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.

Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis.

Background: Nasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it. Objective: To identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR. Methods: Poly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract. Results: We recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p < 0.01; best cut-off ≥7.25%, sensitivity 70.5%, specificity: 90.9%). VAS results also predicted NPT positivity, although with less precision (AUC: 0.77, p < 0.01; best cut-off ≥7, sensitivity: 60.7%, specificity: 81.8%). Conclusions: An index combining the specific activity of IgE to rPhl p 5 and nCyn d 1 predicted with moderate sensitivity and high specificity the outcome of a grass pollen NPT in complex, poly-sensitized pediatric patients with seasonal allergic rhinitis. Further studies are needed to improve the index sensitivity and to assess its usefulness for NPT allergen selection or as an alternative to this demanding test procedure.

Pollens causing allergy and their monitoring by aerobiology and phenology.

Allergies caused by inhalant allergens, particularly pollens, are steadily increasing in urban centers. It is known that atmospheric pollution is strongly related to the inflammatory disease of the upper and lower airways but it is equally important in the development of sensitization towards pollens. Particulate Matter (PM), sulfur dioxide (SO2) and nitrogen dioxide (NO2) have an enhancement function on the persistence of pollens in the air, increasing the concentration and duration of pollinosis. It is therefore essential to use air quality control methods in urban centers to monitor the presence of pollen and fine dust that can drive the doctor and the patient to improve prevention, a step of primary importance in the treatment of allergies. Aerobiology and phenology are essential tools to monitor pollen production. The opportunity for the patients to use social media as information sources, including teletext, sms, mail and social networks, as well as a wide range of apps, allows to have reliable information on the air we breathe and therefore to better manage the methods of prevention at our disposal.

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.

Prevalence of carotid stenosis in type 2 diabetic patients asymptomatic for cerebrovascular disease.

Stroke, with an incidence of 2.5 x 10(3) yr(-1) (95% CI, 2.3-2.8 x 10(3) yr(-1)), is the third most frequent cause of death and the first cause of disability in western society. Diabetes is an important risk factor for ischaemic stroke, second only to hypertension, whereas it does not seem to be associated with an increased risk of haemorrhagic stroke. The incidence of stroke in men and women between 45 and 74 yr has been found to be 2.5 and 3.5 times higher in diabetics than in non-diabetic subjects, with a relative risk higher in females than in males with diabetes and greater in both sexes in the 50-to-60-yr age group but decreased in subjects who were 70 and above. It is known that there is an association between ischaemic stroke and carotid stenosis. However, the prevalence of carotid stenosis in Type 2 diabetes mellitus (T2DM) patients has not been well investigated, mainly in the Italian diabetic population. Therefore, the aim of this study was to evaluate the prevalence of carotid artery stenosis in a population of T2DM patients asymptomatic for cerebrovascular disease selected from the files of the Diabetes Clinics, and from the computerised files of General Practitioners (GPs). Three hundred and sixty-five subjects were examined: 187 were non-diabetic (89 males, 98 females) and 178 were T2DM patients (82 males, 96 females). The mean age of all the subjects was 67 +/- 7.8 yr; 66 +/- 7.9 for the non-diabetic subjects and 67 +/- 7.5 yr in the diabetic subjects. In the echo-Doppler examination of the carotid, a degree of stenosis ranging 10-99% was recorded in 143/365 subjects (39.1%), 49/187 non-diabetics (26.2%) and 94/178 diabetics (52.8%). The differences were highly significant (p < 0.001). Severe stenosis was recorded in 17/143 subjects (12%); 12 of these were diabetic (70%) and 5 non-diabetic (30%). The diabetics were three times more likely to develop carotid stenosis than the non-diabetics with an odds ratio of 3.152, (95% CI, 2.032-4.889).

Real-time three-dimensional color Doppler echocardiography for characterizing the spatial velocity distribution and quantifying the peak flow rate in the left ventricular outflow tract.

Quantification of flow with pulsed-wave Doppler assumes a "flat" velocity profile in the left ventricular outflow tract (LVOT), which observation refutes. Recent development of real-time, three-dimensional (3-D) color Doppler allows one to obtain an entire cross-sectional velocity distribution of the LVOT, which is not possible using conventional 2-D echo. In an animal experiment, the cross-sectional color Doppler images of the LVOT at peak systole were derived and digitally transferred to a computer to visualize and quantify spatial velocity distributions and peak flow rates. Markedly skewed profiles, with higher velocities toward the septum, were consistently observed. Reference peak flow rates by electromagnetic flow meter correlated well with 3-D peak flow rates (r = 0.94), but with an anticipated underestimation. Real-time 3-D color Doppler echocardiography was capable of determining cross-sectional velocity distributions and peak flow rates, demonstrating the utility of this new method for better understanding and quantifying blood flow phenomena.

