The imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response.
To determine changes in Th17 and Treg cell numbers between isolated early responders (ERs) and dual responders (DRs) undergoing allergen inhalation challenge. To identify gene expression profiles associated with Th17 and Treg cells.
14 participants (8 ERs and 6 DRs) with mild allergic asthma underwent allergen inhalation challenge. Peripheral blood was collected prior to and 2 hours post allergen challenge. DNA methylation analysis was used to quantifiy the relative frequencies of Th17, Tregs, total B cells, and total T cells. Gene expression from whole blood was measured using microarrays. Technical replication of selected genes was performed using nanoString nCounter Elements.
The Th17/Treg ratio significantly increased in DRs compared to ERs post allergen challenge compared to pre-challenge. Genes significantly correlated to Th17 and Treg cell counts were inversely correlated with each other. Genes significantly correlated with Th17/Treg ratio included the cluster of genes of the leukocyte receptor complex located on chromosome 19q 13.4.
Th17/Treg imbalance post-challenge may contribute to the development of the late phase inflammatory phenotype.
Allergen inhalation challenge; Asthma, Asthmatic response; DNA methylation; Epigenetic cell counting; Peripheral blood; Th17/Treg ratio, nCounter Elements
There is conflicting evidence about the association between low vitamin D levels in children and development of asthma in later life. The objective of this study was to systematically review the evidence for an epidemiological association between low serum levels of vitamin D and the diagnosis of asthma in children.
We used the Cochrane methodology for conducting systematic reviews. The search strategy included an electronic search of MEDLINE and EMBASE in February 2013. Two reviewers completed, in duplicate and independently, study selection, data abstraction, and assessment of risk of bias.
Of 1081 identified citations, three cohort studies met eligibility criteria. Two studies found that low serum vitamin D level is associated with an increased risk of developing asthma late in childhood, while the third study found no association with either vitamin D2 or vitamin D3 levels. All three studies suffer from major methodological shortcomings that limit our confidence in their results.
Available epidemiological evidence suggests a potential association between low serum levels of vitamin D and the diagnosis of asthma in children. High quality studies are needed to reliably answer the question of interest.
Asthma; Wheezing; Childhood; Pediatric; Vitamin D; Bronchial hyper responsiveness; Lung function tests; Systematic review; Cohort
A previous study has shown that the aggravation of Asian sand dust (ASD) on ovalbumin (OVA)-induced lung eosinphilia was more severe in lipopolysaccharide (LPS)-rich ASD than in SiO2-rich ASD. Therefore, the effects of different LPS contamination levels in ASD on the aggravation of OVA-induced lung eosinophilia were investigated in the present study.
Before beginning the in vivo experiment, we investigated whether the ultra-pure LPS would act only on TLR4 or not using bone marrow-derived macrophages (BMDMs) of wild–type, TLR2-/-, TLR4-/- and MyD88-/- BALB/c mice. ASD collected from the desert was heated to remove toxic organic substances (H-ASD). BALB/c mice were instilled intratracheally with 12 different testing samples prepared with LPS (1 ng and 10 ng), H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), the levels of inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated.
The LPS exhibited no response to the production of TNF-α and IL-6 in BMDMs from TLR4-/-, but did from TLR2-/-. H-ASD aggravated the LPS-induced neutrophilic lung inflammation. In the presence of OVA, LPS increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 at the levels of 1 ng and 10 ng. In the presence of OVA and H-ASD, LPS induced severe eosinophil infiltration and proliferation of goblet cells in the airways as well as remarkable increases in Th2 cytokines IL-5 and IL-13 in BALF. The mixture containing LPS (1 ng) showed adjuvant activity on OVA-specific IgE and IgG1 production.
The results suggest that H-ASD with naturally-occurring levels of LPS enhances OVA-induced lung eosinophilia via increases in Th2-mediated cytokines and antigen-specific immunoglobulin. These results indicate that LPS is a strong candidate for being a major aggravating substance in ASD.
Lipopolysaccharide; Asian sand dust; Ovalbumin; Lung eosinophilia; Cytokine and chemokine; Asthma
Second generation H1 antihistamines (H1A) are currently recommended as first choice medications for allergic rhinitis and rhinoconjunctivitis. However, little is known about what influences the choice of prescription of one second generation (H1A) as opposed to another in real-life conditions.
The aim of the study was to identify the main criteria determining the choice of a second generation H1A by allergy specialists in mainland France.
