Large Bronchi Research Articles

CARBOHYDRATE ANTIGENS OF PIG TISSUES REACTING WITH HUMAN NATURAL ANTIBODIES AS POTENTIAL TARGETS FOR HYPERACUTE VASCULAR REJECTION IN PIG-TO-MAN ORGAN XENOTRANSPLANTATION1

Pig tissues were screened by immunofluorescence with lectins, mAb, and human natural antibodies for the presence of carbohydrate antigens, which may be potential targets for hyperacute vascular rejection in pig to man xenotransplantation. The unfucosylated monomorph linear B-antigen was found at the surface of all porcine vascular endothelial cells. This pig linear-B antigen reacts strongly with the anti-alpha Gal isolectin B4 from Griffonia simplicifolia 1 and with human natural anti-alpha Gal antibodies specifically purified by affinity chromatography on synthetic oligosaccharides containing the terminal nonreducing alpha Gal1-->3 beta Gal-R disaccharide. This antigenic activity is destroyed by treatment of pig tissues with alpha-galactosidase. The localization of this linear-B epitope on vascular endothelium and its reactivity with natural human anti-alpha Gal antibodies suggest that it may play a major role in the hyperacute vascular rejection of pig to man organ xenografts. The lectin from Maackia amurensis reacting with alpha NeuAc2-->3 beta Gal1-->4GlcNAc/Glc was also positive on pig vascular endothelium, but we do not know yet whether there are human natural antibodies reacting with the carbohydrate recognized by this lectin. Epithelial cells of pig renal proximal convoluted tubules, respiratory epithelium, pancreatic ducts, and epidermis express the linear-B antigen, but they are less likely to trigger a hyperacute vascular rejection because they are not directly exposed to the blood. The genetically defined pig A+/A- system controls the expression of A and H antigens in pig epithelial cells from renal distal and collecting tubules, biliary ducts, pancreatic ducts, large bronchi, and digestive mucosa. The pig A antigen may trigger an immune response in human O or B recipients if they are transplanted with organs from A+ pigs, but the pig A antigen is probably not involved in the hyperacute vascular rejection of a xenograft because it is not expressed on vascular endothelium.

Left Lung Asthma

The chest radiograph of a woman with acute asthma showed signs of obstructive emphysema of the left lung. Fiberoptic bronchoscopy excluded obstruction of a large bronchus. The signs disappeared after antiasthmatic treatment, suggesting that they were caused by airway closure. In usual asthma, airway closure affects both lungs; the reason for the unilateral predominance we observed is unknown.

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

We demonstrated immunoreactivity for endothelins (ET)-1, -2, and -3 and for the precursor, big-ET-1, in the pulmonary diffuse neuroendocrine system (PDNES) of newborn cat, rat, hamster, and mouse. ET-like positive neuroepithelial bodies (NEB) were numerous in the intrapulmonary airways and the alveolar parenchyma. Single neuroendocrine cells (NEC) were less often labeled and mainly localized in the larger bronchi. ET-3-reactive neuronal elements were rarely observed. The intensity and number of immunostained NEB were highest for ET-3, followed in declining order by big-ET-1, ET-1, and ET-2. ET-like possessing NEB displayed interspecies differences. We conclude that ET-3 represents a neuroendocrine form of the ET peptide family. NEB expressing several ET isoforms can be grouped into NEB containing either big-ET-1 and ET-1 or ET-3 only. ET-like immunoreactivity was present in a subpopulation of serotonin (5HT)- and/or calcitonin gene-related peptide (CGRP)-positive NEB. As ET, 5HT, and CGRP have potent pulmonary vaso- and/or bronchomotor effects, our observations suggest that they play a separate or synergistic role in regulatory function of the mammalian PDNES, exerting their influence by paracrine, endocrine, and neurocrine pathways or a combination of these.

