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Rationale: Bacterial lung microbiota are correlated with lung inflammation and acute respiratory distress syndrome (ARDS) and altered in severe coronavirus disease (COVID-19). However, the association between lung microbiota (including fungi) and resolution of ARDS in COVID-19 remains unclear. We hypothesized that increased lung bacterial and fungal burdens are related to nonresolving ARDS and mortality in COVID-19. Objectives: To determine the relation between lung microbiota and clinical outcomes of COVID-19-related ARDS. Methods: This observational cohort study enrolled mechanically ventilated patients with COVID-19. All patients had ARDS and underwent bronchoscopy with BAL. Lung microbiota were profiled using 16S rRNA gene sequencing and quantitative PCR targeting the 16S and 18S rRNA genes. Key features of lung microbiota (bacterial and fungal burden, α-diversity, and community composition) served as predictors. Our primary outcome was successful extubation adjudicated 60 days after intubation, analyzed using a competing risk regression model with mortality as competing risk. Measurements and Main Results: BAL samples of 114 unique patients with COVID-19 were analyzed. Patients with increased lung bacterial and fungal burden were less likely to be extubated (subdistribution hazard ratio, 0.64 [95% confidence interval, 0.42-0.97]; P = 0.034 and 0.59 [95% confidence interval, 0.42-0.83]; P = 0.0027 per log10 increase in bacterial and fungal burden, respectively) and had higher mortality (bacterial burden, P = 0.012; fungal burden, P = 0.0498). Lung microbiota composition was associated with successful extubation (P = 0.0045). Proinflammatory cytokines (e.g., tumor necrosis factor-α) were associated with the microbial burdens. Conclusions: Bacterial and fungal lung microbiota are related to nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.

Background: There are few studies regarding severe chronic upper-airway disease (SCUAD) that represents an important socioeconomic problem for the treatment of rhinitis and associated comorbidities, particularly asthma. Objectives: The aim of our study is to evaluate the prevalence of this pathology in patients with allergic rhinitis (AR) in real life, to phenotype allergic patients with SCUAD, and to identify which factors are related to the severity of the disease. Methods: We studied 113 patients with uncontrolled AR despite optimal adherence to therapy according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in a multicenter Italian study, analyzing comorbidity, use of additional drugs, not scheduled visits, and the number of emergency room admissions. Results: Our data suggest that polysensitization is the only statistically significant factor correlating with SCUAD. Asthma does not seem to represent a correlating factor. An important finding is the poor use (20%) of allergy immunotherapy (AIT), although patients were suffering from AR and the ARIA guidelines recommend the use of AIT in moderate/severe AR. Conclusions: The SCUAD population seems not to have a specific phenotype; there is a greater presence of SCUAD in polysensibilized patients, perhaps a sign of greater inflammation.

Background Allergic Rhinitis (AR) is a high-prevalence disease. In Europe about 25% of the general population is affected, and in Italy the prevalence is estimated to be 19.8%. The Allergic Rhinitis and its Impact on Asthma (ARIA) international document underlined that the prevalence of severe or refractory or overlapping rhinitis is increasing and represents a non-negligible socio-economic burden. In general, despite the social healthcare costs, allergic rhinitis remains underestimated, not sufficiently controlled and often undertreated. Aim of the study In this multi-center Italian observational and prospective study we assessed the control of AR in patients (> 16 years) without previous asthma diagnosis, referred to Allergy Centers. Methods Patients of both sexes and older than 16 with rhinitis symptoms and without asthma were studied. A Visual Analogue Scale (VAS) and the CARAT (Control of Allergic Rhinitis and Asthma Test) were used as patient reported outcome. The possible causes of poor control of AR, as per protocol, were assessed accordingly. Results We observed 250 patients in a real-life setting: more than 60% of them had an uncontrolled AR, only about 50% used multiple medications, and only a minority were receiving allergen immunotherapy. Conclusion This survey, conducted in a real-life setting, confirmed that AR is overall poorly controlled. The VAS assessment well correlates with the structured CARAT questionnaire and with the relevant symptoms of AR.

