Combined Symptom Medication Score Research Articles

Contribution of MASK-air® as a mHealth tool for digitally-enabled person-centred care in rhinitis and asthma.

In chronic diseases, mobile health apps may help to (i) improve clinical management and (ii) provide valuable real-world scientific evidence. In allergic rhinitis, a market research study has only identified four mHealth apps which were multilingual, resulted in scientific publications and displayed a comprehensive list of medications. Ot those, MASK-air® was the app with the highest number of scientific publications. MASK-air® has been launched in 2015 and is currently available in 30 countries, having collected data from more than 30,000 users. It comprises a daily monitoring questionnaire, allowing patients to register (i) their daily allergy symptoms by means of visual analogue scales, and (ii) their medication use. The achievements of MASK-air® include the development of two digital biomarkers for daily monitoring of rhinitis and asthma (combined symptom-medication score and electronic daily asthma control score). In addition, MASK-air® data have allowed to assess patients' behaviours, suggesting that patients do not follow guideline recommendations, but rather treat themselves (and often use co-medication) whenever feeling worse. Using MASK-air® data, it has also been possible to quantify the impact of allergic diseases in quality-of-life, school and work productivity. MASK-air® real-world data is being used as a source of evidence for the Allergic Rhinitis and its Impact on Asthma 2024 guidelines, in an innovative process of incorporation of mobile health data into guidelines. This review discusses the clinical and scientific contributions of MASK-air® for person-centred care of rhinitis and asthma, providing an illustrative example on the use of mobile health in chronic diseases.

Features of the formation of early immunological tolerance during immunotherapy with allergens in patients with allergic rhinitis

BACKGROUND: The effectiveness of allergen-specific immunotherapy has been proven in studies. Studying the level and expanded spectrum of Th1, Th2, Treg and Breg cytokines against the background of allergen-specific immunotherapy, as well as allergen-specific IgG4 (asIgG4), is promising, which will clarify the mechanisms of the effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis. AIM: To evaluate the clinical effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis and to identify the most significant biomarkers of the formation of early immunological tolerance. MATERIALS AND METHODS: We examined 30 patients with allergic rhinitis aged 19 to 60 years who received allergen-specific immunotherapy. The clinical effectiveness was assessed using the validated Combined Symptom Medication Score (CSMS). All patients had their serum levels of IL-4, IL-13, IFN-γ, IL-12, IL-10, TGF-β, and asIgG4 of enzyme-linked immunosorbent assay recorded at baseline and 6 months after the start of allergen-specific immunotherapy. RESULTS: Allergen-specific immunotherapy has been demonstrated to be highly clinically effective in achieving control of allergic rhinitis. At baseline, the total CSMS score was 3.75 [3.33; 4.5], at the end of 6 months ― 1.83 [1.17; 2.67] (p=0.000002). When analyzing the dynamics of the cytokine profile and asIgG4, an increasing in the level of TGF-β (p=0.000002), IL-12 (p=0.000002) and asIgG4 (p=0.000003) was revealed, as well as a decreasing in the level of IL-4 (p=0.000024) 6 months after the start of allergen-specific immunotherapy. We did not register an increase in IFN-γ and the expected increase in IL-10 and decrease of IL-13. The correlation and principal component analysis showed that the clinical effect of allergen-specific immunotherapy was associated with an increase in TGF-β and IL-12, a moderate increase in asIgG4 with a decrease of IL-4. CONCLUSION: The results demonstrate the high clinical effectiveness of allergen-specific immunotherapy within 6 months from the moment of its initiation. Significant marker of the effectiveness of allergen-specific immunotherapy at the stage of early tolerance formation is TGF-β, which increasement was in correlation with an increased IL-12 with a decrease of IL-4. The increase in asIgG4 is less pronounced. The conducted correlation and principal component analysis showed the relationship of the discussed biomarkers with the CSMS, which may indicate in favor of their choice as potential biomarkers for assessing the effectiveness of allergen-specific immunotherapy.

Proof-of-concept study of anti-Fel d 1 IgY antibodies in cat food using the MASK-air® app.

