Further observations on luminal deformity and stenosis of nonrespiratory bronchioles in pulmonary emphysema.

In an endeavour to elucidate the anatomical basis for the increased resistance to airflow which characterises the most peripheral conducting air passages in pulmonary emphysema, lumina of nonrespiratory bronchioles of lungs with mainly centrilobular disease were assessed for two- and three-dimensional features by: (1) determination of percentage conformity of the lumina of individual bronchioles in histological sections to hypothetical planes through cylinders (ie, ellipses with the same areas and circumferences), and (2) comparison of luminal areas at regular intervals along bronchiolar longitudinal axes. The lumina of most nonrespiratory bronchioles from normal lungs conformed closely to their respective ellipses, thus corroborating previous observations that they are normally cylindroid. In contrast, there was a substantial excess of plane section deformities in the lumina of nonrespiratory bronchioles from the emphysematous specimens. The incidence of stenotic bronchioles (by both diameter and area determinations) was also greatly increased in emphysema. Since there was a strong positive association between such stenotic lesions and bronchiolar deformity, the latter was concluded to be a major factor in bronchiolar restriction. Furthermore, these characteristics seemed to have three-dimensional expression, for the lumina of stenotic bronchioles in emphysema were irregular in a longitudinal fashion.     

Relationship between bronchial and arterial diameters in normal human lungs.

In order to find an objective method for measuring narrowing of small airways, eight lungs from four people without lung disease were inflated and fixed at 25 cm of water pressure. Eight to nine blocks were taken at random from each of six parasaggital slices from each lung, sectioned, and stained. The size of the bronchioles (airways without cartilage) in relation to their accompanying arteries was determined. The internal bronchiolar diameter was compared with three different arterial diameters (the internal, external medial, and external adventitial). The ratio of the internal bronchiolar diameter to the external adventitial arterial diameter was constant between lungs (0.62 +/- 0.02) and independent of the method of inflation or the position within the lungs. This ratio may provide a useful index of bronchiolar narrowing in disease.     

Tridimensional photographic reconstruction in a study of the pathogenesis of honeycomb lung

Tridimensional photographic reconstruction of the lesions found in honeycomb lung in 10 different types of pulmonary disease was made. The pathological picture was characteristic and well defined by tridimensional microscopy and quite independent of the accompanying disease. The lesions responsible for its appearance involved the whole lobular bronchiolar system but were most marked in the terminal and respiratory bronchioli. The changes were fundamentally diffuse, saccular, and cystic bronchiolectasis. Other bronchiolar lesions were found such as changes in direction and mode of division, amputations, and anastomoses between bronchioles and cysts belonging to anatomically independent airways. There was some evidence that the bullous aspects of honeycomb lung were due to multiple valvular arrangements which let the air in but do not let it out. Honeycomb lung was, in the majority of cases, a complication of interstitial pulmonary fibrosis. Honeycombing was usually due to marked changes in the lobular bronchioles caused by the obliteration or rigidity of alveolar ducts and the corresponding alveoli and even by localization of the interstitial fibrosis in the bronchiolar wall.     

Non-small cell lung cancer coexisting with pulmonary aspergilloma

A 77-year-old male with a long-standing history of smoking and working in mines was referred to our department for the evaluation of an enlarging subpleural mass in the right upper lobe. Both transbron-chial and computed tomography-guided biopsies of the mass were non-diagnostic. A partial resection of the right S² mass under video-assisted thoracic surgery (VATS) confirmed the diagnosis of primary non-small cell lung cancer. VATS right upper lobectomy (ND2a) was then performed for complete resection. Histological examination revealed that the mass composed of adenocarcinoma and the dilated bronchioles contained Aspergillus, the fungal component. Here we report a rare case of non-small cell lung cancer coexisting with pulmonary aspergillosis. The morphologic coexistence pattern of the two pathologies was believed to be the colonization of saprophytic Aspergillus in the bullous air spaces, obstructed by or contained within the tumor, according to the progression of the lung cancer.     

Relation of smoking to immunoreactive endothelin in the bronchiolar epithelial cells.

