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.

Urban air quality and carboxyhemoglobin levels in a group of traffic policemen.

Toxicological potential of carbon monoxide (CO) on humans is well known. Nevertheless, CO is still considered as a useful marker to detect some environmental and occupational human risk factors typical of cities. The role played by traffic pollution, indoor air quality in offices and tobacco smoke on the expression of carboxyhemoglobin (COHb%) levels was investigated in a large group of traffic policemen in Torino city (North-Western Italy). At the end of the working shift, 228 policemen responded to a questionnaire, weight and height recorded, urine spot samples collected to measure cotinine as biomarker of tobacco smoke exposure, and an arterial blood sample was taken to measure COHb levels. Data of outdoor urban air-CO were collected and to each subject a "CO outdoor air measurement" was related to his/her COHb level. Considering the annual trend of air-CO pollution from 2002 to 2004, one can assume that a general improvement of air quality in Torino was evident. Taking into account the environments where policemen work (urban outdoor and indoor), and analyzing their COHb% content, the traffic-congested areas, and, in general, the outdoor urban environment were equally risky as offices. Furthermore, if compared to CO arising from traffic-congested areas or other outdoor environments, the traffic policemen in Torino city demonstrate COHb% levels largely due to smoking habits.

Changing prevalence of asthma in Turin school children between 1994 and 1999.

BACKGROUND: Asthma is a widespread chronic disorder in children and its prevalence has been on the increase in Europe. Only few studies have described the prevalence variation in respiratory symptoms in Italian regions. The aim of this study, conducted in Turin during the 1998/1999 school year, is to investigate the distribution of respiratory symptoms in a sample of Turin school children and to compare the obtained results with the findings of the SIDRIA study performed in 1994-95. METHODS: The sample in study is composed of all the children attending to three elementary schools in Turin. All of the selected schools had already participated in the 94-95 ISAAC-SIDRIA study. A total of 448 pupils aged 6-10 years received a standardised questionnaire to be filled by parents. RESULTS: Response rate is higher than 97% in all the studies. In 1999 we found that the prevalence of wheezing in the past 12 months was 7.3%. The 13.3% of children had asthma at least once in life and the 5.3% reported an attack in the last year. The comparison of our study results with the ISAAC-SIDRIA (1994-95) shows that the prevalence of asthma and asthma-like symptoms is rather stable among children, while the prevalence of bronchitis reveals a reduction of about 5.5%, but not statistically significant (p=0.094; 95%CI:-11.9;0.9). A considerable reduction in exposure to parents' passive smoke is shown: deltaP%=-4.7 (95%CI: -9.4;-0.1) for maternal smoking in pregnancy, deltaP%=-8.2 and -15.2, respectively for maternal and paternal smoking in the first two years of life. CONCLUSIONS: The results indicate a stable prevalence rate in asthma symptoms in children. A possible explanation of slight variation in asthma prevalence may be due to a reduced exposure to outdoor and indoor risk factors as reported in the questionnaires.

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.

[Experimental kidney transplantation: a comparison between different models]. / Trapianto di rene sperimentale nel suino. Modelli a confronto.

AIM: Two different models of kidney transplantation have been compared using 3 different techniques. The kidney grafts were procured from living donors (laparoscopic or laparotomic technique) and from cadaveric donors. METHODS: Twenty-four outbred piglets (Large White, weight range 24-27 kg) underwent kidney transplantation. We divided the recipients into 2 groups with the following characteristics: group 1 (n=12) was represented by orthopic kidney recipients whose grafts were retrieved by laparoscopic or lapartomic technique from living unrelated donors; group 2 (n=12) was constituted by heterotopic kidney recipients whose grafts were retrieved by laparotomic technique from unrelated cadaveric donors. In both groups, Grogoire-Lich technique and Politano-Laedbetter technique were used in order to perform ureteral-vescical anastomosis together with a new technique developed from our experience called Politano-Laedbetter modified. All transplanted pigs underwent double immunosoppressive steroid therapy (tacrolimus and micofenolate mofetil). The pigs were observed for 60 days. RESULTS: The survival rates in group 1 and in group 2 were 75% (n=9) and 66% (n=8), respectively. No significative differences were noted in length of operative time, creatinemia and ureamia levels in both study groups. The Gregoire-Lich technique was associated with a higher rate of complications. CONCLUSION: Two different experimental models of kidney transplantation are feasible in pigs. The classic technique could be combined with the orthopic one based on the type of study needed.

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.

Effects of tobacco smoke exposure on lung growth in adolescents.

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.

Predictors of survival in a group of patients with chronic airflow obstruction.

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.

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.

Production of serine chymotrypsin-like elastate by aspergillus fumigatus strains

Treinta y cuatro cepas de Aspergillus fumigatus aisladas del aire, crín de caballo, suelo agrícola y del hombre, fueron examinadas con el fin de evaluar la producción de elastasa. Las cepas de Aspergillus fumigatus fueron cultivadas en un medio sólido con elastina, apreciándose en ella su amplio solubilización por la acción del hongo. Los aislamientos fúngicos provenientes de muestras aisladas del hobre y de suelos agrícolas fueron detectados como los más altos productores de elastasa. Ocho de las 34 cepas fueron desarrollas en 4 diferentes medios líquidos en las cuales se investigó la actividad proteolítica total y específica. Los resultados de este experimento sugieren que la producción de elastasa es inducida por la presencia de elastina como sustrato y que la primera es una enzima semejante a la quimiotripsina. El perfil inhibitorio comprobó que la elastina de A.fumigatus, es una serina-proteinasa

Non specific immunity in aged healthy subjects and in patients with chronic bronchitis.

