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Any foraging animal is expected to allocate its efforts among resource patches that vary in quality across time and space. For social insects, this problem is shifted to the colony level: the task of allocating foraging workers to the best patches currently available. To deal with this task, honeybees rely upon differential recruitment via the dance language, while some ants use differential recruitment on odor trails. Bumblebees, close relatives of honeybees, should also benefit from optimizing spatial allocation but lack any targeted recruitment system. How bumblebees solve this problem is thus of immense interest to evolutionary biologists studying collective behavior. It has been thought that bumblebees could solve the spatial allocation problem by relying on the summed individual decisions of foragers, who occasionally sample and shift to alternative resources. We use field experiments to test the hypothesis that bumblebees augment individual exploration with social information. Specifically, we provide behavioral evidence that, when higher-concentration sucrose arrives at the nest, employed foragers abandon their patches to begin searching for the better option; they are more likely to accept novel resources if they match the quality of the sucrose solution experienced in the nest. We explored this strategy further by building an agent-based model of bumblebee foraging. This model supports the hypothesis that using social information to inform search decisions is advantageous over individual search alone. Our results show that bumblebees use a collective foraging strategy built on social modulation of individual decisions, providing further insight into the evolution of collective behavior. more...

Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy of AD is mainly based on symptomatic treatment and avoidance of irritating/allergenic factors, house dust mites being particularly important. Allergen immunotherapy (AIT) is suggested to be the only etiologic treatment, to modify the natural history of the disease. Areas covered: The aim of this review is investigating the putative role of AIT in AD through the evaluation of the most recent scientific literature. Several studies have been conducted since 1970, with promising results in improving the clinical outcome of AD, but they often lack the necessary scientific rigorousness. Moreover, heterogeneity of the studies makes it very difficult to compare and to analyze data in a systematic review or meta-analysis. Expert commentary: As a result of the above-mentioned limitations, the treatment of AD with causative aeroallergen can nowadays be suggested only as an add-on therapy in selected patients who are non-responsive to the traditional therapy. more...

Real-life studies offer the opportunity of obtaining outcomes suitable in clinical practice, as controlled trials do not mirror the real patients' population observed in clinical practice. This concept is particularly appropriate for allergen immunotherapy (AIT). Therefore, the current review will present and discuss the most recent and relevant studies published on this topic. Globally, 15 real-life studies on AIT efficacy are available until now, the total of patients amounts to 9090, with an average number of 699 patients per study. This high number significantly decrease the possibility that the observations from real-life study are casual, and confers to such studies a key role in the next years to assess issues other than efficacy and safety, especially those scantly investigated thus far. more...

Selection regimes and population structures can be powerfully changed by domestication and feralization, and these changes can modulate animal fitness in both captive and natural environments. In this review, we synthesize recent studies of these two processes and consider their impacts on organismal and population fitness. Domestication and feralization offer multiple windows into the forms and mechanisms of maladaptation. Firstly, domestic and feral organisms that exhibit suboptimal traits or fitness allow us to identify their underlying causes within tractable research systems. This has facilitated significant progress in our general understandings of genotype–phenotype relationships, fitness trade‐offs, and the roles of population structure and artificial selection in shaping domestic and formerly domestic organisms. Additionally, feralization of artificially selected gene variants and organisms can reveal or produce maladaptation in other inhabitants of an invaded biotic community. In these instances, feral animals often show similar fitness advantages to other invasive species, but they are also unique in their capacities to modify natural ecosystems through introductions of artificially selected traits. We conclude with a brief consideration of how emerging technologies such as genome editing could change the tempos, trajectories, and ecological consequences of both domestication and feralization. In addition to providing basic evolutionary insights, our growing understanding of mechanisms through which artificial selection can modulate fitness has diverse and important applications—from enhancing the welfare, sustainability, and efficiency of agroindustry, to mitigating biotic invasions. more...

Background Atopic dermatitis (AD) is a public health problem, with an increasing prevalence worldwide. AD is a chronic inflammatory disease characterised by skin lesions and severe itching. Immunologically, AD has two forms, IgE-mediated and cell-mediated, but it may also be idiopathic. In the pathogenesis of AD, the gene mutations for filaggrin, a filament-aggregating protein present in the epidermis, are of pivotal importance, but other genetic factors are also operating, including those linked to family atopy. Methods We evaluated the role of family atopy, and of the results of the atopy patch test (APT) in parents, in children with mite-induced AD. 64 children, 38 males and 26 females, mean age 4.97 years, were included for the diagnosis of AD and underwent APT and skin prick test (SPT) with dust mite extracts, with evaluation of atopy and result of APT also in parents. Results A positive family history of atopy was shown for children with positivity to both APT and SPT compared to those with negative or only one positive result to APT or SPT (p = 0.08). Significant associations were found concerning APT results in children and parents. In particular, children of a positive-APT parent had an 18-fold higher risk of APT-positivity in comparison with children of negative-APT parents, while the risk was 6.6-fold higher if APT was positive in father. Conclusion Family atopy and a positive APT in fathers are risk factors to develop cell-mediated AD, as assessed by the APT, in children. more...

