Comparative performance of two inhaler systems to assess distribution of convective ventilation by 99mTc-labeled aerosol scintigraphy in patients with airway obstruction.

AIM: Redistribution of convective ventilation, the leading disorder in airway obstruction, is a target of pharmacological and mechanical ventilation treatments for patients with chronic obstructive pulmonary disease (COPD). Convective ventilation is visualized by ventilation scintigraphy using radiolabeled aerosol particles that should ideally deposit in the terminal airspaces, but not in the conducting airways, and have no Brownian motion (which characterizes diffusive ventilation). Currently available commercial systems do not meet these requirements as they do not ensure an optimal size of aerosol droplets delivered at the mouthpiece. METHODS: A new inhaling system (FAI) was developed and designed so as to yield radioaerosol droplets with smaller particle size and to ensure more efficient aerosol delivery to the terminal airways than that obtained with a widely available commercial system (MMI). A cascade impactor was employed to measure the size of the radioactive droplets at the mouthpiece. Preliminary comparative validation was based on ventilation scintigraphy using the two systems (both followed by a standard lung perfusion scan) in control subjects and in patients with airway obstruction. The time required to reach a certain count rate in the lung fields (1 kc/s) was recorded by means of dynamic g camera acquisition during breathing. Subsequent static images allowed assessment of intrapulmonary distribution of ventilation (by both visual and quantitative evaluation) and of the ventilation/perfusion (V/Q) ratios relative to the upper, middle, and lower thirds of the lung fields. RESULTS. FAI yielded 99mTc-labeled droplets with a count median diameter of 1.4 microm and a geometric standard deviation of 2 microm , versus 3 microm and 2, respectively, produced by the commercial inhaler (MMI). The mean time to reach the 1 kc/s count rate was significantly shorter with the FAI than with the MMI both in control subjects (4.7+/-1.7 min versus 8.2+/-2 min, P<0.04) and in airway-obstructed patients (3.4+/-0.8 min versus 8.4+/-2 min, P<0.001). With the MMI, appreciable radioaerosol deposition in the large bronchi prevented reliable quantitative assessment of ventilation, even in the control subjects. With the FAI, radioaerosol deposition in the central large airways was never observed in the controls and was only sporadically or occasionally observed in patients with COPD or asthma, respectively. This feature allowed quantitative ventilation assessment. The FAI-generated radioaerosol particles reached the peripheral respiratory spaces more efficiently than those generated by MMI; on the ventilation scans, the FAI allowed better discrimination than the MMI of the different pathophysiologic conditions. CONCLUSION: These findings consistently indicate that the smaller-sized radiolabeled droplets generated by FAI, combined with the better breathing dynamics of the inhaler device, result in better overall performance as compared to the commercial system. This makes scintigraphic images obtained with the new device especially suitable for assessing convective ventilation in COPD patients, a particularly helpful feature for analytically describing the distribution patterns observed in airway-obstructed patients and for evaluating the effects of drugs, mechanical ventilation, and other interventions in such patients.

A non-invasive, quantitative method to demonstrate the early effects of therapy in acute pulmonary embolism.

The objective of this study was to quantify the changes in pulmonary perfusion due to therapy for pulmonary embolism (PE). To this end, seven consecutive patients (five men, two women; mean age 64+/-10 years) were studied. After basal pulmonary arteriography had demonstrated the presence of massive PE, patients were injected intravenously with 4 mCi of technetium-99m-labelled human albumin microspheres and were treated soon thereafter with a 2-h infusion of either alteplase 100 mg (five patients) or heparin 1,750 IU/h (two patients). Then, a second pulmonary arteriography study was obtained, and soon afterwards a single-photon emission tomographic (SPET) perfusion scan was performed. Immediately thereafter, a second intravenous injection of 4 mCi of 99mTc-labelled microspheres was administered, followed by a second SPET scan. At the end of the study, the perfusion changes due to therapy were quantified by subtraction of the images of the two SPET studies; the reperfused areas could be visualised and the volumes of reperfusion quantified. This study demonstrates the validity of a newly devised, relatively rapid and non-invasive method for quantification of the early effects of therapy on pulmonary perfusion in patients presenting with acute PE.

Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease.

