STATO DI SALUTE DELLE POPOLAZIONI RESIDENTI NELLE AREE GEOTERMICHE DELLA TOSCANA

Objective The limited scientific knowledge on relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation in Tuscan geothermal area. The study aims to describe the health status of populations living in Tuscany municipalities where concessions for exploitation of geothermal resources were granted. Design This is an ecological study, so it is not useful to produce evidence to sustain a judgment on the cause-effect link. The major limits of this type of study are the use of the residence at municipal level as a proxy of exposure to both environmental and socioeconomic factors and the use of aggregated data of health outcomes that can lead to the well-known ecological fallacy. Setting and participants Sixteen municipalities were included in the study area: eight are part of the so-called "traditional" geothermal area, defined as Northern Geothermal Area (NGA) and eight located in the Amiata Mountain defined as Southern Geothermal Area (SGA). In 2000-2006, the average resident population in the overall area was approximately 43,000 inhabitants. Thirty-one geothermal power plants were active, with a production capacity of 811 MW, 5 of them with 88 MW located in the SGA. Statistical analyses on the entire geothermal area, NGA and SGA subareas, and the sixteen municipalities were performed. Main outcome measures Mortality data were obtained from Tuscany Regional Mortality Registry for the 1971-2006 period, analysing 60 causes of death, of interest for population health status or consistent with "Project SENTIERI" criteria. Hospital discharge records of residents in Tuscany Region in 2004-2006, anywhere admitted to hospital, were analyzed considering only the main diagnosis, excluding repeated admissions for the same cause. The causes taken into account are the same analysed for mortality were considered. Age-standardized mortality rates (TSDM) and the temporal trends of TSDM for four periods (1971-1979, 1980- 1989, 1990-1999, 2000-2006) were computed. Age-standardized mortality/hospitalization ratios (SMR/SHR), with and without adjustment for the deprivation index based on 2001 census data, were calculated: mortality in the years 2000-2006 and hospitalization in 2004-2006. The expected number of events were computed using rates of residents in neighbouring municipalities (municipalities included in 50 km radius circle centred on the study area). Bayesian estimates of mortality/hospitalization ratios (BMR/BHR) at municipal level only and relating maps of the Bayesian risk estimators were elaborated. Congenital malformations (MC) were analysed using data from Tuscan Registry of Birth Defect in 1992-2006 period, relative to outcomes of pregnancies in women resident in the municipalities of study area, wherever the birth or termination of pregnancy occurred. The ratio between observed and expected cases (O/A), with expected defined according to regional rate, were calculated and O/A Bayesian estimates (BMR) are showed only at municipal level . The low weight and the males/females ratio at birth were analysed using data from Tuscany Birth Certificates, covering period 2001-2007, excluding biths occurred in facilities outside Tuscany Region. For Low birth weight (<2,500 grams), very low birth weight (<1,500 grams), low birth weight in women with normal gestational age or greater than 36 weeks, gestational age less than 36 weeks, and the frequency of males, the observed/expected ratio was calculated, with the expected number defined according to regional rate. Results Environmental background High levels of arsenic in drinking water distribution emerges as a critical element, so that several municipalities resorted to granting exemptions for the parameters laid down by the Legislative Decree in force (DLgs 31/01). However, during the final phase of the study, new blast systems activated in the SGA decreased the arsenic levels in the water supply, reaching values not requiring derogations, which, instead, are still effective in some NGA municipalities. Air quality data, from Tuscany Regional Agency for Environmental Protection-ARPAT, show that geothermal activities are able to affect air quality, especially with hydrogen sulphide in NGA, and hydrogen sulphide and mercury in SGA. A significant contribution to the presence of mercury in air is due to previous metallurgical sites. Although mercury levels are belowWHO guideline values, in SGA nearby Siena, values were significantly higher than in other geothermal areas, because of power plant PC2 (turned off in July 2011) in Piancastagnaio municipality. The hydrogen sulphide concentration levels were generally lower than WHO reference values, with occasional excesses over guideline value for health protection (150 &#956;g/m3 as average of the 24 hours). Olfactory pollution was more critic with values exceeding 7-10 &#956;g/m3 range even in areas without geothermal plants.Obiettivo Le limitate conoscenze scientifiche sui rapporti tra esposizione a fattori ambientali correlati all\u27attivit? geotermica e lo stato di salute della popolazione esposta hanno motivato la conduzione di una indagine epidemiologica nell\u27area geotermica toscana basata sull\u27analisi dei dati ambientali e sanitari disponibili negli archivi regionali. Lo studio ha lo scopo di descrivere lo stato di salute delle popolazioni residenti nelle aree geotermiche toscane, identificate con i territori comunali per i quali sono state rilasciate concessioni di sfruttamento della risorsa geotermica. Disegno Lo studio ? di tipo ecologico e quindi non adatto a produrre evidenze che permettano di esprimere un giudizio sul nesso causa-effetto. I maggiori limiti degli studi ecologici derivano dall\u27assunzione che la residenza anagrafica a livello comunale rappresenti una valida misura di esposizione a fattori sia ambientali sia socioeconomici e dall\u27utilizzo di dati aggregati degli esiti sanitari che possono portare a risultati affetti da fallacia ecologica. Setting e partecipanti I comuni