Allergen immunotherapy (AIT) in its two forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) is an effective treatment of respiratory allergy, but is particularly concerned by the issue of compliance.We aimed a real-life study at evaluating the compliance to SLIT and to SCIT administered by a short-course of four injections during a 3-year period of observation.A group of 145 patients (79 males, 66 females, age ranging from 14 to 69 years), suffering from pollen-induced rhino-conjunctivitis with or without asthma, were included in the study. Following adequate education on AIT and according to patient's preference, 72 patients chose to be treated with short-course SCIT and 73 chose to be treated with SLIT. The latter was performed by allergen extracts from different manufacturers according to the suggested schedules.The rate of withdrawal was as follows: after one year, 15.6% for SCIT and 33.4 for SLIT; after two years, 25.6% for SCIT and 44.8% for SLIT; after three years, 26.7 for SCIT and 46% for SLIT. There was no significant difference in the rate of withdrawal between males and females. Regarding the safety, no systemic reaction requiring medical treatment was observed either in SCIT or SLIT group.The findings of this study confirm that involving the patient in the choice of the route of administration is associated to a satisfactory compliance to AIT. In particular, more than 70% of patients treated with a short schedule of SCIT completed the three-years course of treatment that is recommended for AIT, while this goal was reached by 54% of SLIT treated patients. more...

Medical options other than antibiotics or corticosteroids for treating rhinosinusitis include non-specific treatments such as nasal decongestants, naso-sinusal washings, antihistamines, antileukotrienes, mucolytic agents, immunomodulators and immunostimulants, as well as specific agents such as antimycotics in fungal sinusitis or antireflux agents in sinusitis associated to gastroesophageal reflux. In subjects with chronic sinusitis and/or nasal polyposis related to aspirin hypersensitivity protocols of desensitization are available. The available scientific evidence is good for naso-sinus washings with saline solutions, antihistamines in acute allergic rhinosinusitis, antileukotrienes in chronic sinusitis, bacterial lysates for prevention of recurrent sinusitis, and aspirin desensitisation in subjects with aspirin-exacerbated respiratory disease with chronic sinusitis and nasal polyposis. The other treatment options are still in search of scientific demonstration. more...

Rhinosinusitis is an extremely common disease that is often underreported, especially in children. Its clinical spectrum includes acute rhinosinusitis (ARS) — which may present in the forms of ARS with persistent symptoms and ARS with severe symptoms — and chronic rhinosinusitis (CRS), characterized by a duration longer than 12 weeks and prevalence of symptoms such as nasal congestion and cough. Moreover, rhinosinusitis may present with associated disorders, that are nasal polyposis and aspirin sensitivity, asthma, otitis media with effusion, and gastroesophageal reflux. A particular form is fungal rhinosinusitis, presenting in an invasive and noninvasive form, the latter including allergic fungal sinusitis, which is the most common form of fungal rhinosinusitis and should be suspected in children with nasal polyposis and atopy. more...

Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. more...

Clinical and Experimental Allergy Reviews Allergen immunotherapy by subcutaneous route was demonstrated by meta-analysis studies as an effective treatment in allergic asthma, but the clinical efficacy on asthmatic symptoms of the sublingual route is less investigated. We evaluated the effects of high-dose sublingual immunotherapy (SLIT) on quality of life (QoL) and clinical control of the disease in patients with seasonal asthma. Thirteen patients (six males, seven females, mean age 32.7 ± 6.2 years) with seasonal allergic asthma from at least 2 years were included in the study. In six cases asthma was caused by grass pollen, in five by ragweed pollen, and in two by birch pollen. SLIT was performed by extracts from Stallergenes standardized in index of reactivity (IR) by a build-up phase in 11 days and a maintenance phase with 300 IR three times a week for the duration of the study. An equal number of patients (seven males, six females, mean age 31.8 ± 7.1 years) was treated with an association of 500 mcg of fluticasone and 50 mcg of salmeterol b.i.d. each day during the pollen season. Before and after the treatment, QoL was measured by the Mini Asthma Quality of Life Questionnaire (AQLQ), and clinical control was assessed by the asthma control test (ACT). The mean scores of the Mini-AQLQ before and after treatment were 3.45 ± 0.51 and 5.59 ± 0.48 for SLIT, and 3.32 ± 0.63 and 5.23 ± 0.39 for salmeterol-fluticasone association. The mean scores of the ACT before and after treatment were 11.46 ± 3.38 and 20.54 ± 2.47 for SLIT, and 10.87 ± 2.28 and 19.12 ± 3.20 for salmeterol-fluticasone association. All these differences had a comparable significance, with a P < 0.001. High-dose SLIT with standardized extracts of the most common pollens significantly improves QoL and asthma control in patients with seasonal asthma, with a level of changes comparable with the fluticasone-salmeterol association. more...