An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients. After a baseline evaluation, the cats ate only the cat food for the following 4months. Daily evaluation of efficacy was performed for 2weeks at baseline and after 1, 2 and 3months of intervention for periods of 2weeks. The MASK-air app was used daily to assess symptoms, work productivity and medications. Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK-air data at all 3 evaluation periods. The primary end point (visual analogue scale[VAS] for global allergy symptoms) was significantly improved (p<0.0001). Allsymptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1month (p<0.0001) and 14% at 3months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results. A cat diet containing anti-Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study. clinicaltrials.gov: NCT05656482.

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

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. 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. 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. 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

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. To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app. 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. 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. 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-centred digital biomarkers for allergic respiratory diseases and asthma: the ARIA-EAACI approach.

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 centre of the health system and is likely to optimise the practice of allergy. ARIA (Allergic Rhinitis and its Impact on Asthma) 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, randomised 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, were 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.

Long-term efficacy of HDM-SCIT in pediatric and adult patients with allergic rhinitis

BackgroundSubcutaneous immunotherapy (SCIT) is a well-validated and effective disease modification treatment for house dust mites (HDM)-induced allergic rhinitis (AR). Long-term post-treatment comparisons in children and adults treated with SCIT have rarely been published. This study aimed to evaluate the long-term efficacy of HDM-SCIT administered under a cluster schedule in children compared to adults.MethodsThis was an open-design, observational, long-term clinical follow-up study on children and adults with perennial AR treated with HDM-SCIT. The follow-up consisted of a three-year treatment duration plus a post-treatment follow-up of over three years.ResultsPatients in the pediatric (n = 58) and adult (n = 103) groups completed a post-SCIT follow-up of over three years. The total nasal symptom score (TNSS), combined symptom medication score (CSMS), and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) score decreased significantly at T1 (three-year SCIT completed) and T2 (follow-up completed) in the pediatric and adult groups. In both groups, the improvement rate of TNSS (T0-T1) was moderately correlated with the baseline TNSS (r = 0.681, p < 0.001 and r = 0.477, p < 0.001 for children and adults, respectively). Only in the pediatric group, TNSS was significantly lower at T2 compared with that right after SCIT cessation (T1) (p = 0.030).ConclusionsChildren and adults with HDM-induced perennial AR could achieve a sustainable post-treatment efficacy for over three years (up to 13 years) following a three-year SCIT. Patients with relatively severe nasal symptoms at baseline may benefit more from SCIT. Children who have completed an adequate course of SCIT may gain further improvement in nasal symptoms after SCIT cessation.

Serum vitamin D3 deficiency can affect the efficacy of sublingual immunotherapy in children with allergic rhinitis: a retrospective cohort study.

Sublingual immunotherapy (SLIT) is effective and convenient for many allergic patients but it is still ineffective for many children with allergic rhinitis (AR). In previous studies, most of the patients with poor efficacy of SLIT used the method of individualized adjustment of drug dosage. Currently, there are few reports on the relationship between serum vitamin D3 level and the efficacy of SLIT. In this study, 153 patients with AR who received SLIT were selected as the study objects. All patients collected serum for vitamin D3 test before treatment. The clinical characteristics of the patients were collected, and all patients were regularly followed up for at least 6 months. The improvement rates were assessed according to the combined symptom medication score (CSMS). A receiver operating characteristic (ROC) curve was drawn, and the optimal cut-off point was determined according to the Youden index. Univariate and multivariate logistic regression were used to analyze the relationship between serum vitamin D3 and SLIT efficacy. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. Of 153 AR patients, 101 patients entered the final statistical analysis. According to CSMS, 29.7% of patients in low response (LR) group. The mean vitamin D3 level was (20.42±7.48) ng/mL. The optimal cutoff point for vitamin D3 was 22.25 ng/mL. Univariate logistic regression analysis of SLIT efficacy showed that whether the patient also had a food allergy (P<0.001) or asthma (P=0.011), whether they used acarid products (P=0.002), and whether vitamin D3 is sufficient (P=0.001) were significantly related to the efficacy of SLIT. Multivariate logistic regression analysis showed that after adjusting for whether the patient also had asthma and whether they had used acarid products, whether the patient also had a food allergy (OR: 12.13, 95% CI: 3.57-41.18, P<0.001) and whether vitamin D3 is sufficient (OR: 22.21, 95% CI: 4.04-122.30, P<0.001) were independent factors affecting the efficacy of SLIT. Serum Vitamin D3 deficiency can affect the efficacy of SLIT in children with AR. This study provided a new therapeutic approach for SLIT patients with poor efficacy.

