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PubMed2003

The Eurotransplant Study on Twin Lung Transplants (ESOTWIN): 90 paired single-lung transplants from the same donor.

BACKGROUND: Despite its reduced benefit for a single recipient, the transplantation of two single-lung allografts as opposed to one bilateral lung transplant has the indisputable advantage of maximizing the number of patients that benefit from a single donor. METHODS: In the period 1997 to 1999, 90 paired single-lung transplants (SLTx) from 45 donors were performed in 16 lung centers in Eurotransplant, with a complete follow-up of 1 year. RESULTS: No significant differences between left- and right-lung allograft recipients were observed regarding age, sex, primary disease, number of human leukocyte antigen mismatches, cold ischemic time, and donor-to-recipient cytomegalovirus match. Early posttransplant outcome, as assessed by oxygenation index at 12, 24, and 48 hr, also did not differ significantly, and there were no differences in time to extubation and time spent in the intensive care unit. In the first month, six left- and three right-lung allograft recipients died. Bronchiolitis obliterans syndrome developed in 5 of 39 left-lung and 10 of 42 right-lung allograft recipients. If the retrieval team was different from the transplanting team, a significantly worse 1-year posttransplant survival rate was seen in patients who underwent left SLTx compared with those who underwent right SLTx (62% vs. 92%, respectively; P=0.04). CONCLUSIONS: More fatal posttransplant complications occur in patients undergoing left SLTx compared with right SLTx. A less optimistic assessment of the left lung by the not-implanting retrieval team is warranted.

Adolescent↗
PubMed1982

Lung volume and lung mechanics in infancy lateral or supine posture?

In 23 infants and young children aged from 3 wk to 2 1/2 years, lung volume, by plethysmography, dynamic lung compliance and total pulmonary resistance with air-filled balloons and pneumotachography, have been measured in the supine and right lateral postures in order to observe any possible systematic differences in either body position. Fourteen subjects were studied under light sedation, the remaining nine under general anaesthesia before elective surgery. In the sedated group, no significant differences were found between the two positions for lung mechanics. In the anaesthetised group the only measurement that varied with position was dynamic lung compliance, being lower in the supine posture (P less than 0.05). In one of the sedated infants with predominantly left sided lung disease, large position dependent changes in lung volume and lung mechanics were observed suggesting that care should be taken in interpreting lung function tests in infants with unilateral lung disease. In the anaesthetised subjects, the finding of reduced ratios of esophageal to mouth pressure change during brief airway occlusions, suggests that under these conditions pleural pressure changes were unequally distributed.

Adult↗
PubMedDate not supplied

Audit of referral and explant diagnoses in lung transplantation: a pathologic study of lungs removed for parenchymal disease.

BACKGROUND: Lung transplantation is performed for an increasing range of pulmonary conditions in which the diagnosis is often clinical or based on limited biopsy material. Diagnosis may be made late in the course of the disease where specific features are no longer present. Posttransplantation complications and disease recurrence may relate to the primary disease, and accurate diagnosis is therefore essential. METHODS AND RESULTS: A pathologic review of 183 explanted lungs over a 10-year period (heart-lung = 109, single lung = 65, double lung = 9) showed 29 significant discrepancies or additional features likely to effect outcome. The final pathologic diagnosis was cystic fibrosis (n = 66), emphysema (59), bronchiectasis (17), pulmonary fibrosis (19), sarcoidosis (10), Langerhans cell histiocytosis (3), pulmonary veno-occlusive disease (3), posttransplantation obliterative bronchiolitis (2), primary hemosiderosis (1), rheumatoid obliterative bronchiolitis (1), extrinsic allergic alveolitis (1), pneumoconiosis (1). Unsuspected diagnoses included tuberculosis (8) (four cases of which were active and in single lung recipients requiring antituberculous chemotherapy), sarcoidosis (9), (of which, six were unsuspected primary diagnoses and three were additional diagnoses), veno-occlusive disease (3), carcinoma (1), pneumoconiosis (1), and pulmonary fibrosis (2). Aspergillus infection (2) and bronchocentric granulomatosis (3) were found in patients with cystic fibrosis. One active tuberculosis case also showed an aspergilloma. Unsuspected infections requiring therapy in immunosuppressed patients and previously unsuspected sarcoidosis, which is known to recur in the graft, were the major novel diagnoses. Discrepancy rate was 12 of 65 in single lungs (19%) and 17 of 109 in heart-lungs (16%). CONCLUSIONS: These results emphasize the need for accurate preoperative diagnosis especially when the similarly diseased native lung remains in situ.

