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Inhibition of lung fibroblast growth by human lung mononuclear cells.

Mononuclear cell-fibroblast interactions in the normal human lung are poorly understood. To investigate these interactions, we characterized the effect on lung fibroblast growth of supernatants from nonadherent lung mononuclear cells cultured with or without phytohemagglutinin (PHA). Supernatants from unstimulated cells had no effect on fibroblast growth. Supernatants from lung mononuclear cells stimulated by PHA inhibited fibroblast growth in a dose-dependent fashion. This inhibition was mediated by a nondialyzable, noncytotoxic, soluble factor(s) that was partially heat labile and sensitive to digestion with trypsin. Production of this factor(s) was dependent on T-lymphocytes and occurred within 4 h of the initiation of lung mononuclear cell-PHA cultures. Because prostaglandins can mediate mononuclear cell effects on fibroblast growth, we examined the relationship between the inhibition of fibroblast growth caused by PHA-stimulated nonadherent lung mononuclear cells and lung fibroblast prostaglandin production. The nonadherent lung mononuclear cell supernatants stimulated fibroblast PGE2 production, and exogenous PGE2 was capable of inhibiting fibroblast growth. However, the inhibition of fibroblast growth caused by nonadherent lung mononuclear cells stimulated by PHA was not mediated by fibroblast prostaglandin production. Inhibition of lung fibroblast growth by stimulated lung mononuclear cells may be important in regulating fibrosis in the human lung.

Cell Extracts↗

Discrimination of human lung neoplasm from normal lung by two target genes.

Simple tools for discrimination of lung tissues can be useful in a fast machine-aided diagnosis, for example, by tumor-specific microarrays. We demonstrate that an easy ratio technique, based on the expression levels of only two genes differentially expressed in lung tumor and normal lung samples, allows discrimination of normal and neoplastic lung with a sensitivity of 100% and specificity of 90.5%. DNA microarray analysis of 99 lung tumor samples and 15 normal lung tissues revealed that receptor for advanced glycation end products (RAGE) mRNA is reduced fourfold (p = 7.8 x 10(-11)) and cyclin-B2 mRNA is upregulated twofold (p = 5.9 x 10(-18)) in lung carcinoma compared with normal lung. The microarray-calculated expression ratio of RAGE to cyclin-B2 was used in polymerase chain reaction analysis of 84 independent blinded samples to discriminate tumor and corresponding normal lung tissues. In 94.7% of the samples this quotient correctly distinguished non-small cell lung cancer from normal lung tissue, suggesting the RAGE/cyclin-B2 quotient as a potential means for diagnosis of lung cancer.

Adenocarcinoma↗

Postpneumonectomy lung growth: a model of reinitiation of tropoelastin and type I collagen production in a normal pattern in adult rat lung.

Elastic and collagen fibers confer recoil and tensile strength on the pulmonary vasculature, airways, alveolar walls, and pleura. These durable extracellular matrix components are primarily synthesized during lung development and growth, and are expressed at very low levels in healthy adult lung. However, reinitiation of elastin and collagen synthesis in diseases of adult lung, such as idiopathic pulmonary fibrosis, often leads to excessive or aberrant deposition of elastin and collagen which contribute to the pathophysiology of these diseases. We used an experimental model of postpneumonectomy lung growth to determine whether normal patterns of synthesis and deposition of these critical structural components can occur in the adult lung. Male Sprague-Dawley rats (250-300 grams) were subjected to left pneumonectomy and right lobectomy. The remaining lung tissue was harvested for analysis after 3, 7, or 14 days. Compensatory growth of the remaining right lung progressed throughout the time course. Total desmosine and hydroxyproline content increased in the postpneumonectomy lung, reflecting increased elastin and collagen accumulation, but both were normal in content per weight of lung tissue. Northern analysis demonstrated induction of tropoelastin and type I procollagen mRNA expression in lungs of pneumonectomy rats. In situ hybridization localized tropoelastin and type I procollagen mRNA expression to anatomical sites similar to those seen during lung development. These data indicate that the adult lung can reinitiate elastin and collagen production and deposit these extracellular matrix components in a normal pattern.

Animals↗

Long-term antibody production after lung immunization and challenge: role of lung and lymphoid tissues.

After localized lung immunization and challenge, antigen-specific antibody continues to be produced in the immunized lung lobes of dogs for years after the last antigen exposure. Lavage fluid from immunized lung lobes contains significantly more antigen-specific antibody than lavage fluid from control lung lobes, and only cells from lung lobes exposed to antigen produce antibody. Although cells lavaged from the lung produce antibody, it is possible that cells in the lung interstitium or lymphoid tissues may be more important in long-term antibody production after lung immunization and challenge. The goal of this study was to compare the levels of antibody production by cells from dogs 2 yr after pulmonary immunization and challenge. Cells were evaluated from lung lavage, lung tissue, tracheobronchial lymph nodes, and distant lymphoid tissues. The results showed that cells lavaged from lung lobes immunized and challenged with sheep red blood cells (SRBC) were producing anti-SRBC IgG antibody 2 yr after the last antigen challenge. However, cells obtained by mincing tissues from immunized lung lobes were producing significantly higher levels of antibody than lavage cells. In contrast, lavage or tissue cells obtained from the control lobes did not produce detectable antibody. Only a low level of anti-SRBC IgG was produced by cells from the tracheobronchial lymph nodes, and minimal antibody was produced by cells from blood, spleen, or mesenteric and popliteal lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Abolition of fetal breathing movements by spinal cord transection leads to reductions in fetal lung liquid volume, lung growth, and IGF-II gene expression.