We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37 +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/- 24% predicted, and the exponential constant K of pressure-volume curves was 258 +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/- 11% (range 1 to 38%). It showed a highly significant negative correlation with DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no correlation with either Pst(max) or constant K. A significant relationship was found between the natural logarithm of K and the full width at half maximum of the frequency distribution of CT numbers, taken as an index of the heterogeneity of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods of assessing the extent of emphysema by HRCT closely reflect the reduction of CO diffusion constant, but cannot predict the elastic properties of the lung tissue.

Influence of bulla volume on postbullectomy outcome.

OBJECTIVE: To quantify the contribution of the resected volume and the presence of associated, functionally significant emphysema to the postoperative improvement of pulmonary function after resection of giant lung bullae. DESIGN: Patients undergoing elective surgery for giant bullae who had had complete pulmonary function and radiographic studies performed were reviewed retrospectively. SETTING: All 25 patients underwent surgery at the thoracic surgery unit of the University of Pisa, Pisa, Italy. METHODS: Pulmonary function was assessed before and 12 months after surgery. On the chest radiograph, the location of bullae, and the signs of compression and emphysema were evaluated. The radiographic total lung capacity (TLC(x-ray)) and the volume of bullae were measured according to the ellipse method. Postoperatively, functional and radiographic changes were analyzed. The percentage change in forced expiratory volume in 1 s (Delta FEV(1)%) after surgery was the main outcome measure. The influence of factors related to emphysema and bulla volume on the functional improvement postbullectomy was assessed by stepwise multiple regression. RESULTS: Before surgery, the TLC(x-ray) overestimated the TLC measured by nitrogen washout, with a mean difference between the two measurements of 1.095 L. A close relationship was found between the TLC(x-ray) and the plethysmographic TLC (n=6; r=0.95). After surgery, dyspnea lessened (P<0.05) and FEV(1) increased (P<0.01). Statistically, the radiographic bulla volume was the single most important factor determining the Delta FEV(1)% (r=0.80, P<0.0001). CONCLUSIONS: These findings suggest that the preoperative size of bullae is the most important contributor to the improvement in ventilatory capacity after bullectomy, and that it is possible to predict the expected increase of postoperative FEV(1) from preoperative bulla volume.

Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch.

The aim of this retrospective analysis was to assess the extent of smoking reduction in smokers who were compliant to a smoking cessation trial with nicotine patch, and failed to completely quit smoking. Out of 297 smokers in total, 237 participants received active treatment (60 received placebo). Eighty treated subjects attended all the scheduled visits and were classified as either abstainers (nonsmokers), regular smokers or occasional smokers. Compared to the remaining 157 participants, these 80 subjects had significantly lower mean baseline daily cigarette consumption (24 versus 30; p < 0.001), expired carbon monoxide levels (25 versus 33 ppm; p < 0.001), plasma nicotine and cotinine levels, and Fagerström Tolerance Questionnaire score (5.7 versus 7.0; p < 0.001). All subjects received active treatment for up to 18 weeks (full dose for 12 weeks plus tapering dose for 6 weeks), with follow-up visits scheduled up to 1 yr. A statistically significant reduction in cigarette consumption (versus baseline) was observed among both the occasional (-99%) and regular (-77%) smokers between week 1 and week 52 (p < 0.001). Concomitant smoking and patch use was well tolerated since adverse events were infrequent, mild and transient. Thus, in addition to those subjects who successfully quit smoking, a further group of subjects who attended all the follow-up visits during the smoking cessation trial significantly reduced their mean daily cigarette consumption.

Functional significance of the decreased attenuation sign on expiratory CT in pulmonary sarcoidosis : report of four cases.

We describe four patients with proven sarcoidosis and minor pulmonary involvement according to high-resolution CT (HRCT) findings in whom the recently described sign of decreased attenuation on expiratory HRCT scan appeared associated with the reduction of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) and the DLCO adjusted for alveolar volume. These alterations were, in part, reversible under steroid treatment. Major indexes of airway obstruction (FEV(1)/vital capacity ratio and FEV(1)) were normal, while the maximum expiratory flow at 25% above the residual volume of FVC was reduced. These observations suggest that an expiratory HRCT mosaic pattern and diffusion impairment may be early findings in pulmonary sarcoidosis and may be useful for its detection and follow-up.

