[Importance of aspirin challenges in patients with NSAID-exacerbated respiratory disease]. / Stellenwert von ASS-Provokationen beim Analgetika-Intoleranz-Syndrom.

BACKGROUND: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is often characterized by a severe course of chronic rhinosinusitis with nasal polyps (CRSwNP), comorbid asthma, and NSAID hypersensitivity. The gold standard for N-ERD diagnosis is challenge with acetylsalicylic acid (ASA). In expert recommendations, the diagnosis of N-ERD is established based on a plausible positive history of NSAID hypersensitivity and CRSwNP with asthma. OBJECTIVE: The following review describes the performance of ASA challenges and their sensitivity and specificity. It also examines the extent to which a positive history of NSAID hypersensitivity correlates with ASA challenge results in clinical trials and when ASA challenges should be performed. RESULTS AND CONCLUSION: ASA challenges have high sensitivity and specificity. In clinical ASA challenge studies, there is a high concordance between a positive history of NSAID hypersensitivity obtained by rhinologists and the measured data of ASA challenge in patients with CRSwNP and comorbid asthma. Therefore, ASA challenge is primarily indicated in patients with an unclear history of NSAID hypersensitivity.

[Evaluation of subjective scale in allergen nasal provocation test].

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.

Local allergic rhinitis in children.

Local allergic rhinitis (LAR) is one of the endotypes of rhinitis. Despite much data about epidemiology diagnosis and treatment in adult patients with LAR, there is little information on children. Many studies indicate the need for such an assessment of the phenomenon in children, which results in one meta-analysis based on young patients selected from cohorts of patients of different ages.

Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective-a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee.

Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

Evaluation of subjective scale in allergen nasal provocation test / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.

Local allergic rhinitis in children: A systematic review.

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.

Usefulness of the Nasal Allergen Provocation Test in the Diagnosis of Shellfish Allergy

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 (AU)

Pneumococcal colonisation is an asymptomatic event in healthy adults using an experimental human colonisation model.

INTRODUCTION: Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults. METHODS: Healthy participants aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed. RESULTS: Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0). CONCLUSION: Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.

Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen.

BACKGROUND: The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. OBJECTIVE: We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. METHODS: Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. RESULTS: Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. CONCLUSIONS: Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.

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.

Statement of the Spanish Society of Allergology and Clinical Immunology on Provocation Tests With Aspirin/Nonsteroidal Anti-inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated.

Comparison of bronchial and nasal allergen provocation in children and adolescents with bronchial asthma and house dust mite sensitization.

BACKGROUND: Bronchial allergen provocation (BAP) is an established tool for the diagnosis of allergy in patients with asthma, but its use is limited by the potential risk of severe asthmatic reactions. Nasal provocation testing (NPT) may be an alternative safe method and does not require sophisticated equipment. OBJECTIVE: The aim of this prospective study was to evaluate the concordance of both methods in patients with asthma and house dust mite (HDM) sensitization. METHODS: A total of 112 patients with HDM sensitization underwent BAP and had the following parameters analysed: decrease in FEV1, exhaled NO, and total and specific IgE. Within 12 weeks, NPT with HDM was performed in 74 patients with a median age of 9 years (range, 5-16 years). The results were evaluated using the Lebel score which quantifies major symptoms like rhinorrhea, nasal obstruction, sneezes and minor symptoms, such as pruritus, conjunctivitis and pharyngitis. RESULTS: Fifty-seven of 74 patients had an early asthmatic reaction, of which 41 were identified using the Lebel score. The Lebel score had a sensitivity of 71.9% and a positive predictive value (PPV) of 89.1%. In addition, an eNO ≥ 10 ppb (AUC 0.78), a specific IgE Dermatophagoïdes pteronyssinus ≥ 25.6 kU/L (AUC 0.76) and a specific IgE Dermatophagoïdes farinae ≥ 6.6 kU/L (AUC 0.78) were good predictors of an early asthmatic reaction. CONCLUSION: A sequential use of NPT prior to BAP is justified to establish the relevance of HDM allergy. In patients with a negative NPT, BAP is still recommended to rule out a HDM-induced asthmatic reaction.

Diagnostic approach to occupational rhinitis: the role of nasal provocation tests.

