Atmospheric contamination caused by Asian sand-dust (ASD) storms aggravates asthma in both human adults and children. This study aims to investigate a series of manifestations in allergic airway disease caused by co-exposure to allergens and ASD for 6 weeks and 14 weeks.
CD-1 Mice were instilled intratracheally with 0.1 mg of ASD/mouse four times (6 weeks) or eight times (14 weeks) at 2-week intervals (total dose of 0.4 mg or 0.8 mg/mouse) with or without ovalbumin (OVA). The pathologic changes in the airway, cytological alteration in bronchoalveolar lavage fluid (BALF), and levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice.
Four-time co-exposure to OVA and ASD aggravates allergic airway inflammation along with Th2-cytokine IL-13 and eosinophil-relevant cytokine/chemokines IL-5, Eotaxin and MCP-3 in BALF, and fibrous thickening of the subepithelial layer in the airway. On the other hand, eight-time co-exposure attenuates these changes along with a significant increase of TGF-β1 in BALF. Adjuvant effects of ASD toward IgG1 and IgE production in sera were, however, still seen in the eight-time co-exposure.
These results indicate that the immune responses in airways are exacerbated by four-time co-exposure to ASD with OVA, but that there is a shift to suppressive responses in eight-time co-exposure, suggesting that the responses are caused by TGF-β1-related immune tolerance.
Insufficient knowledge of food allergy and anaphylaxis has been identified by caregivers as an important barrier to coping, and a potential cause of fear and anxiety, particularly for those with children newly diagnosed with food allergy.
The purpose of the study was to better understand the experiences of caregivers of children with a first allergic reaction to food, and to identify any deficiencies in the information received at diagnosis.
A mixed-methods study consisting of an online survey administered to the Anaphylaxis Canada online registry (a patient support group database of approximately 10,000 members), and a follow-up qualitative interview with a subset of survey participants. Analysis consisted of frequency analysis (quantitative and qualitative data) and descriptive statistics to calculate proportions and means with standard deviations. Qualitative analyses were guided by the constant comparative method of grounded theory methodology.
Of 293 survey respondents, 208 were eligible to complete the survey (first allergic reaction to food within 12 months of the study), and 184 respondents consented. Identified gaps included education about food allergy, anaphylaxis management, for example, how to use epinephrine auto- injectors, and coping strategies for fear and anxiety. The qualitative follow-up study supported these findings, yielding 3 major themes: 1) lack of provision of information following the episode on the recognition and management of food allergy related allergic reactions, 2) prolonged wait times for an allergist, and 3) significant family anxiety.
The online survey highlighted multiple deficiencies at diagnosis, findings which were supported by the follow up qualitative study. Results will inform the development of educational strategies for patients newly diagnosed with food allergy.
Anaphylaxis; Food allergy; Qualitative methods
Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies.
We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts.
Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important.
We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.
Asthma; Asthma UK; Research impacts; Societal impacts; Clinical guidelines; University spin-out companies; Product development; Immunotherapy; Payback Framework; Research funding strategy
Azelastine has been shown to be effective against seasonal allergic rhinitis (SAR). The Environmental Exposure Unit (EEU) is a validated model of experimental SAR. The objective of this double-blind, four-way crossover study was to evaluate the onset of action of azelastine nasal spray, versus the oral antihistamines loratadine 10 mg and cetirizine 10 mg in the relief of the symptoms of SAR.
70 participants, aged 18-65, were randomized to receive azelastine nasal spray, cetirizine, loratadine, or placebo after controlled ragweed pollen exposure in the EEU. Symptoms were evaluated using the total nasal symptom score (TNSS). The primary efficacy parameter was the onset of action as measured by the change from baseline in TNSS.
Azelastine displayed a statistically significant improvement in TNSS compared with placebo at all time points from 15 minutes through 6 hours post dose. Azelastine, cetirizine, and loratadine reduced TNSS compared to placebo with an onset of action of 15 (p < 0.001), 60 (p = 0.015), and 75 (p = 0.034) minutes, respectively. The overall assessment of efficacy was rated as good or very good by 46% of the participants for azelastine, 51% of the participants for cetirizine, and 30% of the participants for loratadine compared to 18% of the participants for placebo.
Azelastine’s onset of action for symptom relief was faster than that of cetirizine and loratadine. The overall participant satisfaction in treatment with azelastine is comparable to cetirizine and statistically superior to loratadine. These results suggest that azelastine may be preferential to oral antihistamines for the rapid relief of SAR symptoms.
Allergic rhinitis; Azelastine; Environmental exposure unit; Onset of action; Cetirizine; Loratadine
Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.
The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.
Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.
