Positive Nasal Provocation Test Research Articles

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment

Background: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. Objective: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. Patients and Methods: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. Results: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p p p Conclusions: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

Value of allergen nasal provocation test in assessment of the efficacy of house dust mites specific immunotherapy

Objective:To investigate the value of nasal provocation test（NPT） in evaluating the efficacy of allergen immunotherapy（AIT） in patients with dust mite induced allergic rhinitis（AR）. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score（SS）, daily medication score（DMS）, combined symptom and medication score（CSMS）, rhinoconjunctivitis quality of life questionnaire（RQLQ）, NPT and skin prick test（SPT） were assessed before and after 1 year AIT. Results:There were statistical differences in SS（P<0.000 1）, DMS（P<0.000 1）, CSMS（P<0.000 1）, and RQLQ（P<0.000 1） after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment（Kappa=0.437, P<0.001）; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence（Kappa=0.895, P<0.001）. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients（48.00%） showed effective in NPT. However, 10 out of 12 patients（83.33%） with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.

Skin prick test and serum specific IgE in predicting dust mite-induced allergic rhinitis diagnosed from nasal provocation test in chronic rhinitis children.

Allergen skin prick test (SPT) and serum specific immunoglobulin E (sIgE) are effective diagnostic tests in allergic rhinitis (AR), however, positive results may not always correlate with clinical allergies. A nasal provocation test (NPT) can identify the causative allergen for immunotherapy, but it's not routinely performed. To establish the cutoff value for the house dust mite (HDM) SPT mean wheal diameter (MWD) and HDM sIgE level for identifying children with HDM-induced AR diagnosed from NPT. Children aged 5 to 18 years old with chronic rhinitis were evaluated by HDM SPT, sIgE, and NPT. Children with positive NPT results indicated HDM-induced AR. The cutoff values of the HDM SPT and sIgE level for predicting positive NPT were determined using a receiver operating characteristic curve. A total of 245 children with a mean age of 9.53 ± 3 years were enrolled. HDM SPT results were positive (≥ 3 mm) in 160 (65.3%) children. HDM NPT results were positive in 176 (71.8%) children. Among children with positive HDM SPT (n = 160), 153 children (95.6%) were confirmed as having AR on NPT findings. The cutoff values for positive NPT responses were 6.6 mm for HDM SPT (yielding 100% specificity and 100% positive predictive value) and 17.0 kUA/L for sIgE (98.6% specificity and 99.2% positive predictive value). This study proposes HDM SPT and sIgE cutoff values for use in the diagnosis of HDM-induced AR based on NPT. These cutoff values can be used to identify HDM-induced AR children who might benefit from immunotherapy.

Diagnosis and Treatment of Local Allergic Rhinitis.

Some patients with chronic rhinitis have a positive nasal allergen provocation test (NAPT) without systemic IgE sensitization by skin prick tests or serum allergen-specific IgE (sIgE). This novel concept is called local allergic rhinitis (LAR) and affects children and adults worldwide, but is underdiagnosed. LAR is not just the initial state of allergic rhinitis (AR), it is a unique form of chronic rhinitis that is neither classical AR nor non-AR. Many of the features of AR and LAR are similar, such as a positive NAPT, positive type 2 inflammatory markers, including the nasal discharge of sIgE, and a high incidence of asthma. A differential diagnosis of LAR needs to be considered in patients with symptoms suggestive of AR in the absence of systemic atopy, regardless of age. The diagnostic method for LAR relies on positive responses to single or multiple allergens in NAPT, the sensitivity, specificity, and reproducibility of which are high. The basophil activation test and measurement of IgE in nasal secretions also contribute to the diagnosis of LAR. Treatment for LAR is similar to that for AR and is supported by the efficacy and safety of allergen exposure avoidance, drug therapy, and allergen immunotherapy. This review discusses current knowledge on LAR.