inclusi nell\u27area geotermica dello studio sono 16, di cui 8 compresi nell\u27area geotermica cosiddetta ?tradizionale?, che include le localit? di Larderello, Val di Cornia e Radicondoli-Travale (area geotermica Nord) e gli altri 8 situati nella zona dell\u27Amiata senese e grossetana (area geotemica Sud). Nel periodo 2000-2006 la popolazione media residente nell\u27area geotermica complessiva era di oltre 43.000 abitanti. Al momento dello studio erano attive 31 centrali geotermoelettriche con capacit? di produzione di 811 MW, di cui 5 con 88 MW totali nell\u27area geotermica Sud. Le analisi statistiche sono state effettuate a livello di intera area geotermica, delle due subaree geotermiche (Nord e Sud) e dei 16 comuni. Principali misure di outcome La mortalit? ? stata analizzata utilizzando i dati del Registro di mortalit? regionale della Toscana per l\u27intero periodo disponibile (1971-2006), con dettaglio per 60 cause, scelte in quanto di interesse generale per il profilo di salute della popolazione o perch? coerenti con i criteri adottati dal Progetto SENTIERI. L\u27ospedalizzazione ? stata valutata analizzando i dati delle schede di dimissione ospedaliera (SDO) della Re-gione Toscana nel periodo 2004-2006, includendo i ricoverati residenti in Toscana ovunque abbiano effettuato un ricovero, considerando solo la diagnosi principale di ricovero, escludendo i ricoveri ripetuti degli stessi soggetti per la stessa causa. Le cause di ospedalizzazione selezionate per l\u27analisi dei ricoveri sono le stesse utilizzate per l\u27analisi della mortalit?. Per la mortalit? sono stati calcolati i tassi di mortalit? standardizzati per et? (TSDM) e i trend temporali dei TSDM in quattro periodi (1971- 1979, 1980-1989, 1990-1999, 2000-2006). Sia per la mortalit? del periodo 2000-2006, sia per l\u27ospedalizzazione del periodo 2004-2006,sono stati calcolati: &#61692; i rapporti di mortalit?/ospedalizzazione standardizzati per et? (SMR/SHR), con e senza aggiustamento per l\u27indice di deprivazione (ID), utilizzando per il calcolo dell\u27ID i dati del censimento 2001, con gli attesi calcolati usando il tasso di mortalit?/ospedalizzazione della popolazione residente nei comuni limitrofi (comuni con la coordinata geografica del municipio compresa in un cerchio con raggio di 50 km centrato sull\u27area in studio); &#61692; le stime bayesiane dei rapporti di mortalit? (BMR) e di ospedalizzazione (BHR) a livello esclusivamente comunale; &#61692; le mappe (disease mapping) dei rischi bayesiani di mortalit?/ospedalizzazione comunali. Le malformazioni congenite (MC) sono state analizzate utilizzando i dati del Registro toscano dei difetti congeniti (RTDC) nel periodo 1992-2006, relativi a esiti di gravidanze di donne residenti nei comuni dell\u27area in studio, ovunque sia avvenuto il parto o l\u27interruzione di gravidanza. Per le MC ? stato calcolato il rapporto tra casi osservati e casi attesi (O/A), con gli attesi definiti in base al tasso regionale e vengono fornite le stime bayesiane del rapporto O/A (BMR) a livello esclusivamente comunale. Per valutare il basso peso e il rapporto tra maschi e femmine alla nascita sono stati utilizzati i dati dei certificati di assistenza al parto della Regione Toscana, relativi al periodo 2001-2007, con esclusione degli eventi occorsi in presidi di altre regioni. L\u27analisi ? stata condotta considerando i nati con: basso peso alla nascita (LW: peso <2.500 grammi), bassissimo peso alla nascita (VLW: peso <1.500 grammi), basso peso alla nascita nelle donne con et? gestazionale normale e maggiore di 36 settimane (LW36), et? gestazionale inferiore a 36 settimane, e il numero di maschi osservato. Per tutti gli indicatori ? stato calcolato il rapporto osservato/atteso, con l\u27atteso definito in base al tasso regionale. Risultati Il contesto ambientale Dalla descrizione del contesto ambientale, per quanto riguarda l\u27acqua, emerge come elemento di criticit? il riscontro talvolta di elevati livelli di arsenico nelle acque della rete di distribuzione degli acquedotti, tanto che in diverse realt? comunali si ? dovuto far ricorso alla concessione di deroghe ai parametri previsti dal decreto legislativo vigente (DLgs 31/01). Comunque, durante la fase conclusiva dello studio, nell\u27area geotermica Sud i nuovi sistemi abbattitori hanno ridotto i livelli di arsenico nella rete idrica fino a valori tali da non dover pi? ricorrere alle deroghe, ancora attive, invece, in alcuni comuni dell\u27area geotermica Nord. Le informazioni dell\u27ARPAT sui dati dell\u27aria evidenziano che l\u27attivit? geotermica ? in grado di modificare la qualit? dell\u27aria, soprattutto per l\u27acido solfidrico nell\u27area geotermica Nord, e per l\u27acido solfidrico e il mercurio nell\u27area geotermica Sud, in particolare nel versante senese dell\u27Amiata. Per il mercurio nell\u27aria, un contributo rilevante ? legato anche alle emissioni dagli ex siti metallurgici. Sebbene i livelli di mercurio nelle postazioni di monitoraggio rientrino sempre al di sotto dei valori guida raccomandati dall\u27OMS, le concentrazioni riscontrate nell\u27aria dell\u27Amiata senese, e perlopi? legate alla centrale PC2 di Piancastagnaio (spenta nel luglio 2011), sono significativamente superiori a quelle rilevate nelle altre aree geotermiche che, al contrario, sono assestate sugli stessi livelli registrati nei territori non geotermici. I livelli di concentrazione di acido solfidrico sono inferiori ai valori di riferimento, con occasionali superamenti del valore guida di tutela sanitaria OMS (150 &#956;g/m3 come media delle 24 ore). Pi? critici sono i dati di inquinamento olfattivo, che si verifica con il superamento del valore di 7-10 g/m3 di acido solfidrico nell\u27aria, riscontrato con vario grado di intensit? in tutte le postazioni di monitoraggio, anche in aree dove non sono presenti impianti geotermici. In alcune aree con insediamenti produttivi geotermici la frequenza, la persistenza e l\u27intensit? dei cattivi odori sono tali da comportare condizioni di qualit? dell\u27aria scadente