This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
Infants; Gut microbiota; Gut microbiome; Hygiene hypothesis; Microflora hypothesis; Pets; Siblings; Atopy; Allergic disease; Environmental exposures
Helminth infections and allergies are associated with TH2 responses. Whereas the development of TH2 responses and allergic disorders in pediatric populations has been examined in affluent countries, no or little data exist from low income regions of the world.
The aim of this study is to examine factors influencing the development of TH2 responses of children born in areas endemic for helminth infections and to relate these factors to atopic sensitization at 4 years of age.
Data were collected from pregnant mothers on helminth infections, education and socioeconomic status (SES). Total IgE, IL-5 in response to mitogen, and helminth antigens were measured in children at 2, 5, 12, 24 and 48 months of age. Skin prick testing (SPT) and allergen-specific IgE were determined at 4 years of age.
Strong TH2 responses were seen at 5 months of age and increased with time. Although maternal filarial infection was associated with helminth-antigen specific TH2 responses, it was low maternal education or SES but not helminth infection, which was associated with the development of high total IgE and PHA-induced IL-5. At 4 years of age when allergen reactivity was assessed by SPT, the high general TH2 responses did not translate into higher prevalence of SPT. The risk factor for SPT reactivity was low maternal education which decreased the risk of SPT positivity to allergens (adjusted OR, 0.32; 95% CI, 0.12 – 0.87) independently of maternal filarial infection which tended to reduce the child’s risk for being SPT positive (adjusted OR, 0.35; 95% CI, 0.07 – 1.70).
In areas endemic for helminths, potent TH2 responses were seen early in life, but did not translate into a higher SPT reactivity to allergens. Therefore, in many parts of the world TH2 responses in general and IgE in particular cannot be used for diagnosis of allergic diseases.
TH2; IgE; IL-5; Helminth; Atopy; Skin prick test; Children
Drug provocation tests (DPTs) are often needed when evaluating patients with suspected drug hypersensitivity reactions. General considerations on DPTs, with regard to indications, contraindications, methods, limitations and interpretations have been thoroughly addressed and various protocols are published. However, the field of drug allergy is changing and DPTs make no exception. Novel (or sometimes, simply renewed) approaches arise, awaiting to be either validated or refuted in larger studies in the future. Instead of covering the whole topic of DPTs, this paper will address these recent and challenging aspects.
Drug provocation test; Gold standard; Drug hypersensitivity reactions
The editors of Allergy, Asthma & Clinical Immunology would like to thank all of our reviewers who have contributed to the journal in Volume 8 (2012).
We present two cases of food and exercise-induced anaphylaxis (FEIA) in patients with a diagnosis of oral allergy syndrome (OAS) to the implicated foods. Patient A had FEIA attributed to fresh coriander and tomato and Patient B to fresh celery. These food allergens have been implicated in OAS and have structural antigenic similarity to that of birch and/or grass. Both patients’ allergies were confirmed by fresh skin prick tests. In both cases, strenuous exercise was antecedent to the systemic anaphylaxis reaction and subsequent ingestion without exercise produced only local symptoms of perioral pruritus. We review the current proposed mechanisms for food and exercise induced anaphylaxis to oral allergens and propose a novel and more biologically plausible mechanism. We hypothesize that the inhibitory effects of exercise on gastric acid secretion decreases the digestion of oral allergens and preserves structural integrity, thereby allowing continued systemic absorption of the allergen whether it be profilins, lipid transfer proteins, or other antigenic determinants.
Food and exercise-induced anaphylaxis; Food allergy; Exercise; Anaphylaxis; Mechanism
The aetiology of childhood asthma is complex. An early dysfunction in the immunological development of the innate immune system in combination with environmental factors possibly triggers asthma. CD14 and toll-like receptors are important components of the innate immune system. The aim of this systematic review was to obtain a better insight into the relation between CD14 and toll-like receptors and childhood asthma in Caucasians. We searched PubMed and EMBASE for relevant articles. In total, 44 articles were included. The quality of the selected studies was independently assessed by the first two authors using the Newcastle-Ottawa quality assessment scale. Toll-like receptor 2, toll-like receptor 6, toll-like receptor 9, and toll-like receptor 10 appear to have some association with childhood asthma in Caucasians. The evidence for a relation of CD14 with childhood asthma is limited. In conclusion, there is no convincing evidence yet for a role of CD14 and toll-like receptors in relation to childhood asthma. Future studies should include haplotype analysis and take environmental factors into account to further clarify the role of CD14 and toll-like receptors on childhood asthma.
Asthma; Caucasian; CD14; Children; Gene expression; Genetic variants; Polymorphisms; TLR; Wheeze
Uncontrolled asthma remains a frequent cause of emergency department (ED) visits and hospital admissions. Improper asthma inhaler device use is most likely one of the major causes associated with uncontrolled asthma and frequent ED visits.
