@IT2020: An innovative algorithm for allergen immunotherapy prescription in seasonal allergic rhinitis.

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment in patients with seasonal allergic rhinoconjunctivitis (SAR). Its efficacy depends on the precise identification of the triggering allergen. However, diagnostics based on retrospective clinical history and sensitization to whole extracts (SWE) often leads to equivocal results. OBJECTIVES: To assess the usability and impact of a recently established algorithm for a clinical decision support system (@IT2020-CDSS) for SAR and its diagnostic steps [anamnesis, SWE (skin prick test or serum IgE), component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary] on doctor's AIT prescription decisions. METHODS: After educational training on the @IT2020-CDSS algorithm, 46 doctors (18 allergy specialists, AS, and 28 general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the algorithm. The usability and perceived impact of the algorithm were evaluated. RESULTS: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p < .01). AIT prescription for pollen and Alternaria allergy based on anamnesis and SWE was heterogeneous but converged towards a consensus by integrating CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. CONCLUSIONS AND CLINICAL IMPLICATIONS: The implementation of CRD and eDiary in the @IT2020-CDSS algorithm improved consensus on AIT prescription for SAR among AS and GP. The potential usefulness of a CDSS for aetiological diagnosis of SAR and AIT prescription in real-world clinical practice deserves further investigation.

IgE antibody repertoire in nasal secretions of children and adults with seasonal allergic rhinitis: A molecular analysis.

BACKGROUND: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. OBJECTIVE: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. METHODS: Nasal secretions were collected with an absorbent device (Merocel 2000® , Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC-112, TFS) were measured in NS and serum. RESULTS: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. CONCLUSIONS: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire.

Adherence to Prescribed E-Diary Recording by Patients With Seasonal Allergic Rhinitis: Observational Study.

BACKGROUND: Complete diagnosis and therapy of seasonal allergic rhinoconjunctivitis require evidence that exposure to the sensitizing pollen triggers allergic symptoms. Electronic clinical diaries, by recording disease severity scores and pollen exposure, can demonstrate this association. However, patients who spontaneously download an e-diary app show very low adherence to their recording. OBJECTIVE: The objective of our study was to assess adherence of patients with seasonal allergic rhinitis to symptom recording via e-diary explicitly prescribed by an allergist within a blended care approach. METHODS: The @IT-2020 project is investigating the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In the pilot phase of the study, we recruited Italian children (Rome, Italy) and adults (Pordenone, Italy) with seasonal allergic rhinitis and instructed them to record their symptoms, medication intake, and general conditions daily through a mobile app (Allergy.Monitor) during the relevant pollen season. RESULTS: Overall, we recruited 101 Italian children (Rome) and 93 adults (Pordenone) with seasonal allergic rhinitis. Adherence to device use slowly declined during monitoring in 3 phases: phase A: first week, ≥1267/1358, 90%; phase B: second to sixth week, 4992/5884, 80% to 90%; and phase C: seventh week onward, 2063/2606, 70% to 80%. At the individual level, the adherence assessed in the second and third weeks of recording predicted with enough confidence (Rome: Spearman ρ=0.75; P<.001; Pordenone: ρ=0.81; P<.001) the overall patient adherence to recording and was inversely related to postponed reporting (ρ=-0.55; P<.001; in both centers). Recording adherence was significantly higher during the peak grass pollen season in Rome, but not in Pordenone. CONCLUSIONS: Adherence to daily recording in an e-diary, prescribed and motivated by an allergist in a blended care setting, was very high. This observation supports the use of e-diaries in addition to face-to-face visits for diagnosis and treatment of seasonal allergic rhinitis and deserves further investigation in real-life contexts.

A new molecular multiplex IgE assay for the diagnosis of pollen allergy in Mediterranean countries: A validation study.

BACKGROUND: The identification of the primary sensitizing pollen is difficult in Southern European patients with Seasonal Allergic Rhinitis (SAR) if sensitized to various pollen sources with overlapping seasonality. A more precise diagnosis is obtained by IgE assays to allergen molecules, currently available as singleplex or microarrays. OBJECTIVES: To test the analytical performance of a multi-parameter immunoblot molecular "Pollen Test" specifically designed to test IgE antibodies to pollen extracts and molecules clinically relevant in Southern Europe. METHODS: Sera were obtained from 101 children and 98 adults with SAR and tested with a customized multiplex immunoblot assay (EUROLINE Southern European Pollen Profile [ESEP]; EUROIMMUN AG, Luebeck, Germany) containing a comprehensive panel of allergen extracts and molecules. ESEP's outcomes were then compared in selected sera (ESEP positive to negative = 2:1) with those of singleplex IgE assays (ImmunoCAP; ThermoFisher Scientific, Uppsala, Sweden). For each of the examined reagents, qualitative (sensitivity, specificity, accuracy), semi-quantitative (classes) and quantitative (Spearman's rank correlation, Bland-Altmann plots) comparisons were performed. RESULTS: Compared to ImmunoCAP, cumulative ESEP's sensitivity and specificity were 87% (95% CI 84%-90%) and 88% (83%-93%) for extracts and 99% (98%-100%) and 87% (83%-91%) for molecules. Cohen's kappa coefficients (κC ) ranged for extracts from 0.18 (Pellitory) to 0.50 (Cypress) and for molecules from 0.21 (Ole e 1) to 0.68 (Phl p 7). The quantitative outcomes of the two diagnostic tests were highly correlated, with Spearman's rank correlation coefficients always exceeding 0.80. Bland-Altmann plots showed a tendency of ESEP to overestimate serum specific IgE levels, when compared to ImmunoCAP. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitivity and specificity of ESEP in testing serum IgE antibodies against pollen allergen extracts and molecules, in Italian patients with SAR, both exceeded 85%. The advantages and limitations of a multiplex customized immunoblot assay, in the routine clinical use of molecular diagnostics in Southern European pollen allergic patients, deserve to be tested.

