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Biomedical subjects

C Giuntini

Publications and source records attributed to C Giuntini.

At least 19 recordsLinked to original sources
PubMed1992

An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity.

An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy- 7,8,9,10-tetrahydro-BP, requires 100-500 micrograms of DNA, and can measure 1 adduct/10(8) unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a > 90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 ex-smokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6-9.9 adducts of benzo(a)pyrene diol-epoxide/10(8) nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diolepoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diolepoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P-postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diolepoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2.

BACKGROUND: The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. OBJECTIVES: The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. METHODS: Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. RESULTS: The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase-treated patients (p less than 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/- 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. CONCLUSIONS: Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.

Acute Disease↗
PubMed1992

Cigarette smoke inhibits cytosolic but not microsomal epoxide hydrolase of human lung.

The effect of cigarette smoke exposure on the activity of cytosolic and microsomal epoxide hydrolase (EH) has been investigated in human lung. Patients were classified as 'recent smokers' (n = 9) or 'non-recent smokers' (n = 10) according to whether they were or were not still smoking 1 month before surgery. Cytosolic EH was measured with [3H]trans-stilbene oxide as a substrate, whereas microsomal EH was measured with [7-3H]styrene oxide as a substrate. Microsomal EH activity did not differ between recent smokers (2.51 +/- 0.93 nmol min-1 mg-1) and non-recent smokers (2.74 +/- 1.10 nmol min-1 mg-1), whereas cytosolic EH activity was significantly lower in recent smokers (6.46 +/- 1.79 pmol min-1 mg-1) than in non-recent smokers (8.41 +/- 2.09 pmol min-1 mg-1, P less than 0.05). Cytosolic EH activity was correlated with the number of days that had passed since the cessation of smoking (r = 0.58, P less than 0.05) and the effect was dose-dependent, since the enzyme activity was inversely correlated with the number of cigarettes smoked per day (r = 0.85, P less than 0.01). This suggests that recent smoking exposure inhibits the activity of cytosolic EH but not microsomal EH, and that the inhibition increases with the number of cigarettes smoked per day. The contribution of cytosolic enzymes to xenobiotic metabolism may be remarkable in extrahepatic tissues. The inhibition of cytosolic EH by tobacco smoke may reduce the inactivation of carcinogenic epoxides in human lung tissues and so may increase a person's susceptibility to lung cancer.

Adult↗
PubMed1992

Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Residual volume in a general population. Effects of body size, age, cigarette smoking, and respiratory symptoms.

Residual volume (RV) was obtained by subtracting vital capacity from total lung capacity determined by the single breath helium dilution (TLCsb) to measure CO diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population sample. There were 712 normal subjects (243 male and 469 female subjects) selected to evaluate the pattern of RV by age and to derive reference values for internal comparisons. From 8 to 20 years old, RV showed an increase because of the cross-sectional body size effect; after 20 to 30 years, RV was still increasing, however, at a lower level. Age and height coefficients were significantly related to RV in younger and older ages, both in male and female subjects. The RV percent predicted and RV/TLC percent were higher in smokers when compared to nonsmokers and exsmokers (the difference was significant in male subjects). A dose-response effect was observed between RV percent predicted, RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were significantly higher in smokers and nonsmokers with FEV1 percent predicted below the normal limit (the difference was significant in male subjects). Moreover, higher values of RV percent predicted and RV/TLC percent were observed in subjects with wheezy symptoms in male smokers and nonsmokers. A negative significant correlation was observed between RV/TLC percent and the diffusing capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed to the enlargement of terminal air spaces. In conclusion, determination of RV by the single breath helium dilution method is suitable in epidemiology, and it allows additional important information for understanding the physiopathologic mechanisms related to the pathogenesis of chronic obstructive lung disease.

Adolescent↗
PubMed1992

Sarcoidosis in Tuscany. A preliminary report.

A retrospective study was carried out by a computerized questionnaire in a sample of 109 sarcoidosis patients (43 men, 66 women) diagnosed between 1977 and 1990 in Pisa. 94% of the patients were resident in Tuscany. The onset of disease was earlier in the men than in the women; in 73% of the patients the symptoms were first noticed between February and July with two incidence peaks; 71% of them had never smoked; 10% of patients were symptom-free and the disease was discovered by chance; the other patients (90%) underwent chest X-ray because of joint symptoms (35%), erythema nodosum (34%), cough (28%), dyspnoea (27%), and fever (24%) which was often associated with other symptoms. Symptoms from the respiratory tract was present in 66 patients (61%); 58% of patients were resident in rural areas; the level of education was limited to primary school in 50% of the patients; as to the prevailing working positions, 27% were clerical workers, 24% manual workers, and 26% housewives.

