Artificial Intelligence-Supported Development of Health Guideline Questions.

BACKGROUND: Guideline questions are typically proposed by experts. OBJECTIVE: To assess how large language models (LLMs) can support the development of guideline questions, providing insights on approaches and lessons learned. DESIGN: Two approaches for guideline question generation were assessed: 1) identification of questions conveyed by online search queries and 2) direct generation of guideline questions by LLMs. For the former, the researchers retrieved popular queries on allergic rhinitis using Google Trends (GT) and identified those conveying questions using both manual and LLM-based methods. They then manually structured as guideline questions the queries that conveyed relevant questions. For the second approach, they tasked an LLM with proposing guideline questions, assuming the role of either a patient or a clinician. SETTING: Allergic Rhinitis and its Impact on Asthma (ARIA) 2024 guidelines. PARTICIPANTS: None. MEASUREMENTS: Frequency of relevant questions generated. RESULTS: The authors retrieved 3975 unique queries using GT. From these, they identified 37 questions, of which 22 had not been previously posed by guideline panel members and 2 were eventually prioritized by the panel. Direct interactions with LLMs resulted in the generation of 22 unique relevant questions (11 not previously suggested by panel members), and 4 were eventually prioritized by the panel. In total, 6 of 39 final questions prioritized for the 2024 ARIA guidelines were not initially thought of by the panel. The researchers provide a set of practical insights on the implementation of their approaches based on the lessons learned. LIMITATION: Single case study (ARIA guidelines). CONCLUSION: Approaches using LLMs can support the development of guideline questions, complementing traditional methods and potentially augmenting questions prioritized by guideline panels. PRIMARY FUNDING SOURCE: Fraunhofer Cluster of Excellence for Immune-Mediated Diseases.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

Co-occurrence of otitis media with effusion and another environment-dependent disease (selected allergic conditions).

Introduction: Otitis media eith effusion (OME) is an inflammatory condition of the middle ear that involves accumulation of sterile fluid or effusion in the tympanic cavity with the tympanic membrane intact. The pathophysiology of OME is undoubtedly multifactorial. Aim: To assess the co-occurrence of OME, allergic rhinitis, and asthma. Material and methods: The study involved a group of 18,617 subjects aged 6-7 years, 13-14 years, or 20-44 years. ECRHS and ISAAC questionnaires, validated and adopted for Polish conditions, were used in the study. Results: OME increases the risk of developing allergic rhinitis by nearly two-fold (OR = 2.07, 95% CI: 1.738-2.479 in 6-7-year-olds; OR = 1.61, 95% CI: 1.299-1.995 in 13-14-year-olds, and OR = 1.55, 95% CI: 1.262-1.83 in 20-44-year-olds). Protective factors against otitis media with effusion include the number of siblings (the more children in the family, the higher the risk of chronic OM; OR = 2.00, 95% CI: 1.15-1.346) and consumption of dairy products rich in lactic acid bacteria. Conclusions: OME significantly more often co-exists with other conditions, particularly allergic rhinitis.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

The increase in allergic conditions based on a review of literature.

The global interest in allergic disease epidemiology in the 20th and 21st centuries is a result of their growing prevalence of unprecedented, pandemic proportions. According to the 2011 White Book on Allergy, the prevalence of allergic conditions rises dramatically worldwide, both in developed and developing countries, with the rates of asthma ranging from 1% to 20%, allergic rhinitis from 1% to 18%, and skin allergies from 2% to 10% in various populations. The growing prevalence of allergies is particularly noticeable in children, who have been affected most by this trend for the last two decades.

Reactivity of nasal cavity mucosa in the nasal cow's milk allergen provocation test.

Introduction: The nasal allergen provocation test plays an important role in differential diagnostics of rhinitis. Due to its informative potential, the test is also becoming increasingly used in other areas of diagnostics, including the diagnostics of food allergies. Aim: To assess the reactivity of nasal mucosa to the cow's milk protein allergens (as being widely used in powdered form in the food industry). Material and methods: The study material consisted of a group of 31 healthy subjects not sensitized to environmental allergens including cow's milk protein allergens. The study method involved an incremental nasal provocation test with cow's milk protein evaluated using the visual analog scale and acoustic rhinometry. Results: A total of 29 out of 31 volunteers presented with a significant decrease in nasal patency (control solution: 1.112 ±0.161 vs. local allergen application 1.005 ±0.157; p < 0.004) as measured by acoustic rhinometry following the allergen dose of 12.5 µg. Slight changes in complaints were observed using the visual analog scale. Exposure to the widespread food allergens (including powdered cow's milk allergens) presents a potential risk of positive response in non-sensitized individuals. Conclusions: Further studies on dose standardization are necessary in the study area.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part four. The relationship between the concentration of specific IgE antibodies in serum and types of asthma.

