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PubMed2000

Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice.

Aquaporin (AQP) water channels provide a major pathway for osmotically driven water movement across epithelial and microvascular barriers in the lung. We used mice deficient in each of the three principal lung aquaporins, AQP1, AQP4 and AQP5, to test the hypothesis that aquaporins are important in neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury. Wet-to-dry weight ratios (W/D) in lungs from wild-type mice decreased from 7.9 to 5.7 over the first hour after spontaneous delivery. AQP deletion did not significantly affect W/D at 45 min after birth. Alveolar fluid clearance was measured in living ventilated mice in which 0.5 ml saline containing radiolabelled albumin was instilled into the airspaces. Fluid clearance was 17.4 % in 15 min and inhibited >90 % by amiloride, but clearance was not affected by AQP deletion. W/D was measured in established models of acute lung injury - acid aspiration and thiourea administration. Two hours after intratracheal administration of HCl, W/D increased from 3.7 to 7.5 but was not affected by AQP deletion. Three hours after intraperitoneal infusion of thiourea, W/D increased to 5.5 and marked pleural effusions appeared, but there were no differences in wild-type and AQP knockout mice. Hyperoxic subacute lung injury was induced by 95 % oxygen. Neither mean survival (143 h) nor W/D at 65 h (5.1) were significantly affected by AQP deletion. Despite their role in osmotically driven lung water transport, aquaporins are not required for the physiological clearance of lung water in the neonatal or adult lung, or for the accumulation of extravascular lung water in the injured lung.

Acids↗
PubMed2000

[Pretreatment of acid-induced lung injury with specific neutrophil elastase inhibitor ONO-5046 did not exasperate the subsequent bacterial lung infection by Pseudomonas aeruginosa].

Patients with acid lung injuries are at high risk for bacterial pulmonary infections which commonly occur several days after the acid aspiration. We reported that a specific neutrophil elastase inhibitor ONO-5046 inhibited the multi-organ injury caused by acid-instillation into the lung. In this study, we evaluated the effect of ONO-5046 on lung infection by Pseudomonas aeruginosa (PAO-1:Ps.) following acid-induced lung injury in rat lungs. Animals received 0.2 ml of hydrochloric acid (pH = 1) into the right lungs. Pretreated animals were administered ONO-5046 (30 mg.kg-1) i.v. 15 min. before acid instillation. Other groups received vehicle (saline). Twenty four hours later, they were instilled with 0.1 ml of Ps. 1 x 10(8) cfu into the left lungs. Four hours after bacterial challenge, the animals were deeply anesthetized and killed. Bronchoalveolar lavage was done on each lung separately to evaluate neutrophil elastase activity, neutrophil number and protein permeability of lung endothelium and epithelium. The numbers of Ps. in the lungs were measured. In the Ps.-instilled lung, the number of Ps. or the protein permeability was not increased with ONO-5046 pretreatment compared with those in the untreated group. Pretreatment inhibited the exasperation of the protein permeability indirectly caused by Ps. infection in the acid-instilled lung. It was indicated that ONO-5046 could inhibit the indirect lung injury caused by acid-instillation into the lung without aggravating the subsequent bacterial infection.

Animals↗
PubMed2005

Comparison of lung area by chest radiograph, with estimation of lung volume by helium dilution during prone and supine positioning in mechanically ventilated preterm infants: a pilot study.

Measurement of lung volume may be useful in determining the degree of lung disease and for optimizing an infant's mechanical ventilator settings. A chest radiograph (CXR) is often used to estimate lung volume, because direct measurement, e.g., functional residual capacity (FRC), is neither practical nor possible in the neonatal intensive care unit. In supinely positioned infants, good correlation was found between lung area determined by CXR and lung volume, e.g., functional residual capacity (FRC). Whether this is true for the prone position is unknown. Since positioning may affect oxygenation and pulmonary function, we studied the relationship between lung area measured from CXR and FRC during both supine and prone positioning in 14 mechanically ventilated preterm infants. Lung area was determined from CXRs using computed radiography and FRCs obtained by helium dilution at end-expiration in both supine and prone positions. Reproducibility of lung area measurements was demonstrated by high correlations between two observers (R2 = 0.92 and 0.99 for supine and prone, respectively). When supine, lung area was 15.4 +/- 3.1 cm2, and FRC was 19.5 +/- 7.3 ml. In prone position, lung area was 16.7 +/- 4.2 cm2, and FRC 23.0 +/- 9.4 ml. There was a moderate to strong positive correlation between lung area and FRC for both positions (supine: r = 0.57, P < 0.03; prone: r = 0.63, P < 0.02). Lung area measured by computed radiography is a reproducible and practical method for estimating lung volume from routine chest X-rays in both supine and prone positions in mechanically ventilated preterm infants.

