Systemic allergic reactions induced by labile plant-food allergens: Seeking potential cofactors. A multicenter study.

BACKGROUND: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE: To detect the risk factors for systemic reactions induced by labile food allergens. METHODS: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. CONCLUSION: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

Pollen concentrations and prevalence of asthma and allergic rhinitis in Italy: Evidence from the GEIRD study.

BACKGROUND: Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty. AIM: We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy. METHODS: A questionnaire on respiratory diseases was delivered to random samples of 20-44year-old subjects from six centers in 2005-2010. Data on the daily air concentrations of 7 major allergologic pollens (Poaceae, Urticaceae, Oleaceae, Cupressaceae, Coryloideae, Betula and Ambrosia) were collected for 2007-2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept. RESULTS: Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10days=0.989, 95%CI: 0.979-0.999) or at least two pollens (OR=0.974, 95%CI: 0.951-0.998); associations with the number of days with at least one (OR=0.988, 95%CI: 0.972-1.004) or at least two (OR=0.985, 95%CI: 0.970-1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations. CONCLUSIONS: Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level.

Ragweed allergy: Pollen count and sensitization and allergy prevalence in two Italian allergy centers.

BACKGROUND: Ragweed allergy represents a challenge for allergists due to its increase in some geographic areas, mainly northern Italy. OBJECTIVES: To compare two allergy centers in northern Italy by analyzing both the pollen count and the patient characteristics (sensitization and allergy prevalence) over a 10-year period. METHODS: Pollen counts for 10 years (2004-2013) were evaluated and compared in the two centers. Characteristics of patients who were sensitized and allergic to ragweed were analyzed. RESULTS: There was a significantly higher pollen count in Busto Arsizio than in Novi Ligure (p < 0.001). The patients who were seen in the Busto Arsizio center showed more frequent sensitization (p < 0.01) and allergy (p < 0.05) to ragweed than patients who were seen in the Novi Ligure center. The pollen count was significantly (p < 0.01) associated with sensitization and allergy difference. Allergic asthma was more frequent (p < 0.05) in Busto Arsizio. CONCLUSIONS: The pattern of sensitization and allergy prevalence seemed to be associated with ragweed pollen pressure, such as quantity. The knowledge of the pollen count is relevant in clinical practice, mainly for the management of patients with allergy.

Efficacy of a novel food supplement in the relief of the signs and symptoms of seasonal allergic rhinitis and in the reduction of the consumption of anti-allergic drugs.

BACKGROUND: Seasonal Allergic rhinitis (SAR) is characterized by runny nose, congestion, sneezing and sinus pressure. A clinical study was performed to demonstrate the efficacy of Lertal®, an innovative food supplement containing Quercetin, Perilla frutescens and Vitamin D3 formu-lated in a double layer "fast-slow" release tablet form, in the relief of symptoms of seasonal allergic rhinitis and in the reduction of consumption of anti-allergic drugs. PATIENTS AND METHODS: 23 subjects enrolled in the open clinical study had at least one year history of allergic rhinitis and positive skin prick test or RAST to Parietaria officinalis pollen. At baseline, the subjects had symptoms of nasal and/or ocular seasonal allergic rhinitis. The activity of the food supplement was evaluated using the Total Symptoms Score at first (baseline) and second (final) visit, after one month of supplementation. The consumption of anti-allergic drugs was also evaluated. RESULTS: All subjects enrolled completed the study. The comparison of the scores obtained in the two visits (baseline and final) showed a highly significant reduction of the overall symptoms: approximately 70% for symptom scores and 73% in use of anti-allergic drugs. Sneezing, rhinorrhea, nasal obstruction, ocular itching, lacrimation and congestion of the conjunctiva, all showed a highly significant reduction. No noteworthy side effect was recorded and all patients finished the study with good compliance. CONCLUSIONS: The results showed a clear efficacy of the food supplement Lertal® in reducing nasal and/or eye symptoms. This activity was objectively confirmed by the reduction in the consumption of anti-allergic drugs used to relieve symptoms. (www.actabiomedica.it).

Molecular cloning and characterization of Cup a 4, a new allergen from Cupressus arizonica.