IgE Recognition Patterns of Profilin, PR-10, and Tropomyosin Panallergens Tested in 3,113 Allergic Patients by Allergen Microarray-Based Technology

BACKGROUND: IgE recognition of panallergens having highly conserved sequence regions, structure, and function and shared by inhalant and food allergen sources is often observed. METHODS: We evaluated the IgE recognition profile of profilins (Bet v 2, Cyn d 12, Hel a 2, Hev b 8, Mer a 1, Ole e 2, Par j 3, Phl p 12, Pho d 2), PR-10 proteins (Aln g 1, Api g 1, Bet v 1.0101, Bet v 1.0401, Cor a 1, Dau c 1 and Mal d 1.0108) and tropomyosins (Ani s 3, Der p 10, Hel as 1, Pen i 1, Pen m 1, Per a 7) using the Immuno-Solid phase Allergen Chip (ISAC) microarray system. The three panallergen groups were well represented among the allergenic molecules immobilized on the ISAC. Moreover, they are distributed in several taxonomical allergenic sources, either close or distant, and have a route of exposure being either inhalation or ingestion. RESULTS: 3,113 individuals (49.9% female) were selected on the basis of their reactivity to profilins, PR-10 or tropomyosins. 1,521 (48.8%) patients were reactive to profilins (77.6% Mer a 1 IgE(+)), 1,420 (45.6%) to PR-10 (92.5% Bet v 1 IgE(+)) and 632 (20.3%) to tropomyosins (68% Der p 10 IgE(+)). A significant direct relationship between different representative molecules within each group of panallergens was found. 2,688 patients (86.4%) recognized only one out of the three distinct groups of molecules as confirmed also by hierarchical clustering analysis. CONCLUSIONS: Unless exposed to most of the allergens in the same or related allergenic sources, a preferential IgE response to distinct panallergens has been recorded. Allergen microarray IgE testing increases our knowledge of the IgE immune response and related epidemiological features within and between homologous molecules better describing the patients' immunological phenotypes