中心型早期肺癌へのPDTの効用

A phase II was conducted between June 1989 and Feburary 1992 to evaluate the activity and toxicity of photodynamic therapy (PDT) with photofrin II in centrally located early-stage lung cancer and to determine the complete response (CR) rate as the primary end point.Patients and Methods: Patients had histologically proven lung cancer and endoscopically superficial thicking or small protrusions. All lesions were located in subsegmental or larger bronchi. All patients had a performance status (PS) of 0 to 2 and artial oxygen pressure tension (PaO2) ?60 torr. No lymph node or distant metastases were present. All patients received photofrin II (2 mg/kg) intravenously 48 hours before PDT. Tumor lesions were superficially photoradiated by argon dye laser or excimer dye laser. Results: Of 54 patients with 64 carcinomas, 51 with 61 carcinomas were eligible for toxicity evaluation and 49 with 59 carcinomas were assessable for response. Of the 59 assessable carcinomas, 50 (84.8%; 95% confidence interval, 73.0% to 92.8%) showed a CR after initial PDT. The median duration of CR was 14.0+ months (range, 2.0+ to 32.4+) The multiple regression model indicates that estimated length of longitudinal tumor extent was the only independent prognostic factor for CR (p=0.002). Ten carcinomas that had a CR had a local recurrece between 2 months to 19 months after initial PDT (median recurence time, 6 months). The 16 carcinomas that had a CR duration of 24 months, had no local recumence after initial PDT. Regression model shows that a longitudinal extent of tumor was important factor for local recurrence. Conclusion: PDT with photofrin II has an excellent effect on patients with centrally located early-stage lung cancer who have a longitudinal extent of 1 cm or less.

Pulmonary Blastoma

Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung type adenocarcinoma, were examined by immunohisto‐chemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present: they were argyrophilic and expressed pan NE markers, neurose‐cretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated LewisX was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de‐differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium. Acta Pathol Jpn 42: 884–892, 1992.

Regional bioelectric properties of porcine airway epithelium

Ion transport properties of pulmonary small airway epithelia are poorly understood. To characterize these properties, airways were excised from anesthetized pigs. Transepithelial potential difference (PD) and conductance were measured in five airway regions: trachea (T, 7.9 +/- 0.2 mm diam), mainstem bronchi (MB, 5.5 +/- 0.2 mm diam), large bronchi (LB, 1.69 +/- 0.12 mm diam), small bronchi (SB, 0.70 +/- 0.06 mm diam), and bronchioles (BR, 0.25 +/- 0.05 mm diam). T and MB were mounted in Ussing-type chambers, and LB, SB, and BR were cannulated with pipettes and perfused. PDs of control tissues were -9.7 +/- 0.8 mV (T), -4.0 +/- 0.5 mV (MB), -4.3 +/- 1.0 mV (LB), -4.5 +/- 0.4 mV (SB), and -1.5 +/- 0.4 mV (BR), lumen negative. Amiloride significantly (P < 0.05) inhibited PDs by 25-70% in all airway regions and decreased conductance 17-33% in all regions except LB where a 10% increase was observed. Bumetanide significantly reduced the amiloride-insensitive PD 54-62% in all regions except BR. Bumetanide had little effect on conductance in T, SB, and BR, but conductance was increased in MB and LB. All airways except the smallest BR significantly hyperpolarized when the solution that bathed the lumen was replaced with Cl(-)-free solution. In bronchioles, hyperpolarization by luminal Cl(-)-free solution was inversely related to fractional inhibition of PD with amiloride but directly related to lumen diameter. These results suggest that 1) porcine tracheas, bronchi, and bronchioles actively absorb Na+, and 2) secretion of Cl- may occur in all airway regions except small bronchioles.