Sensitization to Cupressaceae pollen has become one of the most important causes of pollinosis in Western countries during winter and early spring. However, the characterization of the extracts, the allergens involved and the cross-reactivity with other pollen sources still remain poorly studied; in the case of Cupressus arizonica only two allergens have been described so far. A new allergen from C. arizonica pollen, Cup a 4, was cloned and expressed in Escherichia coli as an N-terminally His-tag recombinant protein that was characterized biochemically, immunologically and by circular dichroism spectroscopy. The new allergen has high sequence identity with Prickly Juniper allergen Jun o 4 and contains four EF-hand domains. The recombinant protein has structural similarities with other calcium binding allergens such as Ole e 3, Ole e 8 and Phl p 7. Cup a 4 is expressed in mature pollen grains and shares antigenic properties with the recombinant form. Sera from 9.6% C. arizonica allergic patients contain specific IgE antibodies against recombinant Cup a 4.

Possible role of climate changes in variations in pollen seasons and allergic sensitizations during 27 years.

BACKGROUND: Climate changes may affect the quality and amount of airborne allergenic pollens. The direct assessment of such an effect requires long observation periods and a restricted geographic area. OBJECTIVE: To assess variations in pollens and allergic sensitizations across 27 years in relation to climate change in a specific region. METHODS: We recorded pollen counts, season durations, and prevalences of sensitizations for 5 major pollens (birch, cypress, olive, grass, and Parietaria) in western Liguria between 1981 and 2007. Pollen counts were performed using a Hirst-type trap, and sensitizations were assessed by means of skin prick testing. Meteorologic data for the same period included average temperatures, direct radiation, humidity, number of sunny days, and rainfall. RESULTS: There was a progressive increase in the duration of the pollen seasons for Parietaria (+85 days), olive (+18 days), and cypress (+18 days), with an overall advance of their start dates. For Parietaria, there was an advance of 2 months in 2006 vs 1981. Also, the total pollen load progressively increased for the considered species (approximately 25% on average) except for grasses. Percentages of patients sensitized to the pollens increased throughout the years, whereas the percentage of individuals sensitized to house dust mite remained stable. These behaviors paralleled the constant increase in direct radiation, temperature, and number of days with a temperature greater than 30 degrees C. CONCLUSION: The progressive climate changes, with increased temperatures, may modify the global pollen load and affect the rate of allergic sensitization across long periods.

Economic evaluation of sublingual immunotherapy vs. symptomatic treatment in allergic asthma.

BACKGROUND: The worldwide increased prevalence of allergic diseases, and especially of respiratory allergy, is paralleled by increased health costs. This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice. OBJECTIVE: To compare the different economic relevance, over a long evaluation time, of symptomatic pharmacologic therapy and sublingual immunotherapy (SLIT) in patients with allergic asthma. METHODS: Seventy patients with perennial allergic asthma, sensitized to dust mites, were enrolled; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs. The patients were evaluated for 2 years after discontinuing immunotherapy, which was performed for 3 years, to obtain a more complete follow-up. Symptom scores, medication scores, and all other direct medical costs were evaluated with a specific questionnaire. RESULTS: Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment, but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity. CONCLUSION: The economic advantage measured alongside this prospective observational study was long lasting and still present at the fifth year of the follow-up (2 years after discontinuing SLIT) and could positively be related to the persistent good clinical control of patients.

Safety of sublingual immunotherapy started during the pollen season.

BACKGROUND: Sublingual immunotherapy (SLIT) is safer than subcutaneous immunotherapy (SCIT) and this has lead to the reconsideration of the use of ultra-rush schedules for SLIT. The aim of this study was to assess the safety of ultra-rush SLIT in pollen-allergic children according to different timing of administration in relation to the pollen season. METHODS: In total, 34 children with pollen-induced rhinitis and 36 with pollen-induced asthma and rhinitis, were enrolled and assigned to three study groups: group 1 (n = 17 patients): conventional pre-seasonal-SLIT treatment; group 2 (n = 23 patients), seasonal SLIT ended before the pollen seasonal peak; group 3 (n = 30 patients), SLIT began after the pollen seasonal peak and ended after the pollen season. SLIT was performed using extracts from Stallergenes (Antony, France) and following an ultra-rush schedule, consisting in four doses at a 30-min intervals, and maintenance treatment by administering the top dose three times a week. RESULTS: In all, 54 adverse events (AEs) were reported: 12 in nine patients in group 1 (9/17, 52.9%), 22 in 14 patients in group 2 (14/23, 60.9%), and 20 in 13 patients in group 3 (13/30, 43.3%). No statistically significant differences were found between the three groups. Local AEs (oral itching and burning) were short lasting and self-resolving. Systemic AEs were also mild, except for a case of asthma, which lasted 5 days, in a patient from group 1. There were no severe reactions, and none of the patients dropped out. CONCLUSIONS: This study suggests that SLIT with pollen extracts may be safely started at the beginning and also during the pollen season, with a tolerability profile comparable to the conventional pre-seasonal SLIT.