Consecutive patients suffering from allergic rhinitis or rhinoconjunctivitis were included and followed prospectively for 30 days from the prescription of a second generation H1A in monotherapy. Patients were asked to fill in auto-questionnaires at baseline, daily during the first 10 days of the new treatment, and at the end of follow-up. Data on efficacy, tolerance, safety, rate and type of response to treatment, as well as patient satisfaction were recorded and analyzed.
1,080 patients were included between March 2011 and October 2012, mostly suffering from moderate to severe rhinitis (82.0%). The most frequently cited reason for choosing a specific H1A was the expected efficacy (85.3%). The mean time to nasal and ocular recovery was 6 days and 78.2% of patients responded to treatment within this interval. The presence of conjunctivitis was significantly associated with a more rapid response. At the end of follow-up, the satisfaction rate was higher for patients who were switched from a previous treatment (87.5%), compared to those receiving their first treatment (78.8%).
Conclusion and clinical relevance
The main reason for choosing a specific second generation H1A was its expected efficacy. Concomitant conjunctivitis is associated with a more rapid response to treatment. Symptom recovery necessitates a mean of 6 days.
Allergic rhinitis; Quality of life; Second generation antihistamine
Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations.
Epigenetic; Asthma; Allergy; Atopy; Inheritance; Transgenerational; Methylation; Histone; Th2; Amplification hypothesis
Food-allergic children frequently avoid other highly allergenic foods. The NIAID 2010 guidelines state that individuals with an IgE-mediated food allergy should avoid their specific allergens and physicians should help patients to decide whether certain cross-reactive foods also should be avoided. Patients at risk for developing food allergy do not need to limit exposure to foods that may be cross-reactive with the major food allergens. The purpose of this study was to determine if parents of food-allergic children are given advice regarding introduction of allergenic foods; if these foods are avoided or delayed; if there is anxiety when introducing new foods; and if introducing other allergenic foods leads to any allergic reaction. The study also determined if there was a similar pattern seen amongst younger siblings.
An online survey was administered between December 2011 and March 2012 via Anaphylaxis Canada’s website, available to Canadian parents and caregivers who are registered members of the organization and who have a child with a food allergy.
644 parents completed the online survey. 51% of families were given advice regarding the introduction of other allergenic foods. 72% were told to avoid certain foods, and 41% to delay certain foods. 58% of parents did avoid or delay other highly allergenic foods, mainly due to a fear of allergic reaction. 69% of children did not have an allergic reaction when these foods were subsequently introduced. 68% of parents felt moderate or high levels of anxiety when introducing other foods. A similar pattern was seen amongst the younger siblings.
Canadian parents and caregivers of children with food allergies receive varied advice from health care professionals regarding the introduction of new allergenic foods, and feel moderate to high levels of anxiety. A similar pattern may be seen amongst younger siblings. While the majority of children in our study did not have an allergic reaction to a new food, a significant proportion of children did react. A more consistent approach to the advice given by health care professionals may decrease parental anxiety. Further research to support the 2010 NIAID guidelines may be necessary to clarify recommendations.
Food allergy; Siblings; Food introduction; Anxiety
Food allergy (FA) negatively affects quality of life in caregivers of food-allergic children, imposing a psychosocial and economic burden. Oral immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT can be a source of anxiety as it carries risk for allergic reactions. The effect of OIT with multiple food allergens (mOIT) on FA-specific health-related quality of life (HRQL) has never been studied in participants with multiple, severe food allergies. This study is the first to investigate the effects of mOIT on FA-related HRQL in caregivers of pediatric subjects.
Caregiver HRQL was assessed using a validated Food Allergy Quality of Life – Parental Burden (FAQL-PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of participants in two single-center Phase I clinical trials receiving mOIT (n = 29) or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL-PB prior to study intervention and at 2 follow-up time-points (6 months and 18 months). Parents of subjects not receiving OIT (control group, n = 10) completed the FAQL-PB for the same time-points.
HRQL improved with clinical (change < -0.5) and statistical (p < 0.05) significance in the mOIT group (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0; 18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean 3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow-up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the control group (n = 10).
Multi-allergen OIT with or without omalizumab leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the psychosocial and economic burden FA imposes on caregivers of food-allergic children.
Oral immunotherapy; Omalizumab; Anti-IgE; Food allergy; Oral desensitization; Quality of life; Health-related quality of life
A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.
