Vitulia questionnaire: a new instrument to evaluate quality of life in children aged 4-7 years with food allergy.

Summary: Background. Food allergy (FA) negatively affects health-related quality of life (HR-QoL) of children and caregivers. To date, no questionnaire self-compiling assessing the HR-QoL in pre-school children with FA is available. The aim of this study is to develop and validate a self-administered, rapid and easy questionnaire to evaluate the HR-QoL in children ≥ 7 years with IgE-mediated FA. Methods. A two-center prospective study was conducted including children aged 4-7 years with IgE-mediated FA. The Vitulia questionnaire was administered to study participants at the baseline (T0) and after one month (T1). To assess the feasibility and reliability, the Vitulia questionnaire was compared with other two pre-existing questionnaires: FAQLQ-PF and the KiddyKindl, which were also tested at both T0 and T1. The validation phase aimed to assess the following psychometric properties: convergent validity, internal consistency, discriminant validity and sensitivity to change. Results. One hundred patients (62% male, mean age 5.4 ± 1.2 years) were enrolled. The Vitulia questionnaire showed a good internal consistency along with an excellent reliability and repeatability of the measure. Another noteworthy feature of the questionnaire was its discriminant validity as demonstrated by the ability to provide different scores in subgroups, which have differences in terms of quality of life. On the other hand, the questionnaire seems not be sensitive to changes in health status over time. Conclusions. The Vitulia questionnaire represents a valid tool, quick and easy to interpret, which can be used to assess the quality of life in preschool children with IgE-mediated FA.

Atopic Dermatitis Phenotypes in Preschool and School-Age Children: A Latent Class Analysis.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in childhood. Few data are available about AD phenotypes and their nationwide distribution. METHODS: We performed a cross-sectional multicenter study involving some of the main Italian pediatric allergy centers from 9 Italian cities. A structured questionnaire was administered to 371 children with AD. Patients were divided in 2 groups: preschool children (aged ≤5 years) and schoolchildren (aged 6-14 years). A latent class analysis was used to detect AD phenotypes and to investigate their association with risk factors and other atopic diseases. RESULTS: Latent class analysis identified 5 AD phenotypes in preschoolers ("moderate-severe AD, high comorbidity", 8%; "moderatesevere AD, low comorbidity", 35%; "mild AD, low comorbidity", 20%; "mild AD, respiratory comorbidity", 32%; "mild AD, food-induced comorbidity", 5%) and 4 AD phenotypes in schoolchildren ("moderate-severe AD, high comorbidity", 24%; "moderate-severe AD, low comorbidity", 10%; "mild AD, low comorbidity", 16%; "mild AD, respiratory comorbidity", 49%). Parental history of asthma and eczema, early day-care attendance, and exposure to molds were significantly associated with the "moderate-severe AD, high comorbidity" phenotype in preschool children (P<.05). The "moderate-severe AD" phenotypes were also associated with the highest burden in terms of medication use and limitations in daily activities. CONCLUSIONS: The detection of different AD phenotypes highlights the need for a stratified approach to the management of this complex disease and for further studies to predict the course of AD and to develop more efficient therapeutic strategies.

Comparative Effect of Beclomethasone Dipropionate and Cetirizine on Acoustic Rhinometry Parameters in Children With Perennial Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The effect of intranasal corticosteroids and oral antihistamines on acoustic rhinometry parameters has not been directly compared. The primary objective was to compare the effect of a 21-day course of treatment with nasal beclomethasone dipropionate (nBDP) with that of cetirizine (CTZ) on nasal patency measured using acoustic rhinometry in children with perennial allergic rhinitis (PAR). The secondary objective was to compare the effect of both drugs on nasal cytology, symptom severity, sleep quality, and quality of life. METHODS: In this 21-day, open-label, randomized controlled study, 34 children with PAR (age 6-14 years) with a Total 5-Symptom Score (T5SS) ≥5 received nBDP 100 µg per nostril twice daily or CTZ 10 mg tablets once daily. The measures of effect were the least square mean change (LSmc) in nasal volume, minimal cross-sectional area (MCA), and nasal cytology, as well as the scores on the T5SS, Pittsburgh Sleep Quality Index (PSQI), and Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ). RESULTS: After 21 days, nBDP improved nasal volume and MCA more than CTZ (LSmc, 2.21 cm3 vs 0.20 cm3 [P=.013]; and LSmc 0.63 cm2 vs 0.13 cm2 [P=.002], respectively). Compared with the CTZ group, a more marked improvement was found in the nBDP group with respect to eosinophil classes (LSmc, -1.10 vs -0.40; P=.031) and neutrophil classes (LSmc, -0.97 vs -0.17; P=.010), T5SS (LSmc, -5.63 vs -3.54; P=.008), PSQI (LSmc, -1.30 vs -0.19; P=.025), and PRQLQ total scores (LSmc, -1.15 vs -0.69; P=.031). CONCLUSIONS: In children with PAR, nBDP is more effective than CTZ in improving nasal patency measured by acoustic rhinometry, with associated beneficial effects on nasal cytology, symptoms, sleep quality, and quality of life.