Adult↗
PubMed1988

Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas.

Eighty-nine primary lung carcinomas and 23 metastatic lung tumors were immunohistochemically studied for the expression of pulmonary surfactant apoproteins, by using monoclonal (PE-10) and polyclonal antibodies. Surfactant apoprotein was demonstrated in the cytoplasm and/or nuclear inclusion bodies of only primary lung adenocarcinomas (36 of 75 cases), not in any other histologic type of primary lung carcinoma or in metastatic lung tumors. In primary lung adenocarcinoma, although typical type II pneumocyte type adenocarcinoma was not included in the current series, the majority of surfactant apoprotein-positive single cell type tumors were of the Clara cell type, with a single bronchial surface epithelial cell type, according to the light microscopic subclassification of adenocarcinoma cells. The Clara cell type adenocarcinomas could at times be distinguished only with difficulty from adenocarcinoma of type II pneumocyte type. Normal and hyperplastic type II pneumocytes were of course positive for surfactant apoprotein in the cytoplasm. However, none of the positive cells could definitely be identified as Clara cells in non-neoplastic lungs. The findings obtained in this study indicate that surfactant apoprotein is a good marker to distinguish adenocarcinoma of the lung from other histologic types of lung cancer and from neoplasms metastatic to the lung, and that type II pneumocytes and Clara cells, non-neoplastic and neoplastic, are morphologically and functionally closely related and might belong to the same cell lineage.

Adenocarcinoma↗
PubMed1992

Laminin expression in the mouse lung increases with development and stimulates spontaneous organotypic rearrangement of mixed lung cells.

The recent establishment of a role for laminin in mouse lung organogenesis (Schuger et al. 1990a,b, 1991) prompted us to study its expression in the developing lung. Laminin A and B chains were detected in the murine lung from the first hours of development onward. In situ hybridization of mRNA as well as SDS-PAGE studies of lung cells in monoculture indicated that both epithelium and mesenchyme produce complete laminin molecules. Quantitative analysis of the in situ hybridization studies showed a gradual increase in laminin expression during development which was further supported by immunohistochemistry and ELISA. The overall pattern of expression suggested that the effects of laminin in morphogenesis were not restricted to a particular stage of development. Furthermore, the increase in expression during late development supported a role for the molecule in the fetal lung, which was not previously established. We next determined whether the increase in laminin production modulated the behavior of fetal lung cells as compared with their embryonic counterparts. We previously showed that organotypic pattern formation does not occur in cultures of mixed embryonic lung cells unless exogenous laminin is added (Schuger et al., 1990b). Organotypic pattern formation is the result of cell sorting into epithelial and mesenchymal compartments and further rearrangement in a pattern resembling the tissue of origin. In the present study, we demonstrated that organotypic pattern formation occurs spontaneously in cultures of mixed fetal lung cells, which express high laminin levels. Pattern formation was abolished by antibodies to laminin. These studies suggest a correlation between laminin expression and the ability of lung cells in culture to reproduce normal tissue patterns. We conclude that laminin is critical for epithelial-mesenchymal recognition and further morphogenic interaction during both the embryonic and fetal stages of lung development.

Animals↗
PubMed1995

Influence of red blood cells on lung function in an ex vivo rat heart-lung model.