Allergic memory of patients sensitized to castor bean after a long stimulation-free period.

We have taken advantage of the temporary exposure of Marseilles population to castor bean seed proteins to follow 26 allergic patients more than 20 years after sensitization. Skin tests, specific immunoglobulin E (IgE) antibody assays, and specific immunoblots were performed. Skin test reactivity to Ricinus Communis and specific IgE concentrations decreased progressively and almost completely disappeared after 20 years. Specific IgE concentration displayed a fairly exponential decrease, with a half-life of 4.7 years. Thus, in the absence of any antigenic stimulation, directly by castor bean, or indirectly by cross-reactivity to other Euphorbiaceae, especially latex, IgE sensitization is bound to disappear.

Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug treatment in patients with allergic rhinitis and asthma.

Only a few studies analyzed the pharmacoeconomics of allergen immunotherapy compared with drug treatment in subjects with allergic rhinitis and asthma. This study was aimed at evaluating whether allergen immunotherapy has an economic advantage on standard antiallergic drugs in patients with pollen-induced rhinitis and asthma. Thirty patients with rhinitis and asthma caused by Parietaria pollen were included in the study, 20 (11 men and 9 women; mean age, 35.45 +/- 10.45 years) were treated with subcutaneous immunotherapy by a Parietaria judaica extract (Alustal, Stallergénes, Antony, France) by a conventional build-up schedule in 12 weeks and a maintenance treatment every 4 weeks for 3 years, and 10 (6 men and 4 women; mean age, 31.90 +/- 10.97 years) were treated with antiallergic drugs. Each patient was evaluated before starting the treatment and annually for 6 years in the pollen period of Parietaria by means of nose, eyes, and lung symptom scores, along with drug consumption registered in diary cards. In other specifically designated cards general practitioner's or specialist's visits, the number of desensitizing injections and the number of boxes of antiallergic drugs were registered. A significant difference in favor of immunotherapy plus drug treatment versus drug treatment alone was observed, reaching a cost reduction of approximately 15% the second year and 48% the third year, with a highly statistical significance that was maintained up to the sixth year, i.e., 3 years after stopping immunotherapy, when an 80% reduction was found. The net saving for each patient at the final evaluation corresponded to euros 623 (dollars 830)/year. These findings confirm some previous observations in studies from Germany and the United States that subcutaneous immunotherapy has significant economic advantages over antiallergic drug treatment in the long term.

Cloning and Expression of the Olea europaea allergen Ole e 5, the pollen Cu/Zn superoxide dismutase.

