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PubMed2003

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

Animals↗
PubMed2006

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia.

Recent studies suggest that VEGF may worsen pulmonary edema during acute lung injury (ALI), but, paradoxically, impaired VEGF signaling contributes to decreased lung growth during recovery from ALI due to neonatal hyperoxia. To examine the diverse roles of VEGF in the pathogenesis of and recovery from hyperoxia-induced ALI, we hypothesized that exogenous recombinant human VEGF (rhVEGF) treatment during early neonatal hyperoxic lung injury may increase pulmonary edema but would improve late lung structure during recovery. Sprague-Dawley rat pups were placed in a hyperoxia chamber (inspired O(2) fraction 0.9) for postnatal days 2-14. Pups were randomized to daily intramuscular injections of rhVEGF(165) (20 microg/kg) or saline (controls). On postnatal day 14, rats were placed in room air for a 7-day recovery period. At postnatal days 3, 14, and 21, rats were killed for studies, which included body weight and wet-to-dry lung weight ratio, morphometric analysis [including radial alveolar counts (RAC), mean linear intercepts (MLI), and vessel density], and lung endothelial NO synthase (eNOS) protein content by Western blot analysis. Compared with room air controls, hyperoxia increased pulmonary edema by histology and wet-to-dry lung weight ratios at postnatal day 3, which resolved by day 14. Although treatment with rhVEGF did not increase edema in control rats, rhVEGF increased wet-to-dry weight ratios in hyperoxia-exposed rats at postnatal days 3 and 14 (P < 0.01). Compared with room air controls, hyperoxia decreased RAC and increased MLI at postnatal days 14 and 21. Treatment with VEGF resulted in increased RAC by 181% and decreased MLI by 55% on postnatal day 14 in the hyperoxia group (P < 0.01). On postnatal day 21, RAC was increased by 176% and MLI was decreased by 58% in the hyperoxia group treated with VEGF. rhVEGF treatment during hyperoxia increased eNOS protein on postnatal day 3 by threefold (P < 0.05). We conclude that rhVEGF treatment during hyperoxia-induced ALI transiently increases pulmonary edema but improves lung structure during late recovery. We speculate that VEGF has diverse roles in hyperoxia-induced neonatal lung injury, contributing to lung edema during the acute stage of ALI but promoting repair of the lung during recovery.

Animals↗
PubMed2003

Experimental ventilator-associated pneumonia: distribution of lung infection and consequences for lung aeration.

Ventilator-associated pneumonia (VAP) has been described in humans and in experimental animals. The most severe lesions are located in dependent lung segments along a sterno-vertebral axis, however the cephalocaudal distribution of lung infection remains unknown. We used an experimental model to evaluate the distribution of lung infection, considering its anteroposterior and cephalocaudal gradient, and its impact on lung aeration. Ten healthy domestic piglets were anesthetized, paralyzed and mechanically ventilated for 59 hours in the prone position. At the end of the experiment they were sacrificed and their lungs were fixed. Six segments were analyzed: a non-dependant (ND) and a dependant (D) segment of the upper (UL), middle (ML) and lower (LL) lobes. The presence of healthy lung or of histological infectious lesions was analyzed with a semi-quantitative method. The regional distribution of lung infection was compared between upper, middle and lower lobes, as well as between dependant and non-dependant regions. The presence of infectious lesions was correlated with measurements of lung aeration. Nine of the ten piglets developed VAP. Infectious lesions were distributed along a sterno-vertebral and a cephalocaudal gradient; the lower and middle lobes were more frequently infected than the upper lobes. There was an inverse correlation (R= - 0.902) between the development of lung lesions and lung aeration. In conclusion, VAP was a frequent complication in healthy mechanically ventilated piglets, showing an anteroposterior as well as a cephalocaudal gradient. As expected, development of lung infection was accompanied by a corresponding loss of aeration.

Animals↗
PubMed2000

Expression of intercellular adhesion molecule in lung tissues of experimental acute lung injury and the affect of Rhubarb on it.

OBJECTIVE: To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. METHODS: Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LFS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. RESULTS: In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P < 0.01), demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P < 0.01, P< 0.05); the corresponding pathologic change of lung tissue and the biological markers of the lung injury were significantly decreased or ameliorated. CONCLUSIONS: The increase of the expression of ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM-1 mRNA expression.