Adult↗
PubMed1991

Salbutamol plus beclomethasone dipropionate, but not salbutamol alone, completely prevent early and late asthmatic responses to allergen.

The effect of a week treatment with inhaled salbutamol plus placebo (S+P) vs. salbutamol combined with beclomethasone dipropionate (S+BDP) on early and late asthmatic responses to inhaled allergen was studied in ten atopic patients in a randomized, double-blind, cross-over study. All patients had previously shown a dual type response to the specific bronchial provocative test (sBPT). Each patient performed two periods of treatment for a week, with a 15 day interval between them: (a) salbutamol 0.3 mg, tid + placebo; (b) salbutamol 0.3 mg+BDP 0.2 mg, tid; at the end of each treatment period, sBPT was performed and the last treatments were given 1.5-2 h before and 3-4 h after allergen challenge. S + BDP completely prevented both early and late responses to allergen, while S + P reduced but did not completely inhibit early and late responses. The difference between the two treatments was significant for early and late asthmatic responses. Non-specific bronchial hyperresponsiveness to methacholine was performed before each treatment period, after 6 days of treatment before sBPT and the day after sBPT at the end of the treatment period; there was only a mild increase in PD15FEV1 methacholine after 6 days of treatment with S + BDP in comparison with S + P treatment. These results suggest that salbutamol plus beclomethasone may be used effectively in the prophylaxis of early and late asthmatic reactions induced by allergen in sensitized subjects.

Adolescent↗
PubMed1991

Comparison of pulmonary DNA adduct levels, measured by 32P-postlabelling and aryl hydrocarbon hydroxylase activity in lung parenchyma of smokers and ex-smokers.

In order to compare pulmonary DNA adducts and aryl hydrocarbon hydroxylase (AHH) activity, we have measured these two parameters in non-neoplastic surgical lung parenchymal samples from four ex-smokers and 19 smokers, out of 20 patients operated for lung cancer, and three for nonmalignant lung diseases. DNA adducts were determined by scintillation counting after 32P-postlabelling analysis. The microsomal fractions of the same lung specimen were assayed for AHH activity by a fluorometric method. Autoradiograms of DNA adducts found in lungs of smokers revealed two distinct diagonal radioactive zones that were absent in ex-smokers. The smokers had significantly higher levels (1.68-13.4 DNA adducts/10(8) nucleotides; mean +/- SD 5.38 +/- 3.19) than ex-smokers (0.23-2.21; 1.09 +/- 0.84). AHH activity in smokers ranged from 0.01 to 0.69 pmol/min/mg. This activity was significantly (P less than 0.05) higher in smokers (0.26 +/- 0.26) who had smoked until 1 week before surgery than in those who had stopped smoking for greater than 7 days (0.11 +/- 0.11). A positive linear correlation between DNA adduct levels and AHH activity (r = 0.69; P less than 0.001; n = 19) was found in smokers. This relationship could explain why AHH inducibility appears to be a crude marker for lung cancer risk in smokers.

Adult↗
PubMed1991

Does the patient's posture affect the detection of chest radiographic findings suggestive of pulmonary embolism?

Although it is accepted that thoracic structures are enlarged in supine chest radiographs, it is not known whether the lying posture may also influence the radiographic detection of abnormalities, such as those suggestive for pulmonary embolism (PE). For this purpose, we performed planar chest radiographs both in the seated and supine positions, keeping the target-to-film distance at 2 m, in 20 patients with acute PE. Chest radiograph was then repeated 1 month later in either position with the radiological conditions unchanged to investigate the effect of posture on the detection of resolution of signs. The detection of signs due to modifications of preexisting thoracic structures (elevation of the diaphragm and enlargement of the heart, right descending pulmonary artery and azygos vein) in acute PE was different between films taken in the supine and seated positions: both hemidiaphragms were more elevated (p less than 0.001), heart and central vessels were wider (p less than 0.05 or less) when patients were supine. On the contrary, the detection of signs of new occurrences ('sausage'-like appearance of the descending pulmonary artery, linear atelectasis, densities compatible with pulmonary infarction, pleural effusion and focal hyperlucency) was not influenced by the patient's position. During recovery, both kinds of abnormalities were reduced concomitantly in seated and supine radiographs. In conclusion, in acute PE, chest radiographs should be obtained in the seated position since the supine posture may overestimate signs due to modifications of preexisting thoracic structures even though it does not influence the detection of signs of new occurrences. On the contrary, films taken in either position are useful to follow the evolution of PE, provided the film is obtained in the same position and with the same technique as in the acute phase.

