allergy is an emerging epidemic that affects all age groups, with the highest prevalence rates being reported amongst Western countries such as the United States (US), United Kingdom (UK), and Australia. The development of animal models to test various food allergies has been beneficial in allowing more rapid and extensive investigations into the mechanisms involved in the allergic pathway, such as predicting possible triggers as well as the testing of novel treatments for food allergy. Traditionally, small animal models have been used to characterise immunological pathways, providing the foundation for the development of numerous allergy models. Larger animals also merit consideration as models for food allergy as they are thought to more closely reflect the human allergic state due to their physiology and outbred nature. This paper will discuss the use of animal models for the investigation of the major food allergens; cow's milk, hen's egg, and peanut/other tree nuts, highlight the distinguishing features of each of these models, and provide an overview of how the results from these trials have improved our understanding of these specific allergens and food allergy in general. Jenna L. Van Gramberg, Michael J. de Veer, Robyn E. O'Hehir, Els N. T. Meeusen, and Robert J. Bischof Copyright © 2013 Jenna L. Van Gramberg et al. All rights reserved. Mon, 18 Mar 2013 10:08:17 +0000 http://www.hindawi.com/journals/ja/2013/185971/ In recent years, asthma has been defined primarily as an inflammatory disorder with emphasis on inflammation being the principle underlying pathophysiological characteristic driving airway obstruction and remodelling. Morphological abnormalities of asthmatic airway smooth muscle (ASM), the primary structure responsible for airway obstruction seen in asthma, have long been described, but surprisingly, until recently, relatively small number of studies investigated whether asthmatic ASM was also fundamentally different in its functional properties. Evidence from recent studies done on single ASM cells and on ASM-impregnated gel cultures have shown that asthmatic ASM is intrinsically hypercontractile. Several elements of the ASM contraction apparatus in asthmatics and in animal models of asthma have been found to be different from nonasthmatics. These differences include some regulatory contractile proteins and also some components of both the calcium-dependent and calcium-independent contraction signalling pathways. Furthermore, oxidative stress was also found to be heightened in asthmatic ASM and contributes to hypercontractility. Understanding the abnormalities and mechanisms driving asthmatic ASM hypercontractility provides a great potential for the development of new targeted drugs, other than the conventional current anti-inflammatory and bronchodilator therapies, to address the desperate unmet need especially in patients with severe and persistent asthma. Rachid Berair, Fay Hollins, and Christopher Brightling Copyright © 2013 Rachid Berair et al. All rights reserved. Thu, 21 Feb 2013 10:32:44 +0000 http://www.hindawi.com/journals/ja/2013/260518/ IL-23- and IL-17A-producing CD4+ T cell (Th17 cell) axis plays a crucial role in the development of chronic inflammatory diseases. In addition, it has been demonstrated that Th17 cells and their cytokines such as IL-17A and IL-17F are involved in the pathogenesis of severe asthma. Recently, IL-22, an IL-10 family cytokine that is produced by Th17 cells, has been shown to be expressed at the site of allergic airway inflammation and to inhibit allergic inflammation in mice. In addition to Th17 cells, innate lymphoid cells also produce IL-22 in response to allergen challenge. Functional IL-22 receptor complex is expressed on lung epithelial cells, and IL-22 inhibits cytokine and chemokine production from lung epithelial cells. In this paper, we summarize the recent progress on the roles of IL-22 in the regulation of allergic airway inflammation and discuss its therapeutic potential in asthma. Koichi Hirose, Kentaro Takahashi, and Hiroshi Nakajima Copyright © 2013 Koichi Hirose et al. All rights reserved. Wed, 20 Feb 2013 16:08:47 +0000 http://www.hindawi.com/journals/ja/2013/520913/ Background and Aim. Asthma is common in endurance athletes including swimmers. Our aim was