Chronic urticaria; Leukotreine receptor antagonists; Leukotreine; Montelukast; Zafirlukast; Antihistamines
Allergen-specific subcutaneous immunotherapy is an effective treatment for certain allergic disorders. Ideally, it should be administered into the subcutaneous space in the mid-posterolateral upper arm. Injections are commonly given using a standard allergy syringe with a needle length of 13 mm. Therefore, there is a risk of intramuscular administration if patients have a skin-to-muscle depth <13 mm, which may increase the risk of anaphylaxis. The objective of this study was to determine whether the needle length of a standard allergy syringe is appropriate for patients receiving subcutaneous immunotherapy.
Ultrasounds of the left posterolateral arm were performed to measure skin-to-muscle depth in 200 adults receiving subcutaneous immunotherapy. The proportion of patients with a skin-to-muscle depth >13 mm vs. ≤13 mm was assessed and baseline characteristics of the two groups were compared. The proportion of patients with skin-to-muscle depths > 4 mm, 6 mm, 8 mm and 10 mm were also calculated. Multivariable logistic regression was performed to identify predictors of skin-to-muscle depth.
Of the 200 patients included in the study, 80% had a skin-to-muscle depth ≤13 mm; the majority (91%) had a skin-to-muscle depth >4 mm. Body mass index was found to be a significant predictor of skin-to-muscle-depth.
Most patients receiving subcutaneous immunotherapy have a skin-to-muscle depth less than the needle length of a standard allergy syringe (13 mm). These patients are at risk of receiving injections intramuscularly, which may increase the risk of anaphylaxis. Using a syringe with a needle length of 4 mm given at a 45° angle to the skin may decrease this risk.
Allergen-specific immunotherapy; Subcutaneous immunotherapy; Ultrasound; Skin-to-muscle depth; Needle length; Allergy syringe; Injections
Switching primary/secondary immunodeficiency (PID/SID) patients from intravenous immunoglobulin (IVIg) to home-based subcutaneous immunoglobulin (SCIg) therapy reduces nurse time. A nurse shortage in Canada provides an important context to estimate the net economic benefit, the number of patients needed to switch to SCIg to recoup one full-time equivalent (FTE), and potential population-wide savings of reduced nurse time to a payer.
The net economic benefit was estimated by multiplying the hourly compensation for nurses in Canada by the hours required for each administration route. The number needed to switch to SCIg to gain one nurse FTE was estimated by dividing the work hours in a year by the average annual savings in nursing time in a PID population in Canada. The prevalence of treated PID/SID in Canada was calculated using provincial IgG audit data to extrapolate the potential population-wide savings of switching patients to SCIg therapy.
The net economic gain from switching one patient to home-based SCIg care would be C$2,603 (Canadian Dollars) in year 1 and C$2,948 each year thereafter. Switching 37 IVIg patients to SCIg would gain one nurse FTE. Switching 50% of the estimated 5,486 PID and SID patients in Canada receiving IVIg therapy to SCIg has the potential to save 223.3 nurse FTEs (C$23.2 million in labor costs).
A shift from IVIg to less labor-intensive SCIg has the potential to help alleviate nurse shortages and reduce overall health care costs in Canada. Health care professionals might consider advocating for home-based SCIg therapy for PID/SID patients when clinically appropriate.
IVIg; SCIg; Labor costs; Full time equivalents; FTEs; PID; SID; Nurse time
Asthma is the most common chronic disease of childhood and a leading cause of childhood morbidity. The aim of the current study was to assess the effectiveness of montelukast administered as monotherapy or in combination with current inhaled corticosteroids (ICS) in pediatric patients with uncontrolled asthma as per the Canadian Asthma Consensus Guidelines.
Twelve-week, multicentre, open-label, observational study. Primary effectiveness outcome was the proportion of patients achieving asthma control (Asthma Control Questionnaire (ACQ) score ≤0.75) at weeks 4 and 12.