Acute Disease↗
PubMed1991

Effects of daily cigarette consumption on respiratory symptoms and lung function in a general population sample of north-Italian men.

We assessed the respiratory effects of the number of cigarettes smoked daily (CIGD) in 748 male smokers of a general population sample living in the unpolluted area of the Po Delta (Italy). A standardized questionnaire, flow-volume curves (V/V), the diffusing capacity of carbon monoxide (DLCO) and the slope of the alveolar plateau of nitrogen (DN2%/l) were used. Subjects were divided according to the median value of the observed distribution of CIGD (1-19, 20+) and according to the tertile values of the observed distribution of pack-years (an index representing lifetime cigarette consumption; 1-7, 8-21, 22+). In those with a higher CIGD, the prevalence rate of chronic phlegm was always significantly increased, while the prevalence rate of wheeze was significantly higher if they had smoked 8+ pack-years. Using analysis of variance, adjusted for pack-years, DLCO indexes, FEF75-85 and Vmax75 were significantly reduced in those with higher CIGD. When multiple logistic models, accounting for the independent effects of age and pack-years, were used, significantly increased odds ratios (ORs) for symptoms (e.g. OR = 2.0 for phlegm, OR = 1.8 for cough, OR = 1.6 for wheeze) and abnormal DLCO (OR = 1.9) or DN2%/l (OR = 1.6) were associated with a daily consumption of 10 cigarettes. In conclusion, the amount of cigarettes currently smoked may add a negative effect to that caused by lifetime cigarette consumption on respiratory symptoms and lung function. Moreover, the use of diffusing capacity in general population surveys is advisable.

Adolescent↗
PubMed1991

Respiratory effects of occupational exposure in a general population sample in north Italy.

We assessed the effects of occupational exposure in a general population sample living in an unpolluted rural area of North Italy. In the age range of 18 to 64 yr, there were 417 participants who reported any exposure to dusts, chemicals, or gases and 1,218 who reported no exposure. Each subject completed a standardized interviewer-administered questionnaire (CNR-questionnaire). A variable proportion of participants succeeded in performing flow-volume curves, diffusing capacity of carbon monoxide, and slope of alveolar plateau of nitrogen. There was no significant difference for symptom prevalence rates between exposed and nonexposed in men and women who smoke. In nonsmoking women, those exposed showed significantly higher prevalence rates for exertional dyspnea and asthma. Regarding lung function, in exposed male smokers there was a significantly higher slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced expiratory flows were significantly lower. Multiple logistic models in the overall group, accounting for age, smoking, and pack-years, showed that work exposure was associated significantly with higher risks for all symptoms in men (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64 for phlegm); in females, the association was significant for dyspnea (OR = 3.74) and asthma (OR = 3.29). Exposed men also had a significantly higher risk for %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other few epidemiologic surveys in general population samples and contribute to the suggestion of a causal association between occupational exposure and chronic obstructive pulmonary disease.

Adult↗
PubMed1991

[The diagnosis of pulmonary embolism: the role of noninvasive technics].

Today a large group of patients with pulmonary embolism is still undetected because this disease is not suspected. We evaluated the role of routine clinical procedures such as history, chest x-ray, electrocardiogram and blood gas analysis in the diagnosis of this disease. We studied 177 patients sent to our observation with suspicion of pulmonary embolism, which was later confirmed in 97 and excluded in 80. Prolonged immobilization, surgical procedures and deep vein thrombosis are the most frequent predisposing factors (P less than 0.05 or less) in patients with pulmonary embolism with respect to patients with unconfirmed suspicion of embolism. Among symptoms and signs, pleuritic chest pain, sudden onset of dyspnea, tachypnea, fever, enlarged jugular veins, enhanced pulmonary component of the second heart sound, pulmonary systolic murmur and basal hypophonesis were the most frequent signs (P less than 0.005 or less) in patients with embolism. Among radiographic signs "sausage" descending pulmonary artery, diaphragmatic elevation, pulmonary infarction, Westermark sign and azygos vein enlargement were more frequent (P less than 0.05 or less) in patients with embolism with respect to patients with unconfirmed suspicion of embolism. Among electrocardiographic signs, tachycardia, P-R segment displacement and negative T wave in V1-V2 were more frequent in patients with embolism with respect to patients with unconfirmed suspicion of embolism (P less than 0.05 or less). PO2, standard pO2 and pCO2 were significantly lower (P less than 0.001) in patients with embolism. After discriminant analysis of the whole data set most patients were correctly classified as embolic (90/97) and non-embolic (75/80).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗
PubMed1990

Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer.

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.

Aged↗
PubMed1990

Pattern of airway response to allergen extract of Phleum pratensis in asthmatic patients during and outside the pollen season.

In order to evaluate the pattern of airway response to a specific bronchial provocative test (sBPT) with an extract of Phleum pratensis standardized in biological units (BU), we studied 27 patients with seasonal asthma due to grass pollen by means of allergologic evaluations, methacholine inhalation test and sBPT, outside the pollen season in all patients and, in 10 of them, also during the pollen season. We used a DeVilbiss 646 nebulizer with a dosimeter, giving increasing doses (0.01-2.5 BU) of the allergen solution and we monitored FEV1 to assess early (EAR) and late (LAR) airway responses. Outside the pollen season sBPT elicited an isolated EAR in 16 and a dual asthmatic response (DAR) in 11 patients. We observed no significant difference between EAR and DAR patients as regards the provocative dose causing a 15% fall in FEV1 (PD15FEV1) methacholine, EAR (expressed by PD15FEV1 allergen) or allergologic data. There was a significant relationship between PD15FEV1 allergen and PD15FEV1 methacholine (r = 0.43, p less than 0.05). The reproducibility of sBPT was assessed in 11 patients outside the pollen season. The correlation coefficients between the two tests were: r = 0.91, p less than 0.001 for the total delivered dose of allergen during sBPT; r = 0.79, p less than 0.01 for PD15FEV1 allergen; r = 0.95, p less than 0.001 for the maximum percent fall in FEV1 during LAR. Ten patients repeated all tests during the grass pollen season. PD15FEV1 methacholine and baseline FEV1 decreased significantly during the pollen season, but PD15FEV1 allergen did not change significantly during the season.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram.

Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional recovery of these patients, thus giving additional information about the effect of therapy.

Carbon Dioxide↗
PubMed1990

Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate.

To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.

Adult↗
PubMed1990

Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients.

Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking habits and the degree of airway obstruction were investigated. Specimens of peripheral lung parenchyma, free of tumor tissue, were taken and the malondialdehyde (MDA) content was measured in the S-12 fractions. Airway obstruction was assessed by flow-volume curves, and data were expressed as percentage of the predicted values. Cigarettes smoked were expressed as pack-years. The patients with LC and NLC did not differ by MDA content, age, and number of pack-years. On the contrary, FEF75-85 and MEF75 were significantly lower in LC than in NLC patients (p less than 0.05). The MDA content was inversely correlated to number of days patients had refrained from smoking (r = -0.66, p less than 0.001). The MDA content was higher in recent smokers (ie, people smoking during the last 30 days before surgery) than in the other patients (0.136 +/- 0.007 vs 0.116 +/- 0.007 mumol/g of tissue, p less than 0.05) and, by considering only recent smokers, MDA content was higher in LC patients (0.144 +/- 0.008 mumol/g of tissue) than in NLC patients (0.113 +/- 0.014 mmol/g tissue, p = 0.059). When patients were divided into "high MDA" and "low MDA" groups, MEF75 was much lower in the high MDA group (35.1 +/- 3.4 percent) than in the low MDA group (55.1 +/- 8.1 percent) (p less than 0.01). These results suggest the following: (1) enhanced level of prooxidant state in the lungs is associated with recent cigarette smoking; (2) LC patients may be more prone than respective NLC patients to oxidative stress; (3) MDA level and degree of small airway obstruction were associated and differed between LC and NLC patients even though these groups did not differ in the percentage of recent smokers; and (4) a common free-radical mediated pathway may be active for both LC and small airway obstruction.

Glutathione↗