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PubMed1990

MHC class II antigens on lung epithelial of human fetuses and neonates. Ontogeny and expression in lungs with histologic evidence of infection.

An immunohistochemical study with anti-HLA-DP, anti-HLA-DQ and anti-HLA-DR monoclonal antibodies was carried out on lung tissue from 29 fetuses and 19 infants that died within the 1st year of life. The aim of the study was to verify the influence of lung maturation and lung inflammation, caused by intrauterine infection, on the expression of MHC class II antigens on lung epithelia. No positive reaction of lung epithelia was noticed in 6 fetuses of less than 21 weeks' gestation. In fetuses of more than 21 weeks' gestation, lung inflammation strongly correlated with the expression of MHC class II subregion products on lung epithelia. All 4 fetuses with histopathologic evidence of lung infection but only 4 out of 23 fetuses without lung inflammation bore HLA-DR antigens on their immature cuboidal alveolar epithelium. Within the bronchial epithelial layers only scattered MHC class II positive epithelia were found. After birth, MHC class II antigens were almost constantly detected on cuboidal type II pneumocytes of inflamed and noninflamed lung tissue as well. Only 3 infants that died within the 1st week of life did not show any MHC class II antigen expression on their lung epithelia.

Aging↗
PubMed1980

[Lung denervation. A study of therapy of shock lung].

It is the objective of this experiment to study the protective effect of pulmonary denervation in acute respiratory distress syndrome (shock lung). The experiments were performed by means of a model of pulmonary embolization with oleic acid in dogs. In the first series sequential tissue changes in the lung following oleic acid embolism are shown and the clinical changes are demonstrated. By a meticulous description of the anatomy of pulmonary innervation it is demonstrated that surgical denervation of the lung is only possible in the hilar area. A second series of experiments shows the effect of oleic acid embolism in animals after reimplantation of one lung. This means that the reimplanted lung is completely denervated. A description of the technique of pulmonary reimplantation is also given. It is stated that following oleic acid embolism, the reimplanted lung is less damaged than the contralateral innervated lung. In addition, animals with unilateral lung reimplantation have significantly better pulmonary function after oleic acid embolism than healthy animals with bilaterally innervated lungs. Finally, a technique of reversible bilateral denervation of the lung by transbronchial infiltration of both hili with a long acting local anaesthetic via bronchoscopy is described. Animals, whose lungs were denervated in this way were embolized with oleic acid. It could be shown that as long as the reversible denervation is effective there is no significant functional reaction following oleic acid embolism as compared to healthy and non-denervated animals.

Animals↗
PubMed1993

Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. The maintenance of aerobic metabolism during lung preservation.

The lung is the only organ to which oxygen may be supplied after its blood supply is stopped. Before this study, we were not certain whether lung cells were able to maintain aerobic metabolism with the oxygen in the alveoli during preservation. Excised rabbit lungs were used to measure changes in the concentration of oxygen and carbon dioxide in the airway and changes in glucose, glucose-6-phosphate, lactate, adenosine triphosphate, and phosphocreatine levels in the lung tissue during preservation under different conditions. Twenty-seven lungs were flushed with low-potassium dextran electrolyte solution, inflated with room air, and preserved at 1 degree C (n = 8), 10 degrees C (n = 8), or 22 degrees (n = 11) for 4, 12, or 24 hours. Eight additional lungs were inflated with 100% nitrogen and preserved at 10 degrees C for 4 (n = 4) or 24 (n = 4) hours. Oxygen levels decreased and carbon dioxide levels increased in the airway of the lungs that were inflated with room air at rates dependent on the preservation temperature. The increase of carbon dioxide in the lungs that were inflated with 100% nitrogen was very small. When the oxygen was not available in the alveoli, lactate accumulated, and adenosine triphosphate and phosphocreatine decreased in the lung tissue. We concluded that lung cells are able to maintain aerobic metabolism with the oxygen in the alveoli during preservation and that the maintenance of aerobic metabolism may be essential to maintain the optimum viability of preserved lung tissue.

Adenosine Triphosphate↗
PubMed1995

[Quantitative computerized tomography of the lung--respiration controlled diagnosis of diffuse lung diseases].