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients. more...

HDMs are a ubiquitous allergen source, with a very well defined biology, but their role in clinical settings and in everyday clinical practice is not well characterized. Aim of this cross-sectional, questionnaire-based study was to assess the clinical characteristics of HDM-related respiratory allergy in a large population of Italian patients.A structured questionnaire was sent to allergists randomly chosen among those of the Italian Federation of Immunology, Allergy and Clinical Immunology (IFIACI). They were asked to fill it with the clinical data of 10-12 consecutive patients referred for respiratory allergy, positive to HDM skin prick test. The questionnaire assessed type and severity of allergy, demographics, yearly distribution of symptoms, treatment, and satisfaction with the therapy.45 allergists collected data from 499 patients. Within the evaluated population, 42% had rhinitis only, 45% asthma + rhinitis and 13% asthma alone. Rhinitis was moderate/severe in 51% of patients. Asthma was intermittent in 36% of patients, mild in 37% and moderate in 27%. Conjunctivitis was the most frequent comorbidity (36%), followed by rhinosinusitis (16%), adenoid hypertrophy (6%) and polyposis (5%). Out of the population, 56.2% of patients were not at all or partially not satisfied of their treatment for rhinitis, whereas the percentage of dissatisfied patients was about 53% for asthma therapy. 34% patients (n = 170) were monosensitized to HDM. It is confirmed that patients have more symptoms during the fall-winter periods.Patients with HDM allergy have frequently moderate-severe rhinitis, and about 50% of them are not satisfied with their treatment. more...

glucocorticosteroids without the necessity for hospitalization. After resolution, the oral challenge test with a cephalosporin was well tolerated. Another amoxicillin patch test positive patient tolerated the oral challenge with penicillin, thereby revealing an isolated allergy to amoxicillin. As a challenge test would involve the risk for the patients to experience the same signs and symptoms of the previous drug reaction, the decision of four out of eight patients not to perform an oral challenge test was respected. Two of three patients, who were completely negative in the allergy diagnostic tests, agreed to an oral challenge with verum and revealed tolerance to the drug. It can be hypothesized that the third patch test negative subject may also have tolerated amoxicillin challenge. These three individuals may belong to the population, which only has a transient decrease in drug tolerance during EBV infection. Two amoxicillin patch test positive patients could be examined in a follow-up visit 2.2 and 1.5 years, respectively, after the first patch testing. Those patients revealed a patch test reaction similar in strength to the preliminary test result, which is indicative for a persistent delayed-type reaction to amoxicillin. In conclusion, this study does not only provide additional evidence that true delayed-type allergic reactions to aminopenicillins may develop during a florid viral infection, but that they may be definitely more prevalent than previously assumed and published (5, 6). Additionally, follow-up investigations on two patients revealed the persistence of the delayed-type reactions to amoxicillin, an approach, which has to the best of our knowledge not been published before. These observations should encourage the investigation of patients with aminopenicillin-induced exanthema for both, EBV-infection and true drug allergy. Particularly young women should be recommended an oral challenge with cephalosporins and maybe penicillins because the latter are antibiotics which may be given safely during pregnancy. more...

The prevalence of sensitization to cockroach (CR) was evaluated by skin prick test (SPT) in 1299 patients consecutively referred for rhinitis and asthma to five allergy centers in northern, central, and southern Italy. In patients with positive SPT to CR, an SPT with D. pteronyssinus extract was made. RAST inhibition was performed with pooled sera of subjects with positive SPT and RAST of at least Class 3 for CR and D. Pteronyssinus, to assess the cross-reactivity between these two allergenic sources. The protein content of allergen extracts was assayed by isoelectric focusing (IEF). A total of 170 patients (13%) had a positive SPT with CR extract, and 133 of them (78.2%) were also positive for D. pteronyssinus. RAST inhibition showed a cross-reactivity between CR and D. pteronyssinus, and IEF detected in the extracts employed a series of bands focusing at the same pI of CR and D. pteronyssinus relevant allergens. Therefore, the prevalence of sensitization to CR in the population studied, corresponding to 13%, suggests that CR extract might be added to standard SPT panels for respiratory allergy. However, the cross-reactivity with D. pteronyssinus calls for careful evaluation of the clinical importance of this sensitization. more...

