Search

Background: Shellfish allergy is a major cause of food allergy and anaphylaxis worldwide. Several allergenic proteins have been described in the last few years, but the only diagnostic tool that still enables discrimination between allergic and nonallergic sensitized persons is the oral food challenge (OFC). Objective: The aim of this study was to evaluate the usefulness of the nasal allergen provocation test (NAPT) as a diagnostic tool in shellfish allergy. Methods: Forty-five patients with confirmed sensitization to shrimp by a positive skin prick test (SPT) result with a commercial shrimp extract were recruited and classified as sensitized-allergic or sensitized-nonallergic based on current tolerance to shrimp intake, the result of an OFC with a freeze-dried cooked shrimp mixture extract, or a recent history of anaphylaxis induced by shrimp ingestion. These patients and 10 controls not sensitized to shrimp underwent NAPT with a freeze-dried cooked shrimp mixture extract. The response was evaluated using acoustic rhinometry and a visual analog scale. Results: Significant differences (P=.001) were found between the sensitized-allergic group (18/20 positive NAPT, 90%) and both the sensitized-nonallergic group (2/18 positive NAPT, 11.1%) and controls (0/10 positive NAPT). NAPT enables differentiation between allergic and nonallergic persons with a sensitivity of 90%, specificity of 89%, positive predictive value of 90%, and negative predictive value of 89%. Conclusions: Our results indicate that NAPT makes it possible to differentiate between sensitized symptomatic patients and sensitized tolerant patients and could be a valuable diagnostic tool when assessing shrimp allergy.

Local allergic rhinitis (LAR) is, to date, a debated and complex entity, still orphan of global consideration and a multicentric approach. LAR does not seem to find a proper positioning in the classic classifications and phenotypes of chronic rhinitis, and its pathophysiology relies specifically on the presence of local IgE. These patients in fact have a suggestive clinical history of allergic rhinitis in the presence of negative skin prick tests and serum IgE tests for the suspect allergen. Nasal allergen challenge, assessment of local IgE, basophil activation test (BAT), and nasal cytology are, at the moment, the most used tests in the diagnostic approach to the disease, despite their limitations. Considering that the correct interpretation of diagnostic tests and their clinical relevance is fundamental in the assessment of the right diagnosis and the subsequent therapy, we propose a new diagnostic approach that encompasses all of these methodologies and suggest that several pragmatic randomized control trials as well as prospective, multicentric studies directed at the long-term follow-up of LAR be carried out to further investigate this debated entity.

Background: Local allergic rhinitis (LAR) is a well-defined and reported phenotype in adults, but data is scarce for children and adolescents, and it is probably an undiagnosed and highly underestimated condition in childhood. Objectives: The objectives of this systematic review were to identify original observational studies published on LAR in children and adolescents and to describe the prevalence and characteristics of this phenotype in the pediatric age group. Methods: A systematic search was performed in PubMed and EMBASE databases. The search was limited to publications on humans, written in English, published between January 1, 2000 and September 20, 2021. Participants had to be under 18 years old and with a diagnosis of LAR confirmed by nasal allergen provocation test (NAPT). Results: Ten articles were identified. Despite the wide variability of protocols, prevalence rates ranged from 3.7 to 83.3% among children previously diagnosed as having nonallergic rhinitis, being markedly lower in Eastern countries (3.7–16.6%) when compared to Western countries (22.3–83.3%). To date, no relevant clinical characteristics capable of differentiating LAR patients from other childhood rhinitis phenotypes have been identified. Conclusions: LAR is an allergic rhinitis phenotype also found in children. Population and regional differences and differences in NAPT protocols may explain the heterogeneity in LAR prevalence rates observed in different parts of the world. In addition to clarifying this large discrepancy, longitudinal studies are also needed to assess the clinical characteristics of the LAR phenotype in the pediatric age group, and its stability into adulthood must be confirmed.

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.