A total of 328 patients with uncontrolled asthma (ACQ > 0.75) were enrolled with mean ± SD age of 6.9 ± 3.4 years. Among these, 76 (23.2%) were treated with montelukast monotherapy and 252 (76.8%) with montelukast combined with ICS. By 4 weeks of treatment 61.3% and 52.9% of the patients in the monotherapy and combination group, respectively, achieved asthma control. These proportions increased to 75.0% and 70.9%, respectively, at 12 weeks. Within the monotherapy group, clinically significant improvements in the ACQ score (mean ± SD of 1.67 ± 0.69, 0.71 ± 0.70 and 0.50 ± 0.52 at baseline, 4 and 12 weeks, respectively; p < 0.001) and the PACQLQ score (mean ± SD of 5.34 ± 1.14, 6.32 ± 0.89 and 6.51 ± 0.85 at baseline, 4 and 12 weeks, respectively; p < 0.001) were observed. In the combination group, the mean ± SD ACQ score significantly improved from 2.02 ± 0.83 at baseline to 0.90 ± 0.86 at 4 weeks and 0.64 ± 0.86 at 12 weeks (p < 0.001), while the PACQLQ score improved from 4.42 ± 1.35 at baseline to 5.76 ± 1.30 at 4 weeks and 6.21 ± 1.03 at 12 weeks (p < 0.001). After a 12-week montelukast add-on therapy, 22.6% of patients reduced their ICS dosage. Similar results were observed among preschool- and school-aged patients.
Montelukast as monotherapy or in combination with ICS represents an effective treatment strategy for achieving asthma control in pediatric patients and improving caregivers’ quality of life.
This study is registered at ClinicalTrial.gov: NCT00832455.
Asthma; Montelukast; Inhaled corticosteroids; Pediatric; Preschool age; School age
Platelet-activating factor (PAF) is a highly potent phospholipid mediator responsible for the life-threatening manifestations of anaphylaxis. PAF acetylhydrolase (PAF-AH) inactivates PAF and protects against severe anaphylaxis whereas deficiency of PAF-AH predisposes to severe or fatal anaphylaxis. Determinants of PAF-AH activity have not been studied in patients with peanut allergy.
To determine whether plasma PAF-AH activity in patients with peanut allergy is related to formation of circulating complexes with apolipoprotein B (apoB) the main surface protein on low density lipoprotein particles.
Plasma PAF-AH activity and apoB concentrations were measured in 63 peanut allergic patients (35 boys, 28 girls, ages 2 – 19 years). ApoB concentration was measured immunoturbidimetrically using goat anti-human apoB. The correlation between PAF-AH activity and apoB concentration was determined.
A positive correlation was found between PAF-AH activity and apoB concentration (r2 = 0.59, P < 0.0001).
In peanut allergic patients, PAF-AH activity strongly correlates with apoB concentration, suggesting the presence of circulating PAF-AH- lipoprotein complexes.
Anaphylaxis; Platelet-activating factor (PAF); PAF-acetylhydrolase (PAF-AH); Low density lipoprotein (LDL); Apolipoprotein B (apoB)
It is hypothesized that because of higher mast cell numbers and mediator release, mastocytosis predisposes patients for systemic immediate-type hypersensitivity reactions to certain drugs including non-steroidal anti-inflammatory drugs (NSAID).
To clarify whether patients with NSAID hypersensitivity show increased basal serum tryptase levels as sign for underlying mast cell disease.
As part of our allergy work-up, basal serum tryptase levels were determined in all patients with a diagnosis of NSAID hypersensitivity and the severity of the reaction was graded. Patients with confirmed IgE-mediated hymenoptera venom allergy served as a comparison group.
Out of 284 patients with NSAID hypersensitivity, 26 were identified with basal serum tryptase > 10.0 ng/mL (9.2%). In contrast, significantly (P = .004) more hymenoptera venom allergic patients had elevated tryptase > 10.0 ng/mL (83 out of 484; 17.1%). Basal tryptase > 20.0 ng/mL was indicative for severe anaphylaxis only in venom allergic subjects (29 patients; 4x grade 2 and 25x grade 3 anaphylaxis), but not in NSAID hypersensitive patients (6 patients; 4x grade 1, 2x grade 2).
In contrast to hymenoptera venom allergy, NSAID hypersensitivity do not seem to be associated with elevated basal serum tryptase levels and levels > 20 ng/mL were not related to increased severity of the clinical reaction. This suggests that mastocytosis patients may be treated with NSAID without special precautions.
Anaphylaxis; Non-steroidal anti-inflammatory drug; Mastocytosis; Drug allergy; Drug reaction; Pseudo-allergy
Inhaled medications are the cornerstone of asthma therapy. Metered dose inhaler technique is a widely used technique to administer medications like corticosteroids. Meanwhile, the health professionals and patients knowledge and practice towards this metered dose inhaler is quite deficient but arguably understood by policy makers or education expertise.