Ventilation/perfusion scan and dead space in pulmonary embolism: are they useful for the diagnosis?

The diagnostic strategy for pulmonary embolism, based on the mismatch of the ventilation/perfusion scan, was developed some 30 years ago on the following assumption: since the disorder involves the pulmonary vessels, it was surmised that in the embolized regions lung alveoli are unperfused or poorly perfused but well ventilated. Hence, it was inferred that this disorder was characterized, unlike parenchymal disease, by ventilation/perfusion mismatch in the affected lung zones and by an obvious increase of wasted ventilation, i.e., dead space. As matter of fact, experimental evidence on the redistribution of ventilation away from the vascular occluded lung had been already obtained in the early 60s of the last century. More recently, the behavior of regional pulmonary ventilation (V(A)) and blood flow (Q) in patients with acute pulmonary embolism (APE) has been studied by applying the multiple inert gas elimination technique (MIGET). It has been shown that the development of lung units with high V(A)/Q ratio (those with relative prevalence of perfusion obstruction) is accompanied by substantial redistribution of ventilation away from these units. Furthermore, radioisotopic techniques, used to visualize the topographic distributions of V(A) and Q in the same patients studied by MIGET, have shown reduced or absent V(A) in the embolized regions. This may occur by different mechanisms in the various stages of APE: bronchoconstriction mediated by local hypocapnia, atelectasis (occasionally hemorrhagic) related to alteration of surfactant production, bronchiolar obstruction and pulmonary infarction ascribed to degenerative and/or necrotic changes secondary to insufficient blood flow. In dogs and humans alike, the dead space measured by MIGET does not increase and that obtained from CO2 increases far less than the amount of unperfused lung in APE thus confirming a substantial redistribution of ventilation away from the embolized lung zones. Taken together, all these observations provide the pathophysiological explanation of the unacceptedly low level of sensitivity for the diagnostic strategy of APE based on the mismatch of the ventilation/perfusion scan.

Prevalence of airways obstruction in a general population: European Respiratory Society vs American Thoracic Society definition.

STUDY OBJECTIVES: To evaluate the distribution of airways obstruction in a general population sample. METHODS: Cross-sectional epidemiologic survey of a general population sample living in Po Delta area (North Italy). Data on respiratory symptoms, diseases, and risk factors were collected through standardized interviewer-administered questionnaires. Lung function tests were performed, with criteria for defining airways obstruction based on the 1995 European Respiratory Society (ERS) statement (FEV(1)/vital capacity ratio < 88% predicted and < 89% predicted in men and women, respectively), "clinical" criteria (FEV(1)/FVC ratio < 70%), and the 1986 American Thoracic Society (ATS) statement (FEV(1)/FVC ratio < 75%). RESULTS: A total of 1,727 subjects aged > 25 years investigated from 1988 to 1991 were included. Prevalence rates of airways obstruction for subjects 25 to 45 years old and subjects >/= 46 years old were as follows: ERS, 10.8% and 12.2%; clinical, 9.9% and 28.8%; and ATS, 27% and 57%, respectively. When considering only moderate/severe obstruction, the rates were as follows: ERS, 0.4% and 3.6%; clinical, 0.3% and 4.4%; and ATS, 0.5% and 5.2%, respectively. The trend was confirmed after stratifying for smoking habit and the presence/absence of respiratory symptoms/diseases. The highest specificity and predictive value for any respiratory symptom/disease was shown by the ERS, and the lowest was shown by the ATS criterion, while the reverse was true for sensitivity; overall accuracy was slightly lower for the ATS criterion. Multiple logistic regression models indicated a higher number of significant associations with known risk factors for airways obstruction according to clinical and ATS criteria than ERS criterion. CONCLUSIONS: The prevalence of COPD in a general population depends very much on the criterion used for definition of airways obstruction. Further research is needed to reach a standardized and epidemiologically consistent criterion for airways obstruction.

Smooth reference equations for slow vital capacity and flow-volume curve indexes.