Female↗
PubMed1991

Metal concentrations in lung tissue of subjects suffering from lung cancer.

Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States.

The authors conducted a population-based case-control study of lung cancer in nonsmoking women in five metropolitan areas of the United States between December 1, 1985, and November 30, 1990. In-person interviews were conducted with 412 lung cancer cases and 1,253 population controls, yielding information on history of nonmalignant lung diseases that were diagnosed by a physician. When lung cancer cases were compared with controls, history of any previous lung disease was associated with a significant increased risk of lung cancer (adjusted odds ratio (AOR) = 1.56, 95% confidence interval (CI) 1.2-2.0). Several lung diseases, including asthma, chronic bronchitis, pneumonia, and tuberculosis, were reported more often by lung cancer cases than by controls, and the difference was statistically significant for asthma (AOR = 1.67, 95% CI 1.1-2.5) and chronic bronchitis (AOR = 1.60, 95% CI 1.1-2.4). Since significant increased risks were observed for asthma and tuberculosis diagnosed before age 21 years, it is unlikely that reported prior lung diseases were prediagnostic manifestations of lung cancers. The increased risks associated with previous lung disease were observed for adenocarcinomas and other carcinomas of the lung; the point estimates were generally higher for the latter category. The risks associated with previous lung diseases remained unchanged after adjustment for potential confounders, including environmental tobacco smoke exposure during childhood and adult life and dietary factors.

Adenocarcinoma↗
PubMed1996

Endothelin-1 and cell proliferation in lung organ cultures. Implications for lung allografts.

Endothelin-1 (ET-1) is found in bronchoalveolar lavage fluid in patients following lung transplantation. ET-1 causes contraction of isolated pulmonary vessels and bronchi and stimulates proliferation of smooth muscle cells in culture. Therefore, ET-1 could contribute to the smooth muscle hyperplasia and stromal proliferation seen in chronic rejection of lung allografts. Experiments were designed to determine whether (1) ET-1 stimulates proliferation of pulmonary tissue, (2) proliferation is increased in rejecting allotransplanted lungs, (3) endothelin-A receptors mediate the proliferative response, and (4) ET-1 is produced by activated infiltrating immunocompetent cells. Lung organ cultures were prepared from unoperated dogs and dogs with rejecting single lung allografts. Incubation of organ cultures from unoperated dogs with ET-1 (10(-9) to 10(-7) M)) increased positive staining for proliferation cell nuclear antigen (PCNA) in lung parenchyma. PCNA staining was not decreased by the endothelin-A antagonist BQ123 (10(-6) M). In addition, immunostaining for endothelin-B receptors was present in sections of unoperated but not rejecting lungs. PCNA staining in lung cultures from rejecting allotransplanted dogs was significantly greater than that from unoperated dogs. Positive immunohistochemical staining for ET-1 was found in mononuclear cells infiltrating rejecting transplanted lungs. In conclusion, exogenous ET-1 is mitogenic in lung organ cultures through receptors other than endothelin-A. Proliferation in rejecting transplanted lungs is increased compared with unoperated lungs. Mononuclear cells may be a source of endothelin-1 in the rejecting lung. ET-1, therefore could, in synergism with other cytokines, contribute to acute and chronic pathological changes seen in pulmonary rejection.

Animals↗
PubMed1998

Donor-derived antibodies and hemolysis after ABO-compatible but nonidentical heart-lung and lung transplantation.