BACKGROUND: Recombinant DNA technology does provide pure, well-defined and reproducible products to be used for clinical purposes, by cloning and expressing the cDNA of allergens present in a specific extract. Ole e 5 is a pollen allergen of Olea europaea with an IgE-binding frequency of about 35%, which has been identified as a superoxide dismutase (SOD). The aim of this study was to clone the cDNA of Ole e 5, to express Ole e 5 in Escherichia coli and to characterize its immunoreactivity. METHODS: cDNA of Ole e 5 was amplified by nested 3'-RACE PCR and cloned in pGEX vector 6P expression vector. After sequencing of some clones and homology analysis, the rOle e 5 was produced in an E. coli strain as a fusion protein with GST and purified. Then, the protein immunoreactivity was evaluated by patients' IgE binding (ELISA, ELISA inhibition, and immunoblotting) and by rabbit anti-rOle e 5 binding (immunoblotting and immunoblotting inhibition). RESULTS: The sequence analysis of Ole e 5 cDNA confirmed that Ole e 5 is a Cu/Zn SOD, with an identity from 90 to 80% with SOD from other species. rOle e 5 was recognized by IgE from 39% of olive pollen-allergic patients tested; moreover, this binding was inhibited by the olive pollen extract. An anti-rOle e 5 antiserum raised in rabbit strongly reacted with a natural component of about 16-kDa molecular weight present in the olive pollen extract; moreover, this binding was inhibited by the recombinant protein. CONCLUSIONS: Ole e 5 is the first Cu/Zn SOD identified as an allergen in a pollen source. Due to the widespread presence of this enzyme, rOle e 5 allergen, cloned and expressed in a complete form in E. coli, could represent a good tool to investigate the allergen cross-reactivity between O. europaea pollen and other allergenic sources, such as plant foods and other pollens.

Specific immunotherapy effect on interleukin-18 and CD30 serum levels in monosensitized patients with rhinitis.

To clarify the immunologic changes associated with specific immunotherapy (SIT), we analyzed interleukin (IL)-18 and CD30 serum levels in a group of patients with allergic rhinitis before and after SIT. IL-18 is a proinflammatory cytokine that plays an important role in the Th1 response. CD30 is a marker of Th2 lymphocytes. We selected 16 healthy donors (HDs) and 16 patients affected by allergic rhinitis, matched for sex and age. Serum IL-18 and CD30 levels were assayed by an immunoenzymatic method. IL-18 serum levels in the patients were lower than in the HDs before SIT (200.69 +/- 93.48 pg/mL versus 296.50 +/- 66.29 pg/mL; p < 0.05). After SIT, patients showed an increase of serum IL-18 levels (288.69 +/- 146.69 pg/mL versus 200.69 +/- 93.48 pg/mL; p < 0.05). On the contrary, serum CD30 levels were higher in patients before SIT with respect to HDs (14.78 +/- 8.30 IU/mL versus < 1 IU/mL; p < 0.05). SIT caused a decrease of serum CD30 levels in patients who were allergic (5.95 +/- 5.70 IU/mL versus 14.78 +/- 8.30 IU/mL; p < 0.05). In conclusion, in this study we showed for the first time the shift of IL-18 and CD30 production after SIT.

Allergen cross-reactivity between proteins of the latex from Hevea brasiliensis, seeds and pollen of Ricinus communis, and pollen of Mercurialis annua, members of the Euphorbiaceae family.

Allergen cross-reactions among three strongly sensitizing Euphorbiaceae species, i.e., the rubber tree (Hevea brasiliensis), castor bean (Ricinus communis), and the Mediterranean weed Mercurialis annua were studied in Finnish patients (n = 25) allergic to natural rubber latex (NRL), but with no known exposure to castor bean or M. annua, and French patients allergic to castor bean (n = 26) or to M. annua (n = 9), but not to NRL. In immunoglobulin E (IgE)-immunoblotting, 28% of NRL-allergic patient sera recognized castor bean seed and 48% reacted to castor bean pollen proteins. Likewise, 35% of the NRL-allergic patient sera bound to M. annua pollen allergens. Nineteen percent of castor bean-allergic patients showed IgE to NRL and 8% to M. annua proteins. Sera from patients allergic to M. annua reacted in 44% to NRL, in 56% to castor bean seed, and in 78% to castor bean pollen proteins. In immunoblotting, castor bean seed extract inhibited the binding of NRL-reactive IgE to 20 kDa, 30 kDa of NRL, and 55 kDa of proteins; NRL extract, in turn, inhibited the binding of castor bean-reactive IgE to 14, 21-22, 29, and 32-34 kDa of castor bean proteins. In ELISA inhibition, NRL extract inhibited 33% of the binding of M. annua--reactive IgE of pooled sera to M. annua pollen. In conclusion, allergen cross-reactivity in vitro was observed among three botanically related Euphorbiaceae members, H. brasiliensis, R. communis, and M. annua, but the molecular specificity of the observed cross-reactions as well as their clinical significance remains to be elucidated. Allergen cross-reactivity should be taken into account in diagnostic work.