This study tried to assess the pharmacists and druggists competency on MDI who are the professionals at the front line to demonstrate and teach the technique for patients.
A cross sectional study was conducted among registered pharmacists and druggists from different public and private pharmacies and drug stores in Mekelle Town, Ethiopia from March to June, 2013. Evaluation tool was adapted from the National Asthma Education and Prevention Programmes of America (NAEPP) step criteria for the administration of a metered dose inhaler to score the knowledge/proficiency of use of MDIs by the subjects using two evaluators.
The mean score given by evaluators was 4.34 and 4.28 by evaluator I and II respectively. Of the 106 professionals took part in this research, based on the competency on essential steps for optimum therapeutic value of MDI, only 2 (1.9%) and 1 (0.9%) study participants had adequate competency in metered dose inhaler according to evaluator I and evaluator II respectively. The rest, irrespective of their age, sex, educational status and experience, did not achieve adequate score on MDI technique. Of the essential steps, only 25 (23.6%) and 16 (15.1%) participants breathed in and actuating the canister together according to evaluators I and II respectively.
Very poor MDI technique was very common in this sample of healthcare providers. Despite involvement of all participants in patient counselling on inhalers, none of them were able to perform all steps correctly, which shows that patient may not have adequate instruction.
MDI; Asthma; Dispensers; Inhalers
Hereditary Angioedema (HAE) is a rare autosomal dominant condition characterized by episodic angioedema, which may be triggered by invasive procedures and surgery. C1 inhibitor (C1 INH) was approved in the United States and Canada in 2009 and 2010, respectively, for the treatment of acute attacks. Most recently in April 2013, it was approved in Europe for short-term prophylaxis (STP), prior to medical, dental, or surgical procedures, to prevent HAE attacks in both children and adults. Currently, C1 INH is not approved in Canada or the United States for STP of HAE attacks. Our objective was to demonstrate the effectiveness of C1 INH as a short-term prophylactic treatment for patients with Type I HAE undergoing invasive surgical procedures.
A retrospective chart review between 1997-2013 was performed at one Canadian Tertiary Care Allergy and Asthma Clinic affiliated with The Ottawa Hospital, in Ottawa, Canada. The standard dose of C1 INH for STP was 10 or 20 U/kg.
In all 24 procedures, there were no post-procedure HAE attacks after short-term prophylactic administration of C1 INH.
In this retrospective chart review at one tertiary care Allergy and Clinical Immunology Clinic, short-term prophylactic use of C1 INH was found to be effective at preventing post-procedure HAE attacks, in patients diagnosed with Type I HAE.
Hereditary angioedema (HAE); C1 Inhibitor; Short-term prophylaxis (STP); Pre-procedural treatment
Recent data from literature have shown many difficulties in managing allergic diseases in primary care in most countries and a consequently clear need for standardized educational programmes. Drug allergies represent an important medical issue for general practitioners (GPs) in Romania, though no national data about incidence, severity and management exist.The aim of our study was to evaluate epidemiological aspects of drug allergies in primary care practice in Bucharest, especially the diagnostic and therapeutic attitudes of family doctors and their need for education and training in this field of pathology.
A questionnaire with 21specific questions was addressed to 800 family doctors from Bucharest, either directly or via internet, with a response rate of 31,87%.
The answers showed a significant interest of GPs in drug allergies, which are considered an increasing pathology. Almost half of the responders had never attended any form of education in allergology and 96% expressed a clear interest to participate in specialized educational programmes. We have noticed an underestimation of the severity of drug allergy, a surprisingly high percentage of allergy skin tests or blood tests recommended by GPs without specialist advice, and persistant confidence in alternative medicine.
We concluded that the attitude towards and the competence regarding drug allergies of GPs in this study, as well as their collaboration with allergists, are not standardized and updated according to current guidelines. Further educational programs for GPs in drug allergies, based on standardized guidelines and national epidemiological studies for evaluation of drug allergy-related morbidity and mortality are needed.
Drug allergies; Education; Primary care
Chronic rhinosinusitis (CRS) is a societal burden and cause of morbidity in Canada; however, the prevalence of allergic sensitization in Canadian CRS patients has remained poorly characterized.
In this study, we used skin prick test (SPT) and specific immunoglobulin E (sIgE) and G (sIgG) titers to regionally relevant allergen sources in order to determine whether allergic sensitization is more prevalent in CRS patients compared to chronic idiopathic urticaria (CIU) control patients.