STUDY OBJECTIVE: Computed tomography provides measurements of lung attenuation which reflect changes in the air to tissue ratio and can thereby be employed for diagnosis of diffuse lung disease. In this prospective study, we quantitatively analyzed lung density by high resolution computed tomography (HRCT) in 26 healthy volunteers, 15 patients with chronic obstructive pulmonary disease (COPD), and 15 patients with idiopathic lung fibrosis (IPF). The procedure was standardized by examination of 3 scans at the carina +/- 5 cm and by defining inflation levels by %VC using an on-line hand held spirometer. RESULTS: Performance of HRCT at 50% VC provides not only significant and distinguishable group data, but is the easiest to carry out for dyspneic patients. The mean lung density at 50% VC for healthy subjects was -820 +/- 4.2 (mean +/- SEM) Hounsfield units (HU). It was significantly lower (p < 0.01) in COPD patients (-865 +/- 9.2 HU), and considerably higher (-697 +/- 17.8 HU, p < 0.001) in the IPF group. At an inflation level of 20% VC, mean lung density values were similarly distributed, at significantly lower values relative to those at 50% VC, but the procedure was more difficult to perform for patients with dyspnea. In contrast, at 80% VC, lung density values for the COPD and control groups were not significantly different (p = 0.08). The sensitivity to detect COPD was improved by selecting HRCT values lower than -900 HU, which represent the part of the lung with an increased air/tissue ratio. For IPF patients an increase of lung density values above -699 HU was characteristic, indicating a decrease of the air/tissue relationship. CONCLUSION: From our data we propose to perform quantitative HRCT measurements at 50% VC. Diagnosis of diffuse lung disease can be further improved by consideration of specific CT -value intervals. Spirometrically controlled quantitative HRCT is a clinically meaningful tool for the assessment of diffuse parenchymal lung disease.

Adult↗
PubMed2006

Coxsackievirus and adenovirus receptor expression in non-malignant lung tissues and clinical lung cancers.

Adenoviral vector mediated gene delivery has been applied in clinical trials and mechanistic studies to explore new treatment approaches for lung cancers. The expression of coxsackievirus adenovirus receptor (CAR), the primary receptor for the most commonly used adenovirus serotype 5 (Ad5)-based vectors, predominantly determines the permissiveness of lung cancer cells. CAR expression is also suggested to modulate tumor cell proliferation capacity. Here, we studied CAR expression in archival lung cancer specimens by using well-characterized CAR 72 antibodies. High levels of CAR expression were observed in most of the 32 cases of squamous cell carcinoma lung cancers and in all the five cases of small cell lung cancers investigated. In contrast, high levels of CAR expression were detected only in 6 of 22 adenocarcinoma lung cancers. The relative levels of CAR expression did not correlate with the pathologic grade in lung cancers, and was thus inconsistent with a role of modulating cancer cell proliferation. Of note, CAR expression was not detected in non-malignant alveolar cells. Our data suggest a preferred utility of Ad5 vector mediated gene delivery to squamous cell carcinoma lung cancers, small cell lung cancers, but not to the majority of adenocarcinoma lung cancers.

Adult↗
PubMed1990

Lung and heart-lung transplantation.

Unilateral lung transplantation has become a successful method for the treatment of end-stage pulmonary disease, whereas double-lung transplantation has provided benefit to patients with nonfibrotic lung disease such as emphysema and cystic fibrosis. In the past 5 years, 16 single-lung and 13 double-lung transplantations have been performed by the Toronto Lung Transplant Group in patients with end-stage lung disease. Seven perioperative and two late deaths have been recorded so far. Since the introduction of heart-lung transplantation at Stanford in 1981 and at Pittsburgh in 1982 for the treatment of Eisenmenger's syndrome and terminal pulmonary vascular disease, more than 350 combined heart-lung transplantations have been carried out throughout the world. Presently, the 2-year actuarial survival is about 62%. The long-term results have not yet reached the same level of success as those of cardiac transplantation alone. Although several factors have played a role in this difference, a prominent cause has been the lack of a reliable and simple method for pulmonary protection against prolonged ischemia. Most of the techniques proposed against ischemia can be classified as normothermic or static hypothermic cardiopulmonary preservation. The use of the normothermic method has not always been successful. For this reason, interest has now been directed toward the potential for hypothermic preservation of the heart-lung bloc and the use of free-radical scavenger therapy in the reduction of reperfusion injury.

Animals↗
PubMed1987

A radioimmunometric assay for the detection and characterization of lung cancer-associated antibodies in sera of lung cancer patients.

A radioimmunometric assay was developed from P3 lung carcinoma target cells to detect anti-lung cancer antibodies. Of 100 sera from lung cancer patients tested, 80 (80%) were positive. However, only 6/30 (20%) sera from cancer patients with other cancers, 1/25 (4%) of sera from patients with nonmalignant lung disease, and 0/20 sera from healthy donors were positive. Quantitative absorptions showed that sera from lung cancer patients cross-reacted with other lung cancers, gastrointestinal cancers, and/or fetal lung tissues, but not with breast carcinomas, melanomas, sarcomas, fetal skin, or normal lung tissues. Two lung cancer antigens were defined: LCA-1, which shared antigenic determinants with GI tumors and fetal lung tissues, and LCA-2, which showed cross-reactivity only with GI tumors.