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.

Real-life evidence in allergen immunotherapy: Moving forward with mHealth apps.

The efficacy and safety of allergen immunotherapy (AIT) in allergic rhinitis has been classically assessed using randomized controlled trials (RCTs). However, RCTs may have limitations in their external validity, and their evidence may be complemented with that from real-world studies. We aimed to review the mHealth apps that can be used for retrieving real-world data on AIT in allergic rhinitis. We applied an automatic tool to identify the mHealth apps (available in the Google Play and Apple App stores) that can be used to assess patients under AIT for allergic rhinitis. Apps meeting the inclusion criteria were reviewed, and the corresponding scientific evidence was assessed. We identified five apps with scientific publications in the context of allergic rhinitis: AirRater, AllergyMonitor, MASK-air, Husteblume, and Pollen App. Of those, only MASK-air and AllergyMonitor assessed AIT in patients with allergic rhinitis. MASK-air has enabled the comparison of reported symptoms among patients treated vs. not-treated with AIT. MASK-air has also allowed for the development of combined symptom-medication scores that can be used as endpoints for AIT trials. AllergyMonitor has identified that mobile technology can improve adherence to AIT and is set to support the prescription of AIT for patients with allergic rhinitis by a more precise identification of the pollen season. Mobile health tools allow for the collection of large volumes of real-world data and can be useful for generating hypotheses on AIT. However, such hypotheses require confirmation by epidemiological studies and RCTs.

House dust mite allergen immunotherapy for monosensitized versus polysensitized patients with allergic rhinitis: A systematic review and meta-analysis.

Most patients with allergic rhinitis are polysensitized. The efficacy of house dust mite (HDM) allergen immunotherapy (AIT) compared between monosensitized and polysensitized patients remains limited. To systematically review the efficacy and safety of HDM AIT compared between monosensitized and polysensitized patients with allergic rhinitis. We searched PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane central register of Controlled Trials (CENTRAL) until June 2022. The primary outcome was the changes from baseline in total nasal symptom score (TNSS). Secondary outcomes were changes from baseline in total medication score (TMS), combined symptom medication score (CSMS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, immunological parameters, and adverse events (AEs). Of 13 eligible studies, 10 prospective cohorts, 2 retrospective cohorts, and 1 matched cohort, we identified 10 studies for quantitative synthesis. There were 1,113 patients with allergic rhinitis, 566 with HDM monosensitization and 547 with polysensitization to HDM and other allergens. There was no significant difference in the pooled mean changes of the 2 groups in TNSS (SMD -0.05, 95%CI: -0.22 to 0.11, p = 0.532) and VAS (SMD -0.20, 95%CI: -0.42 to 0.01, p = 0.060) with moderate certainty of evidence. The changes in TMS, CSMS, and RQLQ were similar between the 2 groups with very low certainty of evidence. The AEs were mild and comparable between the 2 groups. The immunological indices remained inconsistent and were not predictive of clinical responses. A single HDM AIT similarly improved clinical outcomes in monosensitized and polysensitized patients with allergic rhinitis.

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

Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available. 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. 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. 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]). Allergy symptoms and worse rhinitis control are associated with worse academic productivity, whereas immunotherapy is associated with higher productivity.

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study

Background: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. Methods: Thirty-one patients (age 18–64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin’ sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. Results: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. Conclusions: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.

Automatic market research of mobile health apps for the self-management of allergic rhinitis.

