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[Morphometric investigations of the bronchial tree in chronic bronchitis. Part I. The alterations of lumen and thickness of the walls of bronchi and bronchioli (author's transl)].

The morphometry of bronchi and bronchioles was studied in 22 persons aged between 47 and 78 who had died after suffering from chronic bronchitis for many years. Additionally the lungs of five persons, died due to other reasons and never having suffered from chronic bronchitis (normal persons) were investigated. In compared to the normal conditions no essential alterations in the diameter of the lumen could be found in the proximal bronchi (including the main bronchus till down to the subsegmental bronchus of the third order). The mean diameter of the lumen of distal membranous bronchi is unchanged, as well, but bronchioles in chronic bronchitis has a bigger lumen amounting to 0.4515 +/- 0.027 mm (in normals 0.324 +/- 0.024 mm, P less than 0.05). The calibres in the terminal and respiratory bronchioles varied as follows: Ectasia in 58%, stenosis in 11%, without any alterations in 31%, that means: organic stenosis in the distal bronchi and bronchioles is of minor importance for the mechanisms of obstruction in chronic bronchitis. The thickness of the proximal and distal bronchi is enlarged in chronic bronchitis. As to the histological features lympho-cytoplasmocytic infiltrations of the mucous membrane could be found in nearly all proximal bronchi studied (in 97.5%), sclerosis of the wall in 32.6%, and metaplasia of the lining squamous epithelium in 15%. Cytology of the bronchial secretions revealed the predominance of neutrophiles among all cellular elements when the inflammatory process was exacerbating.

Aged↗

[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↗

Leukotrienes and histamine mediate IgE-dependent contractions of human bronchi: pharmacological evidence obtained with tissues from asthmatic and non-asthmatic subjects.

Isolated human bronchi were challenged with anti-human IgE or specific allergen. The mediators of allergic constriction were characterized by pharmacological interventions. Experiments were performed on more than 180 preparations obtained from 48 non-asthmatic subjects and on 44 bronchial preparations from six asthmatic subjects. Addition of antihistamines (mepyramine and metiamide) to the organ bath abolished the response to exogenous histamine, but failed to alter the dose-response relationship of the reaction to cumulative challenge with rising titres of anti-IgE. On the other hand, pretreatment with drugs which blocked the action (receptor antagonists FPL55712, L-648,051 and ICI 198,615) or formation (biosynthesis inhibitors: U-60,257 and MK886) of leukotrienes consistently resulted in clear-cut inhibition of the allergic constriction in bronchi from both asthmatic and non-asthmatic subjects. In the presence of the most effective inhibitors (ICI 198,615 and MK886), the response to anti-IgE was depressed by more than 60%. In contrast, the cyclooxygenase inhibitor indomethacin and the antagonist of platelet activating factor (PAF) WEB 2086, failed to alter the response, indicating that prostanoids and PAF do not mediate IgE-dependent constriction of human bronchi. After the leukotriene antagonist ICI 198,615 had rendered the bronchi insensitive to exogenous leukotrienes, the residual component of the contractile response to anti-IgE was completely abolished by addition of antihistamines. Similar abolition of the Schultz-Dale reaction in bronchi of two allergic asthmatic patients was noted when antihistamines were administered together with ICI 198,615 or MK886. In conclusion, the leukotrienes appear to be the major and singularly most important mediators of the contraction, whereas histamine accounts for its minor residual component.

Adult↗

Nociceptin inhibits vanilloid TRPV-1-mediated neurosensitization induced by fenoterol in human isolated bronchi.

Chronic exposure to beta(2)-adrenoceptor agonists, especially fenoterol, has been shown to increase smooth muscle contraction to endothelin-1 in human bronchi partly through tachykinin-mediated pathways. The purpose of this work was to further investigate the role of sensory nerves in fenoterol-induced sensitization of human airways and the effect of nociceptin, a nociceptin/orphanin FQ (NOP) receptor agonist, on the increase in contraction after fenoterol exposure. Human bronchi from 62 patients were sensitized to endothelin-1 by prolonged incubation with fenoterol (0.1 microM, 15 h). The sensitizing effect of fenoterol was inhibited by high concentration of capsaicin (10 microM, 30 min before fenoterol sensitization), which induces depletion of mediators from sensory nerves, or co-incubation of fenoterol and capsazepine (1 microM), a vanilloid TRPV-1 receptor antagonist. Moreover, short pretreatment of bronchi with capsaicin (10 microM) or capsazepine (1 microM) after sensitization by fenoterol decreased the rise in smooth muscle contraction to endothelin-1. Nociceptin (1 microM) also inhibited the increased contraction in fenoterol-sensitized bronchi. Tertiapin (10 microM), an inhibitor of the inward-rectifier K(+) channels, but not naloxone (0.1 microM), a DOP/KOP/MOP receptor antagonist, prevented the inhibitory effect of nociceptin. In conclusion, fenoterol induces sensitization of human isolated bronchi to endothelin-1 in part through the stimulation of the vanilloid TRPV-1 receptor on tachykininergic sensory nerves. Nociceptin inhibits airway hyperresponsiveness via NOP receptor activation. This effect involves inward-rectifier K(+) channels.