Introduction: Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. Aim: To determine the relationship between the concentration of specific IgE antibodies in serum and types of asthma. Material and methods: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of asthma, skin-prick tests). Results: sIgE antibodies against any allergen were detected in 9.9% (classes 1-6)/7.6% (classes 2-6) of healthy respondents. Comparing sIgE antibodies of respondents with intermittent asthma to sIgE antibodies of respondents with persistent asthma, no statistically significant differences were identified. Relating to allergens of D. pteronyssinus, cat dander, and A. alternata, sIgE antibodies were more frequently detected in respondents with atopic asthma and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.005 to p < 0.001). Relating to allergens of D. pteronyssinus, cat dander, and timothy grass, sIgE antibodies were more frequently detected in respondents with atopic asthma and a weakly positive skin-prick test as compared to healthy respondents with weakly positive skin-prick test (p < 0.05 to p < 0.001). Conclusions: Regarding subjects with a negative or weakly positive skin test, when sIgE antibodies to the same allergen are detected, asthma is much more likely to occur.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part five. The relationship between the concentration of specific IgE antibodies in serum and types of rhinitis.

Introduction: Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. Aim: To determine the relationship between the concentration of specific IgE antibodies in serum and types of rhinitis. Material and methods: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of rhinitis, skin-prick tests). Results: sIgE antibodies are more frequently detected in respondents with intermittent/seasonal allergic rhinitis and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.05 to p < 0.001). Relating to allergens of D. pteronyssinus and cat dander, sIgE antibodies are more frequently detected in respondents with persistent/perennial allergic rhinitis and a negative or weakly positive skin-prick test as compared to healthy respondents with a negative or weakly positive skin-prick test (p < 0.05 to p < 0.001). Conclusions: The occurrence of intermittent/seasonal allergic rhinitis is much more probable in respondents with a negative skin-prick test, when IgE antibodies against the same allergen are detected. And the occurrence of persistent/perennial allergic rhinitis is much more probable in respondents with a negative or weakly positive skin-prick test with allergens of D. pteronyssinus or cat dander, when IgE antibodies against the same allergen are detected.

Differential diagnostics of food allergy as based on provocation tests and laboratory diagnostic assays.

Due to the scale of the phenomenon, food allergy constitute a significant health problem and significantly impair the quality of life of patients. Differential diagnostics, including skin tests, sIgE detection tests, basophil and mast cell activation tests as well as double-blind placebo-controlled food challenge tests, is the gold standard in the diagnosis of food allergy. Recently, increasing attention has been paid to the potential use of nasal provocation test in the diagnosis of food allergy. Allergen dose, protocol standardization, assessment of subjective complaints and objectivization of test results are important factors determining the applicability of provocation tests.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

A new perspective on acoustic rhinometry in terms of standardisation, including the nasal allergen provocation test.

Acoustic rhinometry is an objective nasal patency assessment technique. Its cognitive value means that it plays a major role in the nasal allergen provocation test. The optimisation of the measured values and the interpretation of the results of the test-based values are critical. When the assessment is based on the minimal cross-sectional areas, the volumes for the different segments of the rhinometric curve indicate changes in nasal patency in the nasal allergen provocation test. It seems that the points on the rhinometric curve which correspond to the different waves for the nasal cavity accurately reflect the level of response of the mucous membrane of the nasal cavity to an allergen.

The normal ranges of selected acoustic rhinometry parameters depending on age and sex-component of standarization in nasal provocation test.

Introduction: Acoustic rhinometry is a non-invasive method of measuring intranasal spaces. As one of the objective techniques for nasal patency, it plays a critical role in evaluating the nasal allergen challenge.Aim: To establish the typical ranges of selected AR parameters for age and sex. Material and methods: The study was conducted in a group of 583 randomly selected subjects (329 females and 254 males). Acoustic rhinometry was done before and 15 min after a two-time application of 0.1% solution of the decongestant xylomethazoline. The evaluated AR parameters (the cross-sectional area 1 (CSA-1) at the level of the isthmus nasi and the distance between the external nares and the isthmus nasi (dCSA-1)) were measured separately for both nasal cavities. Another evaluated parameter was the mean CSA measured 3 cm beyond CSA-1 on the AR curve (CSA-3). Results: The site of the minimum CSA on the acoustic rhinometry curve in the study group was the second notch on the acoustic rhinometry curve (CSA-1), corresponding to the nasal isthmus. With increasing age of the subjects, we observed a systematic increase in nasal spaces. The difference between sexes reached statistical significance at the ages of 17 years and older. Conclusions: The evaluated males show larger nasal cavity volumes than females. The difference between the sexes reaches statistical significance at older ages.