BACKGROUND--Endothelin is a potent bronchoconstrictor which appears to be important in asthma. To ascertain whether cigarette smoking is associated with any alteration in the proportion of bronchiolar epithelial cells which express endothelin immunoreactivity, the airways in the lungs of non-smokers and smokers were analysed. Since an increase in immunoreactivity has been found in the bronchial epithelial cells of asthmatic subjects, cigarette smokers with and without evidence of airway hyperresponsiveness were also selected. METHODS--A point counting method which examined the proportion of endothelin immunoreactive epithelial cells in membranous and respiratory bronchioles was used. RESULTS--Neither smoking itself nor evidence of airway hyperresponsiveness altered the percentage of endothelin immunoreactive epithelial cells in the membraneous and respiratory bronchioles. CONCLUSIONS--Cigarette smoke does not induce endothelin production in bronchiolar epithelial cells, and the airway hyperresponsiveness seen in some patients with lung disease induced by cigarette smoking is not related to exaggerated endothelin production in epithelial cells.     

Immunohistochemical distribution of bombesin-positive pulmonary neuroendocrine cells in a congenital diaphragmatic hernia

Morphometrical analyses of the immunohistochemical expression of bombesin, which is one of the peptides produced by pulmonary neuroendocrine (PNE) cells, were carried out on the bronchioles of human congenital diaphragmatic hernia (CDH) neonates, and the findings were then compared with those in a gestational and postnatal age-matched control group. As a result, no difference was found in the number of bombesin-positive cells between the lungs of the control group and the unaffected side lungs in the CDH group except for the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P<0.05). However, compared with the lungs in the control group, the affected side of the lungs in the CDH group showed a significant increase in the expression of bombesin, namely, the ratio of the bombesin-positive cells per bronchiole (P<0.05), the ratio of the bombesin-positive cells per unit perimeter of the bronchioles (P<0.05), and the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P<0.01). These results thus suggest that hyperplasia of the PNE-cell system in the lungs of the CDH cases, especially on the affected side, exists in human fetuses. We also further speculate that PNE cells may thus play a role in the problems associated with CDH during intrauterine life in human beings.     

Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension.

We induced chronic pulmonary hypertension in one group of rats by exposing them to chronic hypobaric hypoxia (380 mm Hg for three weeks) and in another group by administering a single subcutaneous dose of monocrotaline (60 mg/kg body weight). Both groups of rats showed increase of the right ventricular mean systolic blood pressure and right ventricular hypertrophy. We measured the surface area of histological sections of the left or right lungs and counted all small blood vessels with an external diameter of less than 50 microns and with a definite elastic coat lying distal to respiratory bronchioles. In the 10 rats with chronic hypoxic pulmonary hypertension the mean total number of small pulmonary blood vessels was 428.8 +/- 96.9 (SD) compared with 337.8 +/- 91.9 in 10 untreated control rats. The number of small pulmonary blood vessels per mm2 of lung tissue was 4.0 +/- 1.3 in the chronically hypoxic rats compared with 3.8 +/- 1.2 in the controls. The mean total number of small pulmonary blood vessels in nine rats with monocrotaline-induced pulmonary hypertension was 396.8 +/- 61.7 compared with 384 +/- 55.4 in three control rats. The number of small pulmonary blood vessels per mm2 lung tissue was 3.3 +/- 0.6 in the rats treated with monocrotaline compared with 3.6 +/- 0.6 in the control group. We conclude that the number of small pulmonary blood vessels is not reduced in rats with pulmonary hypertension induced by chronic hypoxia or monocrotaline.     

An artificial lung reduces pulmonary impedance and improves right ventricular efficiency in pulmonary hypertension.