to study gender differences in asthma, allergy, and asthmatic symptoms in swimmers and investigate the effects of varying intensities of physical exercise on competitive swimmers with asthma. Methods. Three hundred highly trained swimmers (156 females and 144 males) were studied by a questionnaire. Their mean (±SD) ages were and years, and they had training history of and years in females and males, respectively. Gender differences in asthma, allergy, and respiratory symptoms were examined. Special attention was focused on asthmatic swimmers, their allergies and respiratory symptoms during swimming at different intensities. Results. The prevalence of physician-diagnosed asthma was 19% for females and males. No gender differences in asthma or respiratory symptoms were found. Males reported allergies significantly more often than females (). Gender difference was found in respiratory symptoms among swimmers with physician-diagnosed asthma because females reported symptoms significantly more often () than males. Asthmatic females also reported symptoms significantly more often at moderate intensity swimming () than males especially for coughing. Discussion. Gender difference in prevalence of asthma was not found in swimmers. However, allergy was reported significantly more by male swimmers. Male swimmers with asthma reported significantly more cases having family history of asthma, which may be a sign of selection of asthma-friendly sport. Moderate intensity swimming seemed to induce significantly more symptoms especially coughing in asthmatic females. Marja Kristiina Päivinen, Kari Lasse Keskinen, and Heikki Olavi Tikkanen Copyright © 2013 Marja Kristiina Päivinen et al. All rights reserved. Thu, 31 Jan 2013 16:53:55 +0000 http://www.hindawi.com/journals/ja/2013/672381/ Angiogenesis and lymphangiogenesis, the growth of new vessels from preexisting ones, have received increasing interest due to their role in tumor growth and metastatic spread. However, vascular remodeling, associated with vascular hyperpermeability, is also a key feature of many chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, and rheumatoid arthritis. The major drivers of angiogenesis and lymphangiogenesis are vascular endothelial growth factor- (VEGF-)A and VEGF-C, activating specific VEGF receptors on the lymphatic and blood vascular endothelium. Recent experimental studies found potent anti-inflammatory responses after targeted inhibition of activated blood vessels in models of chronic inflammatory diseases. Importantly, our recent results indicate that specific activation of lymphatic vessels reduces both acute and chronic skin inflammation. Thus, antiangiogenic and prolymphangiogenic therapies might represent a new approach to treat chronic inflammatory disorders, including those due to chronic allergic inflammation. Silvana Zgraggen, Alexandra M. Ochsenbein, and Michael Detmar Copyright © 2013 Silvana Zgraggen et al. All rights reserved. Wed, 26 Dec 2012 09:48:35 +0000 http://www.hindawi.com/journals/ja/2012/720568/ Maria Leite-de-Moraes, Hamida Hammad, and Michel Dy Copyright © 2012 Maria Leite-de-Moraes et al. All rights reserved. Tue, 25 Dec 2012 09:57:51 +0000 http://www.hindawi.com/journals/ja/2012/156909/ It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma. Gijs Ijpma, Oleg Matusovsky, and Anne-Marie Lauzon Copyright © 2012 Gijs Ijpma et al. All rights reserved. Wed, 19 Dec 2012 10:19:11 +0000 http://www.hindawi.com/journals/ja/2012/258145/ Circulating angiotensin-II protects the circulation against sudden falls in blood pressure and is generated by the enzymatic action of angiotensin converting enzyme (ACE) on angiotensin-I. The ACE genes have 2 allelic forms, “I” and “D.” The “D” genotype has both highest angiotensin-II generation and serum ACE levels compared to “I”. 