Only a small number of apps addressing allergic rhinitis (AR) patients have been evaluated. This makes their selection difficult. We aimed to introduce a new approach to market research for AR apps, based on the automatic screening of Apple App and Google Play stores. A JavaScript programme was devised for automatic app screening, and applied in a market assessment of AR self-management apps. We searched the Google Play and Apple App stores of three countries (USA, UK and Australia) with the following search terms: "hay fever", "hayfever", "asthma", "rhinitis", "allergic rhinitis". Apps were eligible if symptoms were evaluated. Results obtained with the automatic programme were compared to those of a blinded manual search. As an example, we used the search to assess apps that can be used to design a combined medication score for AR. The automatic search programme identified 39 potentially eligible apps out of a total of 1593 retrieved apps. Each of the 39 apps was individually checked, with 20 being classified as relevant. The manual search identified 19 relevant apps (out of 6750 screened apps). Combining both methods, a total of 21 relevant apps were identified, pointing to a sensitivity of 95% and a specificity of 99% for the automatic method. Among these 21 apps, only two could be used for the combined symptom-medication score for AR. The programmed algorithm presented herein is able to continuously retrieve all relevant AR apps in the Apple App and Google Play stores, with high sensitivity and specificity. This approach has the potential to unveil the gaps and unmet needs of the apps developed so far.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study

Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with β-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. The clinical efficacy of a food for special medical purposes-lozenge containing β-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women. In a randomized, double-blind, placebo-controlled pilot study, grass- and/or birch pollen-allergic women (n= 51) were given holoBLG or placebo lozenges over 6 months. Before and after dietary supplementation, participants were nasally challenged and the blood was analyzed for immune and iron parameters. Daily symptoms, medications, pollen concentrations, and well-being were recorded by an electronic health application. Total nasal symptom score after nasal provocations improved by 42% in the holoBLG group versus 13% in the placebo group. The combined symptom medication score during the birch peak and entire season as well as the entire grass pollen season improved in allergic subjects supplemented with the holoBLG lozenge by 45%, 31%, and 40%, respectively, compared with the placebo arm. Participants ingesting the holoBLG lozenge had improved iron status with increased hematocrit values, decreased red cell distribution width, and higher iron levels in circulating CD14+ cells compared with the placebo group. Targeted micronutrition with the holoBLG lozenge seemed to be effective in elevating the labile iron levels in immune cells and reducing the symptom burden in allergic women in this pilot study. The underlying allergen-independent mechanism provides evidence that dietary nutritional supplementation of the immune system is one of the ways to combat atopy.

Allergen immunotherapy in MASK‐air users in real‐life: Results of a Bayesian mixed‐effects model

BackgroundEvidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies.ObjectiveTo compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT.MethodsWe assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season.ResultsWe analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2).ConclusionIn patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.

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

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. 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]). We assessed 317,176days of MASK-air® use from 17,780 users aged 16-90years, 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). 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.

Allergen-specific immunotherapy for local allergic rhinitis: a systematic review and meta-analysis.

Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR. Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events. Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcutaneous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease-specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events. AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients.

High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase.

The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000+5000 with 30minutes apart) SQ-U with 1month in between was evaluated. Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.

Subcutaneous Versus Sublingual Immunotherapy for Adults with Allergic Rhinitis: A Systematic Review with Meta-Analyses.

To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma. Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta-analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1. Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta-analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n=13) and SLIT versus placebo (n=33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD]=0.40; 95% confidence interval [CI]=0.31-0.49), MS (SMD=0.26; 95% CI=0.14-0.39), CSMS (SMD=0.42; 95% CI=0.17-0.67), and RQLQ (MD=0.24; 95% CI=0.04-0.44). Statistically significant results favoring SLIT were found for SS (SMD=0.42; 95% CI=0.32-0.53), MS (SMD=0.40; 95% CI=0.28-0.53), CSMS (SMD=0.37; 95% CI=0.29-0.45), and RQLQ (MD=0.32; 95% CI=0.20-0.43). No significant differences were found between SCIT and SLIT for SS (SMD=-0.02; 95% CI=-0.15 to 0.11), MS (SMD=-0.14; 95% CI=-0.31 to 0.03), CSMS (SMD=0.05; 95% CI=-0.21 to 0.31), or RQLQ (MD=-0.08; 95% CI=-0.31 to 0.15). SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two. Laryngoscope, 132:499-508, 2022.