Overview of systematic reviews in allergy epidemiology.

BACKGROUND: There is a substantial body of evidence on the epidemiology of allergic conditions, which has advanced the understanding of these conditions. We aimed to systematically identify systematic reviews and meta-analyses on the epidemiology of allergic diseases to assess what has been studied comprehensively and what areas might benefit from further research. METHODS: We searched PubMed and EMBASE up to 12/2014 for systematic reviews on epidemiological research on allergic diseases. We indexed diseases and topics covered and extracted data on the search characteristics of each systematic review. RESULTS: The search resulted in 3991 entries after removing duplicates, plus 20 other items found via references and conference abstracts; 421 systematic reviews were relevant and included in this overview. The majority contained some evidence on asthma (72.9%). Allergic rhinitis, atopic eczema and food hypersensitivity were covered in 15.7%, 24.5% and 9.0%, respectively. Commonly studied risk factors for atopic eczema included dietary and microbial factors, while for asthma, pollution and genetic factors were often investigated in systematic reviews. There was some indication of differing search characteristics across topics. CONCLUSION: We present a comprehensive overview with an indexed database of published systematic reviews in allergy epidemiology. We believe that this clarifies where most research interest has focussed and which areas could benefit from further research. We propose that this effort is updated every few years to include the most recently published evidence and to extend the search to an even broader list of hypersensitivity/allergic disorders.

The role of transforming growth factor-ß1 in airway inflammation of childhood asthma.

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking.

Third-hand smoke exposure and health hazards in children.

Smoking still represents a huge public health problem. Millions of children suffer the detrimental effects of passive smoking. An increasing number of countries have recently issued laws to regulate smoking in public places. Instead, homes remain a site where children are dangerously exposed to environmental tobacco smoke (ETS). The combination of tobacco smoke pollutants which remain in an indoor environment, the so-called 'third-hand smoke' (THS), represent a new concept in the field of tobacco control. THS consists of pollutants that remain on surfaces and in dust after tobacco has been smoked, are re-emitted into the gas-phase, or react with other compounds in the environment to form secondary pollutants. Indoor surfaces can represent a hidden reservoir of THS constituents that could be re-emitted long after the cessation of active smoking. Human exposure to THS pollutants has not yet been thoroughly studied. Infants and children are more prone to the risks related to THS exposure than adults because they typically spend more time indoors and have age-specific behaviours that may expose them to potential health hazards from THS. Further investigations are warranted to study the health effects of THS relevant to different exposure pathways and profiles. It would also be very important to evaluate how THS may affect the lung development through the in utero exposure during the pre-natal life. We aimed at reviewing recent findings published about THS, with special reference to the effects on children's health.

Asthma incidence can be influenced by climate change in Italy: findings from the GEIRD study-a climatological and epidemiological assessment.

An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20-84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957-2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. AIMS: Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. METHODS: Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL-19 were confirmed by real-time PCR. The constitutive and stimulated (LPS, TGF ß) expression of IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI 2650). RESULTS: Human Asthma Gene Array showed an increased IL-19 gene expression in NP from patients with CRS in comparison with normal subjects. Real-time PCR confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up-regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot analysis confirmed that IL-19 is increased also at protein level in patients with CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19 increased cell proliferation in nasal epithelial cells. CONCLUSIONS: IL-19 is overexpressed in the epithelium in CRSwNP and increases epithelial cell proliferation.

Serious Games: A new Approach to Foster Information and Practices About Covid-19?

The current Covid-19 pandemic poses an unprecedented global challenge in the field of education and training. As we have seen, the lack of proper information about the virus and its transmission has forced the general population and healthcare workers to rapidly acquire knowledge and learn new practices. Clearly, a well-informed population is more likely to adopt the correct precautionary measures, thus reducing the transmission of the infection; likewise, properly educated healthcare workers are better equipped to manage the emergency. However, the need to maintain physical distancing has made it impossible to provide in-presence information and training. In this regard, new technologies have proved to be an invaluable resource by facilitating distance learning. Indeed, e-learning offers significant advantages because it does not require the physical presence of learners and teachers. This innovative method applied to serious games has been considered potentially effective in enabling rapid and large-scale dissemination of information and learning through content interactivity. We will review studies that have observed the development and use of serious games to foster information and practices about Covid-19 aimed at promoting behavioral changes in the population and the healthcare personnel involved on the front line.