Specific immunotherapy (SIT) efficacy and safety by subcutaneous (SCIT) and sublingual (SLIT) route is supported by literature data. Pre-coseasonal treatment is currently the more accepted option for pollen immunotherapy in terms of costs and patient's compliance. This retrospective study evaluated the patient's preference concerning subcutaneous or sublingual route in pre-coseasonal treatment.We evaluated 145 patients (79 males, 66 females, age ranging from 14 to 69 years), suffering from moderate-severe rhino-conjunctivitis or mild bronchial asthma and with homogeneous characteristic according to allergic disease severity. We proposed either SLIT, with extracts by different producers, or SCIT with Pollinex 4 (Allergy Therapeutics, Worthing, UK), a product designed for ultra-short administration in 4 injections, highlighting for each kind of SIT the major practical advantages or burdens.Of 145 patients, 72 chose Pollinex 4 SCIT and 73 chose SLIT. SCIT-treated patients received a total of 90 vaccines (18 patients had double course of SCIT). SLIT-treated patients received a total of 87 vaccines (14 patients had double course of SLIT). In the SCIT group, there were 49 males and 23 females; in the SLIT group, there were 30 males and 43 females. Mean age was 36.5 years in SCIT group and 28.5 years in SLIT group. Males preferred SCIT (49 of 72 patients) and females preferred SLIT (43 of 73 patients). No severe reaction was observed either in SCIT or SLIT group.Patients are active subjects in decisional process. Trying to apply in real life the indications coming from guidelines about patient's preference is an important matter. In our patients SCIT with ultra short schedule and SLIT are similarly preferred. more...

OBJECTIVES--To define cut off values of bone mineral density (BMD), measured at different forearm sites by single photon absorptiometry, that discriminated postmenopausal women who have had fractures from those who have not, in order to provide an index of fracture risk for screening purposes. METHODS--BMD values were measured at distal third radius (DTR) and ultradistal radius (UDR) sites in two groups of postmenopausal women. Group 1 (n = 398) had not suffered fractures, and group 2 (n = 354) had appendicular fractures. Results were evaluated using receiver operating characteristic (ROC) curves. RESULTS--BMD values were significantly greater (p < 0.001) at both sites in group 1. Weight was lower in group 2 than in group 1 (p < 0.001). The BMD cut off value was 0.596 g/cm2 at DTR (sensitivity 63%, specificity 72%), and 0.310 g/cm2 at UDR (sensitivity 80%, specificity 80%). Values of area under ROC curves estimated for UDR were greater than for those DTR (p < 0.001). CONCLUSION--For screening purposes the BMD cut off value of 0.310 g/cm2 at the UDR may be useful in identifying women at high risk of fracture in an unselected postmenopausal population. BMD measured at UDR appeared to have a better predictive value than that at DTR. more...

The immunoglobulin E (IgE) are a key factor in the pathophysiology of allergic diseases and the important therapeutic role of an anti-IgE antibody was long envisioned. It took time and efforts to solve the safety problems related to the anaphylactogen capacity of anti-IgE, finally crowned by the introduction of the humanized, monoclonal anti-IgE antibody omalizumab. Currently, omalizumab is indicated, based on clear evidence of efficacy, only in severe allergic asthma not controlled by conventional treatment. However, a continuously increasing amount of literature shows that omalizumab is efficacious in a number of disorders concerning the upper and lower airway and the skin, and, most importantly, in anaphylaxis. The latter application was demonstrated successful in placebo-controlled trials and warrants for a new, life-saving, indication for omalizumab. Also, the systemic reactions precluding the performance of allergen immunotherapy, especially concerning Hymenoptera venom, were prevented by omalizumab treatment. The most surprising success of omalizumab regards clinical conditions thus far considered unrelated to IgE antibodies. This is true for intrinsic asthma and for idiopathic urticaria (demonstrated by a placebo-controlled trial), and angioedema, suggesting in these condition a pathophysiologic role of IgE. These observations support a off-label use of omalizumab in patients suffering from IgE-related pathologies other than asthma who are at risk of fatal events or are uncontrolled by the optimal standard treatment. more...

Allergen immunotherapy (AIT) is the only treatment able to act on the causes and not merely on the symptoms of allergy. AIT was introduced 100 years ago but remained an empirical treatment for more than 40 years, when the first controlled trial in 1954 opened the era of scientific evidence. A major advance was the introduction of venom immunotherapy to prevent anaphylaxis from insect stings in 1978. Concerning inhalant allergens, currently AIT may be administered in two forms, subcutaneous (SCIT), and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in a number of meta-analyses, gave sound evidence to the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Adverse systemic reactions are still a drawback for SCIT while safety and tolerability of SLIT are very good, provided recommended doses and schedules of administration are used A significant advance for SLIT development was the registration in Europe of the standardized quality tablets. New applications, such as food allergy and atopic dermatitis, as well as new routes of administration, are currently under evaluation. After 100 years of use, AIT has a central role in the management of allergy and the ongoing improvement seems able to warrant to AIT an even brighter future. more...

