Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. PROMs are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only "rarely" or "sometimes". AD and CU PROM usage is associated with being female, younger, and a dermatologist. POSCORAD and UAS were the most utilized PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. AD and CU PROM users would like training in selecting the proper PROM. CONCLUSION: Even though PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

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.

Sensitization profiles to house dust mite Dermatophagoides pteronyssinus molecular allergens in the Lithuanian population: Understanding allergic sensitization patterns.

BACKGROUND: House dust mite (HDM) allergy is a prevalent global health concern, with varying sensitization profiles observed across populations. We aimed to provide a comprehensive assessment of molecular allergen sensitization patterns in the Lithuanian population, with a focus on Dermatophagoides pteronyssinus (Der p), and investigate patterns of concomitant reactivity among different allergens to enhance the accuracy of HDM allergy diagnostics. METHODS: A comprehensive analysis of 1520 patient test results in Lithuania from 2020 to 2022 was performed. Sensitization patterns to major (Der p 1, Der p 2, and Der p 23) and minor (Der p 5, Der p 7, and Der p 21) Der p allergen components were described using molecular-based diagnostics. Additionally, we investigated sensitization to allergen components from other allergen sources, including tropomyosins (Der p 10, Per a 7, Pen m 1, Ani s 3, Blo t 10) and arginine kinases (Pen m 2, Bla g 9, Der p 20). RESULTS: This study reveals a high prevalence of HDM sensitization in Lithuania - 481 individuals (45.38% of the sensitized group) exhibited sensitization to at least one Der p allergen component. Importantly, within the sensitized group, 37.21% of patients were sensitized to Der p 5, Der p 7, or Der p 21 in addition to major allergenic components. Distinct sensitization patterns were observed across different age groups, indicating the influence of age-related factors. Furthermore, we confirmed cross-reactivity between Der p 5 and Blo t 5 as well as between Der p 21 and Blo t 21, emphasizing the clinical relevance of these associations. We also highlighted the complexity of sensitization patterns among tropomyosins and arginine kinases. CONCLUSION: This study provides valuable insights into HDM allergy sensitization profiles in Lithuania, emphasizing the importance of considering major and minor HDM allergen components for accurate diagnosis and management of HDM-related allergic diseases. Differences between populations and age-related factors impact sensitization patterns. Understanding concomitant reactivity among allergens, such as Der p 5 and Blo t 5, Der p 21 and Blo t 21, tropomyosins, and arginine kinases, is crucial for improving diagnostic strategies and developing targeted interventions for allergic individuals.

Suspected Rivaroxaban-Induced Anaphylaxis Secondary to Ingestion of Rivaroxaban and Nimesulide Without Cross-Reactivity to Dabigatran - A Case Report.

Here, we describe a case of anaphylaxis secondary to rivaroxaban in a 61-year-old woman 24 hours after orthopedic surgery. 10-15 minutes after ingestion of rivaroxaban and nimesulide, the patient's palms started itching, her face and lips swelled, her face flushed, she developed shortness of breath and subsequently lost consciousness. Serum tryptase levels at the time of the anaphylactic reaction were elevated, with subsequent measurement one month later returning a value within the normal range. Dabigatran and meloxicam were identified as suitable alternative drugs by oral provocation at an allergy clinic. Even though rivaroxaban rarely causes serious allergic reactions, when prescribing it, it is important to analyze patients' medical history for possible previously experienced drug-induced allergic reactions and to be aware of the risks of possible undesired drug interactions.

Impairment of EQ-5D-5L Domains According to Allergic Rhinitis and Asthma Control: A MASK-air Real-World Study.

BACKGROUND: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control. OBJECTIVE: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app. METHODS: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone. RESULTS: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma. CONCLUSIONS: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility.

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.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

Oxidative Stress as a Potential Underlying Cause of Minimal and Mild Endometriosis-Related Infertility.

Oxidative stress (OS) plays an important role in a variety of physiological and pathological processes of the female reproductive system. In recent years the relationship between OS and endometriosis has been of particular interest, and a theory has been suggested that OS may be a cause of endometriosis development. While the link between endometriosis and infertility is well established, minimal or mild stages of endometriosis are not considered to cause infertility. Increasing evidence of OS as a leading agent in the development of endometriosis has brought up a theory of minimal/mild endometriosis itself being one of the manifestations of high OS rather than a separate disease which directly causes infertility. Moreover, further development of the disease is thought to contribute to an increased production of reactive oxygen species (ROS) thus leading to the progression of endometriosis itself as well as to other pathological processes in the female reproductive system. Therefore, in case of minimal or mild endometriosis, the less invasive treatment could be offered in order to stop the ongoing cycle of endometriosis-reinforced excess ROS production and to reduce their harmful effects. In this article the existing connection between OS, endometriosis, and infertility is explored.

Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air® approach.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Cutoff Values of MASK-air Patient-Reported Outcome Measures.

BACKGROUND: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested. OBJECTIVE: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms. METHODS: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs. RESULTS: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100). CONCLUSIONS: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management.

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels.

BACKGROUND In this paper we report on the link between increased tryptase levels and prevalence of allergen-specific immunoglobulin E (IgE) in patients with anaphylaxis. The main aim of the study was to assess the corelation between elevated tryptase levels and allergen-specific immunoglobulin E (IgE) in anaphylactic reactions, mastocytosis, and other types of allergic reactions. MATERIAL AND METHODS We enrolled 60 adult patients, aged 18-68 years (mean age 45±8 years). The subjects were divided into 3 groups (20 patients in each group) according to the serum tryptase changes: group 1 consisted of patients with anaphylaxis (serum tryptase level ≥11.4 µg/l), group 2 consisted of patients with mastocytosis (serum tryptase level ≥20.0 µg/l), and group 3 consisted of patients with other allergic reactions with no anaphylaxis as an atopic control group (serum tryptase level <11.4 µg/l). The test material was venous blood serum samples. The allergen-specific IgE assay was carried out by immunoblot. Tryptase concentration was determined by immunoenzymatic assay. RESULTS Allergen-specific IgE was found in 73% of all subjects: 75% in the anaphylactic group, 55% in the mastocytosis group, and 90% in the atopic control group. Polysensitization was common and was significantly different among groups. In the atopic group, there were more patients allergic to 4-7 allergens (P<0.05). CONCLUSIONS We did not find a strong correlation between allergen-specific IgE levels and elevated tryptase levels.

Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities.

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Vaccinating with a COVID-19 Vaccine: Experience of the Tertiary Allergology Center.

Background: Allergic reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but detailed descriptions and further actions are not well characterized. Objective: To describe the symptoms of possible allergic reactions after the mRNA COVID-19 vaccine and outcomes of further vaccination. Methods: We descriptively analyzed data of adult (≥18 years of age) patients, who were sent for vaccination to our outpatient center for the Diagnostics and Treatment of Allergic and Immune diseases. All patients were vaccinated with the Pfizer-BioNTech Comirnaty® vaccine. Results: From January 2021 to July 2021 twenty-two patients were vaccinated in our center. Six patients experienced a reaction after the first Comirnaty® dose in different vaccination centers. The majority of them complained of various types of rashes after the first dose, one case was consistent with anaphylaxis. The latter patient was tested with the skin prick using Pfizer-BioNTech Comirnaty® vaccine and the test was negative. Other sixteen patients were vaccinated in our center from the first dose because of past allergic reactions to other medication or due to concomitant mast cell disorder. All patients were vaccinated without any immediate adverse reactions. Conclusions: None of our patients experienced repeated cutaneous reactions after the second dose. Patients with previous anaphylaxis or mastocytosis also were safely vaccinated.

Mobile health app for monitoring allergic rhinitis and asthma in real life in Lithuanian MASK-air users.

BACKGROUND: MASK-air® is an app whose aim is to reduce the global burden of allergic rhinitis (AR) and asthma. A transfer of innovative practices was performed to disseminate and implement MASK-air® in European regions. The aim of the study was to examine the implementation of the MASK-air® app in Lithuanian adults in order to investigate (i) the rate of acceptance in this population, (ii) the duration of app use and (iii) the evaluation of the app after its use. METHODS: In a longitudinal study, Lithuanian adults with AR and/or asthma were recruited by allergists. They were informed about how to use MASK-air® and were followed closely. They were reviewed after one to 3 months to evaluate satisfaction and were asked to continue using the app. RESULTS: Among the 149 patients recruited (37.2 ± 10.4 years), 52.4% had rhinitis alone, 42.9% had rhinitis, asthma and/or conjunctivitis multimorbidity, and 2.7% isolated asthma. According to the MASK-air® baseline questionnaire, 88.3% of patients considered that their symptoms were troublesome. Data were available for 102 (68.4%) patients. The duration of app usage in patients ranged from 1 to 680 days (median, 25-75 percentile: 54, 23.2-151 days). Forty-two (41.1% of patients who were reviewed) patients agreed to share their opinion on MASK-air® . Most users of the app were satisfied, from 46.5% thinking their allergy was treated more successfully to 90.4% recommending this app to other allergy sufferers. DISCUSSION: When recommended by physicians, MASK-air® was used for a longer period of time.