Perfluorooctanoic acid alters progesterone activity in human endometrial cells and induces reproductive alterations in young women.

Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances (PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor. The aim of this study was to investigate PFAS interference on hormonal endometrial regulation. This study was performed within a screening protocol to evaluate reproductive health in high schools. We studied a cohort of 146 exposed females aged 18-21 from the Veneto region in Italy, one of the four areas worldwide heavily polluted with PFAS, and 1080 non-exposed controls. In experiments on Ishikawa cells included UV-Vis spectroscopy, microarray analysis and qPCR. We report a significant dysregulation of the genetic cascade leading to embryo implantation and endometrial receptivity. The most differentially-expressed genes upon PFOA coincubation were ITGB8, KLF5, WNT11, SULT1E1, ALPPL2 and G0S2 (all p < 0.01). By qPCR, we confirmed an antagonistic effect of PFOA on all these genes, which was reversed at higher progesterone levels. Molecular interference of PFOA on progesterone was confirmed by an increase in the intensity of absorption spectra at 250 nm in a dose-dependent manner, but not in the presence of ß-estradiol. Age at menarche (+164 days, p = 0.006) and the frequency of girls with irregular periods (29.5% vs 21.5%, p = 0.022) were significantly higher in the exposed group. Our results are indicative of endocrine-disrupting activity of PFAS on progesterone-mediated endometrial function.

EBCOG position statement: Vaccination in pregnancy.

Maternal immunization has the potential to reduce morbidity and mortality from infectious diseases worldwide. EBCOG promotes this public health intervention supporting international recommendations about the use of vaccines during pregnancy.

Pregnancy in a woman with recurrent immunoglobulin a nephropathy: A case report.

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis and is increasingly encountered in pregnancy. The obstetric and renal outcomes of pregnancy are controversial, however. Women with IgAN are at higher risk of hypertension, preeclampsia and foetal loss; the prognosis is worse for those who have advanced chronic kidney disease and proteinuria. Here we report the case of a 32-year-old nulliparous woman with chronic hypertension who conceived during an active phase of her IgAN, which had been diagnosed 8 years earlier. Antihypertensive therapies and a low-protein diet were key to her reaching 34 weeks' gestation with acceptable kidney function. Rupture of membranes occurred at 34 weeks 3 days' gestation and a healthy boy was delivered the next day. This report aims to provide clinicians with useful information for the management of patients with IgAN during pregnancy.

Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF.

BACKGROUND: The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy. METHODS: A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5-9, 10-15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life. RESULTS: The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios. CONCLUSIONS: The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS).

Geo-climatic heterogeneity in self-reported asthma, allergic rhinitis and chronic bronchitis in Italy.

BACKGROUND: Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases. AIM: To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy. METHODS: Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20-44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma-like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta-regression models. RESULTS: 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I(2)=59.5%, p=0.022) and CB (I(2)=60.5%, p=0.019), but not in that of asthma-like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p=0.017), but not with differences in the topographic one. CONCLUSIONS: Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean climates, and lower in rainy-cold northern climates.

Adult eczema in Italy: prevalence and associations with environmental factors.

BACKGROUND: Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking. OBJECTIVES: To determine the prevalence of eczema and AD in the Italian adult population, and to investigate risk factors associated with the disease. METHODS: A postal screening questionnaire was administered to 18 357 randomly selected subjects aged 20-44 years in the Gene-Environment Interaction in Respiratory Diseases study, which involved seven centres distributed across northern, central and southern Italy. The questionnaire included items on the occurrence of doctor-diagnosed eczema, asthma and hay fever, socio-demographic characteristics and environmental exposures. RESULTS: In all, 10 464 (57.0%) subjects responded to the questionnaire. The prevalence of current eczema was 8.1% (95% CI: 7.6-8.7%), while the prevalence of eczema with asthma and/or hay fever (EAH), which was adopted as proxy of AD, was 3.4% (95% CI: 3.1-3.8%). About 60% of the subjects with current eczema reported the onset of the disease in adulthood. In multi-variable models, the prevalence of eczema was significantly associated with female sex, older age, living close to industrial plants, high levels of heavy traffic near home and living in central-southern Italy. CONCLUSIONS: Eczema and EAH are highly prevalent in Italian young adults, especially in women. Our results suggest that adult onset is not unusual, and that environmental factors may influence the occurrence of eczema and EAH.

The effect of antituberculosis treatment on interferon-gamma release assay results.