BACKGROUND: Organ donors and transplant recipients are routinely tested for ABO compatibility. ABO-identical organs are preferred, but occasionally the use of an ABO-compatible but nonidentical donor is clinically warranted. In heart-lung transplantation, the incidence of hemolysis from donor-derived anti-ABO antibodies is as high as 70%. The incidence of hemolysis for lung-only transplantation is not known. Our current posttransplantation transfusion policy for ABO-compatible but nonidentical lung-only transplant recipients is, when indicated, to use donor ABO group red blood cells. METHODS: To evaluate the efficacy of our transfusion policy, we reviewed our experience from 1986-96. One heart-lung transplant, four single lung transplant, and three bilateral single lung transplant recipients received ABO-compatible but nonidentical organs. RESULTS: The heart-lung transplant recipient developed a positive direct antiglobulin test (DAT), with anti-A eluted, and severe hemolysis on postoperative day 8 requiring plasma and whole blood exchange. Four of six lung-only transplant patients tested developed a positive DAT with anti-A eluted. Two early lung-only patients, who did not receive donor ABO group red blood cells, demonstrated clinical and laboratory evidence of hemolysis. Three bilateral lung transplant recipients were followed prospectively. The first patient had a negative DAT. The next two patients developed positive DATs on postoperative day 8 and 10, respectively. No evidence of hemolysis was detected in any of these cases. CONCLUSIONS: These results confirm that donor-derived anti-ABO antibodies develop with lung-only transplants. Our current transfusion policy is justified for both heart-lung and lung recipients of ABO-compatible but nonidentical organs. A high index of suspicion for donor-derived antibody causing hemolysis and communication with blood bank personnel are mandatory in this setting.

ABO Blood-Group System↗
PubMed2001

Lung transplantation in interstitial lung disease.

Interstitial lung disease is a heterogeneous group of illnesses, some of which may progress to a fibrosing stage and cause respiratory failure. For selected candidates, lung transplantation is the ultimate therapeutic option. We review data on lung transplantation for various interstitial lung diseases. We address indications, procedures, and outcomes for patients undergoing transplantation. Unique issues affecting morbidity, mortality, and recurrence of disease are discussed. We review the literature of transplantation for specific interstitial lung diseases and the outcomes of transplantation for interstitial lung diseases. Candidates with idiopathic pulmonary fibrosis experience high mortality on the waiting list, but derive significant survival benefit from lung transplantation. Recurrence is reported for several interstitial lung diseases after lung transplantation. Survival with lung transplantation for interstitial lung diseases is comparable with that attained in recipients with other indications. Lung transplantation is a well-tolerated, effective therapy for respiratory failure in interstitial lung disease.

Histiocytosis, Langerhans-Cell↗
PubMed2004

Fetal relative lung volume: quantification by using prenatal MR imaging lung volumetry.

PURPOSE: To retrospectively determine a biometric algorithm for calculating relative lung volume in fetuses with normal lungs and of a wide range of gestational ages by using proved independent variables and to retrospectively investigate the use of this algorithm in fetuses with pulmonary hypoplasia. MATERIALS AND METHODS: Total lung volume (TLV) was measured by using planimetry on single-shot rapid acquisition with relaxation enhancement magnetic resonance (MR) images obtained in 91 fetuses with ultrasonographically (US) normal chests and 28 fetuses with US-determined pulmonary hypoplasia. All fetuses were aged between 18 and 38 weeks gestation. Analysis of covariance was used to identify parameters that were not different between the fetuses with US-determined normal and those with US-determined abnormal chests, and these variables were used to construct an algorithm for calculating predicted lung volume. The relative lung volume-that is, the observed lung volume expressed as a percentage of the predicted lung volume-was then calculated in fetuses with pulmonary hypoplasia. RESULTS: There was no significant difference in mean maternal or gestational age between the two fetus groups. Stepwise regression analysis was used to generate the following equation for predicting fetal lung volume on the basis of independent biometric indexes, with a correlation coefficient of 0.93: TLV = (0.52 . LV) + (0.33 . BD) - (0.06 . FL) - 13.7, with TLV and liver volume (LV) in milliliters and biparietal diameter (BD) and femoral length (FL) in centimeters. In the fetuses with normal chests, relative lung volume varied between 51% and 134%. In the fetuses with pulmonary hypoplasia, relative lung volume varied between 6% and 70%. CONCLUSION: The predicted lung volume in fetuses of a wide range of gestational ages can be calculated with a high degree of accuracy, enabling prenatal MR imaging lung volumetry in which relative lung volume is used to quantify fetal pulmonary hypoplasia.