Crystalloid perfusates commonly are utilized for lung preservation in extracorporeal small animal lung models. However, the function of these grafts is limited. In a new ex-vivo rat heart-lung model the role of red blood cells added to the crystalloid perfusate was investigated. Heart-lung blocks were rapidly excised (n = 9, each group) and the blocks were connected to the extracorporeal perfusion circuit using Krebs-Henseleit solution (KH) or KH with washed bovine red blood cells (hematocrit 38%) (KHRBC). The lungs were ventilated with room air. The coronary system was perfused via the aortic root with oxygenated perfusate. The lungs were perfused via the right ventricle with deoxygenated perfusate (PO2 15 mm Hg). Venoarterial improvement of oxygenation, pulmonary vascular resistance (PVR), and peak inspiratory pressure (PIP) were continuously monitored for 50 min. At the end of the experiment the wet/dry (W/D) ratio was determined using the mediastinal lung lobe while the remaining lung was used for light microscopic (LM) evaluation. After 30 min of perfusion, lung function was significantly better in the KHRBC group (PVR (KH): 752 +/- 193 dyn*sec*cm-5; (KHRBC): 279 +/- 48 dyn*sec*cm-5; PIP (KH): 31 +/- 3.2 mm Hg; (KHRBC): 25.8 +/- 1.9 mm Hg). In addition, lungs perfused with KHRBC showed significantly less edema than those perfused with KH only (W/D ratio (KH): 7.8 +/- 1.2; (KHRBC) 5.1 +/- 0.6; LM (KH): 3.5 +/- 0.9; (KHRBC): 2.3 +/- 0.8). The use of red blood cells in KH perfusate improved functional and structural integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Phospholipase A2-induced lung edema and its mechanism in isolated perfused guinea pig lung.

Lung injury induced by phospholipase A2 (PLA2, 0.046 IU/ml perfusate) was studied in a continuous weighing system of isolated perfused guinea pig lungs. The results revealed that lung weight increased progressively during the 30-min perfusion of PLA2. No change of pulmonary arterial pressure was observed in the same period. Albumin permeability-surface area product, lung index, lung water content, exudate from pleura, and angiotensin-converting-enzyme activity increased significantly at the end of 30 min PLA2 perfusion. p-Bromophenacyl bromide, a PLA2 inhibitor, may block the above changes nearly completely. The effects of inhibitors of cyclooxygenase (indomethacin, IM), lipoxygenase (diethylcarbamaxine, DE), and platelet-activating factor (SRI 63-441) on PLA2-induced lung injury were also studied. We found: (1) PLA2 may induce high permeability lung edema. The role of endothelial injury in the permeability change remains to be further investigated. (2) DE ameliorated lung injury significantly within 10 min of PLA2 treatment but showed no effect after 15 min. IM ameliorated lung injury during the whole experimental period. SRI 63-441 had no effect. It is suggested that PLA2 may damage lung by inducing products of cyclooxygenase and lipoxygenase besides its direct effect.

Acetylcholinesterase↗
PubMed1998

[An experimental study of local chemotherapy for metastatic lung tumor--isolated lung perfusion and pulmonary artery infusion].

PURPOSE: We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases. MATERIAL AND METHODS: Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (i.v.). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed. RESULTS: In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group. CONCLUSION: We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.

Animals↗
PubMed2004

Ultrastructural changes in the contralateral lung tissue following unilateral lung ischemia: an experimental study in rabbits.

PURPOSE: To investigate the acute ultrastructural changes that may occur in the contralateral nonischemic lung tissue after unilateral ischemia of a lung in a rabbit model. METHODS: The animals were divided into three main groups of eight; namely, a 2-h procedure group, a 4-h procedure group, and an 8-h procedure group. Each of these groups was further divided into two subgroups of four rabbits each; namely, a control group, given a sham operation without any ischemic insult, and an ischemia group, in which the main pulmonary arteries, the pulmonary veins, and the main bronchi of the left lungs were ligated after thoracotomy. Tissue samples were taken from the left and right lungs to examine the ultrastructural changes after 2, 4, and 8 h of ischemia. Each sample was given a semiquantitative histological injury score. Statistical analysis was done by the Mann-Whitney U-test. RESULTS: Contralateral ultrastructural damage, evident by heterochromatin in the nuclei, mitochondrial degeneration, cisternal widening of the endoplasmic reticulum, increased lipid droplets, and lysosomes, was determined by electron microscopy after unilateral lung ischemia. The contralateral lung injury was significantly correlated with the duration of ischemia. CONCLUSIONS: Unilateral lung ischemia affected the bilateral lungs in a rabbit model. Therefore, in operations such as single-lung transplantation, pulmonectomy, or lobectomy, if the procedure is unnecessarily prolonged, the contralateral lung may be damaged, which could seriously affect the prognosis of the patient.

Animals↗
PubMed1994

Isolated single-lung perfusion with TNF-alpha in a rat sarcoma lung metastases model.

We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.

Animals↗
PubMed1993

Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge.