120 patients with IgE-anaphylaxis, 119 healthy controls, and 49 atopics had serum ACE levels, ACE genotype, and renin levels determined. Plasma renin levels were identical for all groups. Serum ACE levels and genotypes were similar for healthy controls (HC) and atopics, but lower in anaphylaxis (), with ACE genotypes also showing increased “I” genes (). This effect was more pronounced in subjects manifesting airway angioedema and cardiovascular collapse (AACVS) than mild cutaneous and respiratory (CRA) symptoms. AACVS was significantly associated with the presence of “I” genes. For “ID” genotype OR is 5.6, 95% CI 1.8 to 17.4, and for “II” genotype OR is 44, 95% CI 5 to 1891 within the anaphylaxis group = 0.001. The results show a difference in the genotype frequency between control and anaphylaxis, suggesting a role for the renin angiotensin system in anaphylaxis manifesting with airway angioedema and cardiovascular collapse. V. A. Varney, A. Warner, A. Ghosh, A. Nicholas, and N. Sumar Copyright © 2012 V. A. Varney et al. All rights reserved. Tue, 18 Dec 2012 09:06:31 +0000 http://www.hindawi.com/journals/ja/2012/154174/ Allergic inflammation is an immune response to foreign antigens, which begins within minutes of exposure to the allergen followed by a late phase leading to chronic inflammation. Prolonged allergic inflammation manifests in diseases such as urticaria and rhino-conjunctivitis, as well as chronic asthma and life-threatening anaphylaxis. The prevalence of allergic diseases is profound with 25% of the worldwide population affected and a rising trend across all ages, gender, and racial groups. The identification and avoidance of allergens can manage this disease, but this is not always possible with triggers being common foods, prevalent air-borne particles and only extremely low levels of allergen exposure required for sensitization. Patients who are sensitive to multiple allergens require prophylactic and symptomatic treatments. Current treatments are often suboptimal and associated with adverse effects, such as the interruption of cognition, sleep cycles, and endocrine homeostasis, all of which affect quality of life and are a financial burden to society. Clearly, a better therapeutic approach for allergic diseases is required. Herein, we review the current knowledge of allergic inflammation and discuss the role of sphingolipids as potential targets to regulate inflammatory development in vivo and in humans. We also discuss the benefits and risks of using sphingolipid inhibitors. Wai Y. Sun and Claudine S. Bonder Copyright © 2012 Wai Y. Sun and Claudine S. Bonder. All rights reserved. Mon, 17 Dec 2012 12:42:19 +0000 http://www.hindawi.com/journals/ja/2012/604854/ Introduction. Sexual dimorphism with an increased prevalence in women has long been observed in various autoimmune, allergic, and skin diseases. Recent research has attempted to correlate this female predilection to physiologic changes seen in the menstrual cycle in order to more effectively diagnose and treat these diseases. Cases. We present five cases of cutaneous diseases in women with annular morphology and distributive features that favor one side over the other. In all cases, skin disease improved with ovarian suppression. Conclusion. Sexual dimorphism in the innate and adaptive immune systems has long been observed, with females demonstrating a more vigorous immune response compared to males. Female sex hormones promote T and B lymphocyte autoreactivity and favor the humoral arm of adaptive immunity. In addition to ovarian steroidogenesis and immunity, intricate pathways coexist in order to engage a single oocyte in each cycle, while simultaneously sustaining the ovarian reserve. Vigorous proinflammatory, vasoactive, and pigment-related cytokines emerge during the demise of the corpus luteum, influencing peripherical sex hormone metabolism of the level of the macrophage and fibroblast. We propose that annular and lateralizing lesions are important manifestations of hormone-related inflammation and recognition of this linkage can lead to improved immune and reproductive health. Ramya Kollipara, Chetna Arora, and Colleen Reisz Copyright © 2012 Ramya Kollipara et al. All rights reserved. Tue, 04 Dec 2012 16:22:58 +0000 http://www.hindawi.com/journals/ja/2012/245909/ Leukocyte adhesion molecules are involved in cell recruitment in an allergic airway response and therefore provide a target for pharmaceutical intervention. Neutrophil inhibitory factor (NIF), derived from canine hookworm (Ancylostoma caninum), binds selectively and competes with the A-domain of CD11b for binding to ICAM-1. The effect of recombinant NIF was investigated. Intranasal administration of rNIF reduced pulmonary eosinophilic infiltration, goblet cell