Clinical and anamnestic characteristics and results of allergological testing in children with bronchial asthma and allergic rhinitis in case of allergy to house dust mites

House dust mites (HDM) are a common cause of allergies, however, it is not always easy to suspect a mite allergy from a patient's history. &#x0D; Objective: to determine clinical characteristics of patients, tactics for demonstrating the role of HDM sensitization in pediatric patients with allergic rhinitis (AR) and bronchial asthma (BA) with domestic sensitization. &#x0D; Materials and methods. The study included 420 patients, 256 boys, 164 girls, aged 5 to 17,9 years (mean 8,44 ± 3,06 years), with AR (100%) and AR in combination with BA (41,9%). The prick test on the forearm skin with water-soluble extracts was carried out and evaluated according to the standard method. The test was considered positive with a maximum wheal diameter of ≥3 mm 15 minutes after applying the prick. &#x0D; Results. Among patients with HDM sensitization (n=268), sensitization to both mites was detected in 218 cases (81,3%), and in 139 cases (51,9%) polysensitization to HDM allergens, house dust and epidermal allergens (cat, dog) was found. Patients noted persistent symptoms of nasal congestion, and rhinorrhea; the provoking factor was not determined by history in 46% of cases. In 69,8% of cases (97 children), it was impossible to isolate the leading allergen according to the history, since patients had contact with cats, dogs, dust, and polysensitization according to the prick tests. Nasal provocation test (NPT) with HDM allergens was performed in 92 children. Positive NPT was obtained in 83 cases (90,2%), negative in 9 cases (9,8%). &#x0D; Conclusions. With HDM sensitization, often (46%) the provoking factor is not determined by history. Monotonous symptoms are characteristic with the absence of obvious relationships with allergens, the location and activities of the child. In terms of frequency, the leading variant is sensitization to both mites D.pteronyssinus, D.farinae (81,3%), and polysensitization to HDM, house dust and cat and dog allergens (51,9%). NPT allows in 90% of cases to show the causal role of HDM allergens in polysensitized patients with insufficiently convincing anamnesis data.

Allergen immunotherapy against house dust mites in patients with local allergic rhinitis and asthma

Local allergic rhinitis (LAR) is a clinical rhinitis phenotype characterized by the presence of nasal symptoms of AR in nonatopic patients with a negative skin prick test and undetectable specific IgE (sIgE) in serum against inhalant allergens but with a positive nasal allergen provocation test. This study evaluated the effectiveness of a 12-month course of sublingual immunotherapy (SLIT) for house dust mite (HDM) allergies in adult patients with confirmed LAR and concomitant asthma. Methods The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12-month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed. Results: In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group. Conclusion: SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs.

How reliable is anamnestic data in predicting the clinical relevance of house dust mite sensitization?

PurposeFor perennial inhalant allergens such as house dust mite (HDM), the German guideline on allergen-specific immunotherapy explicitly recommends provocation testing. This procedure is time-consuming, expensive, and potentially dangerous for the patient. Recently it has been discussed whether provocation tests are really necessary for diagnosing allergy to Dermatophagoides species. Thus, our study aimed to analyze the concordance between nasal provocation tests with Dermatophagoides species and anamnestic data.MethodsWe retrospectively analyzed the concordance between patients’ histories including self-reported symptom scores and the results of provocation testing in 471 individuals with proven sensitization to Dermatophagoides species.Results248 patients had a positive nasal provocation test (NPT) result to Dermatophagoides species and 223 individuals a negative NPT result. Patients allergic to HSM suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046) and more from asthma (20% vs. 19%, p = 0.851). Moreover, individuals with clinically silent sensitization complained less about nasal secretion (37% vs. 45%, p = 0.244) but significantly more about nasal dryness (46% vs. 34%, p = 0.046) whereas rates of nasal airway obstruction, ocular complaints and sleep quality were comparable in both groups. Allergic patients reported more often perennial (34% vs. 30%, p = 0.374) and location-dependent (39% vs. 31%, p = 0.090) symptoms. However, the discrepant prevalence of atopic dermatitis was the only statistically significant difference between both groups.ConclusionDespite slight differences between both patient groups, clinical data are not sufficient to distinguish between silent sensitization and clinically relevant allergic rhinitis to HDM. Therefore, nasal provocation testing remains the gold standard for assessing clinical relevance in patients sensitized to Dermatophagoides species.

Local allergic rhinitis - a big challenge in clinical practice

Local allergic rhinitis is a new rhinitis phenotype characterized by symptoms similar to allergic rhinitis, in non-atopic patients with a positive nasal allergen provocation test (NAPT). The disease is diagnosed in over 25% of non-atopic patients with rhinitis, marked as non-atopic rhinitis. It most often has perennial and severe symptoms and a progressive course. It is often associated with conjunctivitis and/or asthma. It is necessary to consider local allergic rhinitis in patients with non-atopic rhinitis. The gold standard for diagnosis is a positive NAPT. Pharmacological therapy fails to stop the natural progression and development of comorbidities. Allergen immunotherapy reduces the symptoms, consumption of medicines and increases the tolerance to allergens responsible for local allergic rhinitis. New studies are needed to confirm the curative effects and evaluate the preventive effects of allergen immunotherapy.

