Airway Nitric Oxide in Children with HDM-Induced Allergic Rhinitis

Background Rhinitis is a common problem in children. Airway nitric oxide (NO) was proposed to represent eosinophilic inflammation. Objectives To evaluate airway NO level in children with house dust mite (HDM)-induced allergic rhinitis Methods Children aged 5 to 18 years old with moderate–severe persistent rhinitis and positive result for the HDM nasal provocation test (NPT) was enrolled. The nasal symptoms evaluated by total nasal symptom score (TNSS) and visual analog scale (VAS) were recorded. Skin prick test (SPT) to common aeroallergens, fractional exhaled nitric oxide (FeNO), nasal nitric oxide (nNO), and blood test for specific IgE (sIgE) to HDM was measured. Rhinitis severity was categorized as severe if the VAS score > 7. Results Forty-eight children with HDM-induced allergic rhinitis with the mean age of 9.3 ± 2.4 years were enrolled. nNO levels and VAS score were significantly correlated (R = 0.398, P = .005). Children with severe rhinitis had significantly higher nNO levels than moderate rhinitis (1652.05 vs 941.30 parts per billion [ppb], P = .002), while there was no difference in FeNO level. ROC curve analysis demonstrated the cut-off value of nNO at 1350 ppb (AUC 0.764, 95% CI: 0.616-0.911, P = .002) for detecting severe HDM-induced allergic rhinitis with the sensitivity of 78% and the specificity of 71%. The level of FeNO in children who had HDM mean wheal diameter (MWD) > 8 mm was significantly higher than those with HDM MWD of 3 to 8 mm and those with a negative test (39.7 vs 14.3 vs 14.4 ppb; P = .006, respectively). Children who had sIgE to HDM < 0.35 KUA/L had significantly lower FeNO than those with sIgE to HDM 0.35 to 50 KUA/L and >50 KUA/L (9.5 vs 19.7 vs 40.4 ppb; P = .029, respectively). Conclusions Cut-off value for the diagnosis of severe HDM-induced chronic rhinitis was proposed. Rhinitis children who had a higher degree of HDM sensitization had a higher level of FeNO.

The effectiveness of oral immunotherapy in patients with Sesame anaphylaxis using Omalizumab

Objective Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. Methods In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after approval by Oral Food Challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. Results All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. Conclusion This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab obviously reduced the severity of reactions.

Type I hypersensitivity promotes Aedes aegypti blood feeding

Mosquitoes play a major role in human disease by serving as vectors of pathogenic microorganisms. Mosquitoes inject saliva into host skin during the probing process. Mosquito saliva contains a number of proteins that facilitate blood feeding by preventing hemostasis. Mosquito saliva also contains potent allergens that induce type I hypersensitivity reactions in some individuals. Type I hypersensitivity reactions in skin involve IgE-mediated degranulation of mast cells, which leads to vasodilation and an itch sensation. We hypothesized that hypersensitivity to mosquito saliva influences blood feeding. To test this hypothesis, we recruited human subjects who consented to Aedes aegypti bites. We measured their first sensation of itch, the strength of their itch sensation, the number of times mosquitoes attempted to feed, the number of times mosquitoes probed their skin, feeding time, engorgement status, and wheal diameter. Here we show that hypersensitive subjects had a stronger itch sensation, and that the time to first itch sensation was inversely correlated with wheal diameter; however, mosquitoes tended to probe less and engorge more on these subjects. Follow-up experiments testing the impact of oral antihistamine treatment on mosquito feeding parameters failed to reveal a statistically significant result. Histamine also failed to promote blood feeding on an artificial membrane feeder. This study suggests that mosquito saliva-induced type I hypersensitivity promotes blood feeding but that this may be independent from histamine or histamine signaling.

Prevalence of Aspergillus fumigatus skin positivity in adults without an apparent/known atopic disease in Uganda

Background: Skin prick testing (SPT) is an important investigation in the evaluation of allergy to fungal pathogens. However, the background sensitivity to fungal allergens among healthy people in Uganda is unknown. Our aim was to assess the background prevalence of Aspergillus fumigatus SPT positivity in apparently healthy adults without known atopic disease in Uganda. Methods: For this pilot study, we recruited 50 healthy volunteers using convenience sampling, 56% of whom were health workers. We performed the SPT for A. fumigatus according to manufacturer’s instructions. A wheal diameter of ⩾3 mm was considered positive. Results: The prevalence of A. fumigatus skin positivity was 60% (30/50). Participants with a positive A. fumigatus SPT were significantly younger than those with a negative result [median age (years): 28 versus 35; p = 0.005]. Conclusion: There is a high skin positivity against A. fumigatus among non-atopic healthy Ugandan adults. There is an urgent need to establish a normal wheal cut-off value for this population. SPT alone may be an unreliable test for the diagnosis of A. fumigatus associated allergic syndromes. More studies are needed to define the prevalence of A. fumigatus skin positivity among non-atopic healthy population in Africa.

