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[Research on the occurrence of functional anomalies of the peripheral bronchi (small bronchi disease) in workers in a factory with respiratory noxious substances].

A group of 908 subjects has been studied, of which two-thirds were males, classified in 5 categories: unexposed, with light exposure, and severely exposed to inhalation of volatile substances, or various types of dust. A B.M.R.C. file was filled for each of the subjects. This file concerns respiratory symptoms. A forced expirogram was also performed, and FEV 25-75%, FEV 75-85%, and TEM were determined. The two expiratory flows (median and final) are frequently disturbed in subjects without respiratory symptoms, more frequently in smokers with a normal FEV 1. In those exposed to respiratory risk the proportion of alterations increases, but association of smoking with inhalation of noxious chemical substances will determine a modification of FEW 1 and anomalies of the peripheral bronchi occur more frequently in smokers. Between the criteria suggesting the presence of small airways disease, the ratio FEV 25-75% under 60%, with a FEV 1/FVC ratio within normal limits, this being the most sensitive of the criteria, also appears as the most reliable.

Adult

Structural variation in the named bronchi of the left lung. A morphometric study.

In order to establish whether or not the named bronchi of the left lung differ structurally from each other, their proportions of cartilage, gland and muscle in normal and chronic bronchitic patients were measured. In the normal subject the lower lobe bronchus contains proportionally more muscle than either the upper lobe bronchus or the segmental bronchi. Its proportion of cartilage is less than that of the main and upper lobe bronchi, and in this respect it is similar to the segmental bronchi. The proportions of gland in the main, upper and lower lobe bronchi are the same. There is no difference between the tissue proportions of the segmental bronchi of the upper and lower lobes. In chronic bronchitics the proportion of gland is increased, and in many cases there is also an increase in muscle. The relatively high proportion of muscle in the lower lobe bronchus is no longer apparent, and its proportion of cartilage is greater than in the normal subject. The main and upper lobe bronchi contain a higher proportion of gland than the lower lobe bronchus and the segmental bronchi. The proportions of the components in the upper and lower segmental bronchi are again similar. It is concluded that in the left lung the tissue proportions of the named bronchi vary. In particular, the normal lower lobe bronchus is characterized by a relatively high percentage of muscle, and a similar cartilage content to the segmental bronchi. Care is therefore needed in selecting airways for morphometric studies.

Aged

Basilar segmental bronchi: thin-section CT evaluation.

Thin (1.5- and 5.0-mm) section contiguous computed tomographic (CT) scans obtained through the basilar segmental bronchi in 31 patients were reviewed in order to delineate normal anatomy and common variations of lower lobe airways. In each case, the frequency with which individual segmental and subsegmental bronchi were seen was established, as were variations in branching patterns. All basilar segmental bronchi were identified except in one case in which images of the left lung were obscured due to respiratory and cardiac motion. In the right lung, a division into subsegmental bronchi was identified in 84 of 150 (56%) visualized segmental bronchi. Six separate patterns of basilar segmental subdivision were found. In the left lung, subsegmental bronchi were identified arising from 51 of 145 (35%) visualized segmental bronchi. Five separate patterns of bronchial subdivision were found in the left lung. It is concluded that thin-section CT allows precise identification of all basilar segmental bronchi and, consequently, can play a significant role in the cross-sectional evaluation of lower lobe bronchial and parenchymal abnormalities.

Bronchi

Pressure-volume and length-stress relationships in canine bronchi in vitro.

Intraparenchymal canine airway segments with branches tied off were mounted between two fluid-filled cannulas in an organ chamber. Airways were inflated to successive volumes ranging from 4 to 100% of the segment volume at 25 cmH2O. At each volume, pressure was monitored during isovolumetric contractions elicited by 10(-3) M acetylcholine. Small bronchi developed pressures greater than 30 cmH2O in response to acetylcholine at all volumes and were able to constrict to closure. Large bronchi developed pressures greater than 30 cmH2O only near maximal volumes and were able to constrict to only 30% of maximal volume. Maximal active pressures occurred at low volumes in small bronchi and at high volumes in large bronchi. However, maximal active circumferential tension and stress occurred at near-maximal volumes in both large and small bronchi. Circumferential length active-stress curves and maximal active-stress development for bronchi and trachealis muscle strips were similar. Similar length active-stress properties in different bronchi may produce significant differences in volume-pressure characteristics.