The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry

The sympathetic and sensory innervation of guinea-pig trachea and lung were studied by means of retrograde neuronal tracing using fluorescent dyes, and double-labelling immunofluorescence. Sympathetic neurons supplying the lung were located in stellate ganglia and in thoracic sympathetic chain ganglia T2–T4; those supplying the trachea resided in the superior cervical and stellate ganglia. Retrogradely labelled sympathetic neurons were usually immunoreactive to tyrosine hydroxylase; the majority also contained neuropeptide Y immunoreactivity. However, a small number were non-catecholaminergic (i.e. tyrosine hydroxylase negative), but neuropeptide Y immunoreactive. Within the airways, tyrosine hydroxylase/neuropeptide Y-immunoreactive axons were found in the smooth muscle layer, around blood vessels including the pulmonary artery and vein, and to a lesser extent in the lamina propria. Periarterial axons contained in addition dynorphin immunoreactivity. Sensory neurons supplying the lung were located in jugular and nodose vagal ganglia as well as in upper thoracic dorsal root ganglia; those supplying the trachea were most frequently found bilaterally in the nodose ganglia and less frequently in the jugular ganglia. A spinal origin of tracheal sensory fibres could not be consistently demonstrated. With regard to their immunoreactivity to peptides, three types of sensory neurons projecting to the airways could be distinguished: (i) substance P/dynorphin immunoreactive; (ii) substance P immunoreactive but dynorphin negative; and (iii) negative to all peptides tested. Substance P-immunoreactive neurons innervating the airways invariably contained immunoreactivity to neurokinin A and calcitonin gene-related peptide. Retrogradely labelled neurons located in the nodose ganglia belonged almost exclusively (⩾99%) to the peptide-negative group, whereas the three neuron types each represented about one-third of retrogradely labelled neurons in jugular and dorsal root ganglia. Within the airways, axons immunoreactive to substance P/neurokinin A and substance P/calcitonin gene-related peptide were distributed within the respiratory epithelium of trachea and large bronchi, in the lamina propria and smooth muscle from the trachea down to the smallest bronchioli (highest density at the bronchial level), in the alveolar walls, around systemic and pulmonary blood vessels, and within airway ganglia. Those axons also containing dynorphin immunoreactivity were restricted to the lamina propria and smooth muscle. The origin of nerve fibres immunoreactive for vasoactive intestinal polypeptide, of which a part were also neuropeptide Y immunoreactive, could not be determined by retrograde tracing experiments. Vasoactive intestinal polypeptide-immunoreactive fibres terminating within airway ganglia may be of preganglionic parasympathetic origin, whereas others (e.g. those found in smooth muscle) may arise from intrinsic ganglia. The results provide a detailed topographical and neurochemical map of the extrinsic innervation of lower airways in the guinea-pig, and reveal an extraordinary degree of complexity: (i) each functional system (sympathetic, sensory, intrinsic) is represented by at least two neurochemically distinct types of neurons; (ii) each peptide occurs in at least two distinct combinations with others; and (iii) some peptides occur in two functionally distinct systems.

Vascular permeability and airway narrowing during late asthmatic response in dogs treated with metopirone

Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR ( p > 0.10), but in LAR, it increased significantly from that of control ( p < 0.01) and JAR ( p < 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 μm) in the trachea, large (diameter, >5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi ( p < 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge ( p < 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase: in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.

Calcium-containing particles as a marker of cigarette smoke exposure in autopsy lungs.

It has been recently reported that the major inorganic particle components of cigarette smoke are calcium and potassium carbonates, potassium sulfate and chloride, and quartz. To determine whether any of these particles might serve as a marker of cigarette smoke exposure in human lungs, we used analytical electron microscopy to compare the mineral particle content in two parenchymal sites and two large bronchi from five nonsmoker autopsy lungs and five age- and sex-matched smoker autopsy lungs. Potassium carbonate, sulfate, and chloride were not identified in any lung. The percentage of quartz was the same in both smoker and nonsmoker lungs. However, lungs from smokers contained a large percentage (average 23% of all particles) of particles composed of calcium, carbon, and oxygen (probably calcium carbonate) in all sample sites, whereas lungs from nonsmokers usually contained no such particles or only minute numbers (average 0.1%). We conclude that calcium-containing particles of this type may serve as a marker of cigarette smoke exposure in humans and may prove useful for examining the distribution of smoke particles in the normal and diseased lung.

