Allergy, Asthma & Clinical Immunology - Latest Articles

Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E

Faisal Khan — 2012-01-20T00:00:00Z

Background: Skin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens.Objectives: In this study, we compared the results of SPT, BAT and FEIA for different aeroallergens. Methods: We performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT). Results: Correlations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE. Conclusion: As an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils.

Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

Narcy Arizmendi — 2011-12-14T00:00:00Z

Background: Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant. Methods: Cockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate. Results: Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol. Conclusions: Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.

Efficacy and Onset of Action of Mometasone Furoate/Formoterol and Fluticasone Propionate/Salmeterol Combination Treatment in Subjects With Persistent Asthma

David Bernstein — 2011-12-07T00:00:00Z

Background: Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma. Methods: Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 mcg (delivered as 2 inhalations of MF-MDI 100 mcg) twice daily (BID), subjects (aged 12 or more years) were randomized to MF/F-MDI 200/10 mcg BID (delivered as 2 inhalations of MF/F-MDI 100/5 mcg) or FP/S administered via a dry powder inhaler (DPI) 250/50 mcg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes. Results: 722 subjects were randomized to MF/F-MDI (n=371) or FP/S-DPI (n=351). Mean FEV1 AUC0-12h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L x h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P<0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n=29]; FP/S-DPI, 8.3% [n=29]). Conclusions: The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints.Trial registration: ClinicalTrials.gov Identifier, NCT00424008

Effects of Lactobacillus rhamnosus GG supplementation on cow's milk allergy in a mouse model

Cin Thang — 2011-12-06T00:00:00Z

Background: Cow's milk allergy (CMA) is one of the most prevalent human food-borne allergies, particularly in infants and young children from developed countries. Our study aims to evaluate the effects of Lactobacillus rhamnosus GG (LGG) administration on CMA development using whole cow's milk proteins (CMP) sensitized Balb/C mice by two different sensitization methods. Methods: LGG supplemented mice were either sensitized orally with CMP and cholera toxin B-subunit (CTB) as adjuvant, or intraperitoneally (IP) with CMP but without the adjuvant. Mice were then orally challenged with CMP and allergic responses were accessed by monitoring hypersensitivity scores, measuring the levels of CMP-specific immunoglobulins (IgG1, IgG2a and IgG) and total IgE from sera, and cytokines (IL-4 and IFN-γ) from spleen lysates. Results: Sensitization to CMP was successful only in IP sensitized mice, but not in orally sensitized mice with CMP and CTB. Interestingly, LGG supplementation appeared to have reduced cow's milk allergy (CMA) in the IP group of mice, as indicated by lowered allergic responses. Conclusions: Adjuvant-free IP sensitization with CMP was successful in inducing CMA in the Balb/C mice model. LGG supplementation favourably modulated immune reactions by shifting Th2-dominated trends toward Th1-dominated responses in CMP sensitized mice. Our results also suggest that oral sensitization by the co-administration of CMP and CTB, as adjuvant, might not be appropriate to induce CMA in mice.

VIP Regulates the Development & Proliferation of Treg in vivo in spleen

Anthony Szema — 2011-11-29T00:00:00Z

Background: Mounting evidence supports a key role for VIP as an anti-inflammatory agent and promoter of immune tolerance. It suppresses TNF- and other inflammatory cytokines and chemokines, upregulates anti-inflammatory IL-10, and promotes immune tolerant cells called T regulatory (Treg) cells. VIP KO mice have recently been demonstrated to have spontaneous airway and pulmonary perivascular inflammatory responses, as part of asthma-like and pulmonary hypertension phenotypes, respectively. Both inflammatory responses are correctable with VIP. Focusing on this model, we have now investigated the influence of VIP not only on inflammatory cells but also on Treg cells. Methods: Using flow cytometric analysis, we examined the relative preponderance of CD25+CD4+ cells and anti-inflammatory Treg cells, in extracts of thymus and spleen from VIP KO mice (5 VIP KO; 5 VIP KO+ VIP; 10 wild-type). This method allowed antibody-based flow cytometric identification of Treg cells using surface markers CD25 and CD4, along with the: 1) intracellular activation marker FoxP3; and 2) Helios, which distinguishes cells of thymic versus splenic derivation. Conclusions: Deletion of the VIP gene results in: 1) CD25+CD4- cell accumulation in the thymus, which is corrected by VIP treatment; 2) more Treg in thymus lacking Foxp3 expression, suggesting VIP is necessary for immune tolerance; and, 3) a tendency towards deficiency of Treg cells in the spleen, which is normalized by VIP treatment. Treg lacking Helios are induced by VIP intrasplenically rather than by migration from the thymus. These results confirm the dual role of VIP as an anti-inflammatory and immune tolerance-promoting agent.