We derived reference values for slow vital capacity (VC) and flow-volume curve indexes (FVC, FEV(1), and flows) from the 1,185 tracings provided by 1,039 "normal" subjects who participated in one or both cross-sectional surveys of the Po River Delta study in 1980-1982 and in 1988-1991. Definition of "normal" was based on negative answers to questions on respiratory symptoms/diseases or recent infections, current/past tobacco smoking, and work exposure to noxious agents. Reference equations were derived separately by sex as linear regressions of body mass index (BMI = weight/height(2)), BMI-squared, height, height-squared, and age. Age entered all the models by natural cubic splines using two break points, except for the ratios FEV(1)/VC and FEV(1)/FVC. Random effects models were applied to adjust for the potential intrasubject correlation. BMI, along with height and age, appeared to be an important predictor, which was significantly associated with VC, FEV(1), FVC, FEV(1)/FVC, and PEF in both sexes, and with FEV(1)/VC and FEF(25-75) in females. Natural cubic splines provided smooth reference equation curves (no "jumps" or "angled points") over the entire age span, differently from the conventional reference equations. Thus, we recommend the use of smooth continuous equations for predicting lung function indexes, along with the inclusion of BMI in the equations.

Effects of nicotine replacement therapy on markers of oxidative stress in cigarette smokers enrolled in a smoking cessation program.

Twenty healthy, asymptomatic long-term cigarette smokers (8 males, 12 females; mean age: 43 +/- 9 years) were selected at random from a larger series receiving nicotine replacement therapy (NRT) for 12 weeks to study the effects of NRT on plasma markers of oxidative stress. Plasma aliquots, obtained at baseline (T0) and after 12 weeks (T12) of NRT, were used to measure malondialdeyde (MDA) and total Trolox-equivalent antioxidant capacity (TEAC). In subjects who completely quit smoking ('quitters', n = 10), MDA was higher at T0 (1.08 mumol/l, interquartile range 0.85-1.16) than at T12 (0.71 mumol/l, range 0.32-0.92; p < 0.01), and TEAC was lower at T0 (1.20 mM, range 1.11-1.31) than at T12 (1.43 mM, range 1.31-1.49; p < 0.05). In subjects who had only reduced the number of cigarettes smoked per day ('reducers', n = 10), differences between the T0 and T12 levels of MDA (0.81 [0.75-0.96] vs. 0.76 [0.58-0.84] mumol/l) and TEAC (1.28 [1.05-1.50] vs. 1.25 [1.09-1.42] mM) were not significant. At T0, MDA and cotinine levels correlated in reducers (r = 0.79, p < 0.05) and, though not significantly, in quitters (r = 0.50, p = 0.12). At T12 this relationship between MDA and cotinine was still present in the reducers (r = 0.70, p < 0.05), while the scatter of points in quitters was completely dispersed (r = (0.09). These results show that smoking cessation but not smoking reduction is associated with decreased markers of oxidative stress in the plasma of active cigarette smokers.

ICAM-1-independent adhesion of neutrophils to phorbol ester-stimulated human airway epithelial cells.

Intercellular adhesion molecule-1 (ICAM-1) is the only inducible adhesion receptor for neutrophils identified in bronchial epithelial cells. We stimulated human airway epithelial cells with various agonists to evaluate whether ICAM-1-independent adhesion mechanisms could be elicited. Phorbol 12-myristate 13-acetate (PMA) stimulation of cells of the alveolar cell line A549 caused a rapid, significant increase in neutrophil adhesion from 11 +/- 3 to 49 +/- 7% (SE). A significant increase from 17 +/- 4 to 39 +/- 6% was also observed for neutrophil adhesion to PMA-stimulated human bronchial epithelial cells in primary culture. Although ICAM-1 expression was upregulated by PMA at late time points, it was not affected at 10 min when neutrophil adhesion was already clearly enhanced. Antibodies to ICAM-1 had no effect on neutrophil adhesion. In contrast, antibodies to the leukocyte integrin beta-chain CD18 totally inhibited the adhesion of neutrophils to PMA-stimulated epithelial cells. These results demonstrate that PMA stimulation of human airway epithelial cells causes an increase in neutrophil adhesion that is not dependent on ICAM-1 upregulation.

Selection of reproducible forced expirograms: percentage or fixed-volume criterion.