Adolescent↗
PubMed1988

Assessment of lung water distribution by nuclear magnetic resonance. A new method for quantifying and monitoring experimental lung injury.

We have developed a new analytical method that uses nuclear magnetic resonance (NMR) imaging data to quantify lung water content and distribution. This new method generates a distribution of lung water density in which the fraction of voxels corresponding to a given water density is plotted on the vertical axis as a function of water density on the horizontal axis, thereby complementing the spatial information provided by the NMR image. We obtained reproducible lung water distribution data at comparable lung volumes in normal excised lungs and in intact living rats. In normal excised unperfused rat lungs, the distribution varied with the degree of inflation, but the changes were small compared with those associated with lung edema. The lung water density distribution changed markedly after induction of lung edema by intrabronchial saline instillation, intravenous oleic acid injection, and rapid intravenous saline infusion. Lung water density distribution data were well correlated (correlation coefficient = 0.948 for the excised lungs and 0.823 for the intact living rats) with gravimetric lung water measurements. The new analytical method is noninvasive, provides easily repeatable measurements, and is as sensitive as the gravimetric technique to lung water changes.

Animals↗
PubMed1992

Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels.

Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Exercise testing in pediatric heart, heart-lung, and lung transplant recipients.

Cardiorespiratory responses to progressive exercise were examined in 38 children who had undergone heart (n = 16), heart-lung (n = 13), or double-lung (n = 9) transplantation, and in 41 healthy controls. The four groups were similar in age, but the control subjects and heart transplant recipients were significantly larger than the heart-lung and lung recipients as assessed by body mass index (BMI). Time since transplant was significantly longer in the heart (601 days) compared with heart-lung (146 days) and lung (125 days) transplant groups. Physical work capacity and peak oxygen uptake were significantly reduced (43 to 64% of predicted) in the three transplant groups compared with the control group. Peak heart rate (percent predicted) was significantly higher in the control subjects (94%) compared with the heart (66%), heart-lung (70%), and lung (77%) transplant recipients. Peak minute ventilation was significantly higher in the control (72.9 L/min) and heart transplant (51.0 L/min) groups than the heart-lung (37.4 L/min) and lung (41.3 L/min) transplant groups. The control group had a higher peak tidal volume than the three transplant groups, and a higher peak respiratory rate than the lung transplant recipients. Correlational analysis revealed that physical work capacity (PWC) was significantly related to heart rate at peak exercise (HRpeak) and minute ventilation at peak exercise (VE-peak) in the heart transplant recipients, BMI, VEpeak, and FEV1 in the heart-lung transplant recipients, and BMI, HRpeak, VEpeak, FEV1, and number of days posttransplant in the lung transplant recipients. In addition to these variables, physical deconditioning and factors related to pharmacotherapy, infection, and rejection may also contribute to the decreased PWC observed in the transplant recipients.

Adolescent↗
PubMed1995

The effects of applied vs auto-PEEP on local lung unit pressure and volume in a four-unit lung model.

BACKGROUND: The application of positive end-expiratory pressure (PEEP) and maintenance of increased mean airway pressure (MAP) has been associated with improved oxygenation in adult respiratory distress syndrome. Recently, attention has been directed toward elevating MAP by establishing auto-PEEP when ventilating with an inverse inspiratory to expiratory ratio in opposition to applied PEEP. We theorized that FRC distribution and local lung unit end-expiratory pressure (EEP) would be different when equal levels of PEEP were established by applying PEEP or by producing auto-PEEP. METHODS: Using a four-chamber lung model with each chamber having a different time constant (TC), we applied equal levels of applied PEEP (I:E ratio 1:3) and auto-PEEP (I:E ratio 3:1) and evaluated local lung unit EEP and end expiratory lung volume (EELV). RESULTS: During all trials with applied PEEP, local lung unit EEP was equal to applied PEEP, whereas during auto-PEEP local EEP differed (p < 0.01). At a tracheal auto-PEEP level of 12.7 cm H2O, the lung unit with the longest TC (slow lung unit) had an EEP of 15.8 cm H2O, while the shortest TC unit (fast lung unit) had an EEP of 10.1 cm H2O (p < 0.01). Similarly, local EELVs were more maldistributed with auto-PEEP than with applied PEEP. At a tracheal PEEP level of 12.7 cm H2O, the EELV increase in the slow lung unit with auto-PEEP was 1,054 mL vs 918 with applied PEEP (p < 0.01), whereas the fast lung unit's EELV increase with auto-PEEP was 142 mL compared with 212 mL with applied PEEP (p < 0.01). CONCLUSION: Comparing equal levels of the auto-PEEP with applied PEEP, a greater maldistribution of local lung unit EEP and EELV was established with the auto-PEEP. During auto-PEEP, the greatest EEP and EELV occurred in the slow lung unit, and the lowest EEP and EELV developed in the fast lung unit.

