Clinical relevance of non-grass pollens respiratory allergies in Italy and effects of specific sublingual immunotherapy: The Rainbow Trial, a multicentre 3-year prospective observational study.

OBJECTIVE: We evaluated, by means of a multicentre, prospective observational trial, the severity in term of symptoms and symptomatic drugs use and the presence of asthma in subjects with tree or cypress or olive, or ragweed or parietaria allergy and we evaluated also the efficacy of a consecutive 2-year specific sublingual immunotherapy treatment. PATIENTS AND METHOD: Consecutive patients suffering of respiratory allergies (rhinoconjunctivitis and/or mild moderate asthma) due to one of the described allergens were enrolled During the specific relevant pollen seasons for each allergens nose and eye symptoms and medication scores (SS and MS) were evaluated Global score (GS) was calculated as the sum of SS and MS. An Asthma symptom score if present, were also, calculated A total of 162 patients were enrolled in 14 Italian Allergic Clinics .Patients were treated with the relevant specific sublingual immunotherapy (SLITOne, ALK) for two consecutive pollen seasons. RESULTS: At baseline prevalence of allergies was the following: tree 18% (30 patients); ragweed 14% (23 patients); olive 7% (11 patients); cypress 7% (12 patients) and pellitory 53% (86 patients). At baseline asthma was detected in 65 patients (40%). Asthma was more common in poli-sensitive subjects in comparison with mono-sensitive (51% vs. 300/o). According to allergen type, asthma was present in 47% of pellitory allergic patients, in 45% of olive allergic subjects, in 38% of ragweed allergic patients, in 26% of tree allergic patients and only in 9% of cypress allergic subjects. In pellitory, olive and ragweed allergic patients the frequency of asthma was statistically significant (P=0.0055) higher in comparison with other groups. At baseline GS mean (SD) in the whole population was 17(7). GS during the following 2 consecutive seasons with SLIT treatment decreased significantly (P=0.0001) to 9 (5) and to 7 (5), respectively (a reduction of 59% in comparison with baseline). In patients with asthma the mean clinical score decreased significantly from baseline value of 2. 7 to 0.3 at the end of the observation period No serious adverse events were reported Local side effects, mainly oral itching, were reported by 14% of patients and were mild and transient in nature. CONCLUSION: In this population pellitory, olive and ragweed allergies are associated with a more severe clinical picture in comparison with tree and cypress allergy. A two-year SLIT treatment was associated with a significant reduction in SS, MS, GS and asthma score in comparison with baseline. SLIT was also safe and well tolerated

Omega-5 gliadin anaphylaxis: an integrated diagnostic approach.

We report the case of a 62-year old man who presented a wheat-dependent, exercise-induced anaphylaxis (WDEIA). The case illustrates the usefulness of skin prick test not only with wheat extract, but also with native gliadin extract. Moreover we confirm the value of recombinant IgE dosage with rTri a 19 omega-5 gliadin in the diagnostic pathway of this condition.

Comparison of different diagnostic products for skin prick testing.

BACKGROUND: Different in vivo methods are used to quantify the amount of allergens in products for skin prick testing. It is unclear how this impacts on the correct diagnosis of allergies. AIM OF THE STUDY: We compared the allergenic potency of three commercial extracts for skin prick testing and evaluated batch-to-batch differences within each product. METHODS: Patients with a mono-sensitization (specific IgE level > 0,70 KU/L, ImmunoCAP, Phadia) to Phleum pratense (N=21), Parietaria judaica (N=20) or Dermatophagoides pteronyssinus (N=28) were evaluated by standard skin prick testing and with the end-point dilution technique using commercial products from Stallergenes (A) (Antony, France), Lofarma Allergeni (B) (Milan, Italy) and ALK Abellò (C) (Hoersholm, Denmark). Results were expressed as mean areas of the wheal (cut-off for positive reactions: 7 mm2). RESULTS: With standard prick testing, the following differences in wheal areas were found: Phleum, C higher than B (p=0.0454); Parietaria, C higher than A (p=0.094); Dermatophagoides, C higher than A (p=0.021). With limiting dilution testing, the following differences in dilutions yielding positive skin prick tests were found: Phleum, C and B higher than A (p=0.0391 and 0.0039, respectively); Dermatophagoides, C higher than A and B (p=0.0010 and 0.0156, respectively). In the batch-to-batch comparison, mean differences between wheal areas of compared undiluted solutions did not significantly differ in any allergen tested, although in single cases large differences were observed. At the 1 to 64 dilution, agreement was significant only with Dermatophagoides from Manufacturer C (p= 0.262). At the 1 to 16 dilution, agreement was significant with Phleum from Manufacturer C (p=0.0116) and with Dermatophagoides from Manufacturer B and C (p=0.0239 and 0.0001, respectively). At the 1 to 4 dilution agreement was significant with Dermatophagoides from the three considered Manufacturers (p=0.0189, 0.0052 and 0.0077, respectively) and with Phleum from Manufacturer B and C (p=0.0336 and 0.0113, respectively). CONCLUSION: There are significant differences among commercially available diagnostic products for skin prick testing.