hyperplasia, and Th2 cytokine production in OVA-sensitized mice. In vitro, transendothelial migration of human blood eosinophils across IL-4-activated umbilical vein endothelial cell (HUVEC) monolayers was inhibited by rNIF (IC50:  nM; mean ± SEM), but not across TNF or IL-1-activated HUVEC monolayers. Treatment of eosinophils with rNIF together with mAb 60.1 directed against CD11b or mAb 107 directed against the metal ion-dependent adhesion site (MIDAS) of the CD11b A-domain resulted in no further inhibition of transendothelial migration suggesting shared functional epitopes. In contrast, rNIF increased the inhibitory effect of blocking mAbs against CD18, CD11a, and VLA-4. Together, we show that rNIF, a selective antagonist of the A-domain of CD11b, has a prominent inhibitory effect on eosinophil transendothelial migration in vitro, which is congruent to the in vivo inhibition of OVA-induced allergic lung inflammation. Silvia Schnyder-Candrian, Isabelle Maillet, Marc Le Bert, Lea Brault, Muazzam Jacobs, Bernhard Ryffel, Bruno Schnyder, and René Moser Copyright © 2012 Silvia Schnyder-Candrian et al. All rights reserved. Tue, 20 Nov 2012 15:09:39 +0000 http://www.hindawi.com/journals/ja/2012/289468/ CD38 is a transmembrane glycoprotein expressed in airway smooth muscle cells. The enzymatic activity of CD38 generates cyclic ADP-ribose from β-NAD. Cyclic ADP-ribose mobilizes intracellular calcium during activation of airway smooth muscle cells by G-protein-coupled receptors through activation of ryanodine receptor channels in the sarcoplasmic reticulum. Inflammatory cytokines that are implicated in asthma upregulate CD38 expression and increase the calcium responses to contractile agonists in airway smooth muscle cells. The augmented intracellular calcium responses following cytokine exposure of airway smooth muscle cells are inhibited by an antagonist of cyclic ADP-ribose. Airway smooth muscle cells from CD38 knockout mice exhibit attenuated intracellular calcium responses to agonists, and these mice have reduced airway response to inhaled methacholine. CD38 also contributes to airway hyperresponsiveness as shown in mouse models of allergen or cytokine-induced inflammatory airway disease. In airway smooth muscle cells obtained from asthmatics, the cytokine-induced CD38 expression is significantly enhanced compared to expression in cells from nonasthmatics. This differential induction of CD38 expression in asthmatic airway smooth muscle cells stems from increased activation of MAP kinases and transcription through NF-κB, and altered post-transcriptional regulation through microRNAs. We propose that increased capacity for CD38 signaling in airway smooth muscle in asthma contributes to airway hyperresponsiveness. Joseph A. Jude, Mythili Dileepan, Reynold A. Panettieri Jr., Timothy F. Walseth, and Mathur S. Kannan Copyright © 2012 Joseph A. Jude et al. All rights reserved. Tue, 20 Nov 2012 10:39:00 +0000 http://www.hindawi.com/journals/ja/2012/125367/ Aim. To identify risk factors for urticaria, to determine the relative proportion of the susceptibility to urticaria that is due to genetic factors in an adult clinical twin sample, and to further determine whether the genetic susceptibility to urticaria overlaps with the genetic susceptibility to atopic diseases. Methods. A total of 256 complete twin pairs and 63 single twins, who were selected from sibships with self-reported asthma via a questionnaire survey of 21,162 adult twins from the Danish Twin Registry, were clinically interviewed about a history of urticaria and examined for atopic diseases. Data were analysed with Cox proportional hazards regression and variance components models. Results. A total of 151 individuals (26%) had a history of urticaria, whereas 24 (4%) had had symptoms within the past year. Female sex, (1.46–2.99), ; hay fever, (1.36–2.72), ; and atopic dermatitis, (1.02–2.06), were significant risk factors for urticaria. After adjustment for sex and age at onset of urticaria in the index twin, the risk of urticaria was increased in MZ cotwins relative to DZ cotwins, (0.63–3.18), . Genetic factors explained 45% (16–74%), , of the variation in susceptibility to urticaria. The genetic correlation between urticaria and hay fever was 0.45 (0.01–0.89), . Conclusions. Susceptibility