BACKGROUND: Segmental antigen challenge in allergic volunteer subjects leads to the recruitment of inflammatory cells, including eosinophils, to the lung and to lung injury as shown by albumin influx into the alveolar air space. The goal of this study was to determine whether eosinophil-active cytokines, including IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor, are released into the lung 24 hours after segmental antigen challenge of ragweed allergic subjects with allergic rhinitis and to determine whether the presence of the cytokine or cytokines is correlated with markers of lung inflammation and lung injury. METHODS: Volunteers underwent challenge with a wide variety of antigen doses, which resulted in the recruitment of inflammatory cell mixtures both with and without eosinophils. RESULTS: Eosinophil survival activity (ESA), the ability of the cytokine to prolong blood eosinophil survival in culture, was found in 5 of 17 ragweed allergic subjects and only in subjects challenged with relatively high doses of ragweed antigen (0.2 ragweed antigen units/ml or more). No ESA was found in bronchoalveolar lavage (BAL) fluid in any of eight nonragweed allergic subjects. This activity could be almost completely neutralized by preincubating BAL fluid with specific antibody to IL-5, although a small contribution by granulocyte-macrophage colony-stimulating factor may also have been present. ESA correlated with eosinophil recruitment (r = 0.72, p < 0.001) and degranulation in the lung (r = 0.63 to 0.81, p < 0.01, for eosinophil granule constituents in BAL fluid) and lung injury as shown by albumin influx into the alveolar air spaces (r = 0.83, p < 0.001). ESA was unrelated to the presence of other inflammatory cells in the lung. Subjects who had IL-5 in BAL fluid appeared to undergo more severe initial reactions to antigen challenge. CONCLUSIONS: We conclude that IL-5 is the most important constituent in ESA in the lung 24 hours after antigen challenge and that it correlates with eosinophil recruitment, degranulation, and lung injury.

Allergens↗
PubMed1993

Lung deposition, lung clearance and renal accumulation of inhaled cadmium chloride and cadmium sulphide in rats.

Rats were exposed 6 h/day over 10 days to 0.3 mg/m3 of water soluble cadmium chloride and 0.2, 1.0 and 8.0 mg/m3 of insoluble cadmium sulphide, then killed at intervals over a 3-month period for serial measurements of lung, renal and faecal cadmium. CdCl2 and high-dose CdS animals showed a transient increase in lung weight. Clearance of both compounds was biphasic. Approximately 40% of deposited material was cleared during the 10-day exposure period. For CdCl2, only 9% of the lung burden was cleared rapidly after the last exposure (half-life 1.0 days) and 47% slowly (half-life 87 days), leaving a residual lung burden of 44%. For CdS, 41% of the lung burden was cleared rapidly (half-life 1.4 days) and 40% slowly (half-life 42 days), leaving a final residue 19%. In the CdS high-dose group, the retention of CdS in the lung was greater than that in the CdS low-dose groups, indicating that clearance mechanisms may possibly have been impaired in the high-dose group by too great a lung burden. For both compounds, faecal cadmium was initially high. Renal accumulation of cadmium was substantial for CdCl2 during the exposure period and continued over the following months until it represented approximately 35% of the total cadmium cleared from the lung. For CdS, renal accumulation was only 1% of the amount cleared from the lung. The bioavailability of Cd from CdS is thus poor, the majority being cleared from the lungs and excreted in the faeces. However, the bioavailability of inhaled CdS measured as cadmium in the kidney is greater than the bioavailability of orally ingested CdS.

Administration, Inhalation↗
PubMed2004

Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water.

