Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

Pilot study on the short-term prediction of symptoms in children with hay fever monitored with e-Health technology.

Forecasting symptoms of pollen-related allergic rhinoconjunctivitis at the level of individual patients would be useful to improve disease control and plan pharmacological intervention. Information Technology nowadays facilitates a more efficient and easier monitoring of patients with chronic diseases. We aimed this study at testing the efficiency of a model to short-term forecast symptoms of pollen-AR at the "individual" patient level. We analysed the data prospectively acquired from a group of 21 Italian children affected by pollen-related allergic rhinoconjunctivitis and recorded their symptoms and medication "Average Combined Score" (ACS) on a daily basis during April-June 2010-2011 through an informatics platform (Allergymonitor™). The dataset used for prediction included 15 variables in four categories: (A) date, (B) meteo-climatic, (C) atmospheric concentration of 5 pollen taxa, and (D) intensity of the patient's IgE sensitization. A Partial Least Squares Discriminant Analysis approach was used in order to predict ACS values above a fixed threshold value (0.5). The best performing predicting model correctly classified 77.8% ± 10.3% and 75.5% ± 13.2% of the recorded days in the model and test years, respectively. In this model, 9/21 patients showed ≥ 80% correct classification of the recorded days in both years. A better performance was associated with a higher degree of patient's atopic sensitization and a time lag > 1. Symptom forecasts of seasonal allergic rhinitis are possible in highly polysensitised patients in areas with complex pollen exposure. However, only predictive models tailored to the individual patient's allergic susceptibility are accurate enough. Multicenter studies in large population samples adopting the same acquisition data system on smart phones are now needed to confirm this encouraging outcome.

Severe anaphylaxis to sheep's milk cheese in a child desensitized to cow's milk through specific oral tolerance induction.

Specific oral tolerance induction to food (SOTI) is a new promising treatmentfor persistent IgE-mediatedfood allergy. Our paper reports a case of a 5-year-old girl with cow's milk allergy, who developed severe anaphylaxis after the ingestion of a croissant containing sheep's milk ricotta cheese, even though she had been previously desensitized to cow's milk through SOTI. The sheep's milk specific allergen causing the severe allergic reaction (a derivative of alpha-casein of 54,1kDa) was identified by SDS-PAGE and immunoblotting. We conclude that SOTI is a species-specific procedure and the induced tolerance to cow's milk doesn't necessarily provide protection against milk of other mammals. Therefore, children desensitized to cow's milk through SOTI should strictly avoid the intake of milk of other mammals, until tolerance to those kinds of milk is documented by an oral food challenge.

Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3.

BACKGROUND: Food-dependent-exercise-induced anaphylaxis (FDEIA) is characterized by anaphylactic symptoms after exercise following ingestion of food. We present a case of FDEIA induced by Rosacee fruits showing some diagnostic problems. MATERIAL AND METHODS: A 12 years-old boy with seasonal allergy to olive and cypressus pollens, experienced two distinct episodes of FDEIA, grade 4 and 3 of the Sampson Scale respectively, during intense exercise, about 30 minutes after eating a peach with peel or some cherries. SPT with commercial peach extract and fresh Rosacee fruits scored positive while SPT with a date palm profilin-enriched extract was negative. On in vitro tests total IgE were 44 kU/l and IgE for peach, cherry, Prup 3, Prup 1, Bet v 1, Bet v 2, Bet v 4 were negative. SPT with Prup 3 UniCAP device (cellulose polymer in a plastic reserve highly binding allergen protein) was negative. An oral food challenge, performed at rest using a commercial peach juice, scored negative. An immunoblot analysis performed with peach extract was negative. DISCUSSION: The main peculiarity of this case of FDEIA is the discrepancy between positive SPT and negative in-vitro findings. The positive SPT with the commercial peach extract suggested hypersensitivity to lipid transfer protein; however, no IgE reactivity to rPrup 3 was found in-vitro. The negative immunoblot analysis, possibly caused by the low levels of specific IgE, did not allow us to investigate the nature of the relevant allergen protein further. It is possible that this patient reacted to a different peach allergen or, alternatively, that he recognized an isoform of LTP that is different fr-om that in Uni-CAP. CONCLUSION: This case emphasizes once more the diagnostic relevance of SPT with extracts and fresh material to be performed before investigating IgE reactivity to single allergen components in-vitro.