Animals

15(S)-hydroxyeicosatetraenoic acid is the major arachidonic acid metabolite in human bronchi: association with airway epithelium.

15(S)-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) was by far the most abundant metabolite of arachidonic acid in chopped human bronchi, as identified by reverse phase HPLC, uv spectrometry, and GC/MS. The quantitation of monohydroxyeicosatetraenoic acids (mono-HETEs) was performed by the use of 16(S)-hydroxy-9(Z),12(Z),14(E)-heneicosatrienoic acid as internal standard. Thus, significant amounts of 15-HETE were obtained in incubations of bronchi in buffer alone, but the addition of exogenous arachidonic acid (3-100 microM), dose-dependently increased the formation, with maximal levels reached at around 10 min. In contrast, challenge with ionophore A23187 or anti-human IgE did not stimulate the production of 15-HETE in the bronchi. Nordihydroguaiaretic acid inhibited the production of 15-HETE, whereas indomethacin did not. Small amounts of 8,15-diHETEs were detected in incubations with exogenous 15H(P)ETE. Lipoxins were however not detected under any of the incubation conditions used. Furthermore, removal of the airway epithelium substantially diminished the production of 15-HETE in the bronchi. Finally, bronchi were obtained from three patients with asthma, and the amounts of 15-HETE in these specimens were significantly higher than those found in tissues from nonasthmatics. Also, in peripheral lung parenchyma and pulmonary blood vessels 15-HETE was the major mono-HETE after stimulation with arachidonic acid but the levels were about 10 times lower than in the bronchi. As another difference, challenge of the parenchyma with the ionophore A23187 made 5-HETE the predominant mono-HETE. Taken together, airway epithelium appears to be the major source of 15-HETE in the human lung and the findings in specimens of asthmatics raise the possibility that 15-HETE somehow is involved in airway inflammation.

Arachidonic Acid

Structural changes in airways of rats exposed to nitrogen dioxide intermittently for seven days. Comparison between major bronchi and terminal bronchioles.

Structural changes caused by exposure to NO2 were compared between the largest intrapulmonary bronchi (major bronchi) and the terminal bronchioles. Rats were exposed to 50 ppm NO2 for 5 h a day for 7 consecutive days, and microscopic findings were assessed subjectively and quantitatively. Destruction of airway epithelium was present on Day 1, and the reparative phase was observed between Days 3 and 7. Light microscopy showed that on Day 1, loss of cilia and disintegration of epithelium occurred, and that the latter was worse in major bronchi than in terminal bronchioles; apical projections of Clara cells in terminal bronchioles were lost almost totally. Recovery of epithelium began by Day 3 and cilia by Day 5, and ciliogenesis progressed less promptly in terminal bronchioles. Clara cells did not return to normal during the experiment. Furthermore, a decrease in the airway diameter occurred in peripheral airways along with an increase in mural thickness in terminal bronchioles. Mural inflammation was also seen more conspicuously in terminal bronchioles. Electron microscopy revealed that epithelial cells lost secretory granules on Day 1 and began to repair them by Day 5 in major bronchi and by Day 7 in terminal bronchioles. It is likely that epithelium in terminal bronchioles is not particularly sensitive to NO2 compared with that in major bronchi, but that recovery occurs more promptly in major bronchi than in terminal bronchioles. Mechanisms underlying bronchoconstriction occurring preferentially in peripheral airways are also discussed.

Animals

Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of naphthalene.