The "comet-tail" is an ultrasound sign detectable with ultrasound chest instruments; this sign consists of multiple comet-tails fanning out from the lung surface. They originate from water-thickened interlobular septa and would be ideal for nonradiologic bedside assessment of extravascular lung water. To assess the feasibility and value of ultrasonic comet signs, we studied 121 consecutive hospitalized patients (43 women and 78 men; aged 67 +/- 12 years) admitted to our combined cardiology-pneumology department (including cardiac intensive care unit); the study was conducted with commercially available echocardiographic systems including a portable unit. Transducer frequencies (range 2.5 to 3.5 MHz) were used. In each patient, the right and left chest was scanned by examining predefined locations in multiple intercostal spaces. Examiners blinded to clinical diagnoses noted the presence and numbers of lung comets at each examining site. A patient lung comet score was obtained by summing the number of comets in each of the scanning spaces. Within a few minutes, patients underwent chest x-ray, with specific assessment of extravascular lung water score by 2 pneumologist-radiologists blinded to clinical and echo findings. The chest ultrasound scan was obtained in all patients (feasibility 100%). The imaging time per examination was always <3 minutes. There was a linear correlation between echocardiographic comet score and radiologic lung water score (r = 0.78, p <0.01). Intrapatient variations (n = 15) showed an even stronger correlation between changes in echocardiographic lung comet and radiologic lung water scores (r = 0.89; p <0.01). In 121 consecutive hospitalized patients, we found a linear correlation between echocardiographic comet scores and radiologic extravascular lung water scores. Thus, the comet-tail is a simple, non-time-consuming, and reasonably accurate chest ultrasound sign of extravascular lung water that can be obtained at bedside (also with portable echocardiographic equipment) and is not restricted by cardiac acoustic window limitations.

Aged↗
PubMed2005

Lung cancer: Preoperative pulmonary evaluation of the lung resection candidate.

Lung resection provides the best chance of cure for individuals with early stage non-small cell lung cancer. Naturally, lung resection will lead to a decrease in lung function. The population that develops lung cancer often has concomitant lung disease and a reduced ability to tolerate further losses in lung function. The goal of the preoperative pulmonary assessment of individuals with resectable lung cancer is to identify those individuals whose short- and long-term morbidity and mortality would be unacceptably high if surgical resection were to occur. Pulmonary function measures such as the forced expiratory volume in 1 second and the diffusing capacity for carbon monoxide are useful predictors of postoperative outcome. In situations in which lung function is not normal, the prediction of postoperative lung function from preoperative results and the assessment of exercise capacity can be performed to further clarify risks. Published guidelines help to direct the order of testing, permitting us to offer resection to as many patients as possible.

Exercise Test↗
PubMed2006

Initial experience with lung-MRI at 3.0T: Comparison with CT and clinical data in the evaluation of interstitial lung disease activity.

OBJECTIVES: We evaluated the feasibility of highfield lung-MRI at 3.0T. A comparison with Computed Tomography (CT) and clinical data regarding the assessment of inflammatory activity in patients with diffuse lung disease was performed. MATERIAL AND METHODS: Prospective evaluation of 21 patients (15 males, 6 females, 43-80 y) with diffuse lung diseases who underwent clinical work-up inclusive laboratory tests, lung-function tests and transbronchial biopsy. After routine helical CT (additional 12 HRCT) a lung-MRI (3.0 Intera, Philips Medical Systems, Best, The Netherlands) using a T2-weighted, cardiac and respiratory triggered Fast-Spinecho-Sequence (TE/TR=80/1500-2500 ms, 22 transverse slices, 7/2mm slice-thickness/-gap) was performed. A pneumologist classified the cases into two groups: A=temporary acute interstitial disease or chronic interstitial lung disease with acute episode or superimposed infection/B=burned out interstitial lung disease without activity. Two blinded CT-radiologists graded the cases in active/inactive disease on the basis of nine morphological criteria each. A third radiologist rated the MRI-cases as active/inactive, depending on the signal-intensities of lung tissues. RESULTS: The pneumologist classified 14 patients into group A and 7 patients into group B. Using CT, 6 cases were classified as active, 15 cases as inactive disease. With MRI 12 cases were classified as active and 9 cases as inactive. In the complete group of 21 patients MRI decisions and CT decisions respectively were false positive/false negative/correct in 2/4/15 respectively 0/8/13 cases. Correct diagnoses were obtained in 72% (MRI) respectively 62% (CT). In the subgroup of 12 cases including HRCT, MRI respectively CT were false positive/false negative/correct in 2/1/9 respectively 0/5/7 cases. Correct diagnoses were obtained in 75% (MRI) respectively 58% (CT). CONCLUSION: Highfield MRI of the lung is feasible and performed slightly better compared to CT in the determination of activity in patients with interstitial lung diseases.

Adult↗
PubMed2003

Quantification of lung water by transpulmonary thermodilution in normal and edematous lung.