Aspirin-exacerbated respiratory disease (AERD) consists of asthma, chronic rhinosinusitis with polyps, and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Nasal Lysine Aspirin Challenge is an effective tool for the diagnosis of hypersensitivity to aspirin and/or NSAIDs in patients with AERD. However, there is no unified international consensus version to perform nasal provocation tests (NPTs).To investigate the effect of a leukotriene receptor antagonist (LTRA), montelukast, on the lysine-acetylsalicylate (L-ASA) nasal challenge.We included 86 patients divided into 3 samples: group A (AERD without LTRA), group B (AERD with LTRA), and the control group (NSAID-tolerant asthmatics). NPT with L-ASA was performed with 25 mg of L-ASA every 30 minutes 4 times followed by rhinomanometry and spirometric measurements and evaluation of symptoms using a novel clinical scale.In group A, 94.5% of patients (35 of 37) developed a positive response to NPT (drop40% in total nasal flow), whereas only 46% of group B subjects (13 of 28) showed a positive response to the nasal challenge (P.001). Control subjects did not show any response to the L-ASA challenge. A novel clinical score demonstrated accuracy in classifying the hypersensitivity to aspirin and/or NSAIDs when patients avoid LTRA (33 of 37).Patients with AERD without LTRA showed a greater positive response to the L-ASA challenge than those taking this drug; therefore, LTRA treatment should be discontinued before the challenge for optimal diagnostic accuracy.

We investigated immunological changes in peripheral blood samples obtained from individuals with allergic rhinitis (AR), triggered by exposure to cat allergen, who were receiving peptide immunotherapy. Ten cat-sensitized AR individuals received cat peptide antigen desensitization (Cat-PAD, Circassia Pharmaceuticals PLC, Oxford, UK)1 , an experimental peptide immunotherapy for AR; participants were treated with four intradermal injections (at 4-week intervals) of 6 nmol Cat-PAD.

The involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients.Nine LAR, 5 allergic rhinitis (AR), and 5 non-atopic healthy control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera.NAC-DP induced an increase in IgEThese results suggest that allergen exposure induces the sequential εCSR of IgG

Background Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization. Objective To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard. Methods Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens. Results One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p Conclusions SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.

Allergen identification is the first step for allergen-specific immunotherapy (AIT) of allergic rhinitis (AR). Currently, the diagnosis of AR is based mainly on the positive results of the skin prick test (SPT) and/or serum specific immunoglobulin E (sIgE) measurement. However, the results of these two tests may not always directly correlate with AR.To investigate the importance of nasal provocation testing (NPT) in the diagnosis ofRhinitis patients willing to undergo AIT (n = 171) were enrolled. The correlations of Der p SPT, sIgE, NPT, and clinical symptom severity were assessed.NPT-positive responses were more common in patients with higher SPT and sIgE levels. The optimal cut-off value for a NPT-positive response for SPT was 5.5 mm and for sIgE was 2.77 kUA/L, based on the respective receiver operating characteristic (ROC) curves. The area under the curve (AUC) of the ROCs was 0.814 (SPT only) and 0.794 (sIgE only) and increased to 0.828 with the combination of SPT and sIgE. The Der p-NPT concentration was inversely correlated with SPT and sIgE levels (For patients who are willing to receive Der p AIT, NPT is a useful and safe test to confirm diagnosis prior to treatment initiation, especially in patients with lower levels of Der p SPT ( 5.5 mm) or sIgE ( 2.77 kUA/L).

Brain activation after nasal histamine provocation in house dust mite allergic rhinitis patientsCallebaut I1, Steelant B1, Backaert W1, Peeters R2-3, Sunaert S2-3, Van Oudenhove L4-5*, Hellings PW1*1Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium2Department of Imaging & Pathology, KU Leuven, Leuven, Belgium3Department of Radiology, University Hospitals Leuven, Leuven, Belgium4Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (CHROMETA), University of Leuven, Belgium5Cognitive and Affective Neuroscience Laboratory (CANlab), Center for Cognitive Neuroscience, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA*Joined senior authorshipTo the editor . The nasal mucosa is armed with a complex nervous system of sensory, sympathetic and parasympathetic nerves, allowing swift defensive responses to physical and chemical stimuli. In allergic rhinitis (AR) patients, nasal allergen deposition leads to mast cell activation with release of allergic mediators such as histamine. Apart from its direct effects on the surrounding tissue, histamine also activates sensory nerve endings giving rise to symptoms like sneezing, rhinorrhoea, and/or congestion(1). Activated nasal sensory nerves transmit action potentials to their cell bodies in the trigeminal ganglion and further to the midbrain where secondary synapses lead to the generation of central reflex signals. Despite activation of neural pathways in AR(2), it is not known which particular regions in the brain are activated by different nasal stimuli. Clinical studies using Positron Emission Tomography scans indicate that there is no isolated itch center in the brain but that different cortical centers are involved in the processing of itch(3, 4). Activation of the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and the inferior paretial lobe partly explains the connection between itching and the related reflex of scratching(4). Using functional magnetic resonance imaging (fMRI), the activation of the superior temporal gyrus, insula and nucleus caudate following painful intranasal trigeminal stimulation has been shown(5). When asthmatic patients are challenged with metacholine or allergens, activity in ACC and insula was associated with markers of bronchial inflammation and obstruction(6).To fill the abovementioned knowledge gap, a prospective, single-blind, cross-over study was designed to investigate brain responses to nasal histamine provocation in healthy volunteers and AR patients.Eight house dust mite (HDM) AR patients and 7 non-allergic healthy controls (HC) were recruited at the outpatient clinic for Otorhinolaryngology of University Hospitals Leuven. HDM allergy was confirmed by a skin prick test. Relevant nasal anatomic abnormalities or rhinosinusitis were ruled out by nasal endoscopy. Non-allergic HC showed a negative skin prick test for all the tested allergens, showed no nasal symptoms and had normal nasal endoscopy. Patients of 50 years of age, having used nasal or oral steroid treatment