Issue 1 - "Update on adverse respiratory effects of outdoor air pollution". Part 1): Outdoor air pollution and respiratory diseases: A general update and an Italian perspective.

OBJECTIVE: to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects. RESULTS: the recent literature indicates that there is strong evidence for causal relationships between PM2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52,300 for PM2.5, 10,400 for NO2 and 3,000 for O3 in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas. CONCLUSIONS: adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients' associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.

Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA(2) LEN taskforce position paper.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations and suggestions for assessing patient-reported outcomes (PROs) including health-related quality of life in patients with urticaria. We recommend that PROs should be used both in clinical trials and routine practice for the evaluation of urticaria patients. We suggest that PROs should be considered as the primary outcome of future clinical trials. Two validated and disease-specific instruments for assessing PROs are available, the urticaria activity score (for symptoms) and the chronic urticaria questionnaire on quality of life CU-Q(2)oL. This latter tool, CU-Q(2)oL, is available in many languages and should be preferred, where available, over more generic instruments for assessing urticaria-specific effects on quality of life. CU-Q(2)oL is only suited for the investigation of patients with chronic spontaneous urticaria. Similar instruments for other forms of urticaria have yet to be developed and validated. Also, tools for assessing other chronic spontaneous urticaria PROs besides quality of life and symptoms are needed.

Recommendations for assessing patient-reported outcomes and health-related quality of life in clinical trials on allergy: a GA(2)LEN taskforce position paper.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre-post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data.

Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA(2)LEN taskforce position paper.

The GA(2)LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient-related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management.

Novel perspectives in the detection of oral and nasal oxidative stress and inflammation in pediatric united airway diseases.

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral and nasal FENO concentrations were increased in children with PER, IA, mA and MA when compared with HCs. Nasal 8-isoprostane was higher in EBC of children with PER and asthma than in HCs. Oral and nasal LTB4 were higher in EBC of children with PER and mA than in HCs. Oral and nasal PGE2 concentrations were higher in EBC of children with PER than in HCs. Positive correlations between oral and nasal biomarkers were found in IA for LTB4 and PGE2, in mA for FENO, 8-isoprostane, LTB4 and PGE2, and in MA for PGE2. No correlations were observed in children with PER and HCs. Our results suggest that non-invasive markers of inflammation and oxidative stress might be useful to study the relationships between oral and nasal compartments in allergic children with PER and concomitant asthma with the aim of defining the UAD.

Sublingual immunotherapy: administration, dosages, use.

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients.

Clinical evaluation and treatment of acute asthma exacerbations in children.

This update on treatment of asthma exacerbations in children is the result of an Italian Pediatric Society Task-force, made up of a panel of experts working in 2007-2008. The aim is to give clear indications on the use of the drugs most employed in children, grading the quality of evidence and the strength of recommendations. Suggestions on their limits due to unlicensed and off-label use are reported. The level of evidence and the strength of recommendations for different therapeutic approaches demonstrate that frequently the use of drugs in children is extrapolated from the experience in adults and that more studies are required to endorse the correct use of different drugs in asthmatic children.

Safety and tolerability of seasonal ultra-rush, high-dose sublingual-swallow immunotherapy in allergic rhinitis to grass and tree pollens: an observational study in 193 children and adolescents.

OBJECTIVE: We conducted a large observational study in 193 children and adolescents with allergic rhinitis due to grass or tree pollens to evaluate the safety and tolerability of an ultrarush high-dose sublingual immunotherapy (SLIT) regimen reaching a maintenance dose of 300 index of reactivity within 90 minutes. METHODS: Children and adolescents aged 5 to 17 years with at least a 1-year medical history of allergic rhinitis with or without mild to moderate asthma due to tree pollens (birch, alder, hazel) or grass pollens (cocksfoot, meadow grass, rye grass, sweet vernal grass, timothy) were recruited. Standardized grass and tree pollen allergen extracts were used for ultrarush titration and subsequent coseasonal maintenance. RESULTS: During ultrarush titration, 60 patients (31%) reported 117 predominantly mild and local adverse events, which resolved within 150 minutes. During the maintenance phase, 562 adverse events were reported; the most frequent local events were oral pruritus, burning sensation, lip or tongue swelling, and gastrointestinal symptoms, and the most frequent systemic events were rhinoconjunctivitis and asthma. There was 1 clinically significant asthma event in an 11-year old boy with known asthma in whom SLIT was resumed after an interval of 4 days. CONCLUSION: Ultrarush titration was safe and well tolerated. Pediatric patients with asthma should be carefully monitored and adequately trained to use their rescue medications.