to urticaria is partly determined by genetic factors. Urticaria is more common in women, and in subjects with hay fever and atopic dermatitis, and shares genetic variance with hay fever. Simon Francis Thomsen, Sophie van der Sluis, Kirsten Ohm Kyvik, and Vibeke Backer Copyright © 2012 Simon Francis Thomsen et al. All rights reserved. Sun, 11 Nov 2012 15:18:23 +0000 http://www.hindawi.com/journals/ja/2012/576017/ Carina Venter Copyright © 2012 Carina Venter. All rights reserved. Sun, 11 Nov 2012 14:32:21 +0000 http://www.hindawi.com/journals/ja/2012/130937/ Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. Abbas Pishdadian, Abdol-Reza Varasteh, and Mojtaba Sankian Copyright © 2012 Abbas Pishdadian et al. All rights reserved. Wed, 07 Nov 2012 14:59:19 +0000 http://www.hindawi.com/journals/ja/2012/176468/ Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in inducing adaptive immunity, tolerance, or allergic response in peripheral organs—lung and skin. The lung DCs are not developed prenatally before birth. The DCs develop after birth presumably during the first year of life; exposures to any foreign antigen or infectious organisms during this period can significantly affect DC developmental programming and generation of distinct DC phenotypes and functions. These changes can have both short-term and long-term health effects which may be very relevant in childhood asthma and predisposition for a persistent response in adulthood. An understanding of DC development at molecular and cellular levels can help in protecting neonates and infants against problematic environmental exposures and developmental immunotoxicity. This knowledge can eventually help in designing novel pharmacological modulators to skew the DC characteristics and immune responses to benefit the host across a lifetime. Shanjana Awasthi, Bhupinder Singh, Robert C. Welliver, and Rodney R. Dietert Copyright © 2012 Shanjana Awasthi et al. All rights reserved. Mon, 05 Nov 2012 17:39:46 +0000 http://www.hindawi.com/journals/ja/2012/718725/ Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies. François-Xavier Bernard, Franck Morel, Magalie Camus, Nathalie Pedretti, Christine Barrault, Julien Garnier, and Jean-Claude Lecron Copyright © 2012 François-Xavier Bernard et al. All rights reserved. Wed, 24 Oct 2012 09:41:43 +0000 http://www.hindawi.com/journals/ja/2012/269376/ Many common foods including cow’s milk, hen’s egg, soya, peanut, tree nuts, fish, shellfish, and wheat may cause food allergies. The prevalence of these immune-mediated adverse reactions to foods ranges from 0.5% to 9% in different populations. In simple terms, the cornerstone of managing food allergy is to avoid consumption of foods causing symptoms and to replace them with nutritionally equivalent foods. If poorly managed, food allergy impairs quality of life more than necessary, affects normal growth in children, and causes an additional economic burden to society. Delay in diagnosis may be a further incremental factor. Thus, an increased awareness of the appropriate procedures for both diagnosis and management is of importance. This paper sets out to present principles for taking an allergy-focused diet history as part of the diagnostic work-up of food allergy. A short overview of guidelines and principles for dietary management of food allergy is discussed focusing on the nutritional management of food allergies and the particular role of the dietitian in this process. Carina Venter, Kirsi Laitinen, and Berber Vlieg-Boerstra Copyright © 2012 Carina Venter et al. All rights reserved. Tue, 23 Oct 2012 09:15:39 +0000 http://www.hindawi.com/journals/ja/2012/108149/ The autonomic nervous system provides both cholinergic and noncholinergic neural inputs to end organs within the airways, which includes the airway and vascular smooth muscle. Heightened responsiveness of the airways to bronchoconstrictive agents is a hallmark feature of reactive airways diseases. The mechanisms underpinning airways hyperreactivity still largely remain unresolved. In this paper we summarize the substantial body of evidence that implicates dysfunction of the autonomic nerves that innervate smooth muscle in the airways and associated vasculature as a prominent cause of airways hyperresponsiveness in asthma. Brendan J. Canning, Ariel