Airway Generation-dependent Induction of Muscarinic Hyperresponsiveness by Thromboxane MimeticIn Vitro

We compared the potentiating effect of U46619, a stable thromboxane analogue, on muscarinic contractile responses of rat trachealis and large and small intrapulmonary bronchi. Cylindrical proximal and distal bronchi and midtracheal strips were excised and mounted on an isometric force transducer in a physiologic tissue bath. Dose-response curves to the muscarinic agonist bethanechol (BCh) alone were compared with responses to BCh plus U46619. Airways were incubated for 2 h prior to and during second BCh curves with a noncontractile dose of U46619. U46619 induced a left shift of the dose-response curve in all airways. This was significant only at the ED10 level in trachealis, and at the ED10, ED20, and ED50 levels in large and small bronchi. Muscarinic hyperresponsiveness induced by U46619 was significantly greater in small airways than in large bronchi or trachealis. Stabilization of endogenously released acetylcholine (ACh) with physostigmine did not alter the responses to BCh plus U46619; therefore, this mechanism does not fully explain the induction of hyperresponsiveness by U46619. Our findings demonstrate the induction of a graded increase in muscarinic responsiveness in isolated airways, and they suggest that results of studies of trachealis or proximal bronchi may not necessarily be generalized to the distal resistance airways.

Effect of tachykinins in small human airways

We have compared the contractile responses of substance P (SP) and neurokinin A (NKA) to that of the non degradable muscarinic agonist, carbachol, in small and large human airways in vitro. We have also investigated the effects of the neutral endopeptidase (NEP) inhibitor, thiorphan (100 μM) on these responses. NKA contracted large and small airways to a different extent (56% vs 92% of carbachol maximal contraction, respectively). NKA was significantly less potent in large vs small bronchi (EC 50 = 150 ± 15 vs 12 ± 5 nM respectively, p < 0.05). SP had a lower contractile effect in large (26% carbachol maximum) and small airways (59%) with EC 50 values higher than 0.5 μM. The enkephalinase inhibitor thiorphan shifted the concentration-response curve to NKA to the left in large (EC 50 = 35.2 ± 8.2 nM) and small bronchi (EC 50 = 2.8 ± 1.3 nM, p < 0.02). This shift was associated with an increase in the maximal contraction to NKA (75% in large vs 123% in small bronchi). The amplitude of contraction to SP was also potentiated in large (45%) and in smaller bronchi (101%). In conclusion, we have demonstrated that NKA has a significantly greater constrictor effect than a cholinergic agent in more peripheral human airways in vitro. This suggests that non cholinergic constrictor pathways are more likely to be important in more peripheral airways.

Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.

Longitudinal dispersion in model of central airways during high-frequency ventilation

We have measured the longitudinal dispersion of boluses of helium, acetylene and sulphur hexafluoride in a plastic model of the human airways - generations zero through six - during high frequency ventilation (HFV). HFV was maintained by a piston pump. Frequency f and tidal volume Vt ranged from 2.5 to 25 Hz and from 5 to 20 ml, respectively. Boluses were injected near the entrance of the zeroth generation (trachea), and the dispersion curves were measured by mass spectrometry at the end of the sixth airway generation. The shapes of the bolus dispersion curves could be well described with Gaussian distribution functions. With the exception of the HFV-conditions with Vt = 5 ml , the effective dispersion coefficient D DISP appeared to be independent of the molecular diffusion coefficient. This independency was also found by other investigators in studies with dogs and human subjects. The measured results for D DISP for different f and Vt could be satisfactorily described with the empirical equation D DISP = 0.0617 f 0.8 V T 1.38 [ cm 2 s −1] . Application of this equation to f and Vt values normally applied in man resulted in D DISP values which should be considered to be too small for maintaining eucapnic ventilation in vivo. On the basis of this result we believe that during HFV in intubated subjects gas transport by longitudinal dispersion will be limited to the instrumental dead space - the endotracheal tube inclusive - and a few generations of large bronchi.