BACKGROUND AND AIM: Monitoring the efficacy of antituberculosis therapy is crucial. The aim of this work is to investigate the effect of tuberculosis treatment on interferon-gamma response using Quanti-FERON-TB Gold in tube (QFT-GIT). METHODS: A total of 216 new pulmonary tuberculosis (TB) cases were tested with QFT-GIT at the start of the treatment and, randomly, once or twice between 90 and 180 days afterwards. Data was analysed using the random effect regression model analysis. RESULTS: 63.4% of patients were positive at the QFT-GIT (> .35 UI cut-off). TB cases showed a significant log-linear increase in interferon-gamma (IFN-gamma) concentration, over time of treatment: IFN-gamma concentration increased by 78% after 6 months of treatment in acid-fast bacilli positive (A) and culture negative cases in culture confirmed cases the increase was 43% if A+ and 20% in A-. CONCLUSIONS: Effective therapy seems to restore cellular responses to Mycobacterium tuberculosis antigens. The potential use of interferon gamma release assay (IGRA) in monitoring response to TB treatment is hampered by the presence of active mycobacterial replication at baseline and needs further evaluation.

Sublingual immunotherapy in polysensitized patients: effect on quality of life.

BACKGROUND: Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. OBJECTIVE: To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. METHODS: We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). RESULTS: The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. CONCLUSIONS: This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Eczema, atopy and allergen exposure in adults: a population-based study.

BACKGROUND: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. OBJECTIVE: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.

Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy.

BACKGROUND: Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease. THE AIMS OF OUR STUDY WERE: (i) to measure the comorbidity of AR and asthma and asthma-like symptoms and (ii) to assess whether asthma, AR, and their coexistence share a common pattern of individual risk factors. METHODS: The subjects are participants from the Italian multicentre, cross-sectional survey on respiratory symptoms in the young adult general population (Italian Study of Asthma in Young Adults, ISAYA). The relationship between individual risk factors and asthma, AR and their coexistence, was studied by means of a multinomial logistic regression. RESULTS: About 60% of asthmatics reported AR. On the other hand, subjects with AR presented an eightfold risk of having asthma compared to subjects without AR. Age was negatively associated with asthma [OR = 0.89, 95% confidence interval (CI): 0.82-0.96], AR (OR = 0.92, 95% CI: 0.86-0.98), and asthma associated with AR (OR = 0.83, 95% CI: 0.79-0.88). The risk of AR without asthma was significantly higher in the upper social classes (OR = 1.23, 95% CI: 1.08-1.39). Active current smoking exposure was positively associated with asthma alone (OR = 1.24, 95% CI: 1.09-1.41) and negatively associated with AR with (OR = 0.69, 95% CI: 0.54-0.88) or without (OR = 0.76, 95% CI: 0.69-0.84) asthma. CONCLUSIONS: Asthma and AR coexist in a substantial percentage of patients; bronchial asthma and AR, when associated, seem to share the same risk factors as AR alone while asthma without AR seems to be a different condition, at least with respect to some relevant risk factors.

Tuberculin reactivity in adult BCG-vaccinated subjects: a cross-sectional study.

INTRODUCTION: Interpretation of the tuberculin skin test (TST) may be complicated by prior bacille Calmette-Guérin (BCG) vaccination. The skin reaction to the vaccination interferes with the management of individuals who may be infected with Mycobacterium tuberculosis. OBJECTIVE: To discriminate between TST reactions due to infection and those due to vaccination in subjects with unknown BCG status. METHODS: Among 60200 subjects tested with 5TU PPD for screening purposes, 4987 contacts of infectious TB cases (Group A), 4962 BCG-vaccinated subjects (Group B) and 5000 subjects from the general population (Group C) were sampled. The frequencies of TST cut-off diameters were calculated for the three groups using a logistic regression model. The frequency of positive subjects in each group and the sensitivity, specificity and predictive values were also computed by means of these cut-offs. RESULTS: The risk of being a contact versus BCG-vaccinated increases 2.43-fold with every mm of TST diameter. The 11 mm cut-off point seems to be the best discriminating value. CONCLUSIONS: Using the traditional 10 mm cut-off, we can consider all vaccinated subjects with a positive TST to be infected. The TST remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated subjects and in populations with high vaccination coverage.

[Hapten selection for patch tests in the diagnosis of allergic contact dermatitis: epidemiologic data]. / La scelta degli apteni per i test epicutanei nella dignosi delle dermatiti allergiche da contatto: osservazioni epidemiologiche.

Aim of the study was to verify the reliability in clinical practice of patch testing with "standard" series and additional series of haptens for the diagnosis of occupational and non-occupational allergic contact dermatitis, evaluating positive reactions and relating those reactions to professional categories. A total of 392 out of 937 patients (41.8%) showed at least one positive reaction to "standard" series testing; the hapten most frequently noted as the cause of positive reaction was nickel sulphate. Professional categories that showed positive reactions to "standard" series most frequently were clerks, hairdressers and hospital auxiliary workers. Among 897 patients tested with nonstandard allergens, only 124 (13.8%) elicited at least one positive reaction, ammonium persulphate being the most frequently positive hapten. A dominant percentage of positive results was seen in hairdressers and cleaning personnel. No positive reactions were observed in a large number of haptens, tested more than 200 times. Haptens of "standard series" elicited a higher number of positive reaction than the additional series, even though there was a high specificity of few additional series haptens in some professional categories. Data suggest some caution in systematically testing additional series, despite a higher accuracy and diagnostic efficacy in some job categories.