Adult↗
PubMed1985

Evidence of sequential opening and closing of lung units during inflation-deflation of excised rat lungs.

In this study we propose a descriptive model of the events occurring in an excised lung during an inflation-deflation cycle. The model was developed by observing changes in small pressure-volume loops superimposed on quasistatic pressure volume curves. It was found that the shape of the small loops during lung inflation was a function of the previous end-expiratory pressure. These experimental results could most easily be explained by a model of the lung in which individual lung units open sequentially as the lung is inflated. During sequential recruitment, individual lung units open quickly to a volume determined by the transpulmonary pressure. The units then homogeneously increase and decrease in size according to pressure-volume curves similar to the deflation curve of the entire lung. Once lung units have been recruited, they remain open until the lung has been deflated to end-expiratory pressures below 3-4 cm H2O. Reducing the end-expiratory pressure to lower values causes additional derecruitment of lung units until a transpulmonary pressure of 0.0 to -1.0 cm H2O has been reached.

Animals↗
PubMed1995

Differential expression of DNA topoisomerases in non-small cell lung cancer and normal lung.

UNLABELLED: DNA topoisomerases are ubiquitous nuclear enzymes, and important targets of cancer chemotherapy. Expression of topoisomerase genes is often correlated with in vitro chemosensitivity. We investigated the expression of the topoisomerase genes in normal lung and non-small cell lung cancer. Expression of topoisomerase II-alpha, topoisomerase II-beta, and topoisomerase I genes has been assessed in tumor samples of 60 patients who underwent operation for a non-small cell lung carcinoma, by RNase protection assay, and by immunohistochemistry. The expression of topoisomerase II-alpha gene was either undetectable or very low in normal lung, while most NSCLC expressed readily quantifiable levels of this gene. No alteration of the topoisomerase II-alpha gene was found by Southern blotting in the NSCLC samples. In contrast to topoisomerase II-alpha, topoisomerase II-beta was expressed in most normal as well as in tumor tissue samples, at a similar level. The levels of expression of both topoisomerase II isoforms was lower than that of human lung cancer cell lines. The results of the topoisomerase II mRNA expression were confirmed by immunohistochemistry. Whereas topoisomerase II-alpha staining was mainly limited to the nucleus, staining with topoisomerase II-beta antibody was exclusively observed in nucleoli. Topoisomerase I was localized in the nuclei and expression was mainly limited to tumor cells. By RNase protection, topoisomerase I expression in NSCLC samples was in the range of that of human lung cancer cell lines. The expression of the topoisomerase genes did not seem to be coordinated. In tumor cells, there was a positive association between expression of topoisomerase II-alpha and Ki-67, a marker of cell proliferation, as assessed by immunohistochemistry, but not with topoisomerase II-beta or topoisomerase I. Clinical characteristics of the patients, and their survival did not appear to be correlated to the level of expression of any of the topoisomerase genes, although a trend towards a shorter survival was observed in patients whose tumors expressed relatively high topoisomerase II-alpha mRNA levels. IN CONCLUSION: (1) the two isoforms of topoisomerase II are differentially expressed in normal lung and NSCLC cells; (2) higher topoisomerase II-alpha expression is associated with higher cell proliferation in NSCLC; (3) the expression of topoisomerase II-alpha and topoisomerase I, but not of topoisomerase II-beta, was higher in tumor cells compared to normal lung. Given the differential expression of topoisomerases in normal lung and tumors, research of more potent and specific topoisomerase inhibitors might prove beneficial in non-small cell lung cancer. Immunohistochemistry may be indicated in prospectively investigating the correlation between expression of topoisomerases and results of chemotherapy treatment.

Aged↗
PubMed2006

Prediction of radiation-induced changes in the lung after stereotactic body radiation therapy of non-small-cell lung cancer.