BACKGROUND: The purpose of this study was to define, in quantitative terms, epithelial alterations produced by the cytochrome P-450-activated Clara cell cytotoxicant, naphthalene, in lobar bronchi and terminal bronchioles of three species with differing sensitivity: mouse, rat, and hamster. EXPERIMENTAL DESIGN: Adult mice, hamsters, and rats were treated intraperitoneally with a single dose of naphthalene ranging from 0 mg/kg up to the approximate LD50. The animals were killed 24 hours postinjection and the changes in airway epithelium characterized by light microscopic morphometry. RESULTS: In mouse, bronchiolar epithelial thickness was significantly elevated by low, but not high, doses; ciliated cell number increased and Clara cell number decreased in a dose-dependent fashion. Vacuolated Clara cell number increased in all treated mice. In rat and hamster, bronchiolar epithelial thickness or cell number did not change. In mice, bronchial epithelial thickness was unchanged except at high doses, but both ciliated and Clara cell number was decreased. In bronchi of rats, epithelial thickness and numbers of nonciliated, ciliated, and basal cells were unchanged. In bronchi of hamsters, both ciliated and nonciliated cell number were decreased. CONCLUSIONS: (a) In mice, naphthalene-induced acute bronchiolar toxicity involves not only Clara cells, but also affects the purported nontarget cell type (ciliated cells). (b) In rats and hamsters, bronchiolar epithelium is insensitive to naphthalene injury. (c) In mice, injury to bronchi occurs at higher doses than in bronchioles and involves both ciliated and nonciliated cells. (d) In rats, bronchi are insensitive. (e) In hamsters, bronchi are more sensitive than bronchioles. This study emphasizes the variability of response by species, airway and epithelial cell type to cytochrome P-450-mediated pulmonary toxicants and the need for precise quantitative methods of defining both cytotoxic and metabolic events.

Animals

[Normal bronchi on high resolution CT].

The delineation of normal bronchi was evaluated by high resolution CT. Under the usual conditions for lung survey, with window width of 1500, window level -650, and slice thickness 10 mm, using high spatial frequency algorithm, the subsegmental bronchi were delineated in 77% of total branches. Sub-subsegmental bronchi were delineated in 8% of branches. Under thin slice high resolution CT, with slice thickness of 1.5 mm and slice interval 10 mm, subsegmental bronchi were delineated in 89% of branches, and sub-subsegmental bronchi were delineated in 35% of branches. In two of the cases in which almost the whole lungs were studied on continuous slice images with thin slice high resolution CT, sub-sub-subsegmental bronchi could be easily delineated, except in for the lingular segment. High resolution CT is very useful for the interpretation of normal pulmonary structures and for diagnosis of bronchial lesions.

Adolescent

Bronchial histamine reactivity: its relationship to the reactivity of the bronchi to allergens.

The aim of this study was to examine the proposal that the magnitude of the response of the bronchi to an immediate allergic reaction depends not only on the degree of sensitization of the bronchi by allergen specific IgE antibody but also on the reactivity of the bronchi to the vasoactive mediators which are released during immediate allergic reactions. This was done by determining the bronchial reactivity to Dermatophagoides pteronyssinus and to histamine of both symptomatic and asymptomatic groups of atopic subjects who had comparable serum levels of D. pteronyssinus specific IgE. Positive bronchial responses to the D. pteronyssinus extract were recorded with both the symptomatic and asymptomatic subjects, the mean bronchial threshold dose of allergen being significantly higher in the asymptomatic than in the asthmatic patients. There was a highly significant correlation between the serum level of allergen specific IgE and the bronchial threshold dose of allergen extract and also between the bronchial threshold dose of allergen extract and of histamine in all groups of subjects. The ability to predict bronchial reactivity to the allergen from the serum level of allergen specific IgE within each group was significantly better if the bronchial reactivity to histamine was included in the correlation analysis. This supports the hypothesis that whether a particular subject who is producing specific IgE antibody will develop symptoms on the inhalation of that allergen depends not only on the amount of allergen which he inhales and on the degree of sensitization of his bronchi but also on the reactivity of his bronchi to the vasoactive mediators which are released by allergen-IgE interaction.

Administration, Intranasal

Influence of lung parenchyma on collapsibility of dog bronchi.