Allergenic Lipid Transfer Proteins from Plant-Derived Foods Do Not Immunologically and Clinically Behave Homogeneously: The Kiwifruit LTP as a Model

BACKGROUND: Food allergy is increasingly common worldwide. Tools for allergy diagnosis measuring IgE improved much since allergenic molecules and microarrays started to be used. IgE response toward allergens belonging to the same group of molecules has not been comprehensively explored using such approach yet. OBJECTIVE: Using the model of lipid transfer proteins (LTPs) from plants as allergens, including two new structures, we sought to define how heterogeneous is the behavior of homologous proteins. METHODS: Two new allergenic LTPs, Act d 10 and Act c 10, have been identified in green (Actinidia deliciosa) and gold (Actinidia chinensis) kiwifruit (KF), respectively, using clinically characterized allergic patients, and their biochemical features comparatively evaluated by means of amino acid sequence alignments. Along with other five LTPs from peach, mulberry, hazelnut, peanut, mugwort, KF LTPs, preliminary tested positive for IgE, have been immobilized on a microarray, used for IgE testing 1,003 allergic subjects. Comparative analysis has been carried out. RESULTS: Alignment of Act d 10 primary structure with the other allergenic LTPs shows amino acid identities to be in a narrow range between 40 and 55%, with a number of substitutions making the sequences quite different from each other. Although peach LTP dominates the IgE immune response in terms of prevalence, epitope recognition driven by sequence heterogeneity has been recorded to be distributed in a wide range of behaviors. KF LTPs IgE positive results were obtained in a patient subset IgE positive for the peach LTP. Anyhow, the negative results on homologous molecules allowed us to reintroduce KF in patients' diet. CONCLUSION: The biochemical nature of allergenic molecule belonging to a group of homologous ones should not be taken as proof of immunological recognition as well. The availability of panels of homologous molecules to be tested using microarrays is valuable to address the therapeutic intervention

Is Aboriginal Food Less Allergenic? Comparing IgE-Reactivity of Eggs from Modern and Ancient Chicken Breeds in a Cohort of Allergic Children

BACKGROUND: Hen's egg allergy ranks among the most frequent primary food allergies in children. We aimed to investigate sensitization profiles of egg allergic patients and compare in vitro IgE reactivities of eggs from ancient chicken breeds (Araucana and Maran) with those from conventional laying hen hybrids. METHODOLOGY: Egg allergic children (n = 25) were subjected to skin prick test, double blind placebo controlled food challenge, and sensitization profiles to Gal d 1-5 were determined by allergen microarray. IgE binding and biological activity of eggs from different chicken breeds were investigated by immunoblot, ELISA, and mediator release assays. PRINCIPAL FINDINGS: We found that Gal d 1 and Gal d 2 are generally major egg allergens, whereas Gal d 3-5 displayed high sensitization prevalence only in patients reacting to both, egg white and yolk. It seems that the onset of egg allergy is mediated by egg white allergens expanding to yolk sensitization in later stages of disease. Of note, egg white/yolk weight ratios were reduced in eggs from Auraucana and Maran chicken. As determined in IgE immunoblots and mass analysis, eggs from ancient chicken breeds did not differ in their protein composition. Similar IgE-binding was observed for all egg white preparations, while an elevated allergenicity was detected in egg yolk from Araucana chicken. CONCLUSION/SIGNIFICANCE: Our results on allergenicity and biological activity do not confirm the common assumption that aboriginal food might be less allergenic. Comprehensive diagnosis of egg allergy should distinguish between reactivity to hen's egg white and yolk fractions to avoid unnecessary dietary restrictions to improve life quality of the allergic child and its family

Sensitization Prevalence, Antibody Cross-Reactivity and Immunogenic Peptide Profile of Api g 2, the Non-Specific Lipid Transfer Protein 1 of Celery

Background: Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. Methodology: 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. Results: IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Conclusions: Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.Christian-Doppler Research Association, Biomay AG, Vienna, AustriaItalian Ministry of Healt

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Age group distribution of the ISAC IgE panallergens-reactive population; n = 3,113.

<p>Black bars: Total 23,077 original allergic population; White Bars: Total 3,113 panallergens allergic population; Dark grey bars: PR-10; Hatched bars: Profilin; Light grey bars: Tropomyosin.</p