Objectives: Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo. Methods: In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity. Results: Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8. Conclusions: Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.

BackgroundThe last 5 years have seen a surge of both clinical and scientific interest in empty nose syndrome (ENS). Although ENS is still considered a controversial diagnosis plagued by a lack of standardized diagnostic criteria, ENS is increasingly becoming recognized as a legitimate, physiologic disease entity. As such, it is important for clinicians to understand the most up-to-date diagnostic tools to assess ENS, confirm the diagnosis, and create a more standardized means to counsel these complex patients.ObjectiveContemporary literature review to discuss diagnostic modalities in the evaluation of ENS, in order to introduce evidence-based diagnostic criteria.MethodsA systematic review was conducted in PubMed and Embase (2013–2019) using the search term “empty nose syndrome” to identify peer-reviewed articles on the topic of ENS. Articles advancing contemporary methods of ENS diagnosis and testing were included. A quality assessment was conducted using The Rational Clinical Examination Levels of Evidence.ResultsThe novel development of the Empty Nose Syndrome 6 Questionnaire (ENS6Q) offers the clinician a validated patient-reported outcome measure to supplement history and physical examination. The in-office cotton test, performed by placing an endoscopically directed cotton plug in the site of tissue loss, may help to identify patients who may benefit from turbinate augmentation. Tools such as the sinus computed tomography scan, computational fluid dynamics, and intranasal trigeminal nerve function testing currently have insufficient evidence to support routine use in the workup of ENS. Up to 66% of ENS patients present with comorbid anxiety or depression.ConclusionThe ENS6Q and cotton test assist in creating a standardized approach to the evaluation of patients suspected of ENS. These instruments should be used as an adjunct, rather than the sole criteria, on which to ascertain the presumptive diagnosis. Patients suspected of ENS should be screened for comorbid psychological dysfunction.

OBJECTIVES To evaluate the correlation between the increased number of sensitized allergens and nasal symptoms in patients with allergic rhinitis who were sensitized to house dust mites (HDMs). METHODS Among the patients who were enrolled in the Allergic Rhinitis Cohort Study for Kids, 174 children with rhinitis symptoms who were sensitized to HDMs were included in the analysis. Skin prick tests, serum total immunoglobulin E, eosinophil count, and bronchial provocation tests were carried out during the initial and 3-year follow-up visits. The patients were divided into two groups depending on the change in the number of sensitized allergens: increased number of sensitized allergens (group I) and maintained or reduced number of sensitized allergens (group II). RESULTS In the analysis of allergen sensitization from baseline to the 3-year follow-up, no significant correlation was observed between the changes in the number of allergens and the total nasal visual analog scale score (R2

Background Local allergic rhinitis (LAR) is characterized by chronic rhinitis with localized nasal allergic response to allergens in the absence of systemic immunoglobulin (IgE)-mediated disease assessed by skin prick test (SPT) or specific serum IgE level. Nasal provocation test (NPT) is the gold standard for the diagnosis of LAR. Nasal eosinophilia is a known inflammatory marker in allergic rhinitis. We hypothesized that nasal eosinophilia can be used as a screening tool for LAR. Objective To determine the applicability of nasal eosinophilia as a diagnostic tool for LAR. Methods Forty-eight perennial nonallergic rhinitis (NAR) patients with SPT negative were recruited. Nasal cytology analysis was performed. NPTs with 3 allergens (mixed mites, mixed cockroaches, and Bermuda grass) were performed to diagnose LAR. Nasal symptoms combined with nasal patency were used to determine the results of NPT. The sensitivity, specificity, positive predictive value, and negative predictive value of nasal eosinophilia as a diagnostic tool of LAR were calculated. Results LAR was diagnosed in 41.6% of the NAR patients. Nasal eosinophilia was found in 58% of the NAR patients. The sensitivity of nasal eosinophilia for diagnosing LAR was 80%, the specificity was 57.14%, the positive predictive value was 57.14%, and the negative predictive value was 80%. The most common allergen of LAR was mixed mites. Conclusion Nasal eosinophilia on nasal cytology was a good screening tool for diagnosing LAR because of its high sensitivity and simplicity of the procedure. Unfortunately, the low specificity of nasal eosinophilia makes the NPT necessary for confirmation of LAR.