Nasal reactivity evaluation in children with allergic rhinitis receiving grass pollen sublingual immunotherapy.

Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home administration, which improves patient comfort and compliance. Objective: The primary outcome of this study was to assess the change in nasal reactivity after grass-pollen AIT treatment. Methods: This was a monocentric, prospective, observational study conducted in Rome from September 2016 to June 2018, in the Pediatric Department of Policlinico Umberto I. We enrolled children, ages between 6 and 12 years, with persistent allergic rhinitis (AR), sensitized to grass pollen. At the first visit (V0, September 2016), one group received the first dose of oral immunotherapy for grass-pollen spray buccal and the other group continued only standard therapy. All the patients had nasal specific immunoglobulin I (IgE) assay (Phl p1, Phl p5), active anterior rhinomanometry with a nasal provocation test (NPT), and spirometry. The patients attended two follow-up visits, in May 2017 (V1) and May 2018 (V2), with the same examinations as at V0. Results: During the treatment, we observed, in the treated group, a significant increase in the mean nasal flow compared with untreated children (p < 0.001). In the AIT group, we found an improvement of nasal function and only 21.05% of all the children in the active group with a positive NPT result at V2. In the control group, we found, at V2, a worsening of nasal function, with 89.47% of the children with a positive NPT result. Furthermore, we found a significant reduction of nasal specific IgE levels at the end of the observation period in the treated group. Conclusion: Analysis of our data provided evidence for a clinical effect of SLIT in inducing clinical changes and allergen tolerance in children with AR.

Nasal Provocation Test with Cat and Dog Extracts: Results according to Molecular Components.

Background IgE sensitization (atopy) to pets is commonly evaluated using pet dander extracts. However, the diagnosis by components seems to be more adequate to evaluate the clinical relevance (allergy) of sIgE sensitization. Objective To study the association between IgE sensitization to pet allergen components and clinical symptoms. Methodology. Dander extracts and sIgE levels to pet components (Can f 1, Can f 2, Can f 3, Can f 5, Fel d 1, Fel 2, and Fel 4) were measured in a rhinitis group (n = 101) and a control group (n = 101) and a control group (Results Dog (34.6% vs. 23.5%) and cat dander (26.7% vs. 8.8%, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1, p = 0.05) IgE sensitization was frequent among rhinitis and no-rhinitis subjects, and it was similar to dog (29.7% vs. 20.5%) and cat (18.8% vs. 8.8%) components. Polysensitization for dog (3.1, 95% CI: 1.5 to 6.1, Conclusions Sensitization to pet dander extract identifies atopic patients, but its utility to predict clinical relevance is poor. Allergenic components could help to define the clinical relevance of sensitization to furry animals and could reduce the need for provocation test.

Molecular Allergy Diagnostics Refine Characterization of Children Sensitized to Dog Dander