The aim of this study was to evaluate whether the intrasession reproducibility of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) depends on height and lung volume. FVC tracings of 740 subjects (350 males) from a general population sample living in North Italy were analyzed. Subjects filled out a standardized questionnaire and performed three acceptable FVC maneuvers following the American Thoracic Society recommendations. The differences between the largest and the second largest FVC and FEV1 were computed as absolute (DeltaFVC, DeltaFEV1) and as percentage values (DeltaFVC%, DeltaFEV1%). The higher the tertiles of the largest FVC and FEV1 were, the higher were DeltaFVC and DeltaFEV1. Regarding FVC, borderline differences in both sexes for DeltaFVC and in males significant differences for DeltaFVC% were found among the tertiles. Regarding FEV1, in both sexes DeltaFEV1 significantly differed among the tertiles. DeltaFVC and DeltaFEV1 correlated with height and lung volume in both sexes, except for DeltaFVC versus the largest FVC in females. When DeltaFVC and DeltaFEV1 were analyzed with respect to respiratory symptoms/diseases and smoking habit, no significant differences were observed in both sexes, except for DeltaFEV1 between ever- and never-smoking males. It may be concluded that the intrasession within-subject variability of FVC and FEV1 is proportional to lung volume and height, regardless of the sex, presence of symptoms and smoking habit. Thus, our results confirm the usefulness of a reproducibility criterion based on a percentage rather than on a fixed volume.

Diagnostic value of gas exchange tests in patients with clinical suspicion of pulmonary embolism.

OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal scans who had normal P(A-a)O2, PaO2 and PaCO2 were 20, 25 and 37%, respectively. No differences were observed in the mean values of arterial blood gas data between patients with pulmonary embolism and those who had abnormal scans and negative angiograms. Among the 773 patients with suspected pulmonary embolism, 364 (47%) had prior cardiopulmonary disease. Pulmonary embolism was diagnosed in 151 (41%) of 364 patients with prior cardiopulmonary disease, and in 161 (39%) of 409 patients without prior cardiopulmonary disease. Among patients with pulmonary embolism, there was no difference in arterial blood gas data between patients with and those without prior CPD. CONCLUSION: These data indicate that arterial blood gas tests are of limited value in the diagnostic work-up of pulmonary embolism if they are not interpreted in conjunction with clinical and other laboratory tests.

Serum antibodies to benzo(a)pyrene diol epoxide-DNA adducts in the general population: effects of air pollution, tobacco smoking, and family history of lung diseases.

Polycyclic aromatic hydrocarbons (PAHs) are almost ubiquitous pollutants that may interact with metabolic systems in human tissues and eventually cause cancer. PAH-adducted DNA becomes antigenic and antibodies anti-benzo(a)pyrene diol epoxide (BPDE)-DNA may be found in serum of PAH-exposed subjects. The presence of serum antibodies anti-BPDE-DNA adduct was investigated in 1345 individuals from family clusters of the general population of a small area in central Italy in whom information about smoking habits, site of residence, and personal and family history of lung diseases, including cancer, were obtained. Anti-BPDE-DNA antibodies in the sera were detected with a direct ELISA and the association of anti-BPDE-DNA antibodies with subjects' data from a standardized respiratory questionnaire including age, occupation, tobacco smoking habits, respiratory symptoms, and family history of respiratory diseases was subsequently tested by multivariate logistic regression analysis. The overall prevalence of subjects with anti-BPDE-DNA antibodies was 21.0% (n=283), with no differences between males and females. Anti-BPDE-DNA positivity was associated with living in the urban area [odds ratio (OR), 1.49; 95% confidence interval (CI), 1.16-1.92], with active tobacco smoking (OR, 1.25; 95% CI, 1.06-1.48), and with family history of lung cancer (OR, 1.30; 95% CI, 0.90-1.88), and positivity increased with the number of members in the family cluster positive to anti-BPDE-DNA antibodies (OR, 1.30; 95% CI, 1.03-1.65). This study on a large general population sample indicates that serum anti-BPDE-DNA antibodies may be considered as biomarkers of exposure to environmental carcinogens and of DNA damage. The genetic and familial components of their association with tobacco smoking lend further support to the argument about the familial predisposition to lung cancer.

Plasma 3-nitrotyrosine in cigarette smokers.