OBJECTIVE: Artificial lungs may have a role in supporting patients with end-stage lung disease as a bridge or alternative to lung transplantation. This investigation was performed to determine the effect of an artificial lung, perfused by the right ventricle in parallel with the pulmonary circulation, on indices of right ventricular load in a model of pulmonary hypertension. METHODS: Seven adult male sheep were connected to a low-resistance membrane oxygenator through conduits anastomosed end to side to the pulmonary artery and left atrium. Banding of the distal pulmonary artery generated acute pulmonary hypertension. Data were obtained with and without flow through the device conduits. Outcome measures of right ventricular load included hemodynamic parameters, as well as analysis of impedance, power consumption, wave reflections, cardiac efficiency, and the tension-time index. RESULTS: The model of pulmonary hypertension increased all indices of right ventricular load and decreased ventricular efficiency. Allowing flow through the artificial lung significantly reduced mean pulmonary artery pressure, zero harmonic impedance, right ventricular power consumption, amplitude of reflected waves, and the tension-time index. Cardiac efficiency was significantly increased. CONCLUSIONS: An artificial lung perfused by the right ventricle and applied in parallel with the pulmonary circulation reduces ventricular load and improves cardiac efficiency in the setting of pulmonary hypertension. These data suggest that an artificial lung in this configuration may benefit patients with end-stage lung disease and pulmonary hypertension with right ventricular strain.     

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia-II

Morphometric analyses of the immunohistochemical expression of surfactant apoprotein A (SP-A) were carried out on the bronchioles of human congenital diaphragmatic hernia (CDH) neonates and then compared with those in a gestational and postnatal age-matched control group. There was no difference in SP-A expression between lung specimens of the control group and unaffected lungs in the CDH group. However, compared with both these lungs, the ipsilateral lungs of the CDH group showed a significant increase in SP-A expression, namely, the number of SP-A-positive cells per bronchiole, the number of SP-A-positive cells per unit perimeter of bronchiole, and the number of SP-A-positive cells per unit bronchiolar surface area. These results suggest that in lungs of CDH cases, especially ipsilateral lungs, there is a possible delay in the functional maturation or development of SP-A synthesis by the bronchiole, and this retardation may play a role in the postnatal respiratory insufficiency observed in CDH patients.     

Expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis

Immunocytochemical techniques have been used to investigate the expression of common determinants of class I, common determinants of class II and DR, DP, and DQ antigens on frozen sections from twenty normal donor lungs, three lungs resected due to carcinoma and nine lungs removed from heart/lung recipients who were undergoing retransplant due to obliterative bronchiolitis. In all lungs, alveolar macrophages expressed common determinants of class I and class II, as well as DR, DP and DQ antigens. In normal lung, class I was expressed on all vascular endothelium, all tracheal epithelium and most, but not all, bronchiolar epithelium. Class II was always expressed on tracheal epithelium, but expression on bronchiolar epithelium and vascular endothelium was variable and sometimes absent. In lungs from transplant patients with severe obliterative bronchiolitis, vascular endothelium, in addition to expressing class I, now consistently expressed class II. Epithelium from trachea, bronchioles, and alveoli also consistently expressed class I and class II. To conclude, there is enhanced expression of class II antigens on endothelial and epithelial cells from lungs with obliterative bronchiolitis.     

Postnatal lung growth after repair of diaphragmatic hernia.

The lungs of two patients who died eight months and 64 months after repair of a left-sided diaphragmatic hernia on the first day of life were examined. Lung volumes were appropriate for the size of the children, and the ratio of right lung volume to left lung volume was also normal in both patients. The lungs, however, were grossly abnormal with evidence of enlargement and destruction of respiratory tissue. The left lung was affected more than the right in both subjects. In one patient the total number of alveoli in the lungs was similar to that of normal children of the same age, but this was because the right lung had more than twice as many alveoli as the left lung. It appears that alveolar multiplication is impaired after repair of diaphragmatic hernia. The number of bronchioles was reduced in the infant with very few alveoli, and there may have been too few bronchioles in the other patient.     

Current operative management of congenital lobar emphysema in children: A report from the Midwest Pediatric Surgery Consortium