Summary Aims: Chronic cough is more frequent and severe in women than in men. Women often have decreased iron stores, because of menses and pregnancies. We investigated if iron deficiency has a role in chronic cough by increasing airway sensitivity to inhaled irritants. Methods: Twenty-two non-smoking women with chronic unexplained cough and iron deficiency (serum ferritin below 15 ng/ml) were examined in baseline, after 2 months empiric treatment with anti H1-histaminic drug and proton pump inhibitor, and after iron supplementation (330–660 mg iron sulphate tablets daily) for 2 months. Outcome measures were cough visual analogue scale (VAS), and histamine thresholds of the larynx (PC25MIF50, concentration causing 25% in MIF50), bronchi (PC20FEV1) and cough (PC5cough). Results: Mean serum ferritin was 9.3 ng/ml (95% CI 7.7–10.9), 13 patients had mild anaemia. All the patients had laryngeal and cough hyperresponsiveness,12 had also bronchial hyperresponsiveness. Empiric treatment produced no significant effect, whereas iron supplementation improved cough VAS from 4.03 (3.6–4.47) to 2.6 (1.9–3.27), p

Summary Background Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane. Objective The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE2) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen. Results At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14–53.61) vs. 21.56 pg/mL (19.92, 23.35), P

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.

BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 ad ...

The aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4-3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5-4.5%). In the sample with asthma in both surveys (n=423), the use of inhaled corticosteroids increased by 12.2% (6.6-17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma.

Microbiological findings at diagnosis and at the end of treatment are relevant for evaluating tuberculosis (TB) treatment programmes. The objectives of this study were to describe the microbiological findings at diagnosis and at the end of treatment in pulmonary and extrapulmonary TB patients treated under programme conditions in Italy. The study was a prospective monitoring activity based on the collection of standard recording and reporting forms from a representative sample of Italian TB Units. The forms with individual data were reviewed and analysed on a quarterly basis, 9 months after enrolment. The complete bacteriological profile of patients was analysed at diagnosis and at the completion of treatment. Individual data on 992 patients were analysed. At diagnosis 320 (32.2%) of cases were pulmonary sputum smear positive, 361 (36.4%) pulmonary smear negative or not done and 311 (33.4%) extrapulmonary; 424 (42.7%) of all TB cases were culture confirmed at diagnosis (368, 50.2%, of pulmonary cases); 575 (84.4%) of pulmonary cases had a culture done at diagnosis and 156 (22.9%) at the end of treatment (p < 0.001); 572 (84%) had a sputum smear done at diagnosis and 164 (24.1%) at the end of treatment (p < 0.001). Although the rate of bacteriologically confirmed cases is similar to that of other European countries, the bacteriological confirmation at diagnosis and, particularly, at the end of treatment, is sub-optimal. The importance of further disseminating national guidelines among physicians managing TB is emphasized, in order to achieve a higher proportion of TB cases bacteriologically confirmed at diagnosis and monitored at the end of treatment.

Fatal familial insomnia (FFI) is an inherited prion disease linked to a mutation at codon 178 of the PRNP gene that results in aspartic acid to asparagine substitution, in coupling phase with methionine at position 129. The disease is characterized clinically by insomnia with disturbances of the autonomic, endocrine, and motor systems and neuropathologically by selective degeneration of the thalamus. Phenotypic variability is well known and has been linked to homozygosity or heterozygosity at PRNP codon 129. We report the clinical, neuropathologic, and biochemical findings and genomic analysis of a patient with FFI from a new Italian kindred. Although homozygous for methionine at codon 129, this patient showed some clinical and pathologic features most commonly found in heterozygotes.

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.

It is uncertain the Forced Expiratory Time (FET) acceptable during spirometry of young people (16-20 years old) because they are not children nor adults. We studied 235 boys and 187 girls of this age and, comparing spirometries with FET3 s and6 s, we found no significative difference (t test) between Vext, DtPEF, FVC and FEV1 repeatibility, while for wheight in males (p =0.0022) and plateau time (p0.00001) in males and females. We conclude that blows with FET6s but3s can be acceptable in young people when other criteria are respected.