Animals↗
PubMed2000

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, Issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies which met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g. , washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Aerosols↗
PubMed2003

Expression of Hoxb-5 during human lung development and in congenital lung malformations.

BACKGROUND: We have previously shown that the Hox gene Hoxb-5 is necessary for normal mouse lung branching morphogenesis. Abnormal Hoxb-5 regulation causes specific alterations in airway branching. We hypothesized that Hoxb-5 is similarly involved in human lung branching morphogenesis, and is abnormally expressed in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), both of which are congenital lung malformations with abnormal airway development. METHODS: The temporal, spatial, and cellular expression of the Hoxb-5 protein was evaluated in normal human lung and BPS and CCAM tissue using Western blot analysis and immunocytochemistry. RESULTS: The expression of Hoxb-5 during human lung development showed strong similarities to that during mouse lung development. Western blots showed high Hoxb-5 protein levels in the pseudoglandular period (PSG), decreased but sustained levels in the canalicular period (CAN), and negligible levels during the alveolar period (ALV). Immunocytochemistry showed Hoxb-5 protein expression in mesenchymal cells around branching airways in the pseuodglandular period, subepithelial fibroblast localization (especially at airway branch points) in the CAN and minimal expression in the ALV. In BPS and CCAM tissue, Hoxb-5 protein levels were increased compared to age- and developmentally-matched lung tissue, and were more similar to the PSG and CAN with Hoxb-5-positive cells in mesenchyme surrounding abnormally branched airways. CONCLUSIONS: Hoxb-5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning. This notion is supported by results from BPS and CCAM tissue, in which Hoxb-5 is maintained in a manner typical of an earlier developmental stage and is associated with development of abnormal lung tissue.

Bronchopulmonary Sequestration↗
PubMed2002

Sequential changes of the DMBT1 expression and location in normal lung tissue and lung carcinomas.

Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain, digestive tract, and lung cancer. Recent studies on its expression in lung cancer have led to divergent results and have raised a controversial discussion. Moreover, DMBT1 has been implicated with epithelial protection in the respiratory tract. We thus wondered how a loss of its expression could be related to carcinogenesis in the lung. To address these issues, we investigated the DMBT1 expression and location in the normal lung and lung cancer. By reverse-transcription PCR, a down-regulation of the DMBT1 expression in lung cancer cell lines is commonly detected. Immunohistochemical studies in situ demonstrate that there are also low steady-state levels of DMBT1 in the normal respiratory epithelium. However, an up-regulation takes place in the tumor-flanking epithelium and upon respiratory inflammation. Lung carcinomas show increased DMBT1 expression compared to that of undiseased lung tissue, but decreased DMBT1 levels compared to that of tumor-flanking and inflammatory tissue. A switch from a lumenal secretion to a secretion to the extracellular matrix takes place during lung carcinogenesis. Our data may resolve the controversial discussion on its expression in lung carcinomas. We hypothesize that the changes of the DMBT1 expression and location do reflect a time course that may point to possible mechanisms for its role in epithelial cancer.

Adult↗
PubMed2006

Lung function tests in neonates and infants with chronic lung disease of infancy: functional residual capacity.

This is the second paper in a review series that will summarize available data and discuss the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses the expansive subject of measurements of lung volume using plethysmography and gas dilution/washout techniques. Following orientation of the reader to the subject area, we focus our comments on areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. Measurements of lung volume are important both for assessing growth and development of lungs in health and disease, and for interpreting volume-dependent lung function parameters such as respiratory compliance, resistance, forced expiratory flows, and indices of gas-mixing efficiency. Acute neonatal lung disease is characterized by severely reduced functional residual capacity (FRC), with treatments aimed at securing optimal lung recruitment. While FRC may remain reduced in established chronic lung disease of infancy, more commonly it becomes normalized or even elevated due to hyperinflation, with or without gas-trapping, secondary to airway obstruction. Ideally, accurate and reliable bedside measurements of FRC would be feasible from birth, throughout all phases of postnatal care (including assisted ventilation), and during subsequent long-term follow-up. Although lung volume measurements in extremely preterm infants were described in a research environment, resolution of several issues is required before such investigations can be translated into routine clinical monitoring.

