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.

Regional, sex, and age inequities in asthma hospital admissions in Spain and Portugal.

BACKGROUND: Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma-related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. METHODS: We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female-to-male ratio in asthma hospital admissions per age group, considering the female-to-male ratio in the overall population. RESULTS: Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher-than-average rate of asthma-related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged <65 years were 2.3 times more likely than in men of the same age, hospitalisations in women aged ≥65 years were 3.5 times higher than in men aged ≥65 years. CONCLUSION: This study suggests that marked regional inequities in asthma hospital admissions exist in Spain and Portugal. Additionally, women are particularly at risk of hospitalisation due to asthma, and such risk increases with age.

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.

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.

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.

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.

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.

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.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

The Allergic Rhinitis and Its Impact on Asthma (ARIA) Approach of Value-Added Medicines: As-Needed Treatment in Allergic Rhinitis.

Drug repurposing is a major field of value-added medicine. It involves investigating and evaluating existing drugs for new therapeutic purposes that address unmet healthcare needs. Several unmet needs in allergic rhinitis could be improved by drug repurposing. This could be game-changing for disease management. Current medications for allergic rhinitis are centered on continuous long-term treatment, and medication registration is based on randomized controlled trials carried out for a minimum of 14 days with adherence of 70% or greater. A new way of treating allergic rhinitis is to propose as-needed treatment depending on symptoms, rather than classical continuous treatment. This rostrum will discuss existing clinical trials on as-needed treatment for allergic rhinitis and real-world data obtained by the mobile health app MASK-air, which focuses on digitally-enabled, patient-centered care pathways.

Academic Productivity of Young People With Allergic Rhinitis: A MASK-air Study.

BACKGROUND: Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available. OBJECTIVE: To use RWD to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale [VAS] education and the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific [WPAI+CIQ:AS] questionnaire), and to identify factors associated with the impact of allergic rhinitis on academic performance. METHODS: We assessed data from the MASK-air mHealth app of users aged 13 to 29 years with allergic rhinitis. We assessed the correlation between variables measuring the impact of allergies on academic performance (VAS education, WPAI+CIQ:AS impact of allergy symptoms on academic performance, and WPAI+CIQ:AS percentage of education hours lost due to allergies) and other variables. In addition, we identified factors associated with the impact of allergic symptoms on academic productivity through multivariable mixed models. RESULTS: A total of 13,454 days (from 1970 patients) were studied. VAS education was strongly correlated with the WPAI+CIQ:AS impact of allergy symptoms on academic productivity (Spearman correlation coefficient = 0.71 [95% confidence interval (CI) = 0.58; 0.80]), VAS global allergy symptoms (0.70 [95% CI = 0.68; 0.71]), and VAS nose (0.66 [95% CI = 0.65; 0.68]). In multivariable regression models, immunotherapy showed a strong negative association with VAS education (regression coefficient = -2.32 [95% CI = -4.04; -0.59]). Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS education (regression coefficient = 0.88 [95% CI = 0.88; 0.92]), higher impact on academic productivity (regression coefficient = 0.69 [95% CI = 0.49; 0.90]), and higher percentage of missed education hours due to allergy (regression coefficient = 0.44 [95% CI = 0.25; 0.63]). CONCLUSION: Allergy symptoms and worse rhinitis control are associated with worse academic productivity, whereas immunotherapy is associated with higher productivity.

A closer look at allergic contact dermatitis caused by topical ophthalmic medications.

BACKGROUND: Allergic contact dermatitis caused by topical ophthalmic medications (OftACD) is frequently difficult to confirm with patch testing and, therefore, it is considered uncommon. METHODS: We collected retrospective data from a cohort of 65 patients with suspected OftACD patch tested in our Dermatology Unit (2005-2021) according to ESCD guidelines, using a series of topical drugs and excipients (Chemotechnique Diagnostics), including betaxolol and timolol 5% pet. kindly supplied by the pharmaceutical industry. Also, frequently used ophthalmic medications as well as patient's own products were also patch tested 'as is' in most patients. RESULTS: Positive patch tests to ophthalmic medications occurred in 44 patients (67.7%) (38F/6M; mean age 63.1 years), with 102 positive reactions. Most positive reactions were associated with active ingredients (n = 56), especially aminoglycoside antibiotics (n = 27), followed by excipients (n = 24) such as sodium metabisulfite (n = 7). There were also positive reactions to topical products tested 'as is' (n = 22), mostly containing beta-blockers, but only five of these reacted to the active ingredient. DISCUSSION: This study reinforces previous findings in OftACD, such as older age of onset, and the importance of antibiotics, contrasting with the progressively lower prevalence of excipients. In addition, it helps raising awareness for the sensitization to beta-blockers, which is probably underestimated. Patch test preparations for the diagnosis of OftACD may require protocol optimization.

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.

Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®.

BACKGROUND: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. METHODS: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test-retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or "VAS Work" (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or "VAS Work" indicating clinical change. RESULTS: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate-high (Spearman correlation coefficient range: 0.437-0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test-retest reliability ICCs ranged between 0.604 and 0.878-"VAS Work" and "VAS asthma" presented the highest ICCs. Moderate/large responsiveness effect sizes were observed-the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. CONCLUSION: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate-high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.