Lung uptake of Tc-99m HMPAO in cigarette smokers expressed by lung/liver activity ratio.

Tc-99m HMPAO, a lipophilic radiopharmaceutical used for brain imaging, has been reported to localize in smokers' lungs. To quantitate this uptake in the lung, 55 patients, who were referred for brain imaging for dementias or strokes, also underwent lung imaging (anterior lung imaging includes a large part of the liver) after IV injection of the radiopharmaceutical. Regions of interest over the liver and the lung were calculated. Of the 55 patients (ages 13-79), 30 were smokers and 25 were nonsmokers. The smokers had been smoking from 6-59 years, and daily cigarette consumption ranged from 8-50 cigarettes. The mean lung/liver ratio for smoking patients were 0.792 +/- 0.042 (SE); the mean lung/liver ratio for nonsmoking patients was 0.408 +/- 0.019 (SE). Lung/liver ratio uptake was significantly higher in the smoking patients (P < 0.01) than in the nonsmokers. Thus, lung/liver uptake of Tc-99m HMPAO may be used as an indicator of cigarette smoking.

Congenital tracheobronchomegaly (Mounier-Kuhn syndrome): a report of 10 cases and review of the literature.

Mounier-Kuhn syndrome is a congenital abnormality of the trachea and main bronchi characterized by atrophy or absence of elastic fibers and thinning of muscle, which allows the trachea and main bronchi to become flaccid and markedly dilated on inspiration with narrowing or collapse on expiration or cough. The abnormal airway dynamics and pooling of secretions in broad outpouchings of redundant musculomembranous tissue between the cartilaginous rings predispose to the development of chronic pulmonary suppuration, bronchiectasis, emphysema, and pulmonary fibrosis. A broad spectrum of clinical abnormalities has been documented in Mounier-Kuhn syndrome, ranging from minimal disease with good preservation of pulmonary function to progressive disease leading to respiratory failure and death. In the appropriate clinical setting, Mounier-Kuhn syndrome is diagnosed in women from chest radiographs when the transverse and sagittal diameters of the trachea exceed 21 mm and 23 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 19.8 mm and 17.4 mm, respectively. In men it is diagnosed when the transverse and sagittal diameters of the trachea exceed 25 mm and 27 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 21.1 mm and 18.4 mm, respectively. The diagnosis can be confirmed easily by computed tomography.

Population characteristics and cigarette yield as determinants of smoke exposure.

Relationships of population characteristics, smoking history, and cigarette yield with smoke exposure as measured by peripheral blood concentrations of thiocyanate, carboxyhemoglobin, nicotine and cotinine were sought in 170 male smokers. This population of smokers had significant elevations of serum thiocyanate, blood carboxyhemoglobin and plasma nicotine and cotinine concentrations as compared with an equal number of age- and sex-matched nonsmokers and these concentrations correlated significantly with past 24-hour cigarette consumption. Although the nicotine yield of the cigarette correlated significantly with plasma cotinine and marginally with plasma nicotine, the reduction in plasma nicotine and cotinine was not proportionate to the reduced yield of the cigarettes, suggesting that smokers partially compensate for the lower yields of their cigarettes. Blood levels of carboxyhemoglobin, nicotine and cotinine were also significantly associated with the weight of the subjects, presumably due to the relationship between weight and the volume of distribution. Univariate and multiple regression analyses provided evidence that coffee and alcohol consumption and years smoked also may be important determinants of smoke exposure.

Puffing topography as a determinant of smoke exposure.

Puffing topography variables were measured in a well-characterized, male population smoking their own brand of cigarette. Of the puffing topography variables, interpuff interval appeared to be the primary determinant of blood concentrations of smoke constituents: however, preliminary data in a homogeneous population according to the nicotine yield of their cigarette suggest that total puff volume per cigarette may also be a significant determinant of blood levels of smoke constituents. Smokers of low nicotine yield cigarettes partially compensated for these lower yields by increasing the total volume puffed per cigarette. Observed differences in puffing topography associated with increased daily cigarette consumption and cumulative smoking history were consistent with a higher smoke exposure per cigarette. Further, although both alcohol and coffee consumption are associated with present and cumulative smoking history, coffee consumption is uniquely associated with differences in puffing topography consistent with a higher smoke exposure per cigarette. However, by multiple regression analyses, neither coffee nor alcohol consumption histories added significantly to the prediction of blood concentrations of smoke constituents over that obtained by smoking history and puffing topography.

Acquired tracheomegaly in adults as a complication of diffuse pulmonary fibrosis.