Diffuse intrinsic pontine glioma (DIPG) is a fatal paediatric malignancy. Tumour resection is not possible without serious morbidity and biopsies are rarely performed. The resulting lack of primary DIPG material has made preclinical research practically impossible and has hindered the development of new therapies for this disease. The aim of the current study was to address the lack of primary DIPG material and preclinical models by developing a multi-institutional autopsy protocol.An autopsy protocol was implemented in the Netherlands to obtain tumour material within a brief post mortem interval. A team of neuropathologists and researchers was available at any time to perform the autopsy and process the material harvested. Whole brain autopsy was performed and primary DIPG material and healthy tissue were collected from all affected brain areas. Finally, the study included systematic evaluation by parents.Five autopsies were performed. The mean time interval between death and time of autopsy was 3 h (range 2-4). All tumours were graded as glioblastoma. None of the parents regretted their choice to participate, and they all derived comfort in donating tissue of their child in the hope to help future DIPG patients. In addition, we developed and characterized one of the first DIPG cell cultures from post mortem material.Here we show that obtaining post mortem DIPG tumour tissue for research purposes is feasible with short delay, and that the autopsy procedure is satisfying for participating parents and can be suitable for the development of preclinical DIPG models.

BACKGROUND: Malignant pediatric brain tumors constitute a heterogeneic group of central nervous system tumors, and general markers of diagnosis and prognosis are not available. Recently, a panel of CD markers (CD15, CD24, CD29) was used to define increasing neural differentiation of embryonic stem cells. Although these CD markers have been associated with worse prognosis due to presence of tumor propagating cells, alterations in adhesion and migration in various cancer types, no studies of multiple CD markers in pediatric brain tumors have been performed. METHODS: We have collected tumors, including medulloblastomas (MB), ependymomas (EP) and juvenile astrocytomas, from >20 pediatric brain tumor patients. Frozen tumor sections and cultured tumor cells were stained for CD15, CD24 and CD29 and analyzed using fluorescence microscopy or flowcytometry. RESULTS: MB contained a mixture of cells with strong CD15 labeling inside vessels and cells with diffuse CD15 staining in the parenchyma of the tumor tissue. Cells strongly labeled with CD15 were also positive for the leukocyte marker CD45. The previously proposed association between CD15 expression and prognosis in MB could instead of reflecting abundance of tumor propagating cells depend on infiltrating immune cells. In low-grade pediatric tumors and EP, larger areas stained weakly for CD15 while few cells displayed strong staining. CD24 was expressed on the vast majority of cells in pediatric brain tumors, despite grade of malignancy. MB, however, displayed an intense and aberrant staining for CD24. Computerized image analysis of frozen tumor sections showed that proliferation of cells and the expression of CD29 correlated in a sub-group of MB. CONCLUSIONS: Our preliminary data show that CD15, CD24 and CD29 are differentially expressed in high- and low-malignant pediatric brain tumors in vivo. By defining the patterns of CD antigen expression in different pediatric tumors their relationship to biological behavior and thus prognosis can be established. (Less)

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- γ 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 QFTGIT (>.35 UI cut-off). TB cases showed a significant loglinear increase in interferon-γ (IFN-γ) concentration, over time of treatment: IFN-γ 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.