Adult↗
PubMed1996

Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer.

We synthesized a potent new antitumor podophyllotoxin derivative (4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin; TOP-53) in our search for a drug that has strong activity against lung cancer and lung metastatic cancer. TOP-53 exhibited twice the inhibitory activity of etoposide (VP-16) against topoisomerase II and induced DNA strand breaks but showed no inhibitory activity against tubulin polymerization. The in vitro cytotoxic activity of TOP-53 assessed as IC50 was 0.016-0.37 microg/ml and 0.26-8.9 microg/ml against marine tumor and human non-small cell lung cancer (NSCLC) cell lines, respectively. TOP-53 exerted significant efficacy equivalent to that of VP-16 on s.c.-implanted murine solid tumors (Colon 26, B16-BL6, and Lewis lung carcinoma) at doses 3-5 times lower than that of VP-16. In human tumor xenografts using NSCLC, TOP-53 was active for four of five tumors, whereas VP-16 was active for two of five tumors. Potent inhibitory activity of TOP-53 was also found against a lung tumor (Lewis lung carcinoma) and four lung metastatic tumors (NL-22 and NL-17 colon cancer, UV2237M fibrosarcoma, and K1735M2 melanoma). TOP-53 appeared to be more active against four of them than VP-16. Thus, TOP-53 is not only active against s.c.-implanted lung cancers but also strongly active against lung localized tumor and metastatic tumors in the lungs. The high selectivity of TOP-53 was attributed to its high distribution into the lung and its persistence. TOP-53 is expected to be highly effective against lung cancer including NSCLC and various lung metastatic tumors in the clinical field.

Animals↗
PubMed1996

Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma.

In the present work we studied the levels of activities of dipeptidyl-peptidase I (or cathepsin C, DPP-I) and dipeptidyl-peptidase II (DPP-II) and examined their isoelectric focusing profiles in matched pairs of human squamous cell lung carcinoma (SQCLC) and the lung from surgically treated patients (n = 33). The mean specific activities of DPP-I and DPP-II were higher in SQCLC (Stages I and II) than in the lung, but only the activity of DPP-II in Stage I SQCLC was significantly higher compared to the lung. The activities of both enzymes were higher in the tumor than in the lung in 10 of 20 Stage I SQCLC patients, but only in 3 of 13 Stage II SQCLC patients. The specific activities of DPP-I and DPP-II in the lungs showed a good correlation while the correlation of both enzyme activities in SQCLCs was poor. We observed only a small and mutually comparable activation of DPP-I in extracts from SQCLCs and from the lungs by dithiothreitol. The isoelectric focusing profile of several DPP-II forms in SQCLCs and the lungs was similar and the single major DPP-II isoform revealed in the tumors and lungs showed a pIapp of 5.3-5.2. The isoelectric focusing profile of DPP-I showed multiple enzyme forms in SQCLCs (pIapp 6.3-4.5) as well as in the lungs (pIapp 6.4-4.8). In SQCLCs, as well as in the lungs, the activities of the DPP-I forms with pIapp values < or = 5.6 were shifted by neuraminidase treatment to the site of the major DPP-I isoform with pIapp of about 6.0 and the zymograms then showed an another DPP-I with pIapp of 5.7, which was less discernible in the lung. In some patients, the DPP-I forms with pIapp values < or = 5.6 from SQCLC retained a greater percentage of activity distribution than did the DPP-I pIapp-counterparts from the lung.

Adult↗
PubMed1997

Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance.