PURPOSE OF REVIEW: The diagnosis of occupational rhinitis is a challenge. Underdiagnosis is substantial as the clinical presentation is nonspecific and often no occupational history is taken. Detection of occupational rhinitis can be improved by including screening questions on occupational exposure in the assessment of every patient with adult-onset rhinitis. RECENT FINDINGS: Case reports, case series and epidemiological studies continuously demonstrate new sensitizers and irritants capable of inducing allergic or nonallergic (irritant-induced) occupational rhinitis. Recent reviews have focused on the value of immunological tests with specific IgE, skin prick tests or basophil activation tests in demonstrating sensitization to occupational agents. Nasal provocation tests (NPT) can establish a definite diagnosis of allergic occupational rhinitis. Several NPT guidelines have been published, however, focusing exclusively on standardized high-molecular weight allergens. When performing NPT with nonstandardized agents -- like most occupational sensitizers -- adapted protocols are needed. SUMMARY: We provide pragmatic guidance to clinicians taking care of rhinitis patients on how to diagnose occupational rhinitis, based on recent insights from the literature. We focus on the challenges in the diagnostic work-up, on how to identify suspected causes, and on the role of NPT.

Statement of the Spanish Society of Allergology and Clinical Immunology on provocation tests with aspirin/nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated

Los antiinflamatorios no esteroideos (AINE) son medicamentos ampliamente utilizados a nivel mundial y frecuentemente implicados en reacciones de hipersensibilidad que pueden comprender desde reacciones locales y/o leves a reacciones sistémicas y graves. La complejidad del diagnóstico ante la falta de pruebas cutáneas o de laboratorio estandarizadas y/o validadas, hace que en muchos casos debamos realizar pruebas de provocación de alto riesgo. Por ello, es necesario un exhaustivo estudio de estos pacientes en los que tienen gran importancia el correcto diagnóstico y la búsqueda de procedimientos más seguros ante pacientes con reacciones graves, así como también la búsqueda de opciones alternativas de tratamientos antiinflamatorios. Actualmente existen diversas guías y protocolos de actuación que describen el manejo de la hipersensibilidad a los AINE aunque con importante variabilidad entre diferentes países. Desde los distintos comités de Asma, Rinoconjuntivitis y Alergia a Fármacos de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC) proponemos un documento de posicionamiento sobre las opciones en las pruebas de provocación con aspirina/ AINE. Este documento es el resultado de una revisión exhaustiva de la evidencia actual, basada en publicaciones recientes sobre el diagnóstico de pacientes con hipersensibilidad a AINE, y de la discusión consensuada de un grupo de expertos de la SEAIC. El objetivo fundamental ha sido elaborar una guía práctica de fácil lectura dirigida a profesionales sanitarios de atención especializada implicados en el estudio y manejo de pacientes con sospecha de hipersensibilidad a AINE. Además, se ha realizado una actualización sobre las indicaciones, contraindicaciones y procedimientos de las pruebas de provocación oral, bronquial y nasal con aspirina/AINE

Cold dry air provocation is a reliable diagnostic tool in nonallergic rhinitis.

BACKGROUND: No diagnostic criteria have been available for nonallergic rhinitis (NAR) to this point in time. Nonspecific nasal hyperresponsiveness (NHR), which could be efficiently assessed by cold dry air (CDA) provocation, is an essential feature of NAR. Thus, this study's purpose was to assess the diagnostic value of CDA provocation in discriminating patients with NAR from healthy individuals. METHODS: CDA provocation was performed among 13 healthy volunteers and 15 NAR patients. Nasal symptom scores, total nasal volume (TNV), total nasal resistance (TNR) and minimal cross-sectional area (MCA) were checked before and after the provocation. Non-paramedic tests and receiver operating characteristic (ROC) curves were used in data evaluation. RESULTS: Subjects in the NAR group showed significantly larger changes after CDA provocation in total nasal symptom score (TNSS) and nasal congestion score compared with healthy volunteers, while the change for rhinorrhea score was comparable. Similarly, significant differences in the change of MCA and TNV were witnessed between both groups. We built a predictive model for NAR, Y = minus 3.285 plus 2.520 times the difference of TNR (%) plus 1.027 times the difference of TNSS minus 6.542 times the difference of TNV (%), whose area under curve was 0.93. According to the Youden index, the criterion was set to be Y greater than -0.52, when its sensitivity and specificity were 93.3% and 84.6%, respectively. CONCLUSIONS: With superior patient-friendliness, safety and efficacy, we successfully performed the first NAR predictive model in the Chinese population, based on a short protocol of CDA provocation, by means of both subjective scores and objective tests (acoustic rhinometry and rhinomanometry).