Comparative study on the effectiveness of Coblation-assisted turbinoplasty in allergic rhinitis.

OBJECTIVES: To evaluate the efficacy of adding Coblation-assisted inferior turbinoplasty to a medical treatment regimen for symptoms associated with hypertrophic inferior turbinates. STUDY DESIGN/SETTING: Prospective, open-label, non-randomized trial with outpatient treatment. Patients were assigned to treatment groups in order of enrolment into the study. SUBJECTS AND METHODS: From June 2007 to June 2008, 220 patients with allergic rhinitis and hypertrophic inferior turbinates were enrolled and assigned into two groups: the surgical group who received radiofrequency thermal ablation inferior turbinoplasty and medical therapy, and the medical group who received medical therapy only. Groups were further divided into two allergen types based on antigen sensitivity: perennial and seasonal. Subjective complaints (nasal obstruction, itching, rhinorrhea, sneezing), clinical rhinoendoscopy and rhinomanometry tests results were recorded at the start of the study and 2 months post-treatment. Effect sizes for the mean improvements after treatment were tabulated for all groups. RESULTS: All study outcomes improved within all groups. Comparison between medical and surgical groups showed higher improvement in both perennial and seasonal, respectively, in nasal obstruction, sneezing, rhinomanometry, and rhinomanometry after NPT. Itching improved only in perennial allergen type. Rhinoendoscopy clinical score showed improvement in surgical group over medical group in both allergen types. CONCLUSION: Coblation-assisted turbinate reduction is a promising adjunct to medical therapy in patients with persistent symptoms associated with allergic rhinitis. Patients undergoing this surgery had greater reduction of symptoms than patients receiving medical therapy alone, where patients with perennial allergies appeared to benefit most.

An evidence based overview of sublingual immunotherapy in children.

In light of the current evidence, subcutaneous immunotherapy (SCIT) can be suggested for use in pediatric allergic rhinitis and asthma as treatment and preventive management. Sublingual specific immunotherapy (SLIT) can be suggested for use in children with allergic rhino-conjunctivitis, and seasonal asthma, especially if they are mono-sensitive, for a duration of no less than three years. The earlier treatment begins, the better is the outcome. Further randomized, long-term trials in SLIT for the treatment of perennial asthmatic children are still needed. As regards the choice between the methods of administration (the traditional SCIT or the innovative SLIT), it is up to the physician to find the right equilibrium in the single patient.

Lack of efficacy of topical furfuryl palmitate in pediatric atopic dermatitis: a randomized double-blind study.

INTRODUCTION: Atopic dermatitis is a common disease in children. It is usually treated with topical steroids and/or calcineurin inhibitors in association with emollients but topical antioxidants have been recently introduced as a therapeutic option for children. The aim of this study was to evaluate the efficacy and tolerability of furfuryl palmitate, a new antioxidant molecule, in a multicenter, randomized, double-blind, vehicle-controlled study. PATIENTS AND METHODS: Children with atopic dermatitis were randomized into 2 groups treated for 2 weeks. One group of children (n = 60) was treated with a basic emollient cream and the other (n = 57) was treated with the same cream enriched with furfuryl palmitate. RESULTS: In both groups, there was a significant reduction (P < .001) in atopic dermatitis-measured using the SCORAD index-after 14 days. The reduction in the per-protocol analysis was higher for the basic cream. Treatment success was defined as a reduction of 20% or more in the SCORAD index from baseline to day 14. Patients who used treatment not permitted by the protocol were also considered treatment failures. The intention-to-treat analysis showed 70% positive results for the basic treatment and 29% for the treatment containing furfuryl palmitate (P < .0001) with a number needed to treat of 2.4 (95% confidence interval, 1.6-4.6). The emollient cream without furfuryl palmitate was observed to be more efficacious by pediatricians and parents, and no differences were reported between the 2 products in terms of tolerability. CONCLUSIONS: Both products proved to be efficacious in treating atopic dermatitis in children, but the emollient cream not containing furfuryl palmitate showed better clinical efficacy.