A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype

Michael Ringenbach — 2011-11-13T00:00:00Z

Alpha-1-antitrypsin (A1AT) deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis.

Antenatal risk factors for peanut allergy in children

Karen Binkley — 2011-10-04T00:00:00Z

Background: Prenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods. Methods: We conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy. Results: Receipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut-containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03). Conclusion: The risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods.Clinical implicationsRh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts.Capsule SummaryIdentification of prenatal factors that contribute to peanut allergy might allow for prevention of this life-threatening condition. This article explores the role of three such factors.

DRESS with delayed onset acute interstitial nephritis and profound refractory eosinophilia secondary to Vancomycin.

Paloma O'Meara — 2011-10-03T00:00:00Z

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a relatively rare clinical entity; even more so in response to vancomycin. Methods: Case report. Results: We present a severe case of vancomycin-induced DRESS syndrome, which on presentation included only skin, hematological and mild liver involvement. The patient further developed severe acute interstitial nephritis, eosinophilic pneumonitis, central nervous system (CNS) involvement and worsening hematological abnormalities despite immediate discontinuation of vancomycin and parenteral corticosteroids. High-dose corticosteroids for a prolonged period were necessary and tapering of steroids a challenge due to rebound-eosinophilia and skin involvement. Conclusion: Patients with DRESS who are relatively resistant to corticosteroids with delayed onset of certain organ involvement should be treated with a more prolonged corticosteroid tapering schedule. Vancomycin is increasingly being recognized as a culprit agent in this syndrome.

Prevalence of asthma symptoms based on the European Community Respiratory Health Survey questionnaire and FENO in university students: gender differences in symptoms and FENO

Tamotsu Ishizuka — 2011-09-19T00:00:00Z

Background: The fractional concentration of nitric oxide in exhaled air (FENO) is used as a biomarker of eosinophilic airway inflammation. FENO is increased in patients with asthma. The relationship between subjective asthma symptoms and airway inflammation is an important issue. We expected that the subjective asthma symptoms in women might be different from those in men. Therefore, we investigated the gender differences of asthma symptoms and FENO in a survey of asthma prevalence in university students. Methods: The information about asthma symptoms was obtained from answers to the European Community Respiratory Health Survey (ECRHS) questionnaire, and FENO was measured by an offline method in 640 students who were informed of this study and consented to participate. Results: The prevalence of asthma symptoms on the basis of data obtained from 584 students (266 men and 318 women), ranging in age from 18 to 24 years, was analyzed. Wheeze, chest tightness, an attack of shortness of breath, or an attack of cough within the last year was observed in 13.2% of 584 students. When 38.0 ppb was used as the cut-off value of FENO to make the diagnosis of asthma, the sensitivity was 86.8% and the specificity was 74.0%. FENO was ≥ 38.0 ppb in 32.7% of students. FENO was higher in men than in women. The prevalence of asthma symptoms estimated by considering FENO was 7.2%; the prevalence was greater in men (9.4%) than women (5.3%). A FENO ≥ 38.0 ppb was common in students who reported wheeze, but not in students, especially women, who reported cough attacks. Conclusions: The prevalence of asthma symptoms in university students age 18 to 24 years in Japan was estimated to be 7.2% on the basis of FENO levels as well as subjective symptoms. Gender differences were observed in both FENO levels and asthma symptoms reflecting the presence of eosinophilic airway inflammation.Trial registration numberUMIN000003244

Supported by science?: What Canadian naturopaths advertise to the public

Timothy Caulfield — 2011-09-15T00:00:00Z

Background: The increasing popularity of complementary and alternative medicines in Canada has led to regulatory reforms in Ontario and British Columbia. Yet the evidence for efficacy of these therapies is still a source of debate. Those who are supportive of naturopathic medicine often support the field by claiming that the naturopathic treatments are supported by science and scientific research. Methods: To compare provinces that are regulated and unregulated, we examined the websites of 53 naturopathic clinics in Alberta and British Columbia to gain a sense of the degree to which the services advertised by naturopaths are science based. Results: There were very few differences between the provinces in terms of the types of services offered and conditions treated. Many of the most common treatments--such as homeopathy, chelation and colon cleanses--are viewed by the scientific community to be of questionable value and have no scientific evidence of efficacy beyond placebo. Conclusions: A review of the therapies advertised on the websites of clinics offering naturopathic treatments does not support the proposition that naturopathic medicine is a science and evidence-based practice.