Adrenergic beta-Agonists↗

Effects of 5-oxo-ETE and 14,15-EET on reactivity and Ca2+ sensitivity in guinea pig bronchi.

The reactivity and Ca2+ sensitivity of fresh as well as organ-cultured guinea pig bronchi challenged with 5-oxo-ETE and 14,15-EET were compared. Tension measurements, performed on fresh and 3-day cultured bronchi, revealed that the contractile responses to 5-oxo-ETE were largely increased in cultured explants, while 14,15-EET induced larger relaxations on Carbamylcholine (CCh) pre-contracted explants. In fresh bronchi, the contractile responses to 5-oxo-ETE were inhibited by 10 microM indomethacin whereas the relaxing responses induced by 14,15-EET were amplified in the presence of COX inhibitors. COX down expression resulted in a lack of indomethacin effect in cultured explants. One micromolar 5-oxo-ETE increased Ca2+ sensitivity in beta-escin-permeabilized cultured explants, while 1 microM Y-27632 abolished this hypersensitivity. In contrast, 1 microM 14,15-EET significantly reduced the Ca2+ hypersensitivity developed by cultured bronchi. In conclusion, pre-treatment of cultured guinea pig bronchi for 48 h with these eicosanoids modifies the pharmacological responsiveness and Ca2+ sensitivity of these cultured explants.

8,11,14-Eicosatrienoic Acid↗

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↗

Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide-like substance.

1. The involvement was assessed of an endogenous nitric oxide-like substance in contractions of canine bronchi to acetylcholine. 2. Canine third order bronchial rings, in some of which the epithelium was removed mechanically, were suspended in organ chambers and isometric tension was recorded. In some experiments, the content of guanosine 3',5'-cyclic monophosphate (cyclic GMP) of the bronchi was also measured. 3. Acetylcholine induced concentration-dependent contractions. The contractions were potentiated by nitro-L-arginine (an inhibitor of the synthesis of nitric oxide), oxyhaemoglobin (a scavenger of nitric oxide), and methylene blue (an inhibitor of soluble guanylate cyclase). The magnitude of the potentiation to acetylcholine-induced contractions by these inhibitors were not significantly different between tissues with and without epithelium. 4. Acetylcholine induced a concentration-dependent increase in intracellular content of cyclic GMP, which was similar in bronchi with and without epithelium. These increases were abolished by nitro-L-arginine and methylene blue. 5. During contractions to acetylcholine, exogenous nitric oxide relaxed the canine bronchi. The relaxations were not affected by nitro-L-arginine, but were augmented by superoxide dismutase plus catalase, and were abolished by methylene blue. 6. These observations suggest that, during contraction evoked by acetylcholine, the production of an endogenous nitric oxide-like substance increases and in turn attenuates the response of the airways to the muscarinic agonist. However, the endogenous nitric oxide-like substance does not play a major role in the epithelium-dependent attenuation of the contraction to acetylcholine in canine bronchi.

Acetylcholine↗

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↗

Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi.

The intrinsic isometric tone of human isolated intralobar bronchi was evaluated in vitro. Human bronchi (inner diameter, 3 to 12 mm) were obtained from patients undergoing lung resection and from organ donors. The organ donor tissue was studied approximately 24 h after resection, during which time it was shipped to the laboratory in RPMI 1640 medium at 4 degrees C. The bronchi obtained from patients with cancer was placed in the same medium and studied within 4 h of resection. All tissues were suspended in 10-ml organ baths containing oxygenated Krebs' solution at 37 degrees C, at an initial load of 2 g. Tissues were washed every 15 min until they exhibited a stable tension (usually 60 min). Under these conditions the amount of active tension in the bronchi studied on the day of resection averaged 65 +/- 9% of the maximal response to BaCl2 (30 mM), whereas after overnight incubation it averaged 31 +/- 6%. Neither indomethacin nor atropine influenced the intrinsic tone in these tissues. By contrast, the LTD4 antagonists SKF 104353 and ICI 198615 and the histamine H-1 antagonists pyrilamine and chlorpheniramine effectively relaxed the bronchi. The 5' lipoxygenase inhibitor zileuton also produced a small fall in tension. Studies in which pyrilamine was combined with the leukotriene receptor antagonists indicated an additive effect. These results indicate that human bronchial smooth muscle exhibits a high degree of intrinsic tone, averaging more than 50% of available tone in fresh tissues studied in vitro under isometric conditions. The results suggest that this tone is due to the continual production and release of histamine and cysteinyl-leukotrienes.