We investigated the effects of aging on some functional activities (chemotaxis, phagocytosis, nitroblue tetrazolium reduction and candidacidal activity) of peripheral polymorphonuclear and mononuclear phagocytes in 96 healthy subjects and 89 patients with chronic bronchitis, aged 40 to 100 years. The subjects were divided according to age into younger (40-65 years) and older (66-100 years) individuals. No subject was taking any drug known to affect phagocytic functions. A few abnormalities in PMN and monocyte functions were observed in aged healthy subjects, in comparison to the younger ones; in fact, only the chemotactic response to complement-derived chemotactic factors was significantly impaired in elderly healthy individuals. On the contrary, multiple alterations of phagocyte activities, i.e., chemotaxis, phagocytosis, and candidacidal activity were observed in aged subjects with chronic bronchitis, compared to healthy adults. However, the results obtained in older and younger patients with chronic bronchitis were superimposable. The present data suggest that the decline in functional activities of phagocytes in the aged could depend on the effect of the underlying chronic bronchitis on the cellular components of the non-specific host defense system, rather than a direct effect of the aging process.

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.

Proteinase/proteinase inhibitor imbalance in sputum sol phases from patients with chronic obstructive pulmonary disease. Suggestions for a key role played by antileukoprotease.

In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/- 0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG], 0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively [mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase-like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007 microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18 microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21 microM; p < 0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.

Protease-antiprotease imbalance: local evaluation with bronchoalveolar lavage.

The protease-antiprotease imbalance is thought to be involved in a variety of destructive lung diseases: pulmonary emphysema, chronic bronchitis, cystic fibrosis and adult respiratory distress syndrome. Bronchoalveolar lavage allowed the investigators to assess the protease-antiprotease shift in such conditions but sometimes gave conflicting results. The role of bronchoalveolar lavage as a research and diagnostic tool in diseases characterised by protease-antiprotease imbalance is reviewed, as well as its potential usefulness in the near future.

Some properties of the alkaline proteinase from Aspergillus melleus.

Seaprose is a semi-alkaline proteinase produced by Aspergillus melleus. The aim of our study was to further characterize the properties of this enzyme, particularly looking at its interaction with alpha 1-proteinase inhibitor, the major human plasma proteinase inhibitor. We studied the cleavage of three synthetic peptide substrates induced by seaprose and the inhibitory profile of the enzyme by means of a panel of inhibitors, including alpha 1-proteinase inhibitor. The interaction between seaprose and alpha 1-proteinase inhibitor was also studied with SDS-PAGE. Finally, the elastolytic activity of seaprose was checked by means of bovine elastin solubilization. We found that seaprose cleaves preferentially the substrate containing a Phe residue in the P1 position. The inhibitory profile showed that seaprose is a serine-proteinase that cannot be inhibited by alpha 1-proteinase inhibitor. The SDS-PAGE revealed that alpha 1-proteinase inhibitor, after incubation with seaprose, underwent a limited proteolysis. Finally, seaprose 10(-2) M and 10(-3) M was able to solubilize bovine elastin. We conclude that seaprose is a serine-proteinase able to inactivate human alpha 1-proteinase inhibitor with limited proteolysis at (or near) the active site and that it has mild elastinolytic capacity.

Alpha 1-antitrypsin variants produced by recombinant DNA: differences in elastase inhibitory activity and resistance to oxidant agents.

Inherited or "acquired" deficiency of alpha 1-antitrypsin (believed to be the cause of pulmonary emphysema) will probably be treated in the future by replacement with alpha 1-antitrypsin purified from human plasma or produced by recombinant DNA, which seems promising because it permits site-specific mutagenesis in the oxidizable active site of the normal human alpha 1-antitrypsin. The aim of this in-vitro study was to investigate the elastase inhibitory activity and the resistance to oxidizing agents of normal human alpha 1-antitrypsin, a recombinant yeast-produced variant (VAL 358) and a recombinant E. coli-produced variant (LEU 358). The inhibitors were exposed to chemical oxidants (NCS, H2O2, xanthine/xanthine oxidase, chloramine-T) and to PMA-activated neutrophils. The elastase inhibitory activity was assayed on porcine pancreatic elastase and neutrophil elastase. Normal alpha 1-antitrypsin and VAL 358 variant were good inhibitors of both elastases. LEU 358 variant was the best inhibitor for neutrophil elastase, but it poorly inhibited the porcine pancreatic elastase. Normal alpha 1-antitrypsin was affected by all oxidants; both variants were almost totally resistant to chemical oxidants and to activated neutrophils. We conclude that recombinant alpha 1-antitrypsin variants differ in their elastase inhibitory activity and offer increased resistance to oxidant agents.

Studies of MR 889, a new synthetic proteinase inhibitor.

We investigated the proteinase inhibitory activity of MR 889, a thiolactic acid derivative. It is able to in vitro inhibit at low concentration (10(-5),10(-6)M) the activity of porcine pancreatic elastase, human neutrophil elastase and bovine chymotrypsin. In addition, MR 889 is able to inhibit the residual activity of alpha 2-macroglobulin-trapped human neutrophil elastase, paralleling the efficacy of phenylmethylsufonylfluoride. Finally, MR 889 has been shown to in vitro reduce the burden of elastase- and chymotrypsin-like activity found in sputum sol-phases of patients admitted for chronic bronchitis exacerbation.