We studied the chest radiographs of 34 consecutive patients with diffuse pulmonary fibrosis to determine the presence of tracheomegaly and to follow its progression with time. Patients had been identified by a computer search of medical records. We measured the internal transverse diameter of the trachea 2 cm above the top of the aortic arch on erect posteroanterior chest radiographs. Transverse diameters greater than 25 mm in men and 21 mm in women were considered indicative of tracheomegaly. Pulmonary-function tests, available in 30 of the 34 patients, showed restrictive lung disease. The transverse tracheal measurements were compared with the cause of fibrosis, severity of restriction, duration of illness, and other clinical variables. Tracheomegaly was present in 10 (29%) of the patients, including four with fibrosing alveolitis, four with sarcoidosis, and two with chronic progressive histoplasmosis. In seven of these patients, serial radiographs showed that the tracheal dilatation had progressed with time. Nine of 24 patients without tracheomegaly also had progressive increase in transverse tracheal diameter over time. Of the 10 patients with tracheomegaly, pulmonary-function tests were available in eight and showed moderate restrictive lung disease in six and severe restrictive lung disease in two. The duration of illness was 3-6 months in two patients, 10-22 years in five patients, and not recorded in three patients. Chronic cough and repeated respiratory infections were slightly more common in those patients with tracheomegaly than in those without. These data suggest that tracheomegaly develops as a complication of diffuse pulmonary fibrosis in patients who have at least moderate restrictive lung disease and prolonged illness, and it may have some association with chronic cough and repeated respiratory infection.

Extracellular killing of inhaled pneumococci in rats.

Early clearance of inhaled Staphylococcus aureus is believed to be caused by phagocytosis by alveolar macrophages. In murine models inhaled pneumococci are cleared even more rapidly than S. aureus. Conventional opsonins appear to play no role in this clearance, and recently it has been shown that murine alveolar lining material contains free fatty acids and other soluble factors that are directly bactericidal for pneumococci. To determine whether non-phagocytic factors are involved in pneumococcal clearance, we compared the site of killing of inhaled pneumococci and S. aureus in rats using histologic methods and bronchoalveolar lavage. Spontaneous lysis of pneumococci was prevented by use of autolysin-defective pneumococci or by substitution of ethanolamine for choline in the cell wall. Histologic studies showed that the percent of inhaled staphylococci associated with alveolar macrophages always exceeded the percent of staphylococci cleared, whereas there was little association of pneumococci with macrophages during clearance. Analysis of the intracellular or extracellular location of iron 59 in bronchoalveolar lavage fluid of rats that had inhaled aerosols of 59Fe-labeled bacteria suggested that staphylococci were killed predominantly in macrophages and pneumococci in the extracellular space. When 59Fe-labeled pneumococci or staphylococci were ingested and killed by macrophages in vitro, the 59Fe remained with the macrophages, suggesting that the extracellular location of 59Fe during pneumococcal killing in vivo was not caused by rapid turnover of 59Fe in macrophages. Studies of the site of killing of inhaled type 25 pneumococci labeled exclusively in the cell wall with carbon 14-ethanolamine confirmed the results obtained with 59Fe-labeled pneumococci. Thus, early killing of inhaled pneumococci, unlike staphylococci, appears to take place outside of macrophages.

Smoking history, cigarette yield and smoking behavior as determinants of smoke exposure.

This study examines how smoking history, cigarette yield and smoking behavior relate to smoke exposure as determined by smoke constituents and their metabolic products in peripheral blood. Recruited without regard to the nicotine yield of their cigarette, male smokers smoked their own cigarettes ad libitum, including one cigarette five minutes prior to venipuncture. Smokers had significant (p = 0.0001) elevations of serum thiocyanate, blood carboxyhemoglobin, plasma nicotine, and cotinine concentrations each of which was significantly associated with past 24-hour cigarette consumption. The nicotine yield of the cigarette significantly correlated with plasma cotinine concentrations and with the smoking behavior variables. Most notably, smokers consuming lower nicotine yielding cigarettes exhibited an increased total puff volume per cigarette, suggesting that smokers of low nicotine yielding cigarettes compensate for these low yields by their smoking behavior. However, the fact that lower plasma cotinine concentrations are present in smokers of low-nicotine cigarettes suggests that this compensation is incomplete. That smoking behavior variables relate to smoke exposure was demonstrated by a significant linear correlation between plasma nicotine and mean puff interval in the total smoking population and between plasma nicotine and total puff volume per cigarette in a subpopulation smoking a single brand of cigarette. These data suggest that smoking history, nicotine yield of the cigarette and smoking behavior are all determinants of smoke exposure. Further, although smokers of low-yield cigarettes appear to compensate by puffing larger volumes per cigarette, this compensation appears to be inadequate to attain an equivalent smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of smoking on inflammatory mediators and their relationship to pulmonary dysfunction.

Study populations of 170 male smokers and 170 age- and sex-matched nonsmokers were used to determine the effects of cigarette smoking on pulmonary function, peripheral blood leukocytes and phase reactive proteins. Further, the interrelationships between these parameters were sought. Consistent with their young age (mean 37 years) and relatively brief smoking history (mean 24 pack-years), the smokers had a significant, yet modest, impairment of pulmonary function as measured by both forced expiratory spirometry and the single breath nitrogen/closing volume test. Smokers exhibited a significant elevation in total peripheral blood leukocytes which was attributable to increases in neutrophils, lymphocytes, monocytes and eosinophils. Similarly, significant increases in the "phase reactive" proteins [i.e., the ninth component of complement (C9), ceruloplasmin and alpha 1-protease inhibitor (alpha 1-PI)] were also observed in smokers. Increases in total leukocytes, neutrophils, C9 and alpha 1-PI were significantly associated with present and cumulative cigarette consumption, blood levels of smoke constituents/metabolites (i.e., carboxyhemoglobin, nicotine and cotinine) and impaired pulmonary function (i.e., FEV1 and FVC). However, duration of smoking (years smoked) and pack-years smoking history were the best predictors of elevations in inflammatory mediators and pulmonary dysfunction. These data support the hypotheses that: a low grade inflammatory reaction is induced in smokers and is dependent upon a dose-related exposure to smoke; and the smoking-induced changes in inflammatory mediators are associated with the observed pulmonary dysfunction.