One hundred and fifty eight subjects (19–70 years of age) were recruited into the study. 101 subjects had a confirmed diagnostic history of CRS and 57 subjects with a clinical diagnosis of CIU were recruited as controls. Enrolled subjects underwent SPT to a panel of perennial and seasonal allergens and sIgE titers were quantified to selected environmental allergen mixes (grass, mold, and tree species) using Phadia ImmunoCAP. sIgG was additionally quantified to Alternaria alternata, Aspergillus versicolor, Cladosporium herbarum, and Stachybotrys atra. Differences between CRS and control CIU patient SPT and serological data were examined by chi-squared analysis and analysis of variance.
Reactivity to at least one SPT extract occurred in 73% of CRS patients. Positive SPT reactivity to A. alternata (odds ratio (OR): 4.34, 95% confidence interval: 1.57, 12.02), cat (OR: 3.23, 95% CI: 1.16, 9.02), and ragweed (OR: 2.31, 95% CI: 1.02, 5.19) extracts were more prevalent in patients with CRS (p < 0.05). Although dust mite and timothy grass sensitization approached statistical significance in the chi-squared analysis of SPT data, other common perennial and seasonal allergens were not associated with CRS. No statistically significant differences were observed between mean sIgE and sIgG titers in CRS and control patients.
This study supports previous data that suggests A. alternata sensitization is associated with CRS; however, these findings additionally highlight the contribution of other regionally important allergens including cat and ragweed.
Allergic rhinitis; Allergic sensitization; Chronic rhinosinusitis; Perennial allergens
Fairly recent data highlight the role of programmed cell death and autoimmunity, as potentially important factors in the pathogenesis of chronic obstructive airway diseases. The purpose of our research was to determine the influence of apoptotic factors on the immunity of patients with atopic bronchial asthma according to the degree of severity.
The study was performed on the peripheral blood of patients with atopic bronchial asthma with different severity. The Immunological aspects were determined with ELISA, the fluorimetric method and the method of precipitation with polyethylene glycol. And the quantification of the parameters of the programmed cell death was performed by the method of flow cytometry and electron microscopy method.
The data obtained from morphological and biochemical parameters show the deregulation of Programmed Death of lymphocytes of patients with atopic bronchial asthma but individual for each group of patients. This dysfunction might induce the secretion of autoantibodies against DNA. This could explain the accumulation of circulating immune complex with average size considered as the most pathogenic in patients with bronchial asthma especially in the patients of serious severity. It should be noted that Patients with bronchial asthma of mild and severe severity had different way and did not have the same degree of deficiency of the immune system.
These data suggested that apoptotic factor of lymphocytes may play an important role in controlling immunity of patients with atopic bronchial asthma.
Programmed cell death; Immunity; Atopic Bronchial Asthma
Childhood asthma may have a fetal origin through fetal growth and development of the immunocompetence or respiratory organs.
We examined to which extent short gestational age, low birth weight and fetal growth restriction were associated with an increased risk of asthma hospitalization in childhood.
We undertook a cohort study based on several national registers in Denmark, Sweden and Finland. We included all live singleton born children in Denmark during 1979-2005 (N = 1,538,093), in Sweden during 1973-2004 (N = 3,067,670), and a 90% random sample of singleton children born in Finland during 1987-2004 (N = 1,050,744). The children were followed from three years of age to first hospitalization for asthma, emigration, death, their 18th birthday, or the end of study (the end of 2008 in Denmark, and the end of 2007 in Sweden or Finland), whichever came first. We computed the pseudo-values for each observation and used them in a generalized estimating equation to estimate relative risks (RR) for asthma hospitalization.
A total of 131,783 children were hospitalized for asthma during follow-up. The risk for asthma hospitalization consistently increased with lower birth weight and shorter gestational age. A 1000-g decrease in birth weight corresponded to a RR of 1.17 (95% confidence interval (CI) 1.15-1.18). A one-week decrease in gestational age corresponded to a RR of 1.05 (95% CI 1.04-1.06). Small for gestational age was associated with an increased risk of asthma hospitalization in term but not in preterm born children.
Fetal growth and gestational age may play a direct or indirect causal role in the development of childhood asthma.