The worldwide prevalence of allergic diseases such as rhinitis, asthma, and atopic dermatitis is continuously increasing, while other allergic disorders such as urticaria and angioedema are less investigated. We performed a population study evaluating the prevalence of any kind of allergic disorders.The entire population of 7,201 inhabitants of Cotignola (Ravenna, Italy) was surveyed by a questionnaire assessing symptoms related to rhinitis, asthma, anaphylaxis, skin symptoms and insect sting allergy as well as the features of clinical presentations, diagnosis, and treatment received.Valid questionnaires were obtained by 6,676 inhabitants (92.7%). The sample was formed by 3,266 males and 3,495 females, the mean age was 45.6 years; 1,035 subjects (15.5%) were aged less than 18 years; 404 subjects (6%) had at least one episode of wheezing/breathlessness in their lifetime, and 243 of them (60.1%) had a diagnosis of asthma; 1,002 subjects (14.8%) had nose symptoms in their lifetime, and 375 of them (37.4%) had a diagnosis of allergic rhinitis or rhinoconjunctivitis. For other allergic manifestations, data were obtained from 5,730 subjects; of them, 178 (3.1%) had skin symptoms, 59 (1.1%) had oral symptoms, and 37 (0.6%) had anaphylaxis; 207 (3.6%) had reactions to insect stings. There were no significant differences in prevalence between Italians and immigrants. Only 51.7% of subjects with asthma, 46.5% of those with rhinitis, 22.7% of those with other allergies, but 97.1% of those with insect allergy, received treatment.These findings confirm recent data on epidemiology of allergic diseases in Europe, particularly in Italy, and add some details on how such diseases are managed. more...

The effectiveness of non-invasive ventilation (NIV) in treating patients with acute respiratory failure (ARF) is showed by its ability to diminish the recurrence to endotracheal intubation (ETI), the occurrence of ETI-associated lung infections as well as related mortality. A specific issue is the outcome of NIV in patients referring to Emergency Department for ARF who receive a do-not-intubate (DNI) order because of too critical conditions or advanced age. Recent data show that elderly patients (mean age 81 years) with ARF who have a DNI order can be successfully treated by NIV, as demonstrated by a survival rate of 83%. The positive outcome was confirmed by a subsequent 3-year observation, that demonstrated an overall survival rate of 54%. These findings clearly suggest to treat by NIV elderly patients also in presence of a DNI order. more...

Sublingual immunotherapy (SLIT) was introduced in the treatment of respiratory allergy as an option to subcutaneous immunotherapy (SCIT), which is clinically effective but has the problem of adverse systemic reactions, quite rare but sometimes life-threatening. A large number of trials, globally evaluated in several meta-analyses, demonstrated that SLIT is an efficacious treatment for allergic rhinitis and allergic asthma and has a satisfactory safety profile, severe reactions being extremely rare, though an increased risk is apparent in subjects undergoing SLIT because of previous systemic reactions to SCIT. The suitability of SLIT is ensured by a good compliance, higher than reported for SCIT, the injections being a major factor for noncompliance with the latter, and by its cost-effectiveness performances. In fact, a number of studies showed that SLIT may be very beneficial to the healthcare system, especially after its stopping, when there is no more the cost of the treatment but its efficacy on symptoms persists. more...

Asymptomatic sensitization is confirmed by a positive response to skin prick tests (SPT) with allergens in the absence of clinical symptoms of allergy. This is a common observation for which no convincing explanation has been provided.We investigated the extent to which the presence of specific immunoglobulin (Ig) E in the nasal mucosa accounts for the occurrence of symptoms.The study population comprised 192 patients with positive SPT results to aeroallergens: 111 had symptomatic allergic rhinitis and 81 were totally asymptomatic. All patients underwent measurement of nasal specific IgE using a validated technique (nasal IgE test).A family history of atopy was significantly more frequent in symptomatic patients than in asymptomatic patients (P.0001). The result of the nasal IgE test was positive in 77.5% of symptomatic patients and in only 13.6% of asymptomatic patients (P.0001). With regard to individual allergens, there was no association between clinical symptoms and a positive response to SPT, although there was a strong association between symptoms and individual allergens tested for nasal IgE. In symptomatic patients, there was only a slight correlation between SPT and nasal tests with allergens.These findings suggest that the absence of specific IgE in the nasal mucosa may explain the absence of symptoms in most sensitized subjects and pave the way for further study of the behavior of mucosal IgE in asymptomatic and symptomatic subjects. more...

Asthma in children is characterized by recurring symptoms such as wheezing, breathlessness, and cough, by airflow obstruction and bronchial hyperresponsiveness, and by underlying inflammation. The presence of allergic sensitization, and allergic rhinitis in particular, is strongly associated with asthma. The goal of management of asthma is to achieve and maintain control of the clinical manifestations of the disease. This can be obtained by drug treatment, education of patients and care givers, and, in allergic asthma, by allergen avoidance and specific immunotherapy. The drugs used in asthma can be classified as controllers - such as inhaled corticosteroids (ICS) and leukotriene receptor antagonists - or relievers (bronchodilators to be used during acute exacerbations of asthma). ICS are the most effective anti-inflammatory controllers for the management of persistent asthma in children of all ages, but there is no consensus about the optimal starting dose. Dose-response studies reported marked and rapid improvement in clinical symptoms and lung function at low doses of ICS, and mild asthma is well controlled by such doses in most children, this ensuring good safety. If there is no improvement with the initial low dose of ICS, an increased ICS dose or additional therapy with leukotriene receptor antagonists or long-acting inhaled β2-agonists should be considered. When asthma is caused by allergy to aeroallergens, specific immunotherapy must be taken into account, in its two forms of subcutaneous or sublingual immunotherapy. The former has complete evidence of efficacy, but the sublingual route is safer and more easily accepted by children. more...