Chronic cough is more frequent and severe in women than in men. Women often have decreased iron stores, because of menses and pregnancies. We investigated if iron deficiency has a role in chronic cough by increasing airway sensitivity to inhaled irritants.Twenty-two non-smoking women with chronic unexplained cough and iron deficiency (serum ferritin below 15 ng/ml) were examined in baseline, after 2 months empiric treatment with anti H1-histaminic drug and proton pump inhibitor, and after iron supplementation (330-660 mg iron sulphate tablets daily) for 2 months. Outcome measures were cough visual analogue scale (VAS), and histamine thresholds of the larynx (PC25MIF50, concentration causing 25% in MIF50), bronchi (PC20FEV1) and cough (PC5cough).Mean serum ferritin was 9.3 ng/ml (95% CI 7.7-10.9), 13 patients had mild anaemia. All the patients had laryngeal and cough hyperresponsiveness,12 had also bronchial hyperresponsiveness. Empiric treatment produced no significant effect, whereas iron supplementation improved cough VAS from 4.03 (3.6-4.47) to 2.6 (1.9-3.27), p0.0001, PC20FEV1 from 10.04 mg/ml (5.37-18.77) to 22.2 (11.7-41.8), p0.001, PC25MIF50 from 3.09 mg/ml (1.9-4.9) to 11.9 (7.3-19.4), p0.001 and PC5cough from 2.1 mg/ml (1.2-3.6) to 8.8 (5.2-15.1), p0.001.In women with unexplained chronic cough unresponsive to targeted treatment, airway and cough hyperresponsiveness may be sustained by iron deficiency. Healthy women with chronic cough should be checked for iron deficiency as iron repletion may resolve such disturbing symptom.

In the three Italian centres involved in the European Community Respiratory Health Survey (ECRHS), prevalence of asthma-like symptoms was assessed through a mailback questionnaire. Since the nonresponse rate was not negligible, ranging 10-18%, we investigated whether nonresponse bias affected the results and, if so, whether the bias could be eliminated from the final estimates of prevalence. A screening questionnaire was sent by mail to 7,000 randomly selected subjects 20-44 yrs of age, and nonresponders were contacted again by phone. Additional information was collected on a subsample of the respondents through a clinical interview. A logistic regression analysis showed that, except for one symptom (awakening for coughing), symptom prevalence significantly decreased from the first to the subsequent contact, when controlling for age, sex, centre and season of interview. The decrease in symptom prevalence was largely independent of smoking habits and socioeconomic status, and was seemingly caused by a symptom-related self-selection. When correcting results according to a linear regression model, observed estimates appeared to be slightly overestimated, by 4-10%. A simulation with the Italian data showed that the bias increased steeply at nonresponse rate higher than 30%, a situation quite common in asthma surveys. In conclusion, nonresponse bias affects the results of ECRHS in Italy, slightly inflating prevalence estimates. To make reliable comparisons on international data in the presence of different nonresponse rates, a correction of the observed prevalence seems necessary.

Carcinoembryonic antigen and CA 19.9 are markers of colorectal neoplasms, often related to tumor burden. Elevated pre-operative levels parallel disease extent and may foresee adverse prognosis. CEA and CA 19.9 may increase post-operatively, indicating tumor recurrence. Only limited data are available on the influence of chemotherapeutic treatments on these two markers, to detect chemotherapy-induced cytolysis. We measured CEA and CA 19.9 before and after a chemotherapy regimen of five days consisting of folinic acid and 5-fluorouracil in forty patients with colorectal cancer. No consistent fluctuation was detected, the examined tumor markers being related in a given patient only to tumor burden.

Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane.The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2) ) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen.At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.85, P0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.52, P=0.001).The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma.

834 consecutive patients (630 female), aged between 26 and 46 years, who wort 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 its sex, age and occupation on the patch test remits, and the coexistence of 2 or more unrelated but statistically significant sensitivities.

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.

International audience; BACKGROUND: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey. METHODS: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL. RESULTS: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively. CONCLUSION: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.

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.To discriminate between TST reactions due to infection and those due to vaccination in subjects with unknown BCG status.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.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.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.

Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies.To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors.The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean).Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P0.001), higher annual mean temperature (16.2 degrees C vs. 12.9 degrees C), lower temperature range (16.0 C degrees vs. 22.1 degrees C) and lower NO2 levels (31.46 microg/m3 vs. 57.99 microg/m3) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 microg/m3 in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28).Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.