Airway Resistance↗
PubMed1987

Progress in lung cancer: non-oat cell (non-small cell lung cancer).

Lung cancer remains the greatest killing cancer in the United States with 149,000 new cases expected in 1987. The present expected mortality rate is 87 per cent. More women in the United States died of lung cancer than breast cancer in 1986. Asymptomatic, early and curable lung cancer in high risk individuals is usually found by routine chest X-ray. So-called Stage I lung cancer was reported to have a 83 per cent survival rate at three years by Martini and Beattie in 1977 and 70 per cent five year survival rate subsequently. When the more than 30,000 volunteer males were enrolled in the National Cancer Institute, national lung program for screening, 223 unsuspected lung cancers were found. 47 per cent were Stage I with a survival rate at five years of over 76 per cent. The PMI-Strang/Memorial Sloan Kettering Cancer Center study found 53 cancers in its first screen and 235 lung cancers over the next eight years of the study. Forty per cent were Stage I with a five year survival rate of 70 per cent. Sputum cytology as compared to chest X-ray was of little additional value. Studies (Martini) of Nl lung cancer was found to have a 49 per cent survival rate following resection. The N2 group of lung cancers where the mediastinal tumor was surgically removable and followed by external radiation therapy had a 27 per cent survival rate at five years. Those tumors with solitary brain metastases where the solitary brain metastasis could be resected and the primary tumor controlled, gave a 27 per cent survival rate at six years. The group of advanced N2 disease where the mediastinum could not be completely cleared were a serious group of cancers. A study of 100 patients treated from 1977 to 1980 with surgery plus internal radiotherapy followed by external radiotherapy had an overall 22 per cent survival rate for four to eight years with most of the deaths occurring because of metastases outside the chest. More recently chemotherapy has been used pre-operatively for those individuals with advanced lung cancer in the chest then followed by a combination of surgery, internal radiotherapy, external radiotherapy and more chemotherapy, if chemotherapy sensitive. This is the so-called multidisciplinary approach. In our present early studies it seems that those so treated who are chemotherapy sensitive have a 44 per cent, two year survival rate in a group of patients considered to have extremely poor prognosis.

Adolescent↗
PubMed2004

MR assessment of fetal lung development using lung volumes and signal intensities.

The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42 weeks) were examined on a 1.5- T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90 ms, slice thickness/gap 3-5/0 mm, FOV 26-40 cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5 cm(3) in correlation with gestational age ( P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age ( P=0.001). All SI ratios measured were unrelated to gestational age. Diagnoses in the seven abnormal fetuses were hydrothorax ( n=2), congenital cystic adenomatoid malformation ( n=2), diaphragmatic hernia ( n=2) and pulmonary sequestration ( n=1); their absolute and relative lung volumes were below normal ( P<0.001). The SI ratios did not differ significantly from those in the normal population. Normative MR fetal lung volumes may have important clinical applications in confirming and quantifying intrauterine pulmonary hypoplasia and in complementing ultrasound in the planning of fetal and post-natal surgery. No clinical relevance was found for fetal lung SI values.

Fetal Organ Maturity↗
PubMed1986

Effects of lung volume and airflow on the frequency spectrum of vesicular lung sounds.

UNLABELLED: The purpose of this study was to determine whether the vesicular lung sound frequency spectrum is affected by changes in lung volume and airflow. Nine healthy young nonsmokers were studied. The dependent variables were the points that divide the power spectrum of the vesicular lung sound into quarters (1st, 2nd and 3rd quartiles (Q1, Q2 and Q3]. Recording sites were the right upper anterior (RUL) and lower posterior (RLL) chest wall. Lung sounds were high-pass filtered at 100 Hz. To evaluate the effect of volume, lung sounds were recorded during an inspiratory vital capacity (VC) maneuver at near constant airflow rates. The spectral parameters were determined at each sixth of the VC. To assess the effects of airflow, 5 of the subjects breathed from resting lung volume at peak inspiratory airflows of between 1 and 3.0 L/sec for a total of 16 breaths each and the frequency parameters of the lung sounds occurring during peak inspiratory airflows were determined. RESULTS: Volume effects: only at the RUL was there a small but significant decrease in all three parameters with increasing lung volume. Airflow effects: all parameters were independent of airflow except for a weakly positive relationship (r = 0.285, P less than 0.05) for Q3 at the RUL location. Individually, there were weakly significant trends in three of the five subjects. These data suggest that the frequency composition of the vesicular lung sound in groups of healthy adults is not systematically affected by changes in lung volume or airflow.