Pulmonary rehabilitation (PR) is a non pharmacologic treatment of demonstrated efficacy indicated for symptomatic patients with chronic lung diseases. In the pulmonary rehabilitation programs (PRPs), exercise training is a cornerstone component, recommended for improving muscle function. Its aim is to address the disability, intended as the reduction in functional performance and quality of life, derived from muscle deconditioning caused by physical inactivity due to chronic breathlessness, fatigue, and impairment of daily activities claimed by patients with chronic pulmonary diseases. Other components of PRPs are educational, psychosocial and nutritional interventions. Moreover, any PRP should include an outcome assessment, needed for an objective evaluation of program effectiveness, and of patient progress through the time. Although its pivotal role is now accepted worldwide, this was not the prevailing thought during the 1980's and the 1990's, when the pathophysiologic rationale of PR was still not demonstrated, condemning it to be an ancillary treatment to add to standard COPD treatment. The following ascent of PR was mainly due to the number of studies providing its effectiveness, overcoming skepticism and convincing physicians and institutions about its efficacy. Today PR clearly improves exercise tolerance, dyspnea, and quality of life, but despite such demonstration, it is mostly overlooked by health professionals, and only about 2% of patients with COPD undergo to PRPs. A proper consideration of the capability of PR is warranted to ensure optimal management of COPD when the disease causes symptoms and a decrease in physical capacity. more...

Hymenoptera venom immunotherapy (VIT) is a safe and effective approach to insect sting allergy. However, after discontinuation, relapses can occur in some patients, especially those with a high occupational risk, and they may need to prolong VIT indefinitely. In order to improve adherence, we propose extending the interval between injections of maintenance VIT (MVIT).To evaluate the safety, efficacy, and patient acceptance of a 3-month interval between MVIT injections in a group of Hymenoptera-allergic patients who are occupationally exposed to insect stings.We included 72 patients with severe systemic reactions to Hymenoptera stings. MVIT was administered for 4 years at intervals increasing up to 3 months and then continued for a further 2 years. Patients were informed of the risk of relapse after discontinuation and of the need for indefinite treatment at 3-month intervals.During the 3-month interval maintenance phase, only 235 local reactions (17.8%) were observed in 17 patients. Sixty patients experienced 125 field re-stings and only 1 experienced a systemic reaction with generalized urticaria.The study confirms that the conventional MVIT interval of 4 to 6 weeks can be extended to 3 months in most patients with no adverse events, while maintaining safety and efficacy, improving adherence, and guaranteeing safe continuation of professional activity. more...

Allergic rhinitis and asthma have a very high prevalence and constitute a health problem with a relevant burden of disease, concerning medical and economical issues. Among the treatments of allergy, specific immunotherapy (IT) has the capacity to favourably alter the natural history of the disease both during and after its performance, and thus to reduce the direct and indirect costs of allergic rhinitis and asthma. A number of studies reported a cost reduction for traditional, subcutaneous IT (SCIT). We analyzed the available studies on economic evaluation of sublingual immunotherapy (SLIT) in children and adults. Articles were retrieved from Medline and Embase using the terms economic aspects, pharmacoeconomics, cost effectiveness, and sublingual immunotherapy. 18 articles were found in English language, 7 studies investigated the economic advantage of SLIT over standard drug treatment in subjects with respiratory allergy, and 2 of them included a comparison of costs of SCIT and SLIT. The data obtained provide evidence that SLIT is associated to economic advantages and/or monetary savings, specifically in terms of reduction of economic burden of the disease. Although the number of studies is still limited, the available data support a SLIT effect on sparing costs for respiratory allergy. more...

Polysensitization is very common in allergic patients and was previously reported to be associated with more severe symptoms and impaired quality of life. Polysensitization is often considered as a contraindication for specific immunotherapy (SIT). This study is aimed at evaluating the allergist attitude for decision making in choosing SIT in a cohort of Italian polysensitized patients. Moreover, the 1-year effectiveness of the prescribed sublingual immunotherapy (SLIT) in this cohort was evaluated. The study was performed on 244 patients (109 males, 135 females, mean age 28.7 years, S.D. 12.0) with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA criteria) treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, use of drugs, and adverse events were evaluated at baseline and after 1 year. A total of 230 patients were treated with SLIT: 165 with a single extract, and 65 with two different extracts (mix). SLIT treatment significantly improved disease staging, and reduced symptom severity and drug use. No systemic reaction was reported. In conclusion, these findings provide preliminary evidence that SIT is effective and safe in polysensitized patients after 1 year of treatment also using single extracts, and thus does not represent an obstacle for prescribing SIT. more...