Introduction: Although the skin prick test (SPT) is a reliable diagnostic tool in perennial allergic rhinitis (PER) for patients allergic to cats, the minimum necessary SPT wheal size required to distinguish cat sensitization from true allergy remains controversial. The cat nasal challenge test (cNCT) could be considered the gold standard for detecting true cat allergy. Aims: To assess the difference in the frequency of cNCT positivity between cat owners and non-owners and to determine an appropriate cut-off level for SPT wheal size in detecting positive cNCT in PER patients who are candidates for allergen immunotherapy (AIT) with cat allergen extracts. Subjects and Methods: cNCT in the form of a nasal spray was administered to 60 adult patients with PER, i.e., cat owners (n = 19) and cat non-owners (n = 41) with positive SPT to cat fur allergen (Diater, Spain). Subjective (total nasal symptom score [TNSS]) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal patency and nasal eosinophil count [NEo]) were used to assess the nasal response. Peak expiratory flow (PEF) was used as a safety parameter during cNCT. Results: No differences were obtained in SPT wheal size and cNCT positivity between cat owners and non-owners. Positive cNCT detecting true cat allergy could be predicted by a cat SPT wheal size > 6.5 mm with 71.11% sensitivity and 100% specificity. Conclusions: In adult patients with PER, the frequency of cat allergy was similar among cat owners and non-owners. A cat SPT wheal size ≥6.5 mm could be helpful in detecting true cat allergy by avoiding the demanding, time-consuming, and often unavailable cNCT when cat AIT is needed.

Rhinitis treatment may improve attention-deficit/hyperactivity symptoms in children. The current study evaluated changes in inattentive and hyperactive symptoms after treatment in children with chronic rhinitis.Children aged 5-18 years with chronic rhinitis were enrolled in a 3-month prospective study. The nasal provocation test for house dust mites (HDM) and evaluation of allergen sensitization, including the skin prick test and the Phadiatop test, were performed. The severity of rhinitis was assessed according to the ARIA guideline. The total nasal symptom score and the Vanderbilt ADHD Diagnostic Rating Scale (VADRS) score for assessing inattentive and hyperactive symptoms were recorded at baseline and at 1 and 3 months after rhinitis treatment. Children with rhinitis were classified into the following two groups: HDM-induced allergic rhinitis (AR group) and non-allergic rhinitis to HDM (NAR group) based on the NPT.Overall, 83 children completed the 3-month prospective study, and they had a mean age of 9.12 ± 2.89 years and 44.6% were boys. After rhinitis treatment, VADRS scores assessed by the parents and teachers were significantly decreased compared with those at baseline (p = 0.005). In subgroup analysis, 61 (73.49%) children had AR, and 22 (26.5%) children had NAR. No significant difference in the baseline VADRS score was found between the AR and NAR groups. After treatment, VADRS scores assessed by the parents and teachers were significantly decreased only in the AR group (p 0.001). Forty-five (54.2%) children had moderate persistent rhinitis, 29 (34.9%) had mild persistent rhinitis, and 9 (10.8%) had mild intermittent symptoms. There were no differences in baseline VADRS scores assessed by the parents and teachers among children with mild intermittent, mild persistent, or moderate persistent symptoms. The total nasal symptom score and VADRS score were significantly decreased after treatment for all severities of rhinitis compared with those at baseline. A greater baseline VADRS score was associated with substantial improvement of inattentive and hyperactive symptoms after treatment.Early treatment for rhinitis may improve inattentive and hyperactive symptoms in school-aged children.