Adult↗
PubMed1995

Contribution of opening and closing of lung units to lung hysteresis.

The recruitment and derecruitment of lung units is one explanation of the hysteresis observed in an excised lung during inflation and deflation. A simplified model has been proposed in which the recruitment-derecruitment process is a function of end-expiratory pressure (Frazer, D.G., K.C. Weber and G.N. Franz, Respir. Physiol. 61: 277-288, 1985). The object of this study was to test this model with three experimental procedures. During the first set of experiments, progressively larger pressure-volume (PL-VL) loops were recorded with end-expiratory pressure held at either -5 cmH2O, where all lung units are assumed to be closed, or +5 cmH2O, where all recruited lung units are assumed to be open. In the first case hysteresis is maximal, in the second, minimal. The difference in hysteresis is presumed to arise from the recruitment-derecruitment process. In the second set of experiments, excised lungs are slowly inflated and then deflated at a constant rate while constant-amplitude sinusoidal volume oscillations are superimposed. The end-expiratory pressure of the superimposed loops gradually rose as the lung was inflated and fell as the lung was deflated. Hysteresis was minimal when end-expiratory pressure was above 4 +/- 1 cmH2O even as peak-to-peak loop pressure greatly varied. This supports the notion of an end-expiratory pressure dependent mechanism of recruitment/derecruitment. During the third set of experiments lungs were inflated to either 50%, 75%, or 100% TLC. Volumes of air were then withdrawn and replaced so that the initial volume was restored in sinusoidal fashion as the amplitude of the volume excursions increased. For PL-VL loops with end-expiratory pressures between +4 and -2 cmH2O, pressure amplitudes rose and the hysteresis index (loop area/tidal volume) increased, regardless of the initial lung volume. These results are consistent with the previously described model of Frazer et al. (1985) which assumed that PL-VL curves can be divided into an 'opening' region, an 'open' region and a 'closing' region and that the demarcation of these regions depends on transpulmonary pressure, specifically end-expiratory pressure, and to a much lesser degree on lung volume.

Animals↗
PubMed2006

N-acetylcysteine attenuates the acute lung injury caused by phorbol myristate acetate in isolated rat lungs.

Acute lung injury (ALI) caused by phorbol myristate acetate (PMA) is characterized by pulmonary edema and inflammatory cells infiltration. PMA-activated neutrophils in vivo and in vitro to release free radicals, pro-inflammatory cytokines, nitric oxide (NO) and other mediators. These mediators may be the causes of pulmonary hypertension and increased microvascular permeability. In the present study, we used isolated perfused rat lungs from Sprague-Dawley (SD) rats. The purpose was to evaluate the effects of pretreatment of N-acetylcysteine (NAC) on the PMA-induced ALI and associated changes. PMA (2 microg kg(-1)) was introduced into the lung perfusate. NAC (150 mg kg(-1)) was administered 10 min before PMA. Thirty isolated lungs were randomly assigned to receive vehicle (dimethyl sulfoxide, DMSO, the solvent for PMA, 100 microg g(-1)), PMA alone and PMA with NAC pretreatment. There were 10 lungs in each group. We measured the lung weight (LW) to body weight (BW) ratio (LW/BW), LW gain (LWG), exhaled nitric oxide (NO) and protein concentration in bronchoalveolar lavage (PCBAL). The pulmonary arterial pressure (PAP) and microvascular permeability (K(fc)) were assessed. The concentration of nitrate/nitrite, methyl guanidine (MG), tumor necrosis factor(alpha) (TNF(alpha)) and interleukin-1(beta) (IL-1(beta)) in lung perfusate were determined. In addition, we also evaluate the lung injury by histopathological examination and by grading system for the lung injury score (LIS). PMA caused severe ALI as evidenced by the marked increases in LW changes, exhaled NO, PCBAL, histopathological changes, and LIS. It also increased the nitrate/nitrite, MG, TNF(alpha), and IL-1(beta) in lung perfusate. Pretreatment with NAC significantly attenuated these changes and abrogated the extent of ALI. Our results suggest that NAC exerts strong protective effects on the PMA-induced ALI and associated alterations. The mechanisms are possibly attributable to its antioxidant actions, inhibition of pro-inflammatory cytokines, and restoration of glutathione enzymes.