Woo, and Stuart B. Mazzone Copyright © 2012 Brendan J. Canning et al. All rights reserved. Sun, 21 Oct 2012 13:21:54 +0000 http://www.hindawi.com/journals/ja/2012/236075/ In both human asthmatics and animal models of allergy, allergen-specific IgG can contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an important role for IgG and Fc-gamma receptor (FcγR) signaling on antigen presenting cells (APC) for the induction of airway inflammation. These studies suggest a positive feedback loop between IgG produced by the adaptive B cell response and FcγR signaling on innate immune cells. Studies of IgG and FcγRs in humans with asthma or allergic lung disease have been more controversial. Some reports have identified associations between allergen-specific IgG and severity of allergic responses, while other studies have found associations of IgG subclass IgG4 with allergic tolerance. In this paper, we review the literature to help define the nature of IgG and FcγR signaling on innate immune cells and how it contributes to the development of allergic immune responses. Jesse W. Williams, Melissa Y. Tjota, and Anne I. Sperling Copyright © 2012 Jesse W. Williams et al. All rights reserved. Thu, 18 Oct 2012 16:39:58 +0000 http://www.hindawi.com/journals/ja/2012/768982/ A link between airway smooth muscle (ASM) and airway hyperresponsiveness (AHR) in asthma was first postulated in the midnineteenth century, and the suspected link has garnered ever increasing interest over the years. AHR is characterized by excessive narrowing of airways in response to nonspecific stimuli, and it is the ASM that drives this narrowing. The stimuli that can be used to demonstrate AHR vary widely, as do the potential mechanisms by which phenotypic changes in ASM or nonmuscle factors can contribute to AHR. In this paper, we review the history of research on airway smooth muscle’s role in airway hyperresponsiveness. This research has ranged from analyzing the quantity of ASM in the airways to testing for alterations in the plastic behavior of smooth muscle, which distinguishes it from skeletal and cardiac muscles. This long history of research and the continued interest in this topic mean that the precise role of ASM in airway responsiveness remains elusive, which makes it a pertinent topic for this collection of articles. C. D. Pascoe, L. Wang, H. T. Syyong, and P. D. Paré Copyright © 2012 C. D. Pascoe et al. All rights reserved. Wed, 17 Oct 2012 15:35:49 +0000 http://www.hindawi.com/journals/ja/2012/490905/ Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT. Takaya Yamada, Miki Tongu, Kaoru Goda, Noriaki Aoi, Ichiro Morikura, Takafumi Fuchiwaki, and Hideyuki Kawauchi Copyright © 2012 Takaya Yamada et al. All rights reserved. Wed, 17 Oct 2012 10:38:36 +0000 http://www.hindawi.com/journals/ja/2012/157047/ The primary functional abnormality in asthma is airway hyperresponsiveness (AHR)—excessive airway narrowing to bronchoconstrictor stimuli. Our understanding of the underlying mechanism(s) producing AHR is incomplete. While structure-function relationships have been evoked to explain AHR (e.g., increased airway smooth muscle (ASM) mass in asthma) more recently there has been a focus on how the dynamic mechanical environment of the lung impacts airway responsiveness in health and disease. The effects of breathing movements such as deep inspiration reveal innate protective mechanisms in healthy individuals that are likely mediated by dynamic ASM stretch but which may be impaired in asthmatic patients and thereby facilitate AHR. This perspective considers the evidence for and against a role of dynamic ASM stretch in limiting the capacity of airways to narrow excessively. We propose that lung function measured after bronchial provocation in the laboratory and changes in lung function perceived by the patient in everyday life may be quite different in their dependence on dynamic ASM stretch. Peter B. Noble, Thomas K. Ansell, Alan L. James, Peter K. McFawn, and Howard W. Mitchell Copyright © 2012 Peter B. Noble et al. All rights reserved. Mon, 15 Oct 2012 16:19:00 +0000 http://www.hindawi.com/journals/ja/2012/936870/ Dendritic cells are important residents of the lung environment. They have been associated with asthma and other inflammatory diseases of the airways. In