PurposeThe purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium.MethodsAfter central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009–2015).ResultsFifty-three (10.5%) children with pathology-confirmed CLE were identified among 506 lung malformations. A lung mass was detected prenatally in 13 (24.5%) compared to 331 (73.1%) in non-CLE cases (p < 0.0001). Thirty-two (60.4%) CLE patients presented with respiratory symptoms at birth compared to 102 (22.7%) in non-CLE (p < 0.0001). The most common locations for CLE were the left upper (n = 24, 45.3%), right middle (n = 16, 30.2%), and right upper (n = 10, 18.9%) lobes. Eighteen (34.0%) had resection as neonates, 30 (56.6%) had surgery at 1–12 months of age, and five (9.4%) had resections after 12 months. Six (11.3%) underwent thoracoscopic excision. Median hospital length of stay was 5.0 days (interquartile range, 4.0–13.0).ConclusionsAmong lung malformations, CLE is associated with several unique features, including a low prenatal detection rate, a predilection for the upper/middle lobes, and infrequent utilization of thoracoscopy. Although respiratory distress at birth is common, CLE often presents clinically in a delayed and more insidious fashion.Level of EvidenceLevel III.     

Regional proliferation of HMB-45-positive clear cells of the lung with lymphangioleiomyomatosislike distribution, replacing the lobes with multiple cysts and a nodule.

The authors report a case of a localized lesion of the lung presenting as multiple cysts and as a tumor in the right upper and middle lobes, consisting of a diffuse proliferation of clear cells with intralysosomal glycogen granules and human melanin black (HMB)-45 immunoreactivity. A 33-year-old woman complained of dyspnea because of the enlargement of bullae in the right upper and middle lung fields without stigmata of tuberous sclerosis. Resection showed multiple, various-size air-filled cysts and a tumor. The cysts in the resected lungs were reminiscent of lymphangioleiomyomatosis (LAM), accompanied by the diffuse proliferation of clear cells in the interstitium. The tumor, 1.8 cm in diameter, resembled a clear cell tumor of the lung (CCTL) and showed proliferation of clear cells with sinusoidlike vascular spaces. Both forms of proliferation were continuous spatially, and both constituent cells showed diffuse HMB-45 immunoreactivity. The cells that comprised a nodule revealed ultrastructurally abundant cytoplasmic glycogen, which was in the form of free and membrane-bound glycogen granules. This case may represent a particular pulmonary lesion consisting of CCTL-LAM hybrid cells, which share the cytologic features with CCTL cells on one hand, and the proliferative pattern and potential with LAM cells on the other.     

Structure of a human pulmonary acinus.

The structure of the human pulmonary acinus has been described infrequently. The aim of the study was to determine the branching pattern of respiratory bronchioles and alveolar ducts in a human acinus from the peripheral part of the lung, where space constraints may have affected airway branching patterns. The lungs were obtained from an 18 year old victim of a motor vehicle accident and fixed in inflation under a pressure of 25 cm H2O. A block was cut from the lower edge of the right lower lobe and embedded in plastic. Serial sections were cut and the branching pattern of airways subtended by a terminal bronchiole were followed. The acinus was bounded on two sides by pleura and on the remaining sides by connective tissue septa. The terminal bronchiole divided into two respiratory bronchioles, each of which gave rise to four systems of alveolar ducts. Between successive systems of alveolar ducts the respiratory bronchioles continued as single airways, becoming progressively more alveolated towards the periphery but not subtending further branches of respiratory bronchioles. The duct systems became less complex towards the periphery, near to the edge of the lung. The total volume of the acinus was similar to that found in previous studies. This branching pattern has not been described previously in a human acinus.     

Role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of adult pulmonary histiocytosis X.

BACKGROUND: Pulmonary histiocytosis X is a disorder characterised by the presence of destructive granulomas preferentially involving distal bronchioles, that contain numerous activated Langerhans' cells. Recent studies have shown that granulocyte-macrophage colony stimulating factor (GM-CSF), which is produced by normal bronchiolar epithelium, may play an important part in the distribution and differentiation of Langerhans' cells. The aim of this study was to evaluate the role of this factor in the pathogenesis of pulmonary histiocytosis X. METHODS: Four patients with pulmonary histiocytosis X were examined by immunohistochemical techniques for GM-CSF and CD1a surface molecules. RESULTS: In early lesions the epithelium of bronchioles affected by the disease was strongly positive for GM-CSF and infiltrated by numerous CD1a+ Langerhans' cells organised into granulomas. In contrast, the expression of GM-CSF was substantially lower in bronchioles not affected by the disease, and these bronchioles contained few Langerhans' cells. When destruction by histiocytosis X lesions was more advanced, only remnants of bronchiolar epithelium could occasionally be identified; these remained strongly reactive for GM-CSF. Langerhans' cells within granulomas also moderately expressed this cytokine. CONCLUSIONS: These results support the hypothesis that GM-CSF could be one of the factors responsible for the local accumulation of lymphostimulatory Langerhans' cells in early lesions of pulmonary histiocytosis X.     