To analyze patterns of immunoglobulin E (IgE) reactivity to dog allergen components in sensitized children and investigate the association between those patterns and clinical symptoms by nasal provocation tests (NPT).Children 10 to 18 years (n = 60) with known sensitization to dog identified by a skin prick test wheal >3 mm or serum-specific IgE >10 kU/L were included.NPTs were performed with a commercial dog extract by using a standardized protocol. The extract was analyzed by radioallergosorbent test inhibition and contained all 6 dog allergens (Can f 1, 2, 3, 4, 5, and 6) used in subsequent analyses. The allergens were present in a wide range of concentrations. Serum-specific IgE levels to dog extract and each of the allergenic components were measured.All but 2 children had allergic rhinitis or conjunctivitis, and 41 out of 60 (68%) reported symptoms with dog exposure. The mean serum-specific IgE level was 11.5 kU/L (interquartile range: 3.15–43.0 kU/L). Sensitization to Can f 1 was most common, followed in frequency by Can f 5, 4, 6, 2, and 3. There was a wide range of IgE levels to the components, with the highest levels to Can f 1, 2, and 5. History of dog-related rhinitis was most common among those sensitized to Can f 3 (94% vs 59% of those not sensitized, P = .012) and Can f 6 (86% vs 63%, P = .007). Similar associations were found for histories of dog-induced asthma. Most patients were sensitized to several components, with great overlap in their sensitization to the proteins belonging to different groups (lipocalins: Can f 1, 2, 4, and 6; serum albumin: Can f 3; and prostatic kallikrein: Can f 5). No single protein group was associated with history of dog-induced airway symptoms, but sensitization to more proteins increased the odds ratio (OR) of dog-induced asthma or rhinitis. Those sensitized to all proteins from all 3 groups were at higher risk of dog-induced rhinitis (OR: 8.36; 95% confidence interval: 1.0–69.5). Forty-two percent (25 out of 60) of patients had positive NPT results, 14 out of 60 (23%) had inconclusive NPTs, and 21 out of 60 (35%) had negative challenges. Those with positive NPT results were significantly more likely to report dog-induced rhinitis and asthma as compared with those with negative NPT results. After adjusting for the effects of different protein groups, only sensitization to the lipocalins (Can f 1, 2, 4, and 6) was associated with positive NPT results. Those sensitized to all 3 groups had the highest OR for a positive NPT result, but as with reported symptoms above, sensitization to increasing numbers of proteins was associated with increasing risk for a positive NPT result.Sensitization to lipocalins and to an increasing number of allergenic dog proteins is associated with dog-induced airway symptoms (dog allergy).“I am not allergic to my dog, but other dogs bother me.” My dog is “hypoallergenic.” How many times have we heard comments like these from patients? Every study that has tried to identify allergenic differences between breeds of dogs has failed to find that elusive hypoallergenic dog. In fact, there is great homology of Can f 1 (the major dog allergen) among breeds. Furthermore, all breeds have comparable amounts of airborne Can f 1 in the homes of dog owners. So, what is going on here? The answer might lie in component-resolved diagnostics (CRD). Commercially available CRDs have already helped our understanding of some food allergies by enhancing our ability to make accurate diagnoses of allergy in sensitized patients. Options for follow-up studies to this one are obvious. Do different breeds of dog produce varying amounts of individual or total lipocalins? Are some patients more highly sensitized to particular proteins or more types of proteins, placing them at differential risk of allergy to certain breeds? Or, are some less highly sensitized, making them more tolerant of different breeds? When those questions are answered and when CRDs for dog allergens are commercially available, we still might not identify a consistently less-allergenic dog. But, we might be able to identify the breeds most likely to be tolerated by a child sensitized to dog.

Efficacy of House Dust Mite Sublingual Tablet in the Treatment of Allergic Rhinoconjunctivitis: A Randomized Trial in a Pediatric Population

To investigate the efficacy, safety, and immunologic response of standardized sublingual house dust mite (HDM) tablets in Japanese pediatric patients.Included in the study were patients ≥5 and ≤16 years of age with allergic rhinitis symptoms for ≥2 years, a score of ≥3 on quantitative analysis of specific immunoglobulin E antibody to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae antigens, positive nasal provocation test result for HDM, and Rhinitis Total Symptom Score ≥6 points per day for 7 days before randomization. Those with symptoms from other allergens, mild persistent or more-severe asthma, or inhaled corticosteroid use were excluded.This multicenter, double-blind, randomized placebo-controlled trial was conducted at 51 Japanese medical institutions from October 2015 to December 2016. Subjects were randomly assigned 1:1 to placebo or HDM tablets with an index of reactivity of 300 daily for 52 weeks. Symptoms and rescue medication use were recorded daily in a patient diary. The primary end point was the average adjusted symptom score for week 48 to 52, derived from daily Rhinitis Total Symptom Scores and adjusted for rescue medication use.Of 438 patients who were randomly assigned, 193 patients in the treatment group and 210 patients in the placebo group completed the study. The average adjusted symptom score was significantly lower in the treatment group compared with placebo (6.32 vs 7.27, P = .0005), with a least-squares mean difference of −13.1%. Improvement was seen at weeks 8 to 10 and was maintained throughout. Nasal Individual Symptom Scores were significantly lower in the treatment group, whereas Average Rescue Medication Scores and Ocular Individual Symptom Scores were not. Specific immunoglobulin E antibodies to HDM nearly doubled, whereas specific immunoglobulin G4 antibodies approximately tripled in the treatment group. Mild or moderate adverse events (oral pruritus, mouth edema, throat irritation, ear pruritus, and mouth swelling) occurred in most patients (96.8% of treated patients, 94.5% of placebo patients), typically from days 1 to 14. Two serious adverse events were reported in the placebo group and 6 were reported in the treatment group, leading to drug discontinuation in 1 patient with pseudocroup. Overall, 8% of randomly assigned patients discontinued the study, mostly because of adverse effects. There were no deaths or anaphylactic events requiring intramuscular epinephrine.This study demonstrates efficacy and safety of HDM sublingual tablets in pediatric patients with perennial allergic rhinitis due to HDM allergy. Treatment conferred significant and sustained improvement in symptom scores, with a similar immunologic response and safety profile, as previously shown in older age groups.This study is limited by a lack of objective outcomes, such as peak nasal inspiratory flow or nasal provocation tests. The investigators also excluded patients with persistent asthma and symptomatic rhinitis due to other allergens, which commonly occur in patients with HDM-triggered rhinitis. Although modest improvement in symptoms was shown, daily therapy over a 52-week treatment course may be impractical for pediatric patients. One likely goal of HDM immunotherapy may be to decrease use of other medications, but this was not seen in the current study. Further studies are needed in this population to assess optimal treatment duration and whether treatment confers sustained benefit after drug discontinuation.