Background: Italian data on the prevalence of allergic rhinitis are sparse and with wide variations, maybe because of different diagnostic criteria and methods of investigation. This study analyzes the information on rhinitis collected in northern Italy through standardized methods within the European Community Respiratory Health Survey. Methods: A screening questionnaire was sent by mail to a random sample of the general population aged 20–44 years, and nonresponders were contacted again by phone, achieving a final response rate of 86% (6031/7000). Among the responders, 914 randomly selected underwent a standardized clinical interview, skin prick test (SPT) and total and specific immunoglobulin (Ig)E determination. Results: The overall prevalence of self-reported allergic rhinitis was 15.9% (95% CI 15.0–16.8%). Allergic rhinitis was more common in men below 35 years and in women older than that (P = 0.006), in urban areas (P

Practical or cost-effective strategies to identify undocumented immigrants with latent tuberculosis infection and to deliver treatment for latent TB infection are still unavailable.To compare completion rates of screening procedures for TB infection and disease among undocumented immigrants at specialised (TB) and unspecialised health services in Italy.A TB unit (TBU) and an unspecialised health service unit for migrants (MHCU) served as recruitment sites for recent undocumented immigrants from TB endemic areas. The screening included a symptom questionnaire, a tuberculin skin test and a chest X-ray.Of 1318 eligible subjects, 1232 (93.4%) accepted the screening. Screening was completed by 993 (80.6%) individuals overall, 86.5% and 71.4% at the TBU and MHCU services, respectively. In a multivariate analysis model, the only variable associated with an increased probability of completing screening was being enrolled at the TBU site (OR 2.5, 95%CI 1.8-3.5; P0.001). Three hundred and ninety-two subjects (39.4%) had a TST test ofor = 10 mm. Eight cases of active tuberculosis were detected, with a calculated prevalence of disease of 650/100,000.Undocumented immigrants to Italy can be screened for TB at an unspecialised health service unit, although not as efficiently as at a specialised TB unit.

Microbiological findings at diagnosis and at the end of treatment are relevant for evaluating tuberculosis (TB) treatment programmes. The objectives of this study were to describe the microbiological findings at diagnosis and at the end of treatment in pulmonary and extrapulmonary TB patients treated under programme conditions in Italy. The study was a prospective monitoring activity based on the collection of standard recording and reporting forms from a representative sample of Italian TB Units. The forms with individual data were reviewed and analysed on a quarterly basis, 9 months after enrolment. The complete bacteriological profile of patients was analysed at diagnosis and at the completion of treatment. Individual data on 992 patients were analysed. At diagnosis 320 (32.2%) of cases were pulmonary sputum smear positive, 361 (36.4%) pulmonary smear negative or not done and 311 (33.4%) extrapulmonary; 424 (42.7%) of all TB cases were culture confirmed at diagnosis (368, 50.2%, of pulmonary cases); 575 (84.4%) of pulmonary cases had a culture done at diagnosis and 156 (22.9%) at the end of treatment (p0.001); 572 (84%) had a sputum smear done at diagnosis and 164 (24.1%) at the end of treatment (p0.001). Although the rate of bacteriologically confirmed cases is similar to that of other European countries, the bacteriological confirmation at diagnosis and, particularly, at the end of treatment, is sub-optimal. The importance of further disseminating national guidelines among physicians managing TB is emphasized, in order to achieve a higher proportion of TB cases bacteriologically confirmed at diagnosis and monitored at the end of treatment.