PURPOSE: To estimate the risk of radiation-induced changes in the lung before single-dose treatment (stereotactic body radiation therapy [SBRT]) of lung cancer, the quantitative dose-response and volume-response relations must be known. METHODS AND MATERIALS: A total of 64 patients treated for non-small-cell lung cancer with single doses of 20-30 Gy were classified according to the occurrence or nonoccurrence of perifocal changes in the lung detected by CT. Patients without toxic events in the lung were required to have >or=6 months of follow-up. The mean dose (D(mean)) in the ipsilateral lung and the volume receiving >7 or 10 Gy (V7 and V10, respectively) were used to calculate the dose-response and volume-response curves. The predictive value of additional variables was also investigated. RESULTS: Of the 64 patients, 83% exhibited the selected endpoint. The tolerance values at a 50% probability of toxic events were 1.2 +/- 0.7 Gy for the D(mean) and 5.8 +/- 3.0% and 3.1 +/- 2.0% for V7 and V10, respectively. A nonsignificant shift to higher doses was seen for the dose-response curve for the upper compared with the lower part of the lung. CONCLUSION: The D(mean), V7, and V10 can be used to predict the risk of lung toxicity after SBRT treatment of non-small-cell lung cancer. Because of the lack of patients with low prescribed doses, however, the related uncertainty of this prediction is still relatively large. The D(mean), V7, and V10 are equally well suited. The additional investigated variables did not provide significant advantages. The lower part of the lung appears to be more radiosensitive than the upper.

Adult↗
PubMed2003

Non-small-cell lung cancer molecular signatures recapitulate lung developmental pathways.

Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.

Adult↗
PubMed1999

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation.

PURPOSE/OBJECTIVE: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Aged↗
PubMed1983

Protein deficiency: effects on lung mechanics and the accumulation of collagen and elastin in rat lung.

Groups of weanling (approximately 50 g) or young adult (approximately 300 g) rats were fed ad libitum casein-based diets varying in protein content from 4 to 16%. A group was also fed the 16% protein diet in an amount on a daily basis restricted to that consumed by the protein-deficient group (4% protein). The rats were fed the diets for either 4 weeks (weanling) or 6 weeks (adults). Protein-deficient or "food-restricted" rats (whether weanling or adults) were smaller and had smaller lungs than rats fed ad libitum the diets containing 16% protein. The lung elastin content was more resistant to dietary manipulation than was the lung collagen content. Lung collagen was significantly decreased in both weanling and adult rats fed the 4% protein diet. In weanling rats, pressure-volume relationships derived from saline-filled lungs (analyzed by exponential curve-fitting methods) suggested that lungs from food-restricted rats may be less compliant than lungs from rats fed the control diet ad libitum. When expressed in absolute terms, lungs from protein-deficient rats also appeared to be less compliant than normal rats; however, on a relative basis (percentage of volume at a given recoil pressure or the expression of volume on a weight basis) differences in compliance were less apparent. It is proposed that in weanling rats the differences in lung composition and compliance are the result of retarded lung growth and perhaps development.

Age Factors↗
PubMed2003

Positive end-expiratory pressure delays the progression of lung injury during ventilator strategies involving high airway pressure and lung overdistention.

OBJECTIVE: Many studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury. DESIGN: Prospective, randomized laboratory animal investigation. SETTING: The University Laboratory of Ospedale Maggiore, Milano, IRCCS. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats. INTERVENTIONS: Three groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H(2)O) and PEEP of 3 and 6 cm H(2)O and a similar index of lung overdistension (Paw(p)/P(100) congruent with 1.1; where Paw(p) is peak airway pressure and P(100) is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained. RESULTS: Rats were ventilated with comparable high airway pressure (Paw(p) of 42.8 +/- 3.1, 43.5 +/- 2.6, and 46.2 +/- 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Paw(p)/P(100) - index of overdistension: 1.17 +/- 0.2, 1.06 +/- 0.1, and 1.19 +/- 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 +/- 14 mins and 60 +/- 17) as compared with zero end-expiratory pressure (18 +/- 3 mins, p <.001). CONCLUSION: These findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to "buy time" in the progression of lung injury.

Air Pressure↗
PubMed1978

Acute changes of lung volumes and lung mechanics in asthma and in normal subjects.

Lung volumes, pulmonary mechanics, and specific airway conductance (sGaw) were studied before and 15 minutes after 200 microgram of aerosol salbutamol in nine asthmatics undergoing mild spontaneous exacerbations of their disease and in five normal subjects. In addition, three of the normal subjects were studied after voluntarily breathing at high lung volumes for one minute. The normal subjects and four of the asthmatics showed no overall changes in lung volumes or pressure-volume (PV) curves after salbutamol, even though airway dilatation was produced in the asthmatic subjects. In another five asthmatics, salbutamol induced a significant fall in the total lung capacity (TLC) in three, and in the residual volume and functional residual capacity in all five. There was a significant displacement of the PV curve downwards and to the right in all five, with increased lung compliance (Cl stat) in two. The fall in TLC could be accounted for by the increase in lung elasticity. There is reason to believe that this change in lung mechanics could be due to the reversal of asthma-induced stress relaxation. Sustained breathing at high lung volume is known to cause stress relaxation of the lung. However, this breathing pattern did not alter the PV curve or TLC in two of three normal subjects, which is consistent with stress relaxation being rapidly reversible. The other normal subject had an acute shift of the PV curve upwards and to the left after breathing at high lung volume. It has been concluded that stress relaxation is usually rapidly reversed but that in some individuals it may only be slowly reversed. This more persistent form of stress relaxation may contribute to the acute changes of TLC found in some asthmatics.