Role of Pulmonary Inflammation in Altered Airway Responsiveness in Three Sheep Models of Acute Lung Injury

Pulmonary inflammation may contribute to increased airway responsiveness in experimental models of acute lung injury. Infusions of endotoxin, phorbol myristate acetate (PMA), or zymosan-activated plasma (ZAP) all result in the accumulation of polymorphonuclear leukocytes (PMNs) in the lung and alterations in lung mechanics. These three interventions have strikingly different effects on airway responses to aerosol histamine: ZAP does not increase airway responsiveness, whereas endotoxin causes a greater increase in airway responsiveness than does PMA. The present histologic study examines the question of whether the pattern and severity of PMN and mast cell accumulation in large- and medium-sized airways and lung periphery could contribute to the differences in airway responsiveness to histamine. Minimally instrumented sheep were given either an infusion of endotoxin (0.5 microgram/kg over 20 min), a bolus injection of PMA (5 micrograms/kg), or repetitive boluses of autologous ZAP (5 ml). Four and a half hours later, the animals were killed, and the left lung was removed and fixed in the distended state. Three levels of the left lung were examined by light microscopy: the large hilar bronchus, a medium-sized bronchus, and peripheral lung. The number of PMNs and mast cells in the airway wall were expressed as cells/mm length of airway circumference and in the lung periphery as cells/100 alveolar profiles. Both endotoxin and PMA caused a significant 2- to 3-fold increase in number of PMNs/mm of large airway circumference, the majority of PMNs being in the blood vessels of the lamina propria and submucosa; ZAP caused only minimal PMN accumulation in the blood vessels of the submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Damage and Repair of Mouse Bronchial Epithelium following Acute Inhalation of Trichloroethylene

The time-course of damage and repair in the bronchial epithelium of the mouse was studied morphometrically after a single inhalation of trichloroethylene (TCE). Mice were exposed for 30 min to 500, 1000, 2000, 3500, or 7000 ppm of TCE under controlled conditions and sacrificed after 2 and 24 h, and 2, 5, and 7 days. At all TCE concentrations, the damage consisted of dilation of endoplasmic reticulum and was selective for nonciliated cells throughout the bronchial tree. Damage was quantitatively evaluated by counting the percentage of vacuolated cells. Injury was maximal 24 h after exposure and was significantly (p less than 0.05) higher in bronchi with a diameter smaller than 0.4 mm (67.0% +/- 8.5%) in comparison with larger bronchi (34.0% +/- 13.2%). Cell turnover was studied by autoradiography after [3H]thymidine injection. Following TCE inhalation, the percentage of [3H]thymidine labeled cells, which in the controls was virtually zero, increased to a maximum of 13.5% +/- 6.8% (average at all doses) 48 h after treatment and then rapidly decreased to baseline values at 7 days (0.2% +/- 0.1%). Repair of some cells occurred after 24 h, and at 48 h the percentage of vacuolated cells decreased and became significantly related (p less than 0.01) to the administered TCE dose (2.4% +/- 1.4% and 21.2% +/- 6.0% average in the 500 and 7000 ppm groups, respectively). Repair of bronchial epithelium took place by both recovery of less damaged cells and proliferation of residual nonciliated cells, leading to restoration of the normal ratio between ciliated and nonciliated cells.

Simulation of airway resistance in forced expiration

On the basis of an analysis of the experimental data and general physical considerations it is shown that under conditions of forced expiration during the development of stenosis the lumen of the large bronchi may deviate from the equilibrium value. A dynamical equation describing the relation between the cross-sectional area of the bronchi at the site of stenosis, the transmural pressure and the physical parameters of the bronchial walls is formulated on the basis of the solution of model problems. The question of calculating the airway resistance in a very simple model of the lungs is also examined.

Lymphocytic infiltrations in the lung of two autopsy cases with HTLV-I-associated myelopathy.