A survey around the Italian pediatric units on current clinical practice for Sleep Disordered Breathing (SDB).

BACKGROUND: During recent years, interest on Sleep Disordered Breathing (SDB) in pediatric age has increased, due to the impact on quality of life, psycho-physical attitude and other serious morbidities if undiagnosed and untreated. METHODS: Italian Pediatric Respiratory Diseases Society (SIMRI) SDB-Working Group carried out an exploratory survey in Italy, from January to December 2016, to assess the diagnostic and therapeutic pathways, perception and relevance of SDB in Italian Hospitals. RESULTS: A questionnaire was sent to 180 Pediatric Units (PUs) distributed throughout the Italy; 102 Pediatric Units (PUs; 56.6%) answered and among them 57% dealt with SDB, and 94% recognized SDB as a major problem. Instrumental tests performed by the PUs were saturimetry (66%), nocturnal polygraphy with complete cardio-respiratory monitoring (46%) and full polysomnography (23%). In addition, hospital pediatricians reported that 54% of parents were unaware of the SDB and 84% did not know their complications. In the Northern Italy, the diagnosis was frequently performed with instrumental tools and the treatment was often surgical. In the Southern Italy the diagnosis was clinical, and the treatment was usually with drugs. CONCLUSIONS: The results of our study showed a heterogeneity in the diagnosis and treatment of SDB throughout Italy. Parents know little about SDB and their complications. The operator satisfaction was associated with the availability of tools for diagnosing SDB.

Evaluation of the antiinflammatory and clinical effects of sublingual immunotherapy with carbamylated allergoid in allergic asthma with or without rhinitis. A 12-month perspective randomized, controlled, trial.

BACKGROUND: The efficacy and safety of sublingual immunotherapy with carbamylated allergoid (allergoid SLIT) is well recognised. Yet, few data concerning its antiinflammatory effects on the respiratory airways are so far available. Thus we decided to evaluate whether it can reduce the allergic inflammation and improve the clinical symptoms in comparison to pharmacotherapy. METHODS: The study was perspective, controlled and randomised. It was conducted on 56 patients allergic to House Dust Mite with (n=36) or without Parietaria. Thirty-three of them were allocated to SLIT (22 M, 11 F mean age 15 years) and 22 (13 M, 10 F, mean age 21 years) to pharmacotherapy They were followed-up for 1 year. Symptoms and drugs consumption were assessed by monthly diary cards. Bronchial reactivity was investigated at baseline and after a 12-month treatment, through a methacholine (MCh) test. An evaluation of the nasal eosinophils was also performed at the same times. RESULTS: There was a greater reduction of the mean symptom score (p < 0.01) and drug consumption (p < 0.001) in the SLIT than in the control group. MCh PD20 increased only in the SLIT group (p < 0.0005) The reduction of nasal eosinophils was statistically greater (p < 0.05) only in the SLIT group. CONCLUSIONS: A 1-year SLIT reduces the allergic symptoms and the respiratory airways inflammation more than pharmacotherapy.

Pharmacoeconomics of subcutaneous allergen immunotherapy.

The current burden of allergic diseases, estimated by both direct and indirect costs, is very relevant. In fact the cost estimation for rhinitis amount globally to 4-10 billion dollars/year in the U.S. and to an average annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The estimated annual costs in Northern America for asthma amounted to 14 billion dollars. Consequently, preventive strategies aimed at reducing the clinical severity of allergy are potentially able to reduce its costs. Among them, specific immunotherapy (SIT) joins to the preventive capacity the carryover effect once treatment is discontinued. A number of studies, mainly conducted in the US and Germany demonstrated a favourable cost-benefit balance. In the nineties, most surveys on patients with allergic rhinitis and asthma reported significant reductions of the direct and indirect costs in subjects treated with SIT compared to those treated with symptomatic drugs. This is fully confirmed in recent studies conducted in European countries: in Denmark the direct cost per patient/year of the standard care was more than halved following SIT; in Italy a study on Parietaria allergic patients demonstrated a significant difference in favor of SIT plus drug treatment for three years versus drug treatment alone, with a cost reduction starting from the 2nd year and increasing to 48% at the 3rd year, with a highly statistical significance which was maintained up to the 6th year, i.e. 3 years after stopping immunotherapy, corresponding to a net saving for each patient at the final evaluation of 623 euros per year; in France a cost/efficacy analysis comparing SIT and current symptomatic treatment in adults and children with dust mite and pollen allergy showed remarkable savings with SIT for both allergies in adults and children.