In five excised dog lobes in the distended state, we inserted several small beads into the bronchi roughly at their third branches and glued them airtight to the bronchial wall with adhesive substance, except for one which was open and through which the entire lobe could be expanded via collateral channels. This permitted us to measure the volume-pressure behavior of bronchi at different fixed lung tensions. From differences in pressure-volume curves of both the bronchi in situ and the bronchi intact within the lung showed a remarkably greater resistance to collapsing that dissected bronchi, and this characteristic tended to be much more intense when lung tension was increased. Determinants of maximum expiratory flow were discussed with these findings.

Animals

Static mechanical properties of bronchi in normal excised human lungs.

Bronchographic studies were performed on 22 normal human lungs at transpulmonary pressures between 20 and 0 cmH2O. Pressure-diameter behavior of 322 bronchi was evaluated. In younger (less than 40 yr) subjects, the airways of males showed greater recoil than those of females. No difference between sexes was seen in older (greater than 40 yr) subjects. Bronchi less than 2.1 mm diam had a significant decrease in recoil with increasing age in males but not in females. Small bronchi had greater recoil than large bronchi in both sexes in the younger group but not in the older group. The younger group had evidence of anisotropic behavior of the bronchi not seen in the older group. The percentage decrease in lung volume for a given decrease in transpulmonary pressure was less in the older than in the younger subjects in both sexes. Measurements of the cube root of lung volume, bronchial length, and the position of markers attached to the pleura indicated that the lungs deflated in an overall, isotropic manner down to a pressure of 3 cmH2O.

Adolescent

Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine.

Bronchial hyperresponsiveness can be demonstrated in asthmatic subjects by inhalation of adenosine, but the action of adenosine at the level of the human airway smooth muscle has received comparatively little attention. We have previously observed that bronchi isolated from one asthmatic patient contracted in response to adenosine. We have therefore, during the course of a 3-yr study, further characterized the effects of adenosine in bronchi prepared from surgical specimens of lung tissue of asthmatics and of nonasthmatics. Contraction responses were always studied in vitro the same day the tissues were obtained. Bronchi from asthmatics (19 strips from six patients) were more sensitive to adenosine than were bronchi from nonasthmatics (21 strips, seven patients). In contrast, there was no difference in sensitivity to histamine or leukotriene C4 between the two groups, nor was the maximal tissue contractility different. The contractile effect of adenosine was inhibited by the adenosine A1-antagonist 2-thio-[(1,3-dipropyl)-8-cyclopentyl]-xanthine as well as by the dual A1 and A2 antagonists 8-(p-sulfo)-phenyltheophylline and theophylline. The combination of leukotriene antagonism (receptor-antagonist ICI 198,615 or biosynthesis inhibitor MK-886) and histamine antagonism (antihistamines mepyramine and metiamide) blocked the contractile effects of adenosine, suggesting that adenosine acts indirectly by liberation of leukotrienes and histamine, possibly from mast cells. The findings of increased sensitivity to adenosine in bronchi from asthmatics to our knowledge represents the first evidence of increased bronchial reactivity in vitro in asthmatics.

Adenosine

Poissons' ratio of lung parenchyma and parenchymal interaction with bronchi.

A simple theory of lung elasticity and its interaction with bronchi was developed which led to the specific results. The experimental procedure for establishing these results used lobar bronchi from excised dog lungs, following Takishima, et al. ((1975) J. Appl. Physiol., 38: 875-881). First, we found a semi-direct technique for measuring Poisson's ratio (sigma) of lung parenchyma and the effect of lung parenchyma on bronchi (interdependence). Sigma was measured at 0.424 +/- 0.045; no correlation was observed between sigma and the elastic recoil pressure of the lung (PL). The interdependence increased with a corresponding increase in PL and reduced bronchial volume. Second, we predict that a relationship exists between the specific compliances of intact and excised bronchi, and the specific compliance of the surrounding parenchyma. We suggest that the parenchyma is more important than the bronchus itself in determining the specific compliance of the intact bronchi.

Animals

[Thin-section computed tomography of the bronchi: right middle lobe, left lingular division, and lower lobes].