addition to their antigen-presenting functions, dendritic cells have the ability to modulate the lung environment to promote atopic disease. While it has long been known that respiratory viral infections associate with the development and exacerbation of atopic diseases, the exact mechanisms have been unclear. Recent studies have begun to show the critical importance of the dendritic cell in this process. This paper focuses on these data demonstrating how different populations of dendritic cells are capable of bridging the adaptive and innate immune systems, ultimately leading to the translation of viral illness into atopic disease. Jonathan S. Tam and Mitchell H. Grayson Copyright © 2012 Jonathan S. Tam and Mitchell H. Grayson. All rights reserved. Tue, 02 Oct 2012 12:27:03 +0000 http://www.hindawi.com/journals/ja/2012/321949/ Bronchodilators are the first line therapy during acute asthmatic exacerbations to reverse airway obstruction primarily by relaxing airway smooth muscle. Only three categories of bronchodilators exist in clinical practice: -adrenergic agonists, anticholinergics, and methylxanthines. Each of these categories have specific drugs dating back to the early 20th century, raising the question of whether or not we can find better bronchodilators. While caffeine, theophylline, atropine, and epinephrine were the first generations of therapeutics in each of these drug classes, there is no question that improvements have been made in the bronchodilators in each of these classes. In the following editorial, we will briefly describe new classes of potential bronchodilators including: novel PDE inhibitors, natural phytotherapeutics, bitter taste receptor ligands, and chloride channel modulators, which have the potential to be used alone or in combination with existing bronchodilators to reverse acute airway obstruction in the future. Elizabeth A. Townsend, Peter D. Yim, George Gallos, and Charles W. Emala Copyright © 2012 Elizabeth A. Townsend et al. All rights reserved. Sat, 29 Sep 2012 11:07:03 +0000 http://www.hindawi.com/journals/ja/2012/341282/ Airway hyperresponsiveness (AHR) is one of the cardinal features of asthma. Contraction of airway smooth muscle (ASM) cells that line the airway wall is thought to influence aspects of AHR, resulting in excessive narrowing or occlusion of the airway. ASM contraction is primarily controlled by agonists that bind G protein-coupled receptor (GPCR), which are expressed on ASM. Integrins also play a role in regulating ASM contraction signaling. As therapies for asthma are based on symptom relief, better understanding of the crosstalk between GPCRs and integrins holds good promise for the design of more effective therapies that target the underlying cellular and molecular mechanism that governs AHR. In this paper, we will review current knowledge about integrins and GPCRs in their regulation of ASM contraction signaling and discuss the emerging concept of crosstalk between the two and the implication of this crosstalk on the development of agents that target AHR. Chun Ming Teoh, John Kit Chung Tam, and Thai Tran Copyright © 2012 Chun Ming Teoh et al. All rights reserved. Sat, 29 Sep 2012 09:56:44 +0000 http://www.hindawi.com/journals/ja/2012/948901/ The study of immune regulation and tolerance has been traditionally associated with self/nonself-discrimination. However, the finding that dominant tolerance, a model that puts in evidence the active role of regulatory T cells, can develop to nonself-antigens suggests that the imposition of tolerance can be context dependent. This paper reviews the emerging field of acquired immune tolerance to non-self antigens, with an emphasis on the different subsets of induced regulatory T cells that appear to specialize in specific functional niches. Such regulatory mechanisms are important in preventing the onset of allergic diseases in healthy individuals. In addition, it may be possible to take advantage of these immune regulatory mechanisms for the induction of tolerance in cases where pathological immune responses are generated to allergens occurring in nature, but also to other immunogens such as biological drugs developed for medical therapies. Ana Agua-Doce and Luis Graca Copyright © 2012 Ana Agua-Doce and Luis Graca. All rights reserved.