Acetylcysteine↗
PubMed2005

Peripheral lung volume reduction improved early graft function in severe size mismatched living donor lobar lung transplantation.

BACKGROUND: Lung transplantation from adults to infants or small children is still challenging because of concerns related to size disparity. Peripheral lung volume reduction for size disparity in cadaveric donor lung transplantation has been widely performed; however, little is known about the efficacy and the functional outcomes of downsizing the implanted lobes for severe size disparity in living donor lobar lung transplantation. METHODS: Thirteen size-mismatched (donor/recipient lung volume ratio > 2.82) bilateral living donor lobar lung transplants were performed with (reduction group, n = 6) or without (no-reduction group, n = 7) peripheral lung volume reduction. RESULTS: On spontaneous respiration, PaO2 in the reduction group was significantly higher than that in the no-reduction group (P < .01) and PaCO2 in the reduction group was significantly lower than that in the no-reduction group (P < .001). Pulmonary vascular resistance in the reduction group remained significantly lower than that in the no-reduction group throughout the assessment periods after chest closure (P < .05). Peak airway pressure in the no-reduction group increased significantly at the time of chest closure (P < .001) and remained significantly higher than that in the reduction group throughout the assessment period on mechanical ventilation (P < .01). The percentage of weight reduced from implanted grafts significantly correlated with donor/recipient lung volume ratio (r = 0.82, P < .05). CONCLUSIONS: Peripheral lung volume reduction is useful to improve early graft function in severe size mismatched experimental living donor lobar lung transplantation. The technique might allow for further flexibility in donor size and for increasing the donor pool for small recipients.

Adult↗
PubMed1997

Incidence of lung nodules found in patients undergoing lung volume reduction.

BACKGROUND: The risk of lung cancer is increased with cigarette smoking and obstructive lung disease. Patients having a lung volume reduction operation represent a high-risk population for cancer. METHODS: Between March 1994 and December 1996, 281 patients underwent a lung volume reduction operation. All had severe obstructive lung disease with hyperinflation. The incidence of lung nodules and their management were addressed. RESULTS: Of the 281 patients, 39.5% had at least one lung nodule identified. Fifty-two nodules had typical benign calcification patterns. Of the remaining nodules, 78 were resected and 20 were followed up. Seventeen nodules resected were cancerous, of which 13 were primary lung cancers. Of the resected nodules there were 28 nodules not identified by the preoperative radiologic evaluation. CONCLUSIONS: Nodules are frequently seen in patients undergoing lung volume reduction operations. The overall incidence of cancer was 6.4%, with several only identified in the pathologic examination. Survival at short follow-up has been excellent for those with primary lung cancer. Nodules seen in this group of patients should be aggressively diagnosed and managed.

Aged↗
PubMed2002

Lung toxicity following chest irradiation in patients with lung cancer.

Classical radiation pneumonitis has been described after single dose whole lung irradiation in experimental animals where above a threshold dose of irradiation, there is a sigmoid dose response curve with increasing morbidity and mortality. After clinical fractionated irradiation, however, acute radiation pneumonitis consisting of cough shortness of breath and patchy radiological changes, occurs in <10% of patients, has dyspnoea out of proportion to the volume of lung irradiated and usually resolves completely without long-term effects. There is increasing evidence that this represents a bilateral lymphocytic alveolitis or hypersensitivity pneumonitis and has been termed sporadic pneumonitis. Late radiation toxicity results in pulmonary fibrosis. This is a consequence of repair, which is initiated by tissue injury within the radiation portal. It follows release of chemotactic factors for fibroblasts including transforming growth factor-beta, fibronectin and platelet derived growth factor. Radiation fibrosis is the clinically more significant syndrome for patients. It may result in progressive dyspnoea and mortality in patients. The most predictable change in laboratory lung function tests is a decrease in transfer factor due to damage at the capillary-alveolar level. It also results in decreased lung compliance, which will affect the total lung capacity and the forced vital capacity. The forced expiratory volume in 1 s is less affected, although this seems to depend on the volume of lung irradiated. There is also a decrease in perfusion in the irradiated lung. Radiation fibrosis seems to depend, amongst other factors, on the volume of lung, which is irradiated above a threshold of 20-30 Gy. The morbidity of radiation fibrosis may therefore be minimized by the use of dose volume histogram to minimize the volume of normal lung irradiated in patients at high risk, e.g., patients with who present with poor lung function. The importance of the baseline perfusion in the irradiated areas continues to be studied.