Pulmonary involvement in two autopsy cases with HTLV-I-associated myelopathy (HAM) was observed histopathologically and immunohistochemically. Case 1 was a 59-year-old woman who fell ill after having a blood transfusion, and died immediately of acute heart failure. Case 2, a 55-year-old man, died of pelvic tumor after a long period of steroid medication for the myelopathy. Histologically, in case 1, the submucosal stroma of bronchioles was thickened with T-lymphocyte infiltration. In addition, clusters of B-lymphocytes were aggregated beneath the epithelial layer of respiratory bronchiole; the alveolar septum was infiltrated with a few T-lymphocytes. Furthermore, many B-lymphocytes were aggregated in the submucosal stroma of large bronchi. On the other hand, obvious pathological changes were not seen in the lung tissues of case 2. The long period of steroid medication may account for the fewer findings in case 2. These results present the possibility that latent inflammatory changes develop in the lung of HAM patients, although clinical manifestations are not obvious, and that steroid therapy can modify those inflammatory changes.

Hyperreactive Site in the Airway Tree of Asthmatic Patients Revealed by Thickening of Bronchial Muscles: A Morphometric Study

Under the assumption that the more hyperreactive the bronchial muscles are, the greater their work hypertrophy, we analyzed the distribution of hypertrophic smooth muscles along airways to see where in the bronchial tree asthmatic constrictions mainly occur. Autopsy lungs from 16 patients with bronchial asthma, 13 with other COPDs, and 20 controls were submitted to morphometry of the bronchial muscles. In microscopic slides, cross sections of airways were taken from the segmental bronchi to the terminal bronchioles. The perimeter length L of the basement membrane and the area S of muscles were measured, and the anatomic radius R and the muscular thickness D were calculated in a standardized circular state, in which the basement membrane was stretched into a circle without changing L or S. On bilogarithmic coordinates of D and R on which data from the asthmatics were pooled, it was shown that hypertrophy of muscles was the most pronounced in larger bronchi where constriction was most likely to occur. Closer analysis of patients, however, revealed that besides this typical pattern, which we designated Type I asthma, there was a group of patients (Type II) in whom hypertrophy involved the entire range of airways, including the bronchioles, suggesting that the site of asthmatic response varies among patients. In nonasthmatic patients with COPD, only mild hypertrophy of muscles was found in the large airways, despite the presence of obstructive lesions mainly in the small airways.

Clinicopathologic and Immunohistochemical Characteristics of Bronchial Gland Cell Type Adenocarcinoma of the Lung

Twenty-three cases of bronchial gland cell (BGC) type lung adenocarcinoma were examined clinicopathologically and immunohistochemically. BGC type adenocarcinoma was defined as adenocarcinoma showing histologic and cytologic differentiation toward the bronchial gland. This type of adenocarcinoma occurred more frequently in younger patients (mean age, 50.5 years) than in patients with other types of adenocarcinoma (mean age, 60.1 years). It had a tendency to arise from relatively large bronchi and show endobronchial growth. However, there was no difference in disease stage based on tumor, nodal involvement, metastases (TNM) factors and outcome between BGC type adenocarcinoma and peripheral type adenocarcinoma. Immunohistochemically, 50%, 68%, and 64% of BGC type adenocarcinomas were positive for carcinoembryonic antigen, surfactant apoprotein, and secretory component, respectively. Peripheral type adenocarcinomas showed similar rates of immunohistochemical stainability of these antigens. The positive reaction of BGC type adenocarcinomas with anti-surfactant apoprotein antibody may indicate maintenance of traces of differentiation toward peripheral airway epithelium. Lactoferrin is characteristically detected in BGC type adenocarcinomas, although the positive rate was not very high.

Laryngotracheobronchial Foreign Bodies

A retrospective review was conducted on 46 cases of foreign body aspiration seen during 1 Muharram 1401H (8 November 1980) to 30 Dhu Al-Hijjah 1408H (12 August 1988) at the King Fahad Hofuf Hospita...