Asthma; Birth weight; Gestational age; Hospitalization; Small for gestational age
Home based oral immunotherapy (OIT) for food allergy has often been used for young children in Japan, the majority of whom are believed to outgrow the allergy by the school age, therefore the true efficacy of the therapy has been controversial. The aim of this study was to evaluate the efficacy and safety of a newly developed slow- type home-based oral immunotherapy (OIT) regimen in children with hen’s egg (HE) allergy, who had low likelihood of outgrowing the allergy, with treatment involving only elimination diet.
We retrospectively reviewed the medical records of 43 children with egg allergy (30 males; median age 6) who fulfilled Burks et al.’s criteria of being unlikely to outgrow the allergy. Thirty children who agreed to start OIT were assigned to the treatment group, and 13 who did not want to participate immediately were assigned to the untreated group; the patients underwent an elimination diet for 1 year, during which they were monitored. The OIT regimen involved the intake of the maximum tolerated dose 2 to 3 times a week at home, with initial dose introduction followed by dose build-ups with medical supervision. We statistically evaluated the rate of children who changed their threshold up to 32 g of egg – defined as, oral tolerance induction– in both the groups for 1 year and in the OIT group for 2 years, as well as the rate of children who fulfilled Savage et al.’s criteria of clinical tolerance after reaching the abovementioned remission stage.
The rate of children who achieved oral tolerance induction to 32 g of egg after 1 year in the OIT group (9/30) was significantly higher than that in the untreated group (0/13). The total rate within the OIT group was significantly increased from 9/30 at 1 year to 17/30 at two years without any severe adverse reaction; of the above 17 children, we followed 14 children, and noted that 11 of these were able to obtain clinical tolerance.
The home-based OIT with an intermittent loading protocol was very safe and effective in children with a low likelihood of outgrowing egg allergy.
Egg allergy; Home- based oral immunotherapy; Intermittent loading protocol; Unlikely to outgrow
Wheat is one of the most common food allergens in children. The purpose of this study is to define the natural course of wheat allergy in children with dominant gastrointestinal symptoms and identify factors that help predict development of tolerance.
The prospective analysis covered 50 children with positive food challenge results (DBPCFC) and positive wheat IgE test result. Resolution of wheat allergy was determined on the basis of food challenge results (open challenge). The impact of each of the studied factors on the age when tolerance developed was assessed by means of the Cox proportional hazard regression model.
The median age of tolerance development was 69.5 months (37-192 mo.). The rates of resolution were 20% by the age of 4 years, 52% by the age of 8 years, and 66% by 12 years, and 76% by 18 years. The median age of the tolerance development in children with peak wheat IgE level below10 kU/L was 41.4 months, with peak wheat IgE from 10 to 19.9 kU/L was 44.5 months, with peak IgE from 20 to 49.9 kU/L – 84,9 months and with peak IgE ≥ 50 kU/L – 190.5 months. The median of the age when the highest levels of IgE for wheat were reached was 33 months (2-52 mo.) in children with resolved wheat allergy and 67 months (36-178 mo.) in children with persistent allergy (p = .001).
1. The majority of children with wheat allergy can tolerate wheat by adolescence. 2. The age when tolerance to wheat developed depended on the level and the age of reaching the highest levels of specific IgE for wheat. The higher the values of the above parameters, the older a child was when they developed tolerance to wheat.
Food allergy; Food tolerance; Wheat allergy; Specific immunoglobulin E; Children
Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein.
To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously.
Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries.
Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks.
These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.
Food allergy; Oral immunotherapy (OIT); Specific Oral Tolerance Induction (SOTI); Multiple food allergy; Safety; Efficacy; Omalizumab; Desensitization
Bjerkandera adusta (B. adusta) is one of the most important etiological fungi associated with chronic cough. However, precise details of the inflammatory response to exposure are not well understood yet. B. adusta was recently identified in Asian sand dust (ASD) aerosol. Therefore, in the present study the exacerbating effects of ASD on B. adusta-induced lung inflammation and B. adusta + ASD on ovalbumin (OVA)-induced murine lung eosinophilia were investigated using experimental mice.
In order to prepare testing samples, B. adusta obtained from ASD aerosol was inactivated by formalin and ASD collected from the atmosphere was heated to remove toxic organic substances (H-ASD). CD-1 mice were instilled intratracheally with 12 different samples prepared with various combinations of B. adusta, H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in bronchoalveolar lavage fluid (BALF), and the levels of inflammatory cytokines/chemokines in BALF were investigated.