经食管超声心动图在肺移植术中的作用

目的 探讨术中经食管超声心动图(TEE)在肺移植术中的应用价值.方法 2005年8月至2009年8月,19例平均年龄(48.35±13.04)岁的肺疾病晚期病人行肺移植手术.于肺移植术前麻醉后送入TEE探头,检测左、右肺静脉开口和肺动脉血流速度,右室壁运动,左、右心室容积,右室射血分数.观察房间隔有无交通.肺移植术中分别于断肺后和供肺支气管、肺静脉、肺动脉全部吻合开放后连续观察上述指标.结果 19例中6例为序贯式双肺移植,13例单肺移植,其中左叶肺移植2例、右叶肺移植11例.术中阻断一侧被移植肺的动、静脉后,该侧肺动、静脉血流消失,右室容积轻度增大.供体肺与受体肺全部气管、肺静脉、肺动脉吻合完毕开放后,右室容积恢复.TEE依次检测肺静脉、肺动脉吻合口,吻合口流速均轻度增快.开放后发现1例右肺动脉血流速度显著增快,经重新吻合后血流速度降低,血氧分压恢复.术中发现3例卵圆孔未闭.结论 TEE在肺移植术中监测肺动脉和肺静脉血管吻合口直径和血流速度,检测右心功能,对并发症的预测等起重要作用.

Abstract：

Objective To investigate the clinical value of transesophageal echocardiography during the lung transplanta tion. Methods From August 2005 to August 2009, 19 patients with advanced lung diseases received lung transplantation.The average age was(48.35±13.04) years. The echocardiographic probe was placed in patient's esophagus before surgery.The left and right pulmonary venous openings, artery blood flow velocity, right ventricular wall motion, left and right ventricular volume, right ventricular ejection fraction were recorded at different time intervals during lung transplantation, especially at the break and after completion of bronchus, pulmonary veins, and pulmonary artery anastomosis. Results The procedure included sequential-type lung transplantation in 6 cases and single lung transplantation in 13. The blood flow disappeared when blocking pulmonary artery and vein and right ventricular volume increased slightly. The right ventricular volume restored after completion of trachea, pulmonary veins, pulmonary artery anastomosis. TEE detected that the blood flow velocity of pulmonary veins, pulmonay artery anastomosis increased slightly. In 1 case the opening of the right pulmonsry artery blood flow velocity increased significantly and blood flow velocity decresed and blood oxygen partial pressure resumed after re-anastomosis of pulmonary artery. Conclusion TEE play an important role in monitoring pulmonary artery and vein anastomosis diameter and blood flow velocity and right ventricular function and predicting complications during lung transplantation.     

Hemodynamic unloading leads to regression of pulmonary vascular disease in rats

OBJECTIVE: Treatment options for patients with advanced pulmonary vascular disease caused by a congenital heart defect are still mainly limited to heart-lung transplantation or lung transplantation with repair of the cardiac lesion. Because we have previously shown that the structural changes associated with pulmonary hypertension can be reversed by stress unloading in an organ culture model, we now investigate whether hemodynamic unloading will lead to regression of pulmonary vascular disease in the intact animal. METHODS: Right middle and lower lobectomy and monocrotaline injection were performed in Lewis rats (n = 22) to cause pulmonary vascular disease from a combined hemodynamic and toxic injury. Twenty-eight days later the left lungs were examined (n = 10) or exposed to normal pulmonary artery pressure for an additional 14 (n = 5) or 28 (n = 7) days by transplantation into healthy recipients. Pulmonary artery pressure, ventricular weight, and pulmonary artery morphology were evaluated in each group. RESULTS: Pulmonary hypertension (50 vs 16 mm Hg; P <.001) and right ventricular hypertrophy (right ventricular/left ventricular weight 0.69 vs 0.32; P <.001) associated with pulmonary artery medial hypertrophy (28.2% vs 7.2% wall thickness; P <.001) and muscularization of small pulmonary arteries (92.3% vs 19.4%; P <.001) developed by day 28 (compared with untreated controls). However, transplantation into healthy recipients effectively unloaded the lungs (mean pulmonary artery pressure 17 and 24 mm Hg at 14 and 28 days after transplantation) and resulted in progressive normalization of medial hypertrophy (15.6% and 12.1% at 14 and 28 days) and muscularization (65.1% and 42.2% at 14 and 28 days) relative to nontransplanted controls (P <.005 in each case). CONCLUSIONS: Hemodynamic unloading of lungs with pulmonary vascular disease results in progressive normalization of pulmonary artery structure. These results are the first to provide a rationale for attempting to induce regression of pulmonary vascular disease by pressure unloading of the pulmonary circulation. Methods to mechanically unload the pulmonary circulation should be critically evaluated as a strategy for staged surgical repair of congenital heart defects despite presumed irreversible pulmonary hypertension.     