Validation Parameters of Patient-Generated Data for Digitally Recorded Allergic Rhinitis Symptom and Medication Scores in the @IT.2020 Project: Exploratory Study.

BACKGROUND: Mobile health technologies enable allergists to monitor disease trends by collecting daily patient-reported outcomes of allergic rhinitis. To this end, patients with allergies are usually required to enter their symptoms and medication repetitively over long time periods, which may present a risk to data completeness and quality in the case of insufficient effort reporting. Completeness of patient's recording is easily measured. In contrast, the intrinsic quality and accuracy of the data entered by the patients are more elusive. OBJECTIVE: The aim of this study was to explore the association of adherence to digital symptom recording with a predefined set of parameters of the patient-generated symptom and medication scores and to identify parameters that may serve as proxy measure of the quality and reliability of the information recorded by the patient. METHODS: The @IT.2020 project investigates the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In its pilot phase, 101 children with seasonal allergic rhinitis were recruited in Rome and instructed to record their symptoms, medication intake, and general conditions daily via a mobile app (AllergyMonitor) during the relevant pollen season. We measured adherence to daily recording as the percentage of days with data recording in the observation period. We examined the patient's trajectories of 3 disease indices (Rhinoconjunctivitis Total Symptom Score [RTSS], Combined Symptom and Medication Score [CSMS], and Visual Analogue Scale [VAS]) as putative proxies of data quality with the following 4 parameters: (1) intravariation index, (2) percentage of zero values, (3) coefficient of variation, and (4) percentage of changes in trend. Lastly, we examined the relationship between adherence to recording and each of the 4 proxy measures. RESULTS: Adherence to recording ranged from 20% (11/56) to 100% (56/56), with 64.4% (65/101) and 35.6% (36/101) of the patients' values above (highly adherent patients) or below (low adherent patients) the threshold of 80%, respectively. The percentage of zero values, the coefficient of variation, and the intravariation index did not significantly change with the adherence to recording. By contrast, the proportion of changes in trend was significantly higher among highly adherent patients, independently from the analyzed score (RTSS, CSMS, and VAS). CONCLUSIONS: The percentage of changes in the trend of RTSS, CSMS, and VAS is a valuable candidate to validate the quality and accuracy of the data recorded by patients with allergic rhinitis during the pollen season. The performance of this parameter must be further investigated in real-life conditions before it can be recommended for routine use in apps and electronic diaries devoted to the management of patients with allergic rhinitis.

Heterogeneous validity of daily data on symptoms of seasonal allergic rhinitis recorded by patients using the e-diary AllergyMonitor®.

BACKGROUND: Patient-generated symptom and medication scores are essential for diagnostic and therapeutic decisions in seasonal allergic rhinitis (SAR). Previous studies have shown solid consistencies between different scores at population level in real-life data and trials. For clinicians, the evaluation of individual data quality over time is essential to decide whether to rely on these data in clinical decision-making. OBJECTIVE: To analyze the consistency of different symptom (SS) and symptom medication scores (SMSs) at individual level in two study cohorts with different characteristics and explore individual patient trajectories over time. METHODS: Within the pilot phase of the @IT.2020 project on diagnostic synergy of mobile health and molecular IgE assessment in patients with SAR, we analyzed data of 101 children and 93 adults with SAR and instructed them to record their symptoms and medication intake daily via the mobile app AllergyMonitor®. We then assessed the correlation between different SMS and a visual analogue scale (VAS) on the impact of allergy symptoms on daily life at population and individual level. RESULTS: At population level, the Rhinoconjunctivitis total symptom score (RTSS) correlated better with VAS than the combined symptom and medication score (CSMS). At individual level, consistency among RTSS and VAS was highly heterogeneous and unrelated to disease severity or adherence to recording. Similar heterogeneity was observed for CSMS and VAS. CONCLUSIONS: The correlation of clinical information provided by different disease severity scores based on data collected via electronic diaries (e-diaries), is sufficient at population level, but broadly heterogeneous for individual patients. Consistency of the recorded data must be examined for each patient before remotely collected information is used for clinical decision making.

Collection of nasal secretions and tears and their use in allergology.

PURPOSE OF REVIEW: The identification of immunological markers in nasal secretions and tears is becoming essential in the study of allergic diseases. The collection procedure of nasal and ocular secretions directly influences the results, thus it is of paramount importance to validate and standardize the sampling process. RECENT FINDINGS: Current techniques for nasal secretions sampling are mainly based on three principles: collection of spontaneous secretions, nasal washings, and absorption. Collection of spontaneous secretions is appropriate in subjects with nasal hypersecretion, whereas in healthy individuals the collected volume is frequently insufficient. Nasal washings are associated with an unpredictable, high dilution and concentrations of markers often fall below detection limits of immunological assays. Absorption seem to provide the best compromise between sufficient sample amounts and detectability of inflammatory mediators and immunoglobulin E. Tear samples can be obtained by glass capillary tubes, filter paper strips and ophthalmic sponges. Volumes are however small or highly diluted through reflex tearing. SUMMARY: Secretions reflect the local inflammatory activity and provide valuable information about the immunological reaction to allergens at the target organ. There is increasing evidence of the potential clinical role of their analysis, for diagnosis, and monitoring of allergic rhino-conjunctivitis. Appropriate collection and processing is very important and requires special attention.