Lower levels of vitamin C and carotenes in plasma of cigarette smokers.

Plasma levels of vitamins A, C, and E, selenium, and carotenes were determined in 125 male cigarette smokers and 125 age- and race-matched nonsmokers. The smokers had a mean daily consumption of 30.6 cigarettes and a cumulative consumption of 22.8 pack years. Plasma levels of vitamin C and total carotenes were significantly (p less than 0.05) lower in smokers than those of nonsmokers, while levels of vitamin A, selenium, and vitamin E were not significantly different between these two groups. Similar results were found when only those subjects not taking any form of dietary supplements were included for analysis. Except for negative correlation between vitamin A and pack-year, no significant correlates were observed between plasma levels of these micronutrients and indices of smoking status or cigarette consumption in smokers. These data suggest that chronic cigarette smoking is associated with depressed levels of plasma vitamin C and carotenes; however, the relationship between smoking and these plasma micronutrients is still unclear.

Serum antiproteases in smokers and nonsmokers. Relationships to smoking status and pulmonary function.

In this study of 50 relatively young male smokers and an equal number of age- and race-matched male nonsmokers, smokers had a 13.3% (p = 0.007) increase in mean serum alpha 1-proteinase inhibitor (alpha 1-Pl) concentration. This increase in serum alpha 1-Pl concentration was accompanied by increases in both the serum trypsin inhibitory capacity (TIC) (9.9%, p = 0.002) and the elastase inhibitory capacity (EIC) (12.4%, p = 0.001). That cigarette smoking increases serum alpha 1-Pl concentration and total protease inhibitory capacity was further supported by a significant association of alpha 1-PI, TIC, and EIC with increased pack-years smoking history, plasma nicotine, and plasma cotinine concentrations. Pulmonary function did not correlate with serum alpha 1-PI concentration. However, higher serum TIC and EIC did correlate with tests of small airways dysfunction. Highly significant correlations (r greater than or equal to 0.6, p = 0.001) were observed between TIC (or EIC) and alpha 1-PI concentrations. The linear relationships between TIC (or EIC) and serum alpha 1-PI concentration were not significantly different in smokers and nonsmokers. Further, no significant differential effect of smoking on either the TIC or EIC could be demonstrated. A decreased apparent functional activity of alpha 1-PI (i.e., nanomoles of protease inhibited per nanomole of alpha 1-PI) was associated with its higher serum concentration, a phenomenon observed in both smokers and nonsmokers. Thus, although cigarette smoking increases serum alpha 1-PI concentration and total protease inhibitory capacity, no evidence was obtained to suggest that the functional activity of serum alpha 1-PI (against either trypsin or elastase) was directly affected by smoking.

Increased neutrophil myeloperoxidase activity associated with cigarette smoking.

Neutrophils from 49 young male smokers contained significantly higher myeloperoxidase (MPO) activity than those from 49 age-matched, nonsmoking controls, while the elastase-like activity was not different in the two populations. MPO activity was increased in some smokers, but did not correlate significantly with the increased number of peripheral blood neutrophils, cigarette usage (present or cumulative), or the mild pulmonary dysfunction detected by forced expiratory spirometry and the single breath nitrogen test. This increased MPO activity in smokers' neutrophils may contribute to the greater risk of obstructive pulmonary disease in some smokers by an exacerbation of the protease-antiprotease imbalance in the lung. This hypothesis is supported by the prior observations that neutrophils are recruited in greater numbers into the lungs of smokers and that MPO (in the presence of H2O2 and chloride ion) oxidatively inactivates antiproteases of both the alveoli and the mucus-lined airways.

Increased plasma concentrations of C9, C1-inhibitor and alpha 1-protease inhibitor associated with cigarette smoking.

The association between various parameters of acute and chronic smoking status and plasma levels of three proteins, C9, C1-inhibitor (C1-INH) and alpha 1-protease inhibitor (alpha 1-PI) were determined for 49 male cigarette smokers and 49 age-matched nonsmokers (mean age = 32.2 years). The mean number of cigarettes smoked was 28.7 per day while the cumulative consumption was only 18.1 pack-years. Plasma levels of all three proteins were significantly higher in the smokers than nonsmokers. Plasma C9 and alpha 1-PI concentrations correlated with cumulative cigarette consumption and plasma nicotine concentrations. While C1-INH concentration did not correlate with either cumulative cigarette consumption or plasma nicotine concentration, it correlated significantly with serum thiocyanate concentration. No consistent correlation was found between plasma concentration of these proteins and parameters of pulmonary function.