The nasal allergen challenge (NAC) model can be a valuable diagnostic tool for allergic rhinitis. Alongside its clinical use, NACs can be used as primary and secondary endpoints in studies evaluating allergen immunotherapy (AIT) products for allergic rhinitis treatment. This review will discuss the technical aspects of the NAC model and provide a summary of recent studies using NACs to assess existing and new AIT treatments.Over the last 2 years, both titrated and single-dose nasal challenge protocols have been used to evaluate immunotherapies targeting grass, birch, house dust mite, and cat allergens. Early efficacy and dose-finding trials showed improvements in allergic symptoms and nasal tolerance to allergens after AIT treatment with standardized extracts or modified forms of whole allergen. NACs were also used in two proof-of-concept studies to illustrate the efficacy of intralymphatic immunotherapy with two concomitant allergens and subcutaneous immunotherapy with Fel d 1-specific IgG-blocking antibodies.Along with existing therapies, nasal challenges are useful in evaluating AIT treatments in the very early stages of clinical development. However, because of the variety in challenge techniques and symptom assessments available, special attention must be placed in the protocol design in order to compare the study results with existing NAC publications.

Orientador: Ricardo de Lima Zollner Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: Rinite alérgica é uma doença comum com ampla morbidade, que gera aumento considerável nos custos de tratamento médico, redução da produtividade no trabalho e absenteísmo escolar. A aplicação tópica de corticosteróides intranasal é amplamente reconhecida como primeira linha de tratamento antiinflamatório. Espera-se que a maioria dos sprays nasais prescritos como drogas de ação local, ainda não possuam patente permitindo o aumento de cópias genéricas desses medicamentos, levando a concorrência e redução de preço. Estudos de bioequivalência para sprays nasais estão ainda em discussão. Geralmente, os estudos para essa finalidade usa modelos de intervenção terapêutica a longo prazo, com altos custos para o paciente e longo tempo de duração. O objetivo deste trabalho foi mostrar a aplicabilidade da provocação nasal com histamina e rinomanometria em estudos de bioequivalência para sprays nasais. Trata-se de um estudo aberto, cruzado aleatorizado, utilizando dois períodos e duas seqüências para avaliar a equivalência farmacodinâmica entre duas formulações de sprays de dipropionato de beclometasona de manufaturamento distinto. Após estímulo nasal com histamina (0,5 mg/ml em ambas narinas), 25 voluntários saudáveis foram submetidos a rinomanometria anterior nos tempos 0; 15; 30 e 60 minutos para estabelecimento do fluxo, pressão e resistência basal de cada câmara nasal. Os voluntários foram submetidos à utilização do spray nasal com a droga teste (T) ou referência (R) de acordo com o esquema de randomização, e a área sobre a curva foi analisada. De acordo com os parâmetros estudados os resultados obtidos mostraram diferença significativa entre as duas formulações (p= 0,31) indicando a equivalência terapêutica entre as drogas T e R. Assim, estes resultados sugerem que provocação nasal com histamina em indivíduos saudáveis e o emprego da rinomanometria como método quantitativo das alterações provocadas nas câmaras nasais possam ser aplicáveis em estudos farmacodinâmicos de bioequivalência para sprays nasais Abstract: Allergic rhinitis is a common condition with widespread morbidity, increased medical treatment costs, reduced work productivity and lost school days. Topically delivered intranasal corticosteroids are widely recognized to be the first-line anti-inflammatory treatment. It is expected that many of the most-prescribed nasal sprays for local action drugs will go off patent, allowing the increase of the generic copies of these medications, with more products competition and price reduction. The bioequivalence studies for nasal sprays are still in discussion. Usually the studies designs for this purpose use a long-term therapeutic intervention models using patients with high costs and time duration. This study was designed to demonstrate the feasibility of rhinomanometry in bioequivalence studies for nasal sprays. Study design, an open, randomized, crossover study, using two periods and two sequences to evaluate pharmacodynamic equivalence between two formulations of beclometasone dipropionate spray. After nasal challenge with histamine (0.5mg/ml, in both nostrils), 25 healthy volunteers were submited to an anterior rhinomanometry at the time 0; 15; 30 and 60 minutes building a baseline of flow, pression and resistance of nasal chamber. Then, the vontuteers were submited to nasal drug spray (Test (T) or Reference(R)), according to randomized schedule and the Are Under Curve (AUC0-t) analyzed. The results suggest the potential use of nasal histamine challenge and rhinomanometry evaluation in healthy subjects in bioequivalence studies for nasal sprays Mestrado Ciências Básicas Mestre em Clínica Médica

Background Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma. Methods Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381 -11.9 mcg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T cell activation and IL-5 production were measured in peripheral blood mononuclear cells. Results 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 mcg/mL [IQR 0.0380-0.379 mcg/mL] of Bla g 1. Additionally, three children responded to diluent alone, and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (p=0.03), lower cockroach-specific IgG/IgE ratios (children, p=0.002), and increased cockroach-specific IL-5-producing T lymphocytes (p=0.045). The NAC was well tolerated. Conclusion We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.

Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment option for allergic rhinitis (AR) patients with persistent moderate-severe AR for whom traditional pharmacotherapies are ineffective. The nasal allergen challenge (NAC) and allergen exposure chamber (AEC) are two translational models of AR that can be used to investigate the properties, safety, and efficacy of AIT.Peer-reviewed, human-centered articles utilizing AEC or NAC models to investigate AIT between 2010 and 2020 were curated from PubMed, EMBASE, and OVID Medline databases. AECs have been used to evaluate traditional subcutaneous and sublingual administrations of AIT, including cross-protective effects and different dosing regimens. More recently, the effectiveness of novel AIT formulations has been evaluated. NACs are another model used to study AIT, including using novel intralymphatic routes of administration. It is an especially powerful and versatile tool to determine if basic science and animal model findings are clinically translatable.The AEC and NAC models both produce clinically relevant and reproducible results. AECs are more effective for studying many participants but are limited because they require a specialized facility. As more AIT therapies and new formulations are developed over time, the versatility of the NAC will be especially useful.

Background and aim: Skin prick test (SPT) with a wheal diameter of >3 mm, generally accepted as a positive, is most commonly use diagnostic tool for Allergic rhinitis. Aim was to validate wheal size of Skin Prick Test for the Bermuda grass, in desert environment, with positive Bermuda grass Nasal challenge in same environment. Methods: In 53 adults, mean age 33.43 ± 9.36 years, both gender (females: 33.96%), SPT positive on Bermuda grass with cut off wheal longest diameter of 3 mm, Bermuda grass nasal challenge test (bgNCT) was carried out. Response was assessed subjectively (scored) and objectively (PNIF). Safety profile was assessed by PEF measurement. Results: Mean weal size of SPT (mm) was bigger in bgNCT positive patients (n=47; 88.68%) 8 [4, 15] vs 5 [3, 6] (p6.5mm enabled identification of Bermuda challenge with sensitivity of 82.98% and specificity of 100.0% (area under the curve 0.9326, standard error 0.03528; 95% confidence interval (CI): 0.8635 to 1.002; p=0.0006203). Conclusions: A SPT wheal size ≥6.5mm might be considered as an appropriate wheal size for confirming Bermuda grass allergy in adults with SAR, avoiding the demanding, time consuming and often unavailable bgNCT, especially in patients eligible for allergen immunotherapy. In these patients, bgNCT is recommended if SPT wheal size is

Background Three allergic phenotypes of rhinitis have been described in adults: allergic rhinitis (AR), local allergic rhinitis (LAR), and dual allergic rhinitis (DAR, coexistence of AR and LAR). Nevertheless, most centers follow a diagnostic approach only based on skin prick test and serum allergen-specific IgE (collectively called atopy tests, AT). This approach prevents the recognition of LAR and DAR, the diagnosis of which requires a nasal allergen challenge (NAC). Here, we investigate the existence of LAR and DAR phenotypes in children and adolescents, and the misdiagnosis rate associated with a work-up exclusively based on AT. Methods Clinical data were obtained during physician-conducted interviews, and AT and NAC were systematically performed in 5- to 18-year-old patients with chronic rhinitis. The misdiagnosis rate was defined as the proportion of cases where AT and NAC results were discordant. Results A total of 173 patients (mean age 15.1 years, 39.9% male) completed the study. AR (positive AT and NAC), LAR (negative AT and positive NAC), DAR (positive AT and NAC for some allergens and negative AT and positive NAC for other allergens), and non-allergic rhinitis (negative NAC) were diagnosed in 45.7%, 24.9%, 11.6%, and 17.9% of individuals, respectively. The clinical profile was comparable among allergic phenotypes, but allergic patients had a significantly earlier rhinitis onset, higher conjunctivitis prevalence, and more severe disease than NAR individuals. A diagnostic work-up exclusively based on AT misclassified 37.6% of patients. Conclusions LAR and DAR represent relevant differential diagnosis in pediatric rhinitis. NAC increases the diagnostic accuracy of clinical algorithms for rhinitis in children and adolescents.