H-ASD aggravated the lung eosinophilia induced by B. adusta alone, which also aggravated the lung eosinophilia induced by OVA. The mixture of OVA, H-ASD, and B. adusta caused serious fibrous thickening of the subepithelial layer, eosinophil infiltration, and proliferation of goblet cells in the airways along with remarkable increases of IL-13, eotaxin, IL-5, and MCP-3 in BALF.
The results of the present study demonstrated that B. adusta isolated from ASD aerosol induces allergic lung diseases. H-ASD enhanced allergic reactions caused by OVA or B. adusta. A mixture of B. adusta, H-ASD, and OVA caused the most remarkable exacerbation to the allergic airway inflammation via remarkable increases of pro-inflammatory mediators.
Asian sand dust; Bjerkandera adusta; Fungus; Lung eosinophilia; Asthma
Beta-hemolytic Group A Streptococcus invasive disease (iGASd) has been subject to intense research since its re-emergence in the late 1980s. In Quebec, an increase in the number of severe iGASd cases has recently been observed. Because of the inter-individual variability in the severity of iGASd, a hereditary predisposition to invasive disease can be suspected. Given that iGASd occurs in MyD88- and IRAK4-deficient patients, although rarely, the increasing frequency of iGASd in the population of French-Canadian children may be associated with a deficiency in the host’s innate immune response.
In this report, we assessed the influence of: (i) bacterial genotype and virulence factors, (ii) immune-cellular features, and (iii) Myd88/IRAK4-dependent response to GAS in vitro on the susceptibility to iGASd in a paediatric cohort of 16 children: 11 French-Canadian and 5 from diverse origin.
GAS virulence factors and genotype are not implicated in the susceptibility toward iGASd, and cellular and MyD88/IRAK4 deficiencies are excluded in our patients.
Although it has been shown that the MyD88/IRAK4-dependent signal is involved in the response to invasive GAS, our data indicates that a MyD88/IRAK4-mediated signalling defect is not the main factor responsible for the susceptibility to severe iGASd in a paediatric population from the province of Quebec.
Invasive group A Streptococcus; MyD88/IRAK4-mediated signalling; Innate immunity
Asthma is caused by both environmental and genetic factors. The ADRB2 gene, which encodes the beta 2-adrenergic receptor, is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly (+46A > G) and Gln27Glu (+79C > G) polymorphisms in the ADRB2 gene cause changes in the amino acids flanking the receptor ligand site, altering the response to bronchodilators and the risk of asthma through complex pathways. The ADRB2 polymorphisms affect beta-adrenergic bronchodilator action and are a tool to identify at-risk populations.
To determine the frequency of these two polymorphisms in allergic asthma patients and healthy subjects and to correlate these data with the occurrence and severity of asthma.
Eighty-eight allergic asthma patients and 141 healthy subjects were included in this study. The ADRB2 polymorphisms were analyzed using the amplification-refractory mutation system – polymerase chain reaction (ARMS-PCR) technique. The statistical analysis was performed with the SPSS 21.0 software using the Fisher’s Exact and χ2 tests.
The ADRB2 polymorphisms were associated with asthma occurrence. The Arg16Arg, Gln27Gln and Gln27Glu genotypes were risk factors; the odds ratios were 6.782 (CI = 3.07 to 16.03), 2.120 (CI = 1.22 to 3.71) and 8.096 (CI = 3.90 to 17.77), respectively. For the Gly16Gly and Glu27Glu genotypes, the odds ratios were 0.312 (CI = 0.17 to 0.56) and 0.084 (CI = 0.04 to 0.17), respectively. The haplotype analysis showed that there were associations between the following groups: Arg16Arg-Gln27Gln (OR = 5.108, CI = 1.82 to 16.37), Gly16Gly-Glu27Glu (OR = 2.816, CI = 1.25 to 6.54), Arg16Gly-Gln27Glu (OR = 0.048, CI = 0.01 to 0.14) and Gly16Gly-Gln27Glu (OR = 0.1036, CI = 0.02 to 0.39). The polymorphism Gln27Glu was associated with asthma severity, as the Gln27Gln genotype was a risk factor for severe asthma (OR = 2.798, CI = 1.099 to 6.674) and the Gln27Glu genotype was a protective factor for mild (OR = 3.063, CI = 1.037 to 9.041) and severe (OR = 0.182, CI = 0.048 to 0.691) asthma.
The Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene are associated with asthma presence and severity.
Asthma; ADRB2 gene; Lung disease; Arg16Gly; Gln27Glu