Peroxynitrite has been associated with increased oxidative reactions and DNA damage in inflamed tissues as it may cause a reduction of plasma antioxidants as well. Nitration of tyrosine residues of proteins leads to the production of 3-nitrotyrosine (NTYR), which may be considered as a marker of NO.-dependent oxidative damage. We developed a highly sensitive method to detect NTYR in human plasma and tested it in cigarette smokers and in healthy control subjects. Peripheral venous blood (10 ml) was obtained in 20 healthy, asymptomatic cigarette smokers (13 males, 7 females; age: 49 +/- 11 yr) and in 18 healthy nonsmokers (10 males and 8 females; age: 36 +/- 6 yr). In smokers, plasma nicotine, cotinine, and expired CO levels were measured. NTYR was determined with a sequential HPLC/gas chromatography-thermal energy analysis (GC-TEA) technique. The total plasma Trolox-equivalent antioxidant capacity (TEAC) was also measured using metmyoglobin as peroxidase and a phenothiazine as a radical donor. NTYR was detectable (detection limit: 0.02 ng/injection) in 11 smokers (mean +/- SD: 1.60 +/- 1.24 ng/mg protein) and in two nonsmokers (1.10 and 1.20 ng/mg protein, respectively). NTYR was not associated with nicotine and cotinine levels or expired CO in smokers. Plasma TEAC in smokers was significantly lower (0.43 +/- 0.38 mM) than in nonsmokers (1.42 +/- 0.3 mM; p < 0.001) and showed a biphasic, negative relationship with NTYR (r = 0.96, p < 0.001). This highly sensitive HPLC/GC-TEA method for detection and quantitation of plasma NTYR may be used for monitoring oxidative reactions associated with tobacco smoking. This assay might be incorporated into molecular epidemiologic studies for lung chronic inflammatory and neoplastic disorders in which exposure to oxidants may be an important risk factor.

Mortality rates for respiratory disorders in Italy (1979-1990).

Trends in mortality rates for respiratory disorders were investigated in Italy from 1979 to 1990, using data from the Italian Central Statistical Institute (ISTAT). Mortality from lung cancer increased in all age groups, except for those aged 45-64 yrs after 1985. Respiratory diseases showed a consistent reduction; in particular, mortality from emphysema decreased slowly, and mortality from chronic bronchitis showed a significant reduction in all age groups. However, mortality from asthma increased markedly in all age groups up to 1985, and then levelled off and slightly decreased, although remaining at a higher level than in the 1970s. In 1990, data stratified for age group and gender indicated a higher mortality rate in males, that tended to be age-dependent, with the highest rate ratio male/female in those aged 65-74 yrs. Overall, these data indicate a trend to increased mortality from lung cancer and asthma in Italy in the 1980s.

Presence and persistence of serum anti-benzo[a]pyrene diolepoxide-DNA adduct antibodies in smokers: effects of smoking reduction and cessation.

Among biomarkers of tobacco smoke (TS)-induced genotoxic damage, benzo[a]pyrene diolepoxide-DNA adducts (BPDE-DNA) are extensively studied. Adducted DNA becomes antigenic and antibodies anti-BPDE-DNA (BPDE-DNA-Abs) may be found in serum of exposed subjects. Little is known about the persistence of BPDE-DNA, and no study has been performed to evaluate the persistence of BPDE-DNA-Abs after cessation of exposure. Fifty heavy smokers, enrolled in a smoking cessation program with nicotine patch substitution therapy, were evaluated for the presence of BPDE-DNA-Abs before (w0) and 1, 3, 6 and 12 weeks (w1-12) after the start of the program. Nicotine or placebo patches were randomly assigned to the subjects. BPDE-DNA-Abs were determined in serum by non-competitive ELISA. After the start of the cessation program, 28 subjects quit smoking (group Q) and the other 22 reduced by about 75% the number of cigarettes smoked per day (group R). At the start of the program (w0) 8% of subjects were positive. At w1 the prevalence of positivity had increased both in subjects who quit smoking (Q: 21%) and in subjects who had reduced the number of cigarettes per day (R: 27%). Positivity remained stable up to w12 (21%) for group Q, whereas it increased to 41% in group R. Serum BPDE-DNA-Abs can be detected in smokers, and their persistence for months after smoking cessation suggests their usefulness for relatively long-term surveys. The low percentage of positivity in actual heavy smokers and the increase in antibody positivity with smoking cessation or reduction must be taken into account when interpreting serum BPDE-DNA-Ab measurement in exposed individuals.