Left ventricular endocardial surface detection based on real-time 3D echocardiographic data.

OBJECTIVE: A new computerized semi-automatic method for left ventricular (LV) chamber segmentation is presented. METHODS: The LV is imaged by real-time three-dimensional echocardiography (RT3DE). The surface detection model, based on level set techniques, is applied to RT3DE data for image analysis. The modified level set partial differential equation we use is solved by applying numerical methods for conservation laws. The initial conditions are manually established on some slices of the entire volume. The solution obtained for each slice is a contour line corresponding with the boundary between LV cavity and LV endocardium. RESULTS: The mathematical model has been applied to sequences of frames of human hearts (volume range: 34-109 ml) imaged by 2D and reconstructed off-line and RT3DE data. Volume estimation obtained by this new semi-automatic method shows an excellent correlation with those obtained by manual tracing (r = 0.992). Dynamic change of LV volume during the cardiac cycle is also obtained. CONCLUSION: The volume estimation method is accurate; edge based segmentation, image completion and volume reconstruction can be accomplished. The visualization technique also allows to navigate into the reconstructed volume and to display any section of the volume.

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy.

BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

Real-time 3D echocardiographic data analysis for left ventricular volume estimation.

A new computerized semi-automatic method for left ventricular chamber segmentation is presented. The left ventricle is imaged by real-time three-dimensional echocardiography. This real-time data acquisition method allows accurate evaluation of chamber size and shape, even in case there are cavities with irregular geometry. The surface detection model is based on a partial differential equation that propagates interfaces with curvature dependent speeds. The equation is solved by applying numerical methods for conservation laws. The method consists of one step only. Initial conditions are manually established on a small subset of slices of the entire volume. The solution obtained is a surface corresponding to the surface between LV cavity and LV endocardium. This mathematical model is applied to sequences of frames of human hearts (volume range: 34-109 ml) imaged by real-time 3D echocardiography. Volume estimates show an excellent correlation with those obtained by manual tracing (r=0.99).

Dehydroepiandrosterone sulphate plasma levels in normal women and patients with benign breast disease.

Dehydroepiandrosterone sulphate plasma levels were measured in patients with benign breast disease and in healthy women. In addition the adrenal secretion of dehydroepiandrosterone sulphate was assessed by means of an ACTH stimulation test in some patients and control subjects. The results obtained demonstrate that dehydroepiandrosterone sulphate plasma levels of patients with benign breast disease overlap those found in controls and that the adrenal response to ACTH of patients with breast pathology does not differ from that of healthy women.

Endocrine aspects of benign breast disease.

The purpose of this study was to determine the levels of dehydroepiandrosterone sulfate (DHAS) in the plasma of women with benign breast disease (BBD) and in normal subjects. Possible changes in DHAS plasma levels and in its adrenal secretion under adrenocorticotrophin hormone (ACTH) were also investigated in women with BBD before and after bromocriptine therapy. Our results demonstrate that plasma levels of DHAS in women with BBD overlap with those found in controls. Prolactin (PRL) suppression in women with BBD receiving bromocriptine treatment was associated with a significant (p less than 0.02) decrease of baseline DHAS plasma levels and of stimulated ACTH response curve (p less than 0.02). These data suggest a possible relationship between PRL and DHAS secretion in women with BBD.

Prolactin secretion and dehydroepiandrosterone sulphate plasma levels in women with benign breast disease.

The purpose of the present investigation was to verify possible positive correlations between prolactin secretion and dehydroepiandrosterone sulphate levels in plasma of women with benign breast disease. Prolactin secretion was evaluated in terms of basal levels, maximum peak, percent increase above baseline levels, total integrated area, response area after TRH stimulation. No correlation was found between the parameters of prolactin secretion and dehydroepiandrosterone sulphate levels.

Hormonal profile in benign breast disease. Endocrine status of cyclical mastalgia patients.

Plasma levels of prolactin, before and after TRH stimulation, progesterone, estradiol, sex-hormone-binding-globulin, androstenedione, testosterone and dehydroepiandrosterone-sulphate were determined in a group of women with benign breast disease and in control group, in order to correlate a possible hormonal disorder to breast pathology. The hormonal pattern in the patients with benign breast disease was characterized by an increased responsiveness of lactotrophes to TRH stimulation and by higher levels of sex hormone binding globulin, probably sustained by an underlying hyperestrogenism.