Design of an Optimally-Diagnostic Skin Test With Fewer Samples for Diagnosis of Sensitivity to Eight Allergens: a First-In-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects

Background: Skin prick test is usually the preferred test in the diagnostic workup for allergic diseases, while there are few types of standardized allergen extracts available. Besides, standardization and composition give no assurance that the allergen extracts are within the concentration range that give the best chance of a true diagnosis. We designed a first-in-human diagnostic skin test with fewer samples to identify the optimally diagnostic concentration for eight standardized extracts from frequent native allergens, and to assess the safety of the eight allergens extracts’ simultaneous administration for supporting clinical allergen screening.Methods: Patients aged 18-45 years who had a history of allergic diseases were enrolled in this two-part open-label, parallel study: Study 1, each patient was given three concentrations of one allergen extract in turn. Study 2, each patient was given two concentrations of eight allergens extracts. Negative and positive controls were given each time the allergen was given. Both safety and sensitivity were evaluated to determine the optimally diagnostic concentration. Related-Samples Friedman's Two-Way Analysis was used to evaluate the difference of wheal diameter between different concentrations of each allergen. SPSS Statistics 26 was used for statistical analysis, and the significance test level was 0.05.Results: The sensitivity of allergens increased with the increasing of concentration. The eight investigated allergens showed good safety and did not reach the dose limit toxicity whether used alone or in combination. The optimally diagnostic concentration for eight aeroallergens were respectively determined as 33333 DU/mL, 12000 DU/mL, 8667 DU/mL, 50000 DU/mL, 40000 DU/mL, 3333 DU/mL, 7000 DU/mL, and 5000 DU/mL.Conclusions: This study designed a solution to determine the optimally diagnostic concentration with fewer subjects for further clinical trials of the eight investigated allergens and the results of this phase I clinical trial support further clinical research of investigated allergens. Trial registration: The trial was registered on www.chictr.org.cn (ChiCTR1900023952, 06/19/2019, retrospectively registered).

Food-dependent, exercise-induced anaphylaxis in a patient allergic to peach

Determining the single factor that triggered anaphylactic shock can be challenging. We present an interesting case of a 25-year-old female patient with recurrent anaphylactic reactions developing after eating various foods, particularly in presence of co-factors of allergic reactions. Symptoms occurred after consumption of various kinds of foods – peach, pancakes with cottage cheese and fruit, a meal from a Chinese restaurant – all eaten on other occasions without symptoms. During diagnosis, skin prick tests were negative for all tested allergen extracts (both inhalatory and food) from Allergopharma. Prick by prick tests were positive for the peach – wheal diameter – 6 mm, nectarine – 4 mm (histamine 4 mm, negative control 0 mm). Increased levels of asIgE were found for allergens of peach (0.55 kU/L).Open challenge test with one mid-size peach combined with the physical exercise challenge test was positive. ImmunoCAP ISAC test indicated increased levels of IgE specific for the lipid transfer protein (LTP) for walnut (nJug r 3), peach (Pru p 3), wheat (rTri a 14) and plane tree (rPla a 3). The patient was diagnosed with food-dependent, exercise-induced anaphylaxis associated with an allergy to lipid transport proteins (LTPs).

Developing and testing of a screening tool to predict people without IgE-mediated allergy: a quantitative analysis of the predictive value of a screening tool

BackgroundConsultations in primary care for allergies are common. It can be difficult to differentiate between IgE-mediated (atopic) symptoms — which respond to allergen-specific interventions — and those that are non-atopic, without performing objective tests that are largely unavailable in UK general practice.Aim To develop and test a screening tool that can accurately discriminate between atopic and non-atopic individuals.Design and setting A validation study that took place in 2012 in adult volunteers aged >16 years in Scotland.MethodA questionnaire screening tool was developed using questions from a large cohort study and through consultation with experts. Participants answered the questions and had skin prick tests for four aeroallergens (house dust mite, cat, dog, and mixed grasses). Participants were classified as atopic if any average wheal diameter was ≥3 mm bigger than the negative control. Sensitivity, specificity, and positive and negative predictive values of individual and combinations of questions were calculated.ResultsIn all, 143 participants completed the questionnaire and underwent skin prick testing. Of these, 81 (56.6%) were atopic. Negative predictive values for the individual questions ranged from 48.2% (55 not atopic out of 114 negative answers) to 72.0% (18/25). An optimum combination of four questions was identified, in which a negative answer to all four questions was reported by 24 participants, 21 (87.5%) of whom were not atopic.ConclusionThe authors have identified a set of questions that correctly predict negative skin prick tests to common aeroallergens 88% of the time. These may be useful to exclude patients who do not warrant further investigation and who can reliably be advised that allergen avoidance is neither necessary nor helpful.

Local Anesthetics, Procaine, Lidocaine, and Mepivacaine Show Vasodilatation but No Type 1 Allergy: A Double-Blind, Placebo-Controlled Study

Background. Therapy with local anesthetics (LAs), also known as neural therapy, is used in integrative medicine because of its anti-inflammatory properties. Ester-linked LAs are often avoided because of their alleged high allergenicity. Little data supports this assumption and hence the importance of our investigation on type-1 allergies against ester- and amide-linked LAs. We performed a prospective, double-blinded, placebo-controlled observational study. Methods. 177 patients received 340 intracutaneous injections with 1% procaine, 0.5% lidocaine, 1% mepivacaine, or saline solution. Every patient received two different tests on each forearm. Reactions were monitored for 15 minutes. Results. No type-1 allergy was observed. The mean erythema diameter of the wheals after 10 minutes was procaine 8.0±6.4 mm, mepivacaine 7.6±6.3 mm, lidocaine 4.4±4.8 mm, and NaCl 3.7±3.2 mm. The wheal diameter of all substances showed a crescendo-decrescendo phenomenon. The procaine and mepivacaine wheals were significantly larger than those of lidocaine and NaCl. No general signs of hypersensitivity were observed. Diameter and intensity were independent of the injection site, order of injection, age, gender, and body mass index. Conclusion. This study shows no higher type-1 allergenicity of the ester-linked LA procaine, compared to the amide-linked LAs lidocaine and mepivacaine, and supports its use in therapy and short-track surgery.