The prevalence and characteristics of local allergic rhinitis in Poland.

Local allergic rhinitis (LAR) is found in some patients with typical symptoms but who have negative skin prick tests and negative IgE to aeroallergens while presenting with positive nasal provocation tests for proper allergens. Little information about the clinical characteristics and prevalence of LAR has been published. The aim of this study was to determine the prevalence and characteristics of LAR in patients with symptoms of chronic rhinitis. In total, 680 patients out of 3400 pre-screened subjects with chronic rhinitis who were at least 5 years old were included from 17 sites in Poland in the study protocol. The following medical history and diagnostic procedures were performed with aeroallergens: skin prick tests, allergen specific serum IgE and nasal provocation tests. In addition to LAR, allergic rhinitis (AR) and non-allergic (NAR) rhinitis were explored and compared. In total, 621 patients were examined. LAR was diagnosed in 109 (17.6%) patients; AR was diagnosed in 251 (40.4%) patients; and NAR was diagnosed in 261 (42%) patients. In the LAR group, younger, non-smoker patients with allergies to D. pteronyssinus or grass pollen were predominant. Polysensitization was more prevalent in AR patients than in LAR patients. Bronchial asthma was at a similar level in patients diagnosed with AR (38%) and LAR (35%) but was significantly less prevalent in patients diagnosed with NAR (16%). The mean age of disease onset was similar between patients with AR and LAR (17.6 plus or minus 4.8 yrs), and it was significantly lower than that in patients with NAR (24.5 plus or minus 6.9 yrs, p less than 0.05). LAR is a significantly understudied problem in patients of various ages with chronic nasal symptoms. Patients with LAR and AR have similar clinical phenotypes.

NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.

Molecular allergy diagnostics refine characterization of children sensitized to dog dander

Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). Sixty children (age, 10-18years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kUA/L or greater was considered positive. There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P=.01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), inparticular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.

Positive allergen reaction in allergic and nonallergic rhinitis: a systematic review

The diagnosis of allergic rhinitis (AR) is based on cutaneous and serological assessment to determine immunoglobulin E (IgE)-mediated disease. However, discrepancies between these tests and nasal provocation exist. Patients diagnosed as non-allergic rhinitis (NAR) but with positive nasal allergen provocation test (NAPT) may represent a local allergic condition or entopy, still suitable to allergy interventions. The objective of this study was to determine the frequency of nasal reactivity toward allergens among AR and NAR patients, and to describe the diagnostic characteristics of NAPT methodologies. EMBASE (1947-) and Medline (1946-) were searched until December 8, 2015. A search strategy was used to identify studies on AR or NAR patients subjected to diagnostic local nasal provocation. All studies providing original NAPT data among the AR or NAR population were included. Meta-analysis of proportion data was presented as a weighted probability % (95% confidence interval [CI]). The search yielded 4504 studies and 46 were included. The probability of nasal allergen reactivity for the AR population was 86.3% (95% CI, 84.4 to 88.1) and in NAR was 24.7% (95% CI, 22.3 to 27.2). Reactivity was high with pollen for both AR 97.1% (95% CI, 94.2 to 99.2) and NAR 47.5% (95% CI, 34.8 to 60.4), and lowest with dust for both AR 79.1% (95% CI, 76.4 to 81.6) and NAR 12.2% (95% CI, 9.9 to 14.7). NAPT yielded high positivity when defined by subjective end-points: AR 91.0% (95% CI, 86.6 to 94.8) and NAR 30.2% (95% CI, 22.9 to 37.9); and lower with objective end-points: AR 80.8% (95% CI, 76.8 to 84.5) and NAR 14.1% (95% CI, 11.2 to 17.2). Local allergen reactivity is demonstrated in 26.5% of patients previously considered non-allergic. Similarly, AR, when defined by skin-prick test (SPT) or serum specific IgE (sIgE), may lead to 13.7% of patients with inaccurate allergen sensitization or non-allergic etiologies.