In the early 1990s a multicentre survey on asthma was performed on the young adult population (European Community Respiratory Health Survey - ECRHS). This study is to be repeated in order to estimate changes in the prevalence of asthma-like symptoms during the last decade and to assess the social and economic costs of the disease and their variations among countries. The self-administered questionnaire devised for this purpose is a two-page questionnaire. The first page contains the same items as those used in the first survey with four additional questions related to: 1) the frequency and severity of asthma attacks; 2) the presence of chronic bronchitis; 3) smoking habits; and 4) a visual analogue scale assessing perception of outdoor pollution. The second page aims to collect information regarding the direct and indirect costs of asthma. The influence of the length of the questionnaire on the response rate was assessed in a pilot study in Italy. Two random samples of 150 subjects received either the one-page questionnaire (first page) or the two-page questionnaire. The response rate was compared with that obtained from the first postal wave in the 1991-1992 survey. Although the response rate was unchanged when using the one-page questionnaire (45% versus 45%), it decreased by 7% when the two-page questionnaire was used (38% versus 45%). On the basis of these results, no problem should arise if four more questions are added to the one-page questionnaire. The slight reduction in the response rate of the two-page questionnaire is worrying but could be corrected by the use of telephone interviews.

A longitudinal study on exposure to tobacco smoke among adolescents was carried out in Turin (North-Western Italy) in January-February 1992 and in January-February 1993. In 1992, 394 schoolchildren aged 14-16 years were enrolled in a study protocol which consisted in answering a standardized questionnaire, measurement of urinary cotinine and testing of lung function (flow-volume curve--[FVC] and forced expiratory volume in I sec.--[FEV1]). In 1993, 333 schoolchildren from the same group repeated the survey. By comparison to urinary cotinine, findings obtained showed a reduction of increase, from 1992 to 1993, of -0.57% (p = 0.082) for FVC, and -0.66% (p = 0.05) for FEV1. Assuming that the systematic selection bias did not seem to have occurred, findings, obtained from a multiple regression analysis, showed that active and passive exposure to tobacco smoke, as measured by urinary cotinine, had a significant effect on lung growth (as measured by FEV1) in adolescents; this effect, though small, was dose-related.

This article shows the results of a 10-year follow-up study conducted on a cohort of 870 patients affected by severe chronic airflow obstruction (CAO) on spirometric tests. The main aims of the study were to identify those factors associated with reduced survival in CAO patients and to evaluate the effectiveness of a care program on patients' survival. The analysis compared the survival time and causes of death between patients who showed adherence and patients who did not show adherence to the care program. The most important results can be summarized as follows: (1) CAO patients have a high mortality rate for acute respiratory failure, cor-pulmonale, and lung cancer; (2) patient's age at the time of selection to enter follow-up influences the death hazard; (3) patients who need long-term oxygen treatment (LTOT) have a higher death hazard than those who don't need it; (4) the higher is FEV1 or PaO2 value at the time of selection, the lower the death hazard; (5) patients who need, and regularly take, long-term oxygen treatment have a lower death hazard compared to those who need it, but do not take it properly; and (6) patients with a partial reversible airway obstruction (pRAO) who regularly attend the clinic for planned check-ups, have a lower death hazard compared to those who have the same characteristics, but do not show adherence to the care program. These results indicate that an organized program to treat severe CAO patients may improve their survival.

The aims of this study are: (1) to evaluate whether the estimates of the association of risk factors with bronchial hyperresponsiveness (BHR) depends on the accumulated dose administered in challenge tests; and (2) to verify whether a model developed for survival studies (Weibull regression) is suited to analyze methacholine dose-response curves. For these purposes, 863 challenge tests, from EC Respiratory Health Survey in Italy, up to a cumulative dose of 6 mg methacholine, were analyzed by Weibull regression and by traditional methods (logistic model and linear model), both before and after truncation of the curves at 2 mg. With all methods the main risk factors for BHR were respiratory symptoms and atopy while age and airway caliber exerted a protective action. Our results confirmed that in epidemiological surveys 2 mg methacholine is enough to fully appreciate the effect of risk factors on BHR and showed chat the Weibull model explains the observed variability better than linear and logistic regressions. (C) 1998 Elsevier Science Inc.