PURPOSE: To analyze the accuracy of the transpulmonary thermodilution method in the determination of extravascular lung water (EVLW). MATERIAL AND METHODS: Acute lung injury was produced in eight adolescent pigs weighing 28 to 35 kg by bronchoalveolar lung lavage. EVLW was measured by transpulmonary thermodilution method before and after the intratracheal introduction of 250 or 500 mL of saline solution in different lung injury conditions. No corrections for anatomic dead space were made. RESULTS: When 250 mL was introduced, 195 +/- 17 mL was detected in normal (uninjured) lungs versus 74 +/- 57 mL in edematous (injured) lungs (P <.05). When 500 mL was introduced, 343 +/- 67 mL was detected in normal lungs versus 160 +/- 51 mL in edematous lungs (P <.001). Considering all determinations together, there was a very high negative correlation between the baseline EVLW and the percentage of EVLW detected (r = -0.92, P <.001). CONCLUSION: The transpulmonary thermodilution method is very accurate to detect changes in EVLW in normal lungs. In edematous lung, this method may underestimate the EVLW.

Animals↗
PubMed1995

Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma to the lung or diffuse bronchioloalveolar carcinoma.

Eight patients with metastatic sarcoma to the lung (n = 4) or diffuse bronchioloalveolar carcinoma of the lung (n = 4) underwent isolated lung perfusion with chemotherapy in a pilot study. Ages ranged from 18 to 60 years and half were female. The left lung was perfused in three patients (single lung perfusion) and both lungs in five patients (total lung perfusion). Perfusions ranged from 45 to 60 minutes at ambient or normothermic temperatures. One patient received perfusion at moderate hyperthermia (40 degrees C). Escalating doses of doxorubicin (1 to 10 micrograms/ml perfusate) was used in six patients, whereas two received cisplatin (14 and 20 micrograms/ml perfusate). There were two major complications and no objective responses. The isolated perfusion systems gave excellent separation between systemic and pulmonary circulations with zero to 15% of the measured peak drug concentration of the pulmonary perfusate detected in the systemic circulation. Drug concentrations in normal lung and tumor generally increased with higher drug dosages and drug was detectable in mediastinal lymph nodes of three out of four patients in whom sampling was done. Isolated lung perfusion with chemotherapy can be done safely in patients with lung malignancies and evidence suggests that higher drug dosages should be well tolerated.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Tumour response and radiation-induced lung injury in patients with recurrent small cell lung cancer treated with radiotherapy and concomitant interferon-alpha.

The aim of this study was to determine whether either natural or recombinant interferon (IFN)-alpha can improve the response to radiotherapy (RT) in patients with small cell lung cancer (SCLC), and to assess the role of IFN in radiation-induced lung injury. All patients had previously participated in a randomised trial of chemotherapy alone or in combination with IFN-alpha in three arms (arm O: no IFN, arm I: natural IFN-alpha, arm II: recombinant IFN-alpha). Patients with locally progressive disease in the lungs following chemotherapy were treated with RT and they continued with their concomitant IFN-alpha. The RT dose was 50 Gy. Radiation-induced lung injury was assessed by lung function tests, computed tomography and bronchoalveolar lavage fluid (BALF) analysis which included cell findings, Interleukin (IL)-1 alpha/-1 beta expression by alveolar macrophages and surfactant components. Seventeen patients were entered in the study, 16 of whom were evaluable. Response rates in Arms O, I and II were 50, 67 and 50%, respectively. Median survival was 18.5, 7 and 23 months respectively, and 1-year survival was 67, 29 and 75% respectively. Long-term survival as assessed by 2- and 3-year survival rates was 29% in patients receiving natural IFN-alpha as compared to 17% in patients not receiving IFN (not statistically significant findings). Every patient had abnormal results when assessed for radiation-induced lung injury. No statistically significant difference was found in toxicity between the treatment arms. A high surfactant protein (SP)-A/phospholipid ratio and a high level of SP-A in BALF before RT was associated with a high degree of radiation-induced lung injury measured by lung function tests and computed tomography in all arms of the study. Thus, we could not show that the combination of IFN-alpha and RT induced more lung toxicity than RT alone as we did in our previous study. The role of high SP-A/phospholipid ratios and high SP-A levels in BALF before RT as predictors of the development of lung injury after RT needs to be determined in the future.

Adult↗