Specific nasal provocation test with Dermatophagoides pteronyssinus, monitored by acoustic rhinometry, in children with rhinitis.

Currently, the diagnosis of allergic rhinitis (AR) is arrived at predominantly by a clinical history and by systemic sensitization tests, but specific nasal provocation tests (NPT) may establish a better direct correlation between etiologic surveyed allergens and nasal symptoms. To standardize the specific NPT with one of the most important house-dust mites, Dermatophagoides pteronyssinus, monitored by acoustic rhinometry, in children and adolescents, and propose a simplified specific NPT to improve its clinical applicability as a diagnostic tool. Sixteen controls (group 1) and 17 patients with an AR diagnosis sensitized to D. pteronyssinus (group 2) underwent a specific NPT with D. pteronyssinus. The acoustic rhinometry was performed after instillation of 0.15 mL of increasing concentrations of D. pteronyssinus (5000 BU/mL). The test was finalized after (1) instillation of the final concentration of D. pteronyssinus, or (2) after a 20% or more reduction in the volume of the first 5 cm of the nasal cavity (V5), or (3) a score of >3 in the symptoms questionnaire (a score from 0 to 7). A simplified specific NPT with two concentrations was proposed and implemented in a group of 10 patients with AR (group 3). At the end of the specific NPT, the median (range) variation in V5 was -5.7% (-9 to 4%) in the control group and -22.8% (-24 to -20%) in group 2. None of the patients in the control group and 88% of group 2 (15/17) showed positive specific NPT results. The simplified specific NPT triggered a positive response in 80% of patients in group 3, with median (range) V5 variation of -30.4% (-36 to -20%). This protocol has been proven safe and useful to differentiate between children and adolescents with AR and controls. Concentrations of 1:1000 and 1:100 D. pteronyssinus were the best for use in simplified specific NPT, which made it simpler and faster, and expanded its clinical applicability.

The response to nasal allergen provocation with grass pollen is reduced inpatients with chronic rhinosinusitis with nasal polyposis and grass sensitization.

The majority of grass pollen-sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens. We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen-sensitized CRSwNP patients. Twelve grass pollen-sensitized CRSwNP patients underwent NAPT with grass pollen and were compared with 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen-specific IgE and tryptase were measured in serum and nasal secretions. NAPT was positive in 6 of 12 of the grass pollen-sensitized CRSwNP patients, and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test. These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared with grass pollen allergic rhinitis patients.

Timothy grass pollen therapeutic vaccine: optimal dose for subcutaneous immunotherapy.

To establish the optimal dose of Phleum pratense subcutaneous immunotherapy (SCIT) in patients with allergic rhinoconjunctivitis with/without asthma. One hundred and fifty-one patients were randomized to receive SCIT 0.25, 0.5, 1.0, 2.0 or 4.0 skin-prick test units (SPT) or placebo. The primary end point was the variation in the concentration of Phleum pratense extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). After 17 weeks, a dose-dependent trend was apparent in the concentration of P. pratense extract needed to produce a positive nasal provocation response. Systemic adverse reactions occurred with 3.2% of administered doses. Grade III (n = 2) and IV (n = 2) events were observed only at the two highest doses. P. pratense depot SCIT showed signs of clinical and immunological efficacy by dose-dependently decreasing the allergen sensitization rate. Risk-benefit favored doses below 1.0 SPT units for confirmatory trials.