Natural rubber latex allergy in children: clinical and immunological effects of 3-years sublingual immunotherapy.

BACKGROUND: We previously demonstrated that one year of sublingual immunotherapy (SLIT) with natural rubber latex (NRL) was safe and efficacious in paediatric patients with NRL allergy. RESEARCH DESIGN AND METHODS: We studied 12 NRL-allergic children (age 4-15), previously assigned to the treated arm of a double-blind placebo controlled study, who received a commercial latex SLIT for three years. Adverse reactions were monitored. The primary end-point was the NRL glove-use test. As secondary end-points, skin prick test with NRL and NRL serum specific IgE were used. MAIN OUTCOMES MEASURES: No SLIT-related side effects were observed. A significant reduction of the glove-use score was observed after one-year treatment (5.1 +/- 4.2 vs. 14.8 +/- 5.7, p=0.0031). This parameter was further reduced in the second year since SLIT start (2.0 +/- 2.7, p=000007). After 3 years of SLIT all patients had a negative glove-use test (p<0.0001). Baseline wheal areas of skin prick test (6.8 +/- 2.5 mm2) were significantly reduced after 2 (5.3 +/- 1.8 mm2) and 3 years (4.0 +/- 1.8 mm2) of SLIT (p=0.039 and 0.027, respectively). Baseline values of serum specific IgE (23 +/- 34 KU/l) were significantly reduced after 3 years since SLIT start (6.4 +/- 5.0, p=0.0371). CONCLUSIONS: Three years of latex SLIT is safe and consolidates the efficacy previously observed after one year of treatment in paediatric patients.

Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.

Methodology and potential pitfalls in allergic diseases study designs: measurements for the assessment of the overall severity of atopic dermatitis--the four step severity score (FSSS), SCORAD-related, electronic system, for the simple and rapid evaluation of the skin and mucosal allergic inflammation.

Medical statistics may contribute to ameliorate research by improving the design of studies and identifying the optimal method for the analysis of results. Sometimes, nevertheless, it could be misemployed flawing the benefit potential. Allergic diseases pathogenesis is recognized to be systemic but global initiatives such as GINA and ARIA documents define allergic asthma and rhinitis as organ diseases; such an asymmetrical view raises a set of known and unknown confounding that could influence the quality of the process of evidence-based decision-making (topic symptomatic therapeutic interventions versus systemic pathogenetic interventions). This article shows the first scoring system for the assessment of atopic dermatitis lesions developed in the allergy-area. A four-step severity score (FSSS) was chosen in agreement with those developed for asthma and rhinitis in global initiatives, to avoid any further differences in evaluating the severity of allergic diseases. FSSS relates each step with the objective signs of the SCORAD and rates the disease course as intermittent or persistent. A devoted electronic program has been also framed to allow a quick and simple contemporary evaluation of the SCORAD Index (Section I) and of the FSSS (Section II); the program furthermore foresees a third section named ESAS (Extra Skin Allergic Signs) (Section III) in which it is possible to check whether organs other than the skin are involved by the allergic inflammation. The limitations potential generated by a misemployment of medical statistics for clinical trials designed to establish benefits rising from specific immunotherapy for allergic diseases have been also discussed extensively.

Hydrological simulation of Po River (North Italy) discharge under climate change scenarios using the RCM COSMO-CLM.

The impacts of climate change on Po River discharges are investigated through a set of climate, hydrological, water-balance simulations continuous in space and time. Precipitation and 2m mean temperature fields from climate projections under two different representative concentration pathways, RCP4.5 and RCP8.5, have been used to drive the hydrological model. Climate projections are obtained nesting the regional climate model COSMO-CLM into the global climate model CMCC-CM. The bias in climate projections is corrected applying the distribution derived quantile mapping. The persistence of climate signal in precipitation and temperature after the bias correction is assessed in terms of climate anomaly for 2041-2070 and 2071-2100 periods versus 1982-2011. To account for the overall uncertainty of emission scenarios, climate models and bias correction, the hydrological/water balance simulations are carried out using both raw and bias corrected climate datasets. Results show that under both RCPs, either considering raw and bias corrected climate datasets, temperature is expected to increase on the whole Po River basin and in all the seasons; the most significant changes in precipitation and discharges occur in summer, when the reduction of precipitation leads to an increase in low flow duration and occurrence likelihood, and in autumn and winter where precipitation shows a positive variation increasing the high flows frequency.

Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.

A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed.

[The lipid model in hemodialyzed patients]. / Il modello lipidico negli emodializzati.