Asthma as a social problem requiring systemic solutions in Poland.

Introduction: Due to its physiopathology and chronic character, asthma constitutes a considerable burden to health care and public health. Aim: The main aim of this study was to determine and present the problems of patients diagnosed with asthma and to suggest solutions to meet the individual and public expectations. Material and methods: The study included 18,874 patients and was part of the System for the Prevention and Early Detection of Allergic Diseases in Poland. The study method was a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and International Study of Asthma and Allergies in Childhood (ISAAC). Results: Nearly 90.1% of patients aged 6-7 years reported periodic difficulty in breathing, with over three episodes per week (3.6 in adults, 3.6 in women, 3.1 in men, 3.3 in urban residents, and 4.6 in rural residents) of reported asthma attacks interrupting patients' sleep. Recent asthma attacks were reported mainly by women living in urban areas. Conclusions: Health problems of asthma patients have a measurable impact on the need to introduce systemic solutions, to ultimately minimize the risk of complications for the individual as well as to minimize the social burden of chronic asthma in Poland.

Gold standard diagnostic algorithm for the differential diagnosis of local allergic rhinitis.

Local allergic rhinitis, defined as a localized allergic response of the nasal mucosa in the absence of systemic atopy, poses a considerable clinical issue due to its prevalence. The gold standard in local allergic rhinitis diagnostics is primarily the patient's history taking and nasal allergen provocation testing or, alternatively, the basophil activation test, described as "an allergic reaction in a test tube".

Changes in the cross-sections of the nasal cavity assessed by acoustic rhinometry in the study population as a guideline for attempts to standardize nasal provocation tests.

Introduction: A specific difficulty in the standardization of nasal allergen challenge tests as measured by acoustic rhinometry is the lack of reference values measured according to dependent changes, for example height and weight/height- or weight-dependent changes. Human growth and development rates and other changes the human body undergoes throughout the lifetime depend closely on the environment, sex, and race. Aim: To assess selected anthropometric (body weight and height) and rhinometric (nasal cross-sectional areas) measurements concerning subject age and sex. Material and methods: The study was conducted in 633 subjects selected in multistage, stratified sampling (324 females and 309 males). Body weight and height were measured with a sliding weight scale and height measure. Nasal cavity cross-sectional areas were measured via acoustic rhinometry. Results: We observed parallel increases in the evaluated anthropometric measurements and nasal cavity cross-sectional areas both in males and females aged ≤ 14 years, with the two sexes starting to differ significantly in terms of those measurements over the age of 14 (p < 0.0001; p < 0.000001). The evaluated rhinometric measurements showed a greater correlation with height than with body weight. The time of the most diversified and dynamic changes in anthropomorphic measurements was the age of > 12 years: with boys demonstrating significantly higher mean values of height and body weight than girls. Conclusions: Height showed a better correlation with rhinometric measurements (cross-sectional area of the nasal cavity) in younger subjects (at their age of development) than in older ones.

Place of residence, gender, month of birth and age influence on the concentration of specific IgE antibodies in serum. The Epidemiology of Allergic Diseases in Poland (ECAP survey): part three.

Introduction: Specific immunoglobulins E (sIgE) are important parameters to estimate the severity of allergic diseases. Aim: To determine the influence of gender, age and place of residence on the concentration of specific IgE antibodies in serum. Material and methods: The concentration of sIgE antibodies against allergens of Dermatophagoides pteronyssinus, cat dander, timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated with answers to ECAP questionnaires. Results: IgE antibodies are less frequently detected in respondents living in the country (p < 0.05 to p < 0.005); and they are less frequently detected in respondents living in cities of hardly industrialised regions than in respondents living in cities of industrialised regions (D. pteronyssinus p < 0.05, cat dander p < 0.01). IgE antibodies are more frequently detected in men (p < 0.005 to p < 0.001). IgE antibodies are more frequently detected in respondents born in May-July (timothy grass p < 0.005, Alternaria alternata p < 0.005) and less frequently detected in respondents born in August-October (timothy grass p < 0.005, Alternaria alternata p < 0.05). Conclusions: Characteristics of the urban environment, non-specific factors and gender affect the concentration of specific IgE antibodies in serum. Influence of seasonal allergens within the first months of life and/or in the course of the foetal period alters the production of specific IgE antibodies.

Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms.

BACKGROUND: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. METHODS: We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®- Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking-OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). RESULTS: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. DISCUSSION: There are major differences between countries in terms of rhinoconjunctivitis medication usage.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19.

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.