Adult↗
PubMedDate not supplied

Donor lung pathology: correlation with outcome of transplanted contralateral lung.

To compare clinical results of single lung transplantation with pretransplantation pathology, we reviewed 15 human lungs from 12 donors, which clinically satisfied donor lung criteria but were not transplanted. In nine of these cases the contralateral lung was transplanted. Seven of these nine unused lungs showed mild pathologic changes, including emphysema, focal fibrosis, and old and recent hemorrhage, which had no impact on the outcome of the transplanted contralateral lung. One case had moderate generalized emphysema, which also did not affect the outcome because the other lung was given to a patient with severe emphysema. One donor lung showed severe overinflation artifact, which we think contributed to the early graft failure in a patient with primary pulmonary hypertension. We conclude that, despite satisfying standard donor lung criteria, many lungs have abnormal pathology. This may impact both short- and long-term survival.

Adult↗
PubMed1997

Assessment of xanthine oxidase in human lung and lung transplantation.

Oxygen free radical generation by xanthine oxidase (XO) is a possible mechanism in the injury following reperfusion of transplanted organs. This study was undertaken to investigate XO in human lung, and to investigate whether XO is released into the blood stream during the immediate postoperative period after lung transplantation. XO activity was measured in healthy human lung tissue, and XO protein and the adenine nucleotide catabolic products hypoxanthine, xanthine and uric acid were analysed in the plasma samples collected during human heart-lung transplantation (n=4), double lung transplantation (n=2), and single lung transplantation (n=1). Neutrophil degranulation was assessed by plasma lactoferrin measurements. The results indicated that XO activity (detection limit 5 pmol x min(-1) x mg(-1) protein) and protein (detection limit 5 ng x mg-1 protein) were undetectable in the lungs of five healthy individuals. Similarly, no XO protein could be found in the plasma samples from the right ventricle or left atrium during and after the transplantation in any of the cases. Plasma xanthine and hypoxanthine concentrations were elevated 2-10 fold immediately after the reperfusion of the transplant, indicating washout of high-energy phosphate degradation products from the ischaemic lung. Plasma uric acid decreased rather than increased immediately after the surgery and during the following 24 h. Lactoferrin was elevated during the surgery. In conclusion, these results show that XO activity in human lung is low, it is not released into the blood stream during human heart-lung transplantation, and it is unlikely to contribute to postoperative complications in these patients.

Chromatography, High Pressure Liquid↗
PubMed2000

Pulmonary nodules and masses after lung and heart-lung transplantation.

The authors assess clinical and radiographic findings of pulmonary nodules and masses after lung and heart-lung transplantation. One hundred and fifty nine patients who survived at least 3 months after lung and heart-lung transplantation were followed by serial chest radiographs for a median of 27 months. Single or multiple lung nodules or masses were noted at chest radiography in 15 (9.4%) of 159 patients. Imaging findings and causes of these nodules and masses were reviewed retrospectively. Infection was found in 10 (6%) of 159 patients. Specific pathogens (11 pathogens in 10 patients) were Aspergillus (n = 4), Mycobacteria (n = 4), and other bacteria (n = 3). Noninfectious causes were found in 5 (3%) of patients and included B-cell lymphoma (n = 2), bronchogenic carcinoma (n = 2), and pulmonary infarcts (n = 1). Nodules and masses appeared a median of 11 months after transplantation (range: 0.2 to 36 months). Five patients (33%) had single lesions; the other 10 (67%) patients had multiple lesions (range 2 to 50). Aspergillus lesions were most commonly located in the upper lobes, were cavitary in three of four patients, and all were fatal. Nodules and masses arose in the transplanted lung in 12 (80%) of the patients, and in the native lung in 3 (20%) of the patients (2 bronchogenic carcinoma, 1 M. tuberculosis simulating bronchogenic carcinoma). Nodules and masses detected by chest radiography are not uncommon (9.4%) after lung and heart-lung transplantation. Infections are more common than noninfectious causes of posttransplant nodules and masses. Specific clinical and imaging characteristics may provide clues to etiology.

Adolescent↗