Summary Allergic skin disorders include urticaria, angioedema, contact dermatitis and atopic dermatitis, but the model fitting most closely the systemic concept of allergy is atopic dermatitis (AD), the pathogenesis of which is linked to a complex interaction between skin barrier dysfunction and environmental factors such as allergens and microbes. In particular, an important advance was the demonstration that the mutation of the skin barrier protein filaggrin is related strictly to allergen sensitization and to the development of asthma in subjects with AD. The altered skin barrier function, caused by several factors, results in the passage of allergens through the skin and to systemic responses. A pivotal role in such a response is exerted by Langerhans cells which, via their immunoglobulin E (IgE) receptor, capture the allergens and present them to T cells. When T helper type 2 (Th2) cells are activated, the production of a proinflammatory cytokines and chemokines pattern sustains the persistence of inflammation. Known AD-related cytokines are interleukin (IL)-5, IL-13 and tumour necrosis factor (TNF)-α, with emerging importance for IL-17, which seems to drive airway inflammation following cutaneous exposure to antigens, and IL-31, which is expressed primarily in skin-homing Th2 cells. Skin-homing is another crucial event in AD, mediated by the cutaneous lymphocyte-associated antigens (CLA) receptor, which characterizes T cell subpopulations with different roles in AD and asthma. more...

Prevalence of smoking among healthcare workers has been steadily decreasing in recent years but is still higher than in the general population. This may have a negative impact in the process of recognizing smoking as the major avoidable cause of morbidity and mortality.In this study we evaluated the prevalence and the attitudes to smoking in healthcare workers, divided into inpatient and outpatient staff in order to assess the possible role of stress in favouring smoking.A standardized questionnaire on smoking was submitted to all employees of the "Istituti Clinici di Perfezionamento", a public hospital in Milan, Italy, covering 1597 subjects.An overall number of 383 subject (24%) answered the questionnaire. Thirty (7.8%) were non-smokers and not exposed to second-hand smoking, 175 (45.7%) were non-smokers but exposed to second-hand smoking, 79 (20.6%) were ex-smokers, and 99 (25.8%) were current smokers. The comparison between inpatient and outpatient staff did not reveal any significant diferences. As to smoking attitudes, 29 subjects (29.3%) were not interested in quitting, 26 (26.3%) tried unsuccessfully to quit, 27 (27.3%) believed they could succeed in quitting, and 17 (17.2%) wanted to quit but did not know how. Also in this case there were no significant differences between inpatient and outpatient staff.These findings confirm the decrease in the prevalence of smoking observed in recent years in healthcare professionals but suggest the need to continue information, counselling and medical support campaigns aimed at achieving cessation of smoking. more...

Sublingual immunotherapy (SLIT) is currently considered a valid option to subcutaneous immunotherapy (SCIT), but only a few studies made a direct comparison of their effectiveness. The aim of this study was to compare the clinical and immunological effects of SCIT and SLIT in pollinosis induced by Betulaceae.Forty-seven adult patients were randomized to receive SCIT or SLIT, performed by Betulaceae (alder, birch, and hazel) extracts from Stallergenes (Antony, France) standardized in index of reactivity (IR) with the treatment schedules proposed by the producer. The clinical effects were established by symptom-medication scores recorded during the month of March. Side effects were reported directly by the physicians for SCIT and were registered in diary cards by the patients for SLIT. Immunologic evaluation was done by measuring specific IgE and IgG4 to Bet v 1.Thirty-four patients (19 for SCIT and 15 for SLIT) completed the registration of symptoms and drug consumption during pollen period of Betulaceae. Mean cumulative doses of respectively 50.65 IR by SCIT and 4653.1 IR by SLIT were administered, with a SLIT/SCIT ratio of 92. There was no significant difference in mean symptom-medication score between SCIT and SLIT. Systemic reactions occurred in 16% of SCIT treated but in none of SLIT treated. As to immunologic evaluation, Bet v 1 specific IgE did not rise after the pollen season in SCIT treated, while increased non significantly in SLIT treated. Bet v 1 specific IgG4 increased in both treatment, buy only the increase with SCIT was significant (p = 0.001).SLIT and SCIT with a ratio of about 100 are equally effective in controlling rhinoconjunctivitis caused by tree pollen allergy. SLIT is safer than SCIT, but does not show the same immunologic effects on serum specific IgE and lgG4 antibodies. more...