In the context of metabolic alteration in dialysis patients the Authors have studied the characteristics, incidence, pathogenesis, effect of dialysis, atherogenic risk and therapeutic approach to hyperlipemia in hemodialysis patients. Hypertriglyceridemia secondary to reduced lipolytic activity is the most frequent alteration observed in hemodialytic patients (36.7% of cases). In addition, hemodialysis reduces the levels of lipoprotein in the blood whereas the atherogenic role of hyperlipemia does not appear to be as important as that of arterial hypertension and smoking. Simvastatin breaks down the lipidic fractions which are involved in atherogenesis and coronary cardiopathy, thus acting as a valuable prevention against cardiovascular involvement in dialysis.

[The intradialytic kinetics of uremic toxins in the diffusion-convection hemodialysis method]. / La cinetica intradialitica delle tossine uremiche nell'emodialisi a meccanismo diffusivo-convettivo.

A kinetic evaluation of dialytic methods using a diffusive-convective mechanism in comparison to the standard bicarbonate dialysis was performed in order to verify the possible therapeutic uses. The "kinetic" comparison of PFD and HDF to HBD, using equal quantities of dialysate, showed no significant change in the mention of uremic toxins of small molecular weight and a more efficient capacity to extract beta 2M by the diffusive-convective methods. The biophysical evaluation of dialysis still appears to represent the best means of defining the clearance possibilities and of identifying the most suitable technique for achieving a dialytic adequacy.

Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy.

Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.

Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years.

BACKGROUND: The age below 5 years is considered a prudential limit for immunotherapy in view of the possible severity of side-effects. Sublingual immunotherapy (SLIT) seems to be safe, but no study in very young children is available. We performed a safety post-marketing surveillance study in children below 5 years. METHODS: Children aged 3-5 years with respiratory allergy receiving SLIT were followed-up for at least 2 years. A diary card for side-effects was filled by parents at each dose given. Local and systemic side-effects were graded as: mild (no intervention, no dose adjustment), moderate (medical treatment and/or dose reduction), severe (life-threatening/hospitalization/emergency care). The comparative safety of different allergens and regimens was also assessed. RESULTS: One hundred and twenty-six children (mean age 4.2 years, 67 male) were included. Seventy-six (60%) had rhinitis with asthma, 34 (27%) rhinitis only and 16 (13%) only asthma. Immunotherapy was prescribed for mites (62%), grasses (22.2%), Parietaria (11.9%), Alternaria (2.4%) and olive (1.5%). Eighteen children underwent an accelerated build-up. The total number of doses was about 39,000. Nine side-effects were reported in seven children (5.6% patients and 0.2/1000 doses). Two episodes of oral itching and one of abdominal pain were mild. Six gastrointestinal side-effects were controlled by reducing the dose. All side-effects occurred during up-dosing phase. No difference in terms of safety among the allergens used was observed. CONCLUSION: SLIT is safe also in children under the age of 5 years.

A pre-seasonal birch/hazel sublingual immunotherapy can improve the outcome of grass pollen injective treatment in bisensitized individuals. A case-referent, two-year controlled study.

BACKGROUND: The study tests the hypothesis of a reduction of priming due to tree allergy in patients sensitised to both birch/hazel and grass pollen undergoing an associated preseasonal Sublingual/Injective immunotherapy. METHODS: 36 out of 49 bisensitized candidates were pair-matched into 18 case-referent couples. During two years all patients were administered preseasonal grass-SIT and one patient in each couple received also birch/hazel-SLIT. Diary cards were fulfilled for three consecutive grass pollen seasons. Specific Nasal Provocation Test (NPT) for grass and aspecific bronchial challenge were done; sera were analyzed for specific IgE and IgG. RESULTS: During the peak of the grass pollen season both groups showed a significant improvement in total symptom-score. Conjunctivitis and cough improved significantly more in patients with associated therapies. While antihistamine score decreased significantly in both groups, antiasthmatics did only in the SLIT-SIT group. The follow-up documented a significant increase in grass- and birch-specific IgG and a decrease in grass-specific IgE. Grass-NPT threshold was clearly higher in SLIT-SIT-group (p = 0.01) and only in this group PD20 methacholine improved significantly (p < 0.05). CONCLUSIONS: Combined birch/hazel-SLIT and grass-SIT are safe and improve clinical outcomes of SIT alone in young bisensitized patients. Priming reduction is supported by specific NPT and bronchial hyperresponsiveness.

Effects on inflammation parameters of a double-blind, placebo controlled one-year course of SLIT in children monosensitized to mites.

BACKGROUND: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor. METHODS: Twenty-four children (age range 4-16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double-blind, placebo-controlled design. Before treatment and 10-12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite-specific IgE (sIgE), allergen-specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT. RESULTS: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group. CONCLUSIONS: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms.

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.