Efectos preventivos de la inmunoterapia sublingual en niños: un estudio abierto, aleatorizado y controlado / Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

Objetivos. Evaluar los efectos clínicos y preventivos de la inmunoterapia sublingual (SLIT) con respecto a la aparición de asma persistente, nuevas sensibilizaciones, síntomas clínicos e hiperreactividad bronquial (HRB). Los objetivos secundarios fueron: evaluar la magnitud del efecto clínico y el efecto sobre la HRB; ver la seguridad y adhesión a la SLIT. Material y métodos: Participaron 216 niños, de ambos sexos, entre 5 y 17 años, pacientes del Hospital Cuasso al Monte, Varese, Italia, con rinitis alérgica de al menos 2 años de evolución, con o sin síntomas de asma intermitente, y con diagnóstico de etiología alérgica confirmado para ácaros, gramíneas, árboles y malezas. Se excluyeron pacientes con asma persistente o VEF1 <80%, uso previo de inmunoterapia, anormalidades anatómicas de las vías aéreas superiores, enfermedades sistémicas crónicas (malignas o autoinmunes) y sensibilizaciones a epitelios y hongos anemófilos. Para los diagnósticos de rinitis y asma se emplearon las guías actuales (ARIA, GINA). Se realizaron prick test con panel estándar de alérgenos relevantes (ALK Abelló), histamina 1% y control negativo al principio y al final del estudio. Las pruebas de función pulmonar consistieron en espirometría computarizada con cabina pletismográfica y prueba de provocación no específica con metacolina con dosis progresivas desde 30 a 1.290 µg, durante el período de máxima exposición alérgenica según sensibilidad de cada paciente, al inicio y al final del estudio. A los pacientes con prueba negativa (descenso del VEFI <20%) se los consederaba con diagnóstico de rinitis exclusivamente. El estudi tuvo un período basal de 1 año de observación y luego una fase de aleatorización de 3 años de tratamiento abierto con dos ramas. Un grupo de pacientes utilizó drogas exclusivamente, y otro grupo drogas más SLIT (con una distribución 1/2).

Safety and tolerability of ultra-rush induction, less than one hour, of sublingual immunotherapy in children.

BACKGROUND: The safety and tolerability of sublingual immunotherapy (SLIT) has been documented in allergic patients both in the build-up phase as well as during maintenance, but only two studies have evaluated the occurrence of adverse reactions with an ultra-rush regimen of SLIT induction in a mixed paediatric/adult population. Moreover one of these two studies used a chemically modified extract (allergoid). The aim of the present study was to evaluate the occurrence of immediate or late adverse reactions in allergic children after a very fast (40 min) ultra-rush SLIT induction with two different allergen extract solutions. METHODS: We studied 100 children (64 boys, mean age of 9.6 years, range 3.5-16.8), with a history of intermittent/persistent rhinitis and/or intermittent/mild persistent asthma due to inhalant allergens. The ultra-rush build-up phase involved the administration, every 10 min, of increasing doses of the highest-concentration vial of SLIT of two different manufacturers (Anallergo and Stallergènes). RESULTS: All patients completed the treatment, side-effects have been recorded in 19% of the cases: 10% within 1 h after the build-up phase, 7% within 48 h and 2% mixed. A major difference (p = 0.0001) was recorded between Anallergo (6 patients, 8.7%) and Staloral (13 patients, 41.9%), but all the reactions were mild: principally oral symptoms, in 1 case rhinorrhoea and cough, and delayed abdominal pain and diarrhoea in another patient. CONCLUSIONS: No severe adverse reactions were observed with this ultra-rush SLIT induction also in the paediatric age; statistical differences have been documented between the two different extracts.