Allergen specific immunotherapy is an important option for the treatment of respiratory allergy and its clinical efficacy has been clearly demonstrated by several studies. However, the injective route of administration and the possibility of severe side effects has limited its use in children and led to the introduction of new forms of administration. Sublingual immunotherapy (SLIT) has proven to be an effective and safe treatment for respiratory allergy. However, its mechanism of action is still debated. Pharmacokinetic studies showed that, differently from nasal mucosa, allergen extracts administered by SLIT are not immediately adsorbed but are long retained before being drained to local lymph nodes. This difference may be responsible of the absence of severe side effects and instead of short-lasting local symptoms. Studies by biopsies of the oral mucosa should greatly help in defining the presence and the role of cells involved in the mechanisms of oral tolerance. more...

A case of cat-pork syndrome with subsequent follow-up in a 17-year-old male patient is reported. At the initial observation, the patient was sensitized to cat epithelium--along with house dust mites and grass pollen--from two years. In 2001 he had an immediate reaction with urticaria, angioedema and dyspnea after eating grilled meat and sausage, and skin tests and CAP/RAST revealed a sensitization to pork meat, with a value of 4.7 KU/L for pork meat, and of 55 KU/L for cat epithelium. The patient was followed up for three years with annual repetition of diagnostic tests. The elimination of pork meat from the diet was incomplete, with slight skin reactions to small amounts of cooked pork meat but tolerance to seasoned pork products such as salami. A challenge test with pork meat in 2004 was positive, with angioedema and asthma symptoms, and CAP/RAST showed a value of 43 KU/L for cat epithelium and 4 KU/L for pork meat. RAST inhibition confirmed the significant cross-reactivity between the two allergen sources. These findings provide some knowledge on the natural history of the cat-pork syndrome, and confirm that very prolonged avoidance of the offending foods are needed to expect a loss of sensitization. more...

A case of anaphylaxis to honey in a 19 year old female sensitized to Compositae pollen is described. The patient suffered from summer rhinoconjunctivitis since seven years; in January 2006, ten minutes after eating bread and honey she developed angioedema of the lips and tongue, runny nose, cough, dyspnoea, and collapse, requiring hospitalization and treatment with high dose corticosteroids and anti-histamines. After two weeks, skin prick tests (SPT) with a standard panel of inhalant allergens and prick + prick with a number of kinds of honey were performed. SPTs were positive to mugwort, ragweed, dandelion, and goldenrod. Concerning honey, the prick + prick was positive to "Millefiori" (obtained from bees foraging on Compositae) and also to sunflower, limetree, and gum tree honey, while was negative for other kinds of honey, including the frequently used chestnut honey and acacia honey. The allergenic component responsible of anaphylaxis in this case seems to be a molecule occurring in Compositae pollens, as previously reported for other three reports, but also in pollen from plants of different families. Honey contains a large number of components derived from bees, such as gland secretions and wax, as well as from substances related to their foraging activity, such flower nectar and pollens (1, 2). Honey as a food has been associated to allergic reactions and particularly to anaphylaxis (3-6). Among the pollens, the role of Compositae is somewhat controversial, since its responsibility is clear in some studies (3, 5, 6) but considered negligible in others (7). Here we present the case of a patient sensitized to Compositae pollen who had an anaphylactic reaction to the ingestion of honey obtained from bees foraging on Compositae flowers and was tested with a number of different varieties of honey. more...

The role of allergic sensitization in chronic sinusitis in childhood is currently unclear, as contrasting results were reported in the studies thus far available.We evaluated by a cross-sectional study the prevalence of sensitization to common inhalant allergens in children with chronic sinusitis.Among 2200 children referring to our Paediatric out-patient Unit for evaluation of chronic respiratory symptoms, subjects satisfying at least two of major criteria for the definition of chronic sinusitis were recruited, and underwent to allergen sensitization workup by skin prick test (SPT) with common inhalant allergens and total IgE determination. Participants were stratified according to age inferior to three years (Group 1), age between three and six years (Group 2), and age above six years (Group 3) for the purpose of evaluation.In all, 351 children (217 boys, 134 girls, mean age 5.23 ? 2.11 years, range 4-15 years) were available for evaluation and were stratified (27 in Group 1, 261 in Group 2 and 63 in Group 3). Prevalence of both sensitization to at least one inhalant allergen by SPT and of high total IgE was 29.9%. Prevalence of SPT sensitization was significantly different across age groups, with a value of 7.4% in Group 1, 31.4% in Group 2 and 33.3% in Group 3 (p = 0.028), but after adjusting for age, sinusitis and aeroallergen sensitization did not correlate significantly. The difference across groups for high total IgE did not reach statistical significance, with 22.7%, 30.1% and 32.1% for each group respectively.The prevalence of sensitization to aeroallergens in children with chronic sinusitis is comparable to that of the general paediatric population, as assessed in the Italian arm of the ISAAC study. This does not account for routine investigation for allergy in children diagnosed with such disease. more...