Bronchi↗

Release of [3H]acetylcholine in human isolated bronchi. Effect of indomethacin on muscarinic autoinhibition.

Receptor-mediated regulation of acetylcholine release in the airways, particularly in humans, remains unclear. In the present study, the tissue content of acetylcholine and release of [3H]acetylcholine were measured in freshly dissected human bronchi obtained at thoracotomy. Large (main and lobar bronchi) and small (segmental and subsegmental bronchi) airways contained considerable amounts of endogenous acetylcholine (300 +/- 50 pmol/100 mg wet weight), whereas significantly less was found in lung parenchyma (60 +/- 30 pmol/100 mg). Isolated small bronchi incubated in an organ bath with the precursor [3H]choline synthesized significant amounts of [3H]acetylcholine (26,000 +/- 4,000 dpm/100 mg). Subsequent transmural stimulation (four 20 s trains at 15 Hz) of radiolabeled bronchi caused an enhanced tritium outflow that was abolished by removal of extracellular calcium or by tetrodotoxin. HPLC analysis of the medium collected before, during, and after transmural stimulation showed that the electrically stimulated tritium outflow represented exclusively [3H]acetylcholine, whereas the outflow of [3H]choline and [3H]phosphorylcholine was not affected by electrical stimulation. Oxotremorine (0.1 and 1 mumol/L) inhibited evoked [3H]acetylcholine release in a concentration-related manner, whereas atropine (0.03 mumol/L) enhanced evoked [3H]acetylcholine release. Inactivation of cyclooxygenase activity by 3 mumol/L of indomethacin did not impair the inhibitory effect of 0.1 or 1 mumol/L of oxotremorine. In conclusion, the present experiments indicate a considerable cholinergic innervation of human large and small airways.

Acetylcholine↗

Segmental necrosis of small bronchi after prolonged intakes of Sauropus androgynus in Taiwan.

Since 1994 an endemic of chronic obstructive pulmonary disease (COPD) has developed in Taiwan after a prevalent use of a body-weight-reducing vegetable, Sauropus androgynus (SA). All conventional treatments for COPD, including steroids and bronchodilators, had been ineffective. Studies of limited lung biopsy specimens from these patients revealed bronchiolitis obliterans. A few patients died, but many developed protracted chronic respiratory failure. Because of the chronic debilitation and ineffective conventional treatments, single lung transplants were performed as the last resort in four patients. The excised lungs revealed focal fibromuscular sclerosis and obliteration of bronchial arteries in the wall of large bronchi 4 to 5 mm in diameter with segmental necrosis of bronchi 2 to 4 mm in diameter. Bronchi immediately proximal to the necrotic zone showed fibrosis and atrophy of cartilage, bronchial glands, and smooth muscle cells; bronchioles immediately distal showed obstruction or dilatation. Most bronchi larger than 5 mm, pulmonary vessels, small bronchioles, and alveoli were little altered. The pathologic changes were most consistent with segmental ischemic necrosis of bronchi at the water-shed zone of bronchial and pulmonary circulation. The specific etiologic agent and detail of pathogenesis of this SA-related COPD needs further investigation.

Adult↗

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↗

Increased responsiveness to cholinergic stimulation of small compared to large diameter cartilaginous bronchi.

Model studies incorporating known morphological properties of the airways predict different narrowing characteristics between large and small bronchi. However, the flow-response characteristics of airways from different regions in the bronchial tree are still unknown. We compared the responsiveness of large and small bore bronchi of the pig to luminal or adventitial stimulation by acetylcholine (ACh) during perfusion of the airways at optimal driving pressure. Subsequently, each segment was measured morphometrically. Resting flow through the lumen was directly related to the fourth power of the segment internal diameter (ID). The sensitivity of small bronchi (2.00 mm ID) to ACh applied adventitially was about 870 times greater than large (5.85 mm ID) with a longer latency time of contraction in large bronchi. When perfused luminally the sensitivity difference was 42 fold, and after removing the epithelium the sensitivity difference was reduced to approximately five fold. Maximum concentrations of ACh produced airway closure in small segments (100% reduction in flow) but in large segments a plateau developed at 60-90% flow reduction. Similar findings were obtained with carbachol. Morphometry of the airway wall showed increasing cartilage, mucosal and smooth muscle thickness with increasing diameter, but a decreasing relative wall area. The marked differences in sensitivity to narrowing between large and small bronchi are, in part, related to differences in morphological properties of the mucosa (the epithelium) and adventitia, and to airway location. Airway size plays an important role in the maximum response of airway narrowing, with small airways showing closure and large airways a plateau.