Dose Fractionation, Radiation↗
PubMed2003

Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry.

OBJECTIVES: Early lung cancer detection and treatment remain a challenge. The efficacy of surface-enhanced laser desorption/ionization (SELDI) technology in lung cancer detection, has not been defined. This study identifies specific protein peak patterns in malignant lung tumors, and in pre-malignant airways epithelium showing neoplastic transformation. METHODS: Lung tumor specimens taken from patients participating in a lung cancer screening study (H. Lee Moffitt Cancer Center, Tampa, FL) were laser capture microdissected to obtain pure cell populations from frozen sections of normal lung, atypical adenomatous hyperplasia (AAH) and malignant tumors. SELDI mass spectrometry was used to generate protein profiles in each epithelial cell type. RESULTS: SELDI mass spectroscopy is highly reproducible in detecting lung tumor-specific protein profiles. Three peaks at 17-23 kDa mass range from tumor cells showed markedly increased compared with normal cells. The peak at 17250 Da was not detected in any of the normal cells. This peak appeared to be present at low levels in the atypical cell samples. CONCLUSIONS: This study demonstrates the feasibility of detecting "malignant" protein signatures from lung tumor and pre-malignant pulmonary epithelium using SELDI mass spectrometry. Although additional study is necessary to validate these patterns as unique diagnostic tools, these "malignant" protein signatures lend themselves to identification of populations at high-risk for lung cancer and for monitoring response to lung cancer chemopreventive agents.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

In-situ topical cooling of lung grafts: early graft function and surfactant analysis in a porcine single lung transplant model.

OBJECTIVE: Improvement of organ preservation is essential to facilitate acceptance of marginal donor lungs for transplantation. Thus, recruiting non-heart-beating donors (NHBD) may be one reasonable strategy to augment the organ-pool especially in the field of pulmonary transplantation. Topical cooling (TC) of donor lungs could provide fast organ-protection and is an available procedure even in smaller centers. In this study transplanted lung function and surfactant activity in same lungs, which were preserved by TC, were assessed following transplantation. METHODS: Twelve porcine allogeneic single lung transplants were performed. Six lungs that were flush preserved through the antegrade route served as controls. The other six lungs were preserved by TC for 30 min after induction of cardiac arrest by repeated application of cold saline (8 degrees C) to both pleural cavities. Lungs of both groups were stored in LPD solution for 24 h at 8 degrees C. After transplantation, the recipient's right bronchus and right pulmonary artery were clamped. Major endpoints included early graft function over a period of 7 h. Hemodynamic measures and respiratory functions were recorded in 30-min intervals. Surfactant function was determined before transplantation and 2 h after reperfusion by broncho-alveolar lavage fluid analysis. RESULTS: Only four animals of the control-group survived the 7 h reperfusion period. Right heart failure occurred in two animals after 150 and 240 min of reperfusion. All six animals in the TC group survived the observation period. Pulmonary vascular resistance (p<0.01), pulmonary artery pressure (p=0.03), and lung tissue water content remained significantly lower in topically cooled allografts (p=0.01) vs. controls. Surfactant function after transplantation was comparable in both groups with a trend towards lower protein contents (p=0.07) in the broncho-alveolar fluid of grafts after TC. CONCLUSIONS: In-situ TC seems to be a reliable strategy to preserve lungs for up to 24 h. It even surpasses the results of LPD-perfused grafts in hemodynamic function and survival time.

Animals↗