UNLABELLED: This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to investigate radiation-induced lung changes in eight patients undergoing radiotherapy for lung or breast carcinoma. The sensitivity of the method was compared with chest radiography for detecting radiation-induced changes in the lung, regional alterations within (irradiated region) and outside (shielded region) the treatment ports, effect of irradiated lung volume, and dependence on time after radiotherapy. METHODS: Serial DTPA lung clearance studies were performed before the first radiation treatment (baseline), then weekly during a 5- to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The total activity deposited in the lungs for each study was approximately 150 microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the biological half-time, t 1/2, was computed from the slopes of the least-squares fit regression lines of the time-activity curves for the first 10 min for irradiated and shielded lung regions. RESULTS: Major findings include: (a) significant and early DTPA t 1/2 changes were observed in all patients during and after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both irradiated and shielded lung regions in all patients suggesting a radiation-induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p < 0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2 values were observed in three patients who subsequently presented with clinical symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2 felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three patients occurred 35-84 days before clinical symptoms and/or radiographic changes; and (f) DTPA t 1/2 tended to approach baseline values with time after radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These observations show significant and early alterations in DTPA lung clearance during and after radiotherapy that may provide a sensitive assay to monitor changes in radiation-induced lung injury and may facilitate early therapeutic intervention.

Aerosols↗
PubMed1997

Respiratory mechanics after heart-lung and bilateral lung transplantation.

BACKGROUND: The factors determining respiratory mechanics following heart-lung transplantation (HLT) and bilateral lung transplantation (BLT) are incompletely understood. METHODS: The dynamic and static lung volumes of 15 patients after HLT (n = 6) and BLT (n = 9) with no evidence of obliterative bronchiolitis were analysed to assess the factors which determine lung volumes following transplantation. Post-transplantation total lung capacity (TLCpost) was compared with the size of the recipient's lungs (TLCpre), the predicted capacity of the thorax of the recipient (TLCpred), and the predicted size of the donor's lungs (TLCdon). In addition, the post-transplantation respiratory mechanics were investigated by measuring the static pressure-volume (PV) curve of the lungs and the maximum respiratory pressures in a subgroup of nine patients (four HLT, five BLT). RESULTS: TLCpost was closely related to TLCpred in both groups and showed no correlation with TLCpre. The mean (95% CI) TLCpost was 102.5 (90.2 to 115)% predicted for the recipient in the HLT group and 109 (97.6 to 120)% predicted for the recipient in the BLT group. Despite the near normal TLC, residual volume (RV) and functional residual capacity (FRC) remained increased after transplantation in both groups. These abnormalities were not attributable to either airflow obstruction or expiratory muscle weakness. On average, lung compliance expressed in terms of the shape constant of the static pressure-volume curve of the lungs was mildly reduced in both groups compared with values predicted for the recipient. CONCLUSIONS: These results suggest that at high lung volumes the chest wall adapts to the size of transplanted lungs, while at lower volumes the increase in FRC and RV might be due to a persistent change in the static pressure-volume curve of the chest wall.

Adult↗
PubMed1995

Reduced transplant lung volumes after single lung transplantation for chronic obstructive pulmonary disease.

Single lung transplantation is now an extremely successful option for the treatment of end-stage chronic obstructive pulmonary disease (COPD). This procedure involves placing a normal sized lung in a hyperinflated hemithorax. Preliminary observations of these patients suggest that the transplanted lung volume is smaller than expected and often the native (COPD) lung increases in volume. The purpose of this investigation was to quantify the volume contributions of the transplant and native lung to the total lung capacity. In seven patients who underwent single lung transplant for end-stage COPD the transplant and native lung volumes were measured by computer-analyzed planimetry immediately after transplant and the following 6 mo post-transplant. The transplant lung volume was smaller than predicted immediately after transplant at only 33 +/- 5% (mean +/- SD) of predicted TLC. This did not change significantly over the next 6 mo. Native lung volume increased following transplant to 74 +/- 19% predicted TLC at 1 mo and 80 +/- 16% at 6 mo. Five of the seven patients subsequently underwent measurement of pleural pressures at TLC. The mean static pleural pressure at TLC was low at -16 +/- 5.1 cm H2O. In summary, following single lung transplantation for COPD the transplanted lung is significantly restricted. We conclude that the likely mechanism of this restriction is due to low transpulmonary pressure generation.

Female↗