Acetylcholine↗

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↗

Impaired stimulus-evoked mucus secretion in cystic fibrosis bronchi.

Baseline and agonist-stimulated secretion of fucose, hexose, and protein (markers of mucus secretion) was investigated in vitro in 45 bronchial segments from 14 patients with cystic fibrosis (CF) (three after heart-lung transplant, the remainder < 4.5 h after autopsy), in 51 segments from 26 patients with carcinoma (24 resection, 2 after autopsy), and in 4 segments from 3 patients with bronchiectasis (resection). Basal rates of secretion of each mucus marker by CF bronchi were not significantly different from those by carcinoma bronchi bronchiectatic bronchi. However, rates of secretion of each marker in response to the cholinomimetic methacholine (10 microM; n = 11-18, depending on marker) and the beta 2-adrenoceptor agonist terbutaline (10 microM; n = 9-11) were significantly (p < .05) increased in carcinoma bronchi (by 50-117% above basal), but not in CF airways (n = 11-14). The secretory response to the sensory neuropeptide substance P (1 nM to 10 microM; n = 5-7) was also reduced in CF compared with carcinoma bronchi. Physiological and morphological data indicated that the reduced response by CF tissue could not be accounted for by inclusion of autopsy tissue in the study. These data suggest a defect in autonomic control of bronchial secretion in CF, not in the basal rate of secretion, but in its response to receptor stimulation.

Autopsy↗

[Optimal scanning collimation for segmental bronchi: experimental study with low-dose helical CT].

OBJECTIVE: To evaluate the effects of low-dose helical CT with different scanning collimation on the visualization of segmental bronchi and to determine the optimal scanning collimation in CT screening for early central lung cancer. METHODS: Forty healthy volunteers were randomly assigned to undergo the low-dose helical CT at 120 kVp, 50 mA, 0.75 s and pitch 1. One group (n = 20) underwent the sequential subsection scan of chest with the collimation of 10 mm for the apical and basilar zone, and of 8 mm and 5 mm for the hilar zone. The other (n = 20) went through CT scan with 10 mm collimation of the whole lung. The visualizations of lobar, segmental bronchi were compared at different collimations. ANOVA and multiple comparison were performed. RESULTS: The visualization of segmental bronchi on low-dose scan at 10 mm collimation was 60%, being lower than that at 8 mm (88%) or 5 mm (91%) collimation (P < 0.01). The segmental bronchi of right upper lobe were easily identified at collimation of 10 mm (82%), 8 mm (96%) and 5 mm (98%), as well as those of left upper lobe at 10 mm (83%), 8 mm (95%) and 5 mm (97%), whereas those of lingular lobe were difficultly identified at 10 mm (30%), 8 mm (60%) and 5 mm (70%). CONCLUSION: The lobar and segmental bronchi were visualized reliably by CT with 50 mA and 8 mm collimation, and therefore the sequential subsection scan of chest divided into three zones can be adapted to CT screening for early lung cancer.

Adult↗

[Numerical study on inspiratory flows in two and three generation bronchi of human lung airways].

The main physiological function of respiratory system is exchange of oxygen and carbon dioxide between atmosphere and blood. Its physiological process is closely related with air flow and transport in respiratory airway. This paper studies numerically the inspiratory flows in a two generation and a three generation bronchial airway. The numerical results of the two generation bronchi show that the present computations fit the available experiments very well. For three generation bronchi, no separation appears within the whole airway under normal breathing rate, which is contrary to the occurrence of separation at even low Reynolds number by the previous two dimensional models. Strong secondary flow phenomenon, skew and m-shaped main flow velocity profiles are found in the airways due to geometrical curvature and bifurcation. These increase shear stress acting on the inner wall as well as on the anterior and posterior wall in the bifurcating airways. In the end bronchi of the three generation airway, the mass flow rates in medial and lateral bronchi are unequal, and the mass flow ratio between the medial and the lateral bronchi is 1.2 at the flow conditions considered.

Bronchi↗