Prion diseases are transmissible neurodegenerative conditions characterized by the accumulation of protease-resistant forms of the prion protein (PrP), termed PrPres, in the brain. Insoluble PrPres tends to aggregate into amyloid fibrils. The anthracycline 4′-iodo-4′-deoxy-doxorubicin (IDX) binds to amyloid fibrils and induces amyloid resorption in patients with systemic amyloidosis. To test IDX in an experimental model of prion disease, Syrian hamsters were inoculated intracerebrally either with scrapie-infected brain homogenate or with infected homogenate coincubated with IDX. In IDX-treated hamsters, clinical signs of disease were delayed and survival time was prolonged. Neuropathological examination showed a parallel delay in the appearance of brain changes and in the accumulation of PrPres and PrP amyloid.

This article presents the AIPO-TB proposal for protection of health care workers from risks related to exposure to airborne biological agents and especially TB, according to law 626/94. The risk of contagion among health care workers arises mainly from contact with contagious patients (not diagnosed or not isolated after diagnosis). The proposal puts forward classification criteria for health structures and services according to risk level. It also suggests procedures for risk limitation (respiratory isolation and individual protection) and epidemiological and health surveillance. Guidelines for a tuberculin survey, vaccination and special risk situations are also provided.

The results of the sweat tests performed in Turin CF Centre in the last four years were reviewed. The opportunity of changing the range of doubt, commonly situated between 40 and 70 mEq/l Cl-, has been considered. The sweat test appears worth to be repeated only for values60, unless clinical signs and symptoms persist.

Patients with asthma-like symptoms may not have asthma but obstruction of the extrathoracic airway (EA). To evaluate if dysfunction of the EA causes asthma-like symptoms, we assessed bronchial and EA responsiveness to inhaled histamine in 441 patients who presented with at least one of three key symptoms--cough, wheeze, dyspnoea--but had neither documented asthma nor bronchial obstruction. The histamine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) and a 25% fall in maximal mid-inspiratory flow (PC25MIF50) were used as respective thresholds of bronchial and EA responsiveness. Values 8 mg/mL or less indicated bronchial (B-HR) or EA hyper-responsiveness (EA-HR). The influence of concurrent upper respiratory tract diseases, such as post-nasal drip (PND), pharyngitis, laryngitis and sinusitis, was also assessed. We found four response patterns to the histamine challenge: EA-HR in 26.5% of the patients, B-HR in 11.1%, combined EA-HR and B-HR in 40.6%, and no-HR in 21.8%. Cough was reported by 79% of the patients, wheeze by 53%, and dyspnoea by 40%. Patients with cough as the sole presenting symptom (34.2%), as compared with those with wheeze and/or dyspnoea (20%), had significantly greater probability of having EA-HR (OR 5.35, 95% CI 3.25-8.82) and lower probability of having B-HR (OR 0.45, CI 0.28-0.70); patients with cough plus wheeze and/or dyspnoea (45.8%) had significantly greater probability of having both EA-HR and B-HR than either those with cough alone (OR 2.48, CI 1.49-4.13), or those with wheeze and/or dyspnoea but not cough (OR 1.74, CI 1.36-2.22). EA-HR alone or combined with B-HR was strongly associated with EA diseases, particularly pharyngitis and PND. Cough was significantly associated with PND, either when it was the sole symptom (OR 2.16, CI 1.14-4.09) or when it was combined with wheeze and/or dyspnoea (OR 3.53, CI 1.97-6.33). Our results suggest that extrathoracic airway dysfunction may account for asthma-like symptoms, particularly chronic cough. This abnormality seems to be sustained by chronic diseases of the upper respiratory tract.

The EC Respiratory Health Survey (ECRHS) design is presented: the survey aim is to estimate asthma prevalence and risk factors distribution in the various European countries population. In Italy three centres are involved: Pavia, Turin and Verona. EC Health Respiratory Survey is an international two stages cross-sectional survey on probability samples of general population aimed to asses asthma prevalence in different countries. In the first stage a random sample was sent a Screening Questionnaire by post; in the second stage a subsample was invited to clinical centres in order to undergo lung function tests, allergy tests and a standardised clinical interview. The analysis of the response pattern in Italy shows that both in stage 1 and in stage 2 a selection bias overestimating real prevalence is present. Some methodological issues concerning the design of cross sectional surveys are addressed.