To evaluate the inhaler technique among asthmatic patients seen in ED, and to investigate the characteristics of these patients and factors associated with improper use of inhaler devices and its relationship with asthma control and ED visits.
A cross-sectional study of all the patients who visited the ED with bronchial asthma attacks over a 9-month period was undertaken at two major academic hospitals in Saudi Arabia. Information was collected about demographic data and asthma management and we assessed the inhaler techniques for each patient using an inhaler technique checklist.
A total of 450 asthma patients were included in the study. Of these, 176(39.1%) were males with a mean age of 42.3 ±16.7 years and the mean duration of asthma was 155.9 ± 127.1 weeks. The improper use of asthma inhaler devices was observed in 203(45%) of the patients and was associated with irregular clinic follow-ups (p = 0.0001), lack of asthma education (p = 0.0009), uncontrolled asthma ACT (score ≤ 15) (p = 0.001), three or more ED visits (p = 0.0497), and duration of asthma of less than 52 weeks (p = 0.005). Multiple logistic regression analysis revealed that a lack of education about asthma disease (OR =1.65; 95% CI: 1.07, 2.54) or a lack of regular follow-up (OR =1.73; 95% CI: 1.08, 2.76) was more likely to lead to the improper use of an asthma inhaler device.
Improper asthma inhaler device use is associated with poor asthma control and more frequent ED visits. We also identified many avoidable risk factors leading to the improper use of inhaler devices among asthma patients visiting the ED.
Asthma control; Inhaled corticosteroid; Emergency department; Inhaler devices; Asthma education
A diagnosis of peanut allergy has a major impact on an individual’s quality of life. Exposure to even small amounts of peanut can trigger serious reactions. Common cleaning agents can easily remove peanut allergen from surfaces such as table tops. Parents of children with peanut allergy frequently ask if peanut allergen can persist on surfaces if they have not been cleaned.
The purpose of this study was to determine the persistence of peanut allergen on a typical table surface over time.
Five mL of peanut butter was evenly smeared on a 12 inch by 12 inch (30.5 by 30.5 cm) square on a nonporous (laminated plastic) table surface. Five squares were prepared in the same manner. The table was kept in a regular hospital office at room temperature and ambient lighting. No cleaning occurred for 110 days. Samples were taken at regular intervals from different areas each time. A monoclonal-based ELISA for arachis hypogaea allergen 1 (Ara h 1), range of detection 1.95-2000 ng/mL, was used to assess peanut allergen on the table surface.
At baseline, there was no detectable Ara h 1 allergen. Immediately post application and for 110 days of collecting, detectable Ara h 1 was found each time a sample was taken. There was no obvious allergen degradation over time. Active cleaning of the contaminated surface with a commercial cleaning wipe resulted in no detectable Ara h 1 allergen.
Peanut allergen is very robust. Detectable Ara h 1 was present on the table surface for 110 days. Active cleaning of peanut contaminated surfaces easily removed peanut residue and allergen. Regular cleaning of surfaces before and after eating should be reinforced as a safety measure for all individuals with peanut allergy.
Food allergy; Peanut allergen; Contamination; Ara h 1
While a growing body of research is uncovering the aetiology and effective treatments for allergy, research that assess the broader ethical implications of this disease is lacking significantly. This article will demonstrate both the paucity of academic research concerning ethical implications in allergy and explain why ethical analysis is integral to formulating effective health strategies for allergic disease. An exhaustive literature search of publications in French and English identified less than 35 academic articles focussed on the topic of ethics and allergy; this is a miniscule number when compared to the amount of articles published on ethical issues related to other chronic illnesses, such as obesity. It is important to demonstrate to allergy specialists the need for, and utility of, further incorporating ethical analyses in allergology; the current success of Ethical, Legal, Social Implications (ELSI) research programmes in human genetics and nanotechnology will serve as notable examples. Indeed, future research and innovation in allergy will undoubtedly encounter ethical dilemmas and the allergology community should play a significant role in helping to address these issues. However, incorporating ethical analyses in allergology does not imply that the allergology community must acquire extensive knowledge in bioethics; instead, interdisciplinary research that incorporates expertise from allergology and bioethics would enable allergy specialists to advance critical knowledge development in this largely overlooked domain of study.
Allergy; Asthma; Ethics; Literature review; Health policy; ELSI; Knowledge transfer
The gene ORMDL3 was shown to be associated with early-onset asthma susceptibility in multiple independent genome-wide and candidate-gene association studies. Asthmatic patients have elevated expression levels of this gene. ORMDL3 encodes a transmembrane protein localized in the endoplasmic reticulum (ER) that may be involved in ER stress and inflammation. It is essential to validate the genetic associations linking ORMDL3 with asthma through functional studies that confirm the biological relevance of this gene in disease. We investigated the effects of manipulating ORMDL3 expression levels in vitro in airway cells on innate immune inflammatory responses, ER stress and activation of the unfolded protein response (UPR).