Cardiopulmonary effects of oleic acid-induced pulmonary edema and mechanical ventilation

In order to define the mechanisms whereby cardiac output and arterial oxygen transport are reduced by acute permeability pulmonary edema and by positive end-expiratory pressure (PEEP), hemodynamic, respiratory, and lung water changes were measured in 12 mechanically ventilated dogs prior to the injection of oleic acid and at 1, 2.5, and 4 hr after the injection. Measurements were performed at each interval before and after the addition of 20 cm H2O PEEP. Positive end-expiratory pressure was not continued between measurements. One hour after the oleic acid injection, the lung water content and the pulmonary vascular resistance had increased more than 100% while the right ventricular (RV) volume, RV stroke volume, and PaO2 had decreased more than 35%. Each application of PEEP increased the PaO2 to control levels. However, PEEP also significantly increased the lung water content and pulmonary vascular resistance, and decreased the RV volume and stroke volume by 33%. The extravasation of fluid from the intravascular to the interstitial and alveolar spaces of the lung with oleic acid pulmonary edema is associated with substantial decreases in right ventricular volume and stroke volume and significant increases in the pulmonary vascular resistance. Treatment with 20 cm H2O PEEP further increases the lung water content and pulmonary vascular resistance and substantially reduces the right ventricular volume and stroke volume.     

Radioautographic study of human pulmonary tissues

The radioautograms of human lungs were studied after in vitro incubation with tritiated thymidine. Our materials consisted of the lungs of 12 normal foetuses (crown-rump length varied from 7·5 to 16·5 cm.) and of 11 adults (32 to 68 years of age). In the foetal lungs the uptake of tritiated thymidine was highest in the epithelium surrounding small tubular spaces, forerunners of future bronchial epithelium, and in the undifferentiated mesenchyme. The percentage of labelled cells was scarce in the alveolar wall cells of adults (0·05% to 0·65%), was unrelated to age, and appeared to be most frequent in phagocytic elements (so-called alveolar cells). There was an uptake of tritiated thymidine in scattered free alveolar macrophages and in a few interstitial cells. The media and adventitia of blood vessels did not show labelling in most cases. The labelling of epithelium of bronchioles and respiratory bronchioles varied from 0·20% to 0·70%. The findings of other investigators in the study of cell turnover in the lungs of laboratory animals are discussed and compared with the data obtained in the present study.     

Pulmonary capillary permeability to sodium in unilateral transplanted canine lungs.

Five dogs with autotransplanted left lungs, four with allotransplants and immunosuppression, and five with allotransplants but without immunosuppression were studied 4 to 5 days after surgery. The indicator dilution technique was used to measure the pulmonary capillary permeability to sodium from the left and right lungs separately. The permeability in each lung was evaluated with the blood flow (using carbonized microspheres), the steady-state albumin and sodium spaces and the lung morphology. In the allotransplanted lung there was an increase in capillary permeability to sodium, an increase in both water and solid content and a reduction in blood flow. These alterations were most marked in the allotransplants with immunosuppression, but were also present in the contralateral right nontransplanted lung in which pneumonia was frequently present.