Thin (2 mm) section contiguous computed tomographic (CT) scans were obtained through the bronchi of the right middle lobe, the left lingular division, and the lower lobes in 24 patients. All segmental bronchi were identified except subsuperior and medial basilar segmental bronchi. Subsegmental bronchi of the left inferior lingula were seen in only 17%, but other subsegmental bronchi in greater than 75%. Variations in branching patterns were discussed.

Adult

Differential interaction of normal and preneoplastic hamster bronchi with adriamycin.

Advanced bronchogenic carcinoma in humans is notoriously resistant to the cytocidal actions of cancer chemotherapy. The experiments reported here were undertaken as a first step in examining the mechanisms of resistance of carcinogen-altered bronchus to the actions of the commonly used cancerocidal agent Adriamycin. Syrian Golden hamsters were treated with an endobronchial carcinogen in order to produce bronchial neoplasms or with no carcinogen as controls. Hamsters were then given i.v. Adriamycin, and the amounts and metabolism of bronchial Adriamycin were determined. Peak uptake values were found 5 min after Adriamycin administration, and the amounts of Adriamycin in normal and carcinogen-altered bronchi were found to be similar. Whereas no metabolism of Adriamycin was observed in normal bronchi, 40-60% of total Adriamycin fluorescence was found to be due to Adriamycinol and Adriamycin aglycones in bronchi with premalignant changes. In separate experiments, the susceptibility of normal and carcinogen-altered bronchial extracts to drug-induced lipid peroxidation was measured in vitro. A 50% decrease was found in the ability of carcinogen-altered bronchi to act as a substrate for lipid peroxidation mediated by Adriamycin and an approximately 30% decrease for lipid peroxidation induced by t-butyl-hydroperoxide. These results demonstrate two different mechanisms by which bronchogenic carcinomas might become resistant to the chemotherapeutic actions of Adriamycin. These are by the carcinogen induction of metabolism of Adriamycin to less toxic products and by resistance of the bronchi to free radical damage.

Animals

Tumors of the bronchi: role of evaluation with CT.

Computed tomography (CT) was performed in 142 patients thought to have an endobronchial tumor based on clinical or radiologic grounds. In 121 patients an endobronchial mass was confirmed at bronchoscopy with biopsy or at surgery. The CT scans were evaluated independently by two experienced observers (A and B). For statistical purposes the result in each single bronchus from the level of the trachea to the segmental bronchi was considered separately. A total of 361 abnormal and 1,413 normal bronchi were confirmed with bronchoscopy or surgery. Observers A and B identified 100% and 99%, respectively, of the abnormal bronchi and 97% and 96%, respectively, of the normal bronchi on CT scans. For the standard CT examination (8-mm-thick sections) a sensitivity of 94% (observer A) or 91% (observer B) and a specificity of 99% (observers A and B) were found in the diagnosis of a normal or narrowed bronchial lumen. CT proved to be a reliable method for demonstrating tumor lesions of the bronchi.

Bronchial Neoplasms

Aberrant bronchi and cardiovascular anomalies.

In an investigation of malformation associations in consecutive perinatal autopsies, 4 infants were identified as having a displaced or supernumerary bronchus. Each had a different type of bronchial abnormality and 3 had congenital heart defects and other malformations. Review of the literature found 38 other cases of aberrant bronchi with additional defects, especially cardiovascular or costovertebral anomalies. Structural cardiac defects were more common in patients with super-numerary tracheal bronchi (67%) than in those with displaced tracheal bronchi (27%) or bronchoesophageal connections (23%). There was also a strong negative association (P = 0.01) of cardiovascular and costovertebral defects unless multiple anomalies were present. The combinations of anomalies seen appear to reflect relatively specific developmental field defects affected both by the spatial relationships of organs near the developing foregut and by temporal sequence. Recognition of these patterns has clinical and embryological importance. Aberrant bronchi should be considered when children with cardiac defects or multiple anomalies such as the VACTERL association have unexplained respiratory symptoms and surgeons planning to treat such bronchial abnormalities should be aware of the high frequency of abnormal vessels in these cases.

Autopsy