ORMDL3 expression levels were manipulated in airway cells using an overexpression plasmid and siRNA technologies. Successful modulation of ORMDL3 was confirmed at both the gene and protein level. The functional impact of modulation of ORMDL3 expression levels on inflammatory responses and activation of the UPR were quantified using complementary cellular and molecular immunology techniques.
Cells with altered ORMDL3 levels responded equally well to innate immune stimuli and produced similar levels of pro-inflammatory cytokines compared to wild-type cells. Treatment with ER stress inducers, thapsigargin and tunicamycin, resulted in activation of the unfolded protein response (UPR). However, we observed no difference in UPR activation in cells with ORMDL3 knockdown compared to cells with normal ORMDL3 levels.
Our results suggest that ORMDL3 variation in the airway epithelium is unlikely to play a significant role in modulating innate immune responses and the UPR in the lung.
Immune response; Epithelium; Cytokines; Chemokines; Host defense
Immunostimulatory therapy is now being recognized as an alternative to conventional chemotherapy for a variety of disease conditions, involving the impaired immune response of the host. In the present study, the immunostimulatory effect of the butanolic extract obtained from S. mialhesi aerial parts, was evaluated in vivo.
The immunostimulant potential of the plant extract on the phagocytic activity was measured by the carbon clearance rate test.
Our research revealed that at different doses (50, 100 and 500 mg/kg), S. mialhesi extract increased the phagocytic activity in a dose dependant manner when compared with the control and thus the clearance rate of carbon was faster after the administration of the plant extract.
S. mialhesi extract exhibited a dose-dependent immunostimulant effect on the reticuloendothelial system, which could be attributed to the presence of active principles in this butanolic extract.
Immunostimulatory activity; Phagocytic activity; Carbon clearance rate; Reticuloendothelial system; Stachys mialhesi de Noé
Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants.
A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested.
In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.
Anaphylaxis; Allergy; Basophil activation test; Enoxaparin; Heparin; Hypersensitivity; Immunoglobulin E; Immediate-type
Anti-neutrophil cytoplasmic antibodies are typically detected in anti-neutrophil cytoplasmic antibody associated vasculitis, but are also present in a number of chronic inflammatory non-vasculitic conditions like rheumatoid arthritis. Rare cases of granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis, a vasculitic disorder frequently associated with the presence of anti-neutrophil cytoplasmic antibodies) in patients with rheumatoid arthritis have been described in literature.
We report two middle-aged female patients with rheumatoid arthritis who developed anti-neutrophil cytoplasmic antibodies and symptoms reminiscent of granulomatosis with polyangiitis. Despite the lack of antibodies specific for proteinase 3 and the absence of a classical histology, we report a probable case of granulomatosis with polyangiitis in the first patient, and consider rheumatoid vasculitis in the second patient.
Taken together with previous reports, these cases highlight that anti-neutrophil cytoplasmic antibodies have to be evaluated very carefully in patients with rheumatoid arthritis. In this context, anti-neutrophil cytoplasmic antibodies detected by indirect immunofluorescence appear to have a low diagnostic value for granulomatosis with polyangiitis. Instead they may have prognostic value for assessing the course of rheumatoid arthritis.
Granulomatosis with polyangiitis; Rheumatoid arthritis; ANCA associated vasculitis; Rheumatoid vasculitis
In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.
Non-atopic asthma; Cytokines; IFN-g; Monocytes; Atopic-asthma; IgE; Atopy
A seasonal effect of month of birth and risk of allergic disease has been suggested by numerous studies. Few studies have directly measured pollen exposures at different points during pregnancy and in early life, and assessed their effects on risk of respiratory disease outcomes.
Pollen exposure was calculated for the first and last 12 weeks of pregnancy and the first 12 weeks of infancy for all children conceived by women residing in Stockholm, Sweden, between 1988 and 1995. Hospital admission data for respiratory conditions in the first year of life was also collected.
Out of 110,381 children, 940 had been hospitalised for asthma by 12-months of age. Pollen levels showed both marked seasonal variations and between year differences. Exposure to high levels of pollen in the last 12 weeks of pregnancy was associated with an increased risk of asthma hospitalisation (aOR = 1.35, 95% CI = 1.07-1.71 for highest quartile versus remaining infants). Exposure to high levels of pollen in the first three months of life was associated with a reduced risk (aOR = 0.76, 95% CI = 0.59-0.98) but only in children of heavy smoking mothers.
High levels of pollen exposure during late pregnancy were somewhat unexpectedly associated with an elevated risk of hospitalisation for asthma within the first year of life.
Pollen; Early life exposure; Asthma; Hospitalisation