Inadequate antiasthma drug use in the north of Italy.

A multicentre survey of prevalence, determinants and management of asthma (the European Community Respiratory Health Survey (ECRHS)) has shown that the ratio of subjects declaring current use of antiasthmatic drugs to those reporting asthma attacks in the previous 12 months was particularly low (0.54) in the north of Italy. In this study, we used a standardized clinical interview to gather a more detailed insight into the issue of asthma undertreatment in the north of Italy. A total of 1,104 subjects were interviewed, 116 of whom had been defined as asthmatic by the family doctor. Fifty subjects had current asthma and 66 had a history of previous asthma. A considerable percentage (26%) of subjects with current asthma were not being treated with antiasthmatic therapy. Even when only patients with severe asthma were considered, the percentage of untreated patients was still high (21%). Forty two per cent of subjects used inhaled beta2-agonists alone, 28% inhaled steroids plus beta2-agonists, 2% inhaled steroids alone and 2% other drugs. Only 19% of the asthmatics on treatment, 85% of whom had more severe asthma, received daily treatment. Only 65% of the subjects who had received antiasthmatic drug prescriptions declared they had taken all the drugs prescribed; this percentage was 74% when respiratory symptoms were worsening. Of the patients with past asthma, 18% had taken antiasthmatic drugs. Most of these patients were those who had had more severe asthma. In conclusion, antiasthmatic drugs are underused in the north of Italy, at least in part due to low compliance.

[The impact of immigration from high incidence countries on the epidemiology of tuberculosis]. / Impatto sull'epidemiologia della tubercolosi dell'immigrazione da paesi ad alta incidenza.

Immigration in Italy from developing countries is a recent problem and the possible consequences on public health must be taken into account. The present study reports the results of Tuberculosis control activities performed by the Dispensario di Igiene Sociale of Turin, related to this population. Up to now the available data suggest that the immigrant population (mainly from North Africa and Senegal), in spite of representing a small part of residents (approximately 33,000/1,000,000) contributes to one third of Tuberculosis cases. The consequences on Tuberculosis epidemiology in Italy and our operational experience on Tuberculosis control and prevention are discussed.

Using reference values in pulmonary ventilation studies.

The aim of this study was to examine the discriminating power of six widely used, or recently introduced, reference values in the interpretation of pulmonary ventilation (FVC and FEV1) in occupational health surveys. These six reference values were applied to a sample of 400 Italian males; 200 of the sample were foundry workers and the other 200 were workers who were not occupationally exposed to dusts; 50% of each group were smokers. The relationship between the reference values and their capacity to discriminate between the workers occupationally exposed to dusts and the workers who smoked in each group was evaluated. The results showed very significant differences among the various reference values. Generally speaking these differences may be determined by the different selection criteria of the subjects under study, or may be a result of the different characteristics of the population included in the various studies. Our conclusions show the need for a critical approach to the use of reference values, particularly during screening tests.

Results of routine patch testing of 834 patients in Turin.

834 consecutive patients (630 female), aged between 26 and 46 years, who were suspected of having allergic contact dermatitis were patch tested with the GIRDCA standard series during 1989-1990. The most frequent sensitizers observed included nickel sulphate, cobalt, Kathon CG, perfumes, potassium dichromate and balsam of Peru. We have evaluated the influence of individual factors such as sex, age and occupation on the patch test results, and the coexistence of 2 or more unrelated but statistically significant sensitivities.

The differential diagnosis of primary lung cancer: inter-observer agreement and contribution of specific diagnostic procedures.

In order to investigate inter-observer variability in the differential diagnosis of primary lung cancer among women and the contribution of specific diagnostic procedures to this diagnosis, a group of 449 suspect cases of this disease was studied. Based on a standard dossier (including clinical data and the reports, if present, of radiology, bronchoscopy and histology) six different physicians independently judged, for each woman, at each diagnostic step, the presence of a primary lung cancer. A final consensus was organized in order to define the true cases. Radiology and especially histology seem to give the most important contribution to the diagnosis. On the other hand bronchoscopy seems to be useful mainly as a guide for biopsy. A predictive value of 90% was found when both radiology and bronchoscopy were positive; in the other cases histology seems to be needed to reach an adequate discrimination. Inter-rater agreement increases with an increasing amount of information but is not very high even when histology is available.