Topical versus systemic diclofenac in the treatment of temporo-mandibular joint dysfunction symptoms.

The most frequent symptom of craniomandibular dysfunction is pain in the preauricular area or in the temporo-mandibular joint, usually localized at the level of the masticatory musculature. Patients sometimes also complain of reflect otalgia, headaches and facial pain. Osteoarthrosis is a frequent degenerative debilitating chronic disorder that can affect the temporomandibular joint. It causes pain and articular rigidity, a reduction in mobility, and radiological alterations are visible in stratigraphy. The aim of this study was to compare the efficacy of a topically applied non-steroid anti-inflammatory drug that has recently become commercially available (diclofenac sodium in a patented carrier containing dimethyl sulfoxide, that favours transcutaneous absorption) which is commonly used to alleviate pain in knee or elbow joints, versus oral diclofenac, in the treatment of symptoms of temporomandibular joint dysfunction. Dysfunction of the temporomandibular joint was diagnosed in 36 adult patients. The patients were randomized in two age- and gender -matched groups. Group A (18 patients) received oral diclofenac sodium administered after a meal in 50-mg tablets twice a day for 14 days. Group B (18 patients) received 16 mg/ml topical diclofenac (diclofenac topical solution, 10 drops 4 times a day for 14 days). All patients completed a questionnaire at the start and end of therapy. Patients were asked to quantify on a graded visual analogue scale and to reply to questions about the pain and tenderness of the temporomandibular joint and the functional limitation of mouth opening. Patients were also requested to report side-effects of the treatment. All patients showed relief from pain after treatment: the difference between the two groups was not significant (p > 0.05). Post-treatment, 16 patients of group A had epigastralgic symptoms. Three patients treated with topical diclofenac showed a modest irritation of the temporomandibular joint region, and disappeared spontaneously. Our results demonstrate that topically applied diclofenac and oral diclofenac are equally effective in the treatment of temporomandibular joint dysfunction symptoms. Topical diclofenac has the advantage that it does not have adverse systemic effects, whereas oral diclofenac had untoward effects on the gastric apparatus. The efficacy of diclofenac topically applied on the temporomandibular joint region observed in group B is explained by the association of diclofenac with dimethyl-sulfoxide, which enables a rapid effective penetration into the joint tissues. It is noteworthy that dimethyl-sulfoxide favours transuctaneous absorption when used in a multi-dose regime as in our study with 4 doses a day. Thus, single, "as required", applications should be avoided because this practice results in scarce absorption of diclofenac.

State and trait anxiety in patients affected by nasal polyposis before and after medical treatment.

The present study aimed to establish whether anxiety and depression in nasal polyposis play a role in genesis of the disease, or are a consequence of symptoms. Anxiety levels were evaluated in state and trait forms, and depression, in 30 consecutive patients presenting nasal polyposis before and after effective 7 months' medical treatment with nasal mometasone, loratadine and montelukast. Before and at the end of treatment, patients were asked to fill in the State and Trait Anxiety Inventory and the Zung self-rating depression scale. In 63.15% of patients with high levels of state anxiety before therapy, these were reduced (p < 0.004) after treatment. In 61.9% of patients with high levels of trait anxiety before treatment, these were reduced (p < 0.002) after treatment. There were no significant differences in depression. Anxiety in nasal polyposis is present both as a state and as a trait, and is significantly reduced after effective medical treatment, showing that anxiety is a reversible consequence of nasal polyposis in most cases.