Fetal breathing movements (FBM) are considered necessary for normal growth and structural maturation of the fetal lung, but the underlying mechanisms are unclear. The small fluctuations in lung dimensions caused by FBM have been proposed as a stimulus to lung growth, but it is equally possible that FBM act by maintaining the basal level of lung luminal volume, which is an established determinant of fetal lung growth. Our aim, therefore, was to determine the effects of abolishing FBM, while retaining the integrity of the diaphragm, on the volume and rate of production of fetal lung liquid, gene expression for IGF-II, and fetal lung growth. FBM were abolished in seven fetal sheep by high spinal cord transection at 114 +/- 1.2 d of gestation; seven intact fetuses served as controls. At 119 to 124, 125 to 130, and 131 to 136 d, we measured the volume and secretion rate of lung liquid by dye dilution. At these three age ranges, the lungs of cord-transfected fetuses contained 27 to 53% less lung liquid than controls (p = 0.004), and their rates of secretion were 65 to 138% greater (p = 0.001). At postmortem (135 +/- 0.1 d), the lungs of the cord transected fetuses contained less DNA per kg body weight and tended to be lighter and to contain less protein than controls. IGF-II gene expression in the lungs of cord-transected fetuses was significantly less than that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep.

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In three groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still approximately 30% larger than control values. We conclude that TO at <90 d of gestation in fetal sheep induces a greater increase in lung tissue growth than later in gestation but also causes fetal hydrops and produces changes in lung structure that are not compatible with efficient gas exchange. Thus, increased lung expansion at a similar stage of development in human fetuses is unlikely to induce changes in lung development that would facilitate gas exchange after birth.

Animals↗

Lung adenocarcinomas diagnosed by open lung or thoracoscopic vs bronchoscopic biopsy.

STUDY OBJECTIVES: To examine the characteristics of peripheral lung adenocarcinomas diagnosed by open lung or video-assisted thoracoscopic surgery (VATS) biopsy. DESIGN: We used retrospective analysis to compare tumor stage, pleural involvement, central tumor fibrosis, and the number of bronchi or vessels involved with tumors of small peripheral lung adenocarcinomas diagnosed by bronchoscopic biopsy. PATIENTS: Subjects had lung adenocarcinomas diagnosed by open lung or VATS (n=22) and those diagnosed by bronchoscopic biopsy (n=22), which were matched by tumor size. RESULTS: The T1N0M0 tumor was notably more frequent in the open lung or VATS group (77.3%) than in the bronchoscopic biopsy group (36.4%) (p<0.01). Tumors invading beyond the pleural surface were less frequent in the open lung or VATS group (4.5%) than in the bronchoscopic biopsy group (40.9%) (p<0.01). The grade of in-tumor central fibrosis--a malignancy factor and the cause of bronchi or vessel involvement with tumors-was significantly lower in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.01). The number of bronchi or vessels involved with tumors was significantly fewer in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.001). CONCLUSIONS: (1) Lung adenocarcinomas diagnosed by open lung or VATS biopsy were more frequently T1N0M0 than those diagnosed by bronchoscopic biopsy, which was caused by low grade of central tumor fibrosis rather than small tumor size. (2) They were infrequently diagnosed by bronchoscopic biopsy because few bronchi were involved by tumors due to the low grade of central tumor fibrosis. (3) Small pulmonary nodules not diagnosable by bronchoscopic biopsy should be diagnosed aggressively using VATS biopsy to detect early-stage lung cancer.

Adenocarcinoma↗

Current trends in lung transplantation. Lobar transplantation and expanded use of single lungs.

Heart-lung transplantation remains the only therapeutic option for patients with combined end-stage cardiopulmonary disease. Because of the scarcity of heart-lung donors, we have been investigating other surgical alternatives for patients with end-stage vascular and parenchymal lung disease. From June 1989 through June 1991, 48 patients underwent pulmonary transplantation. Seventeen of the 48 patients underwent single lung transplantation. Of the 17 patients in the single lung group, eight patients had pulmonary hypertension and nine had parenchymal lung disease. Four of the 17 patients underwent repair of a cardiac defect with single lung transplantation. One-year actuarial survival was 68%. Pulmonary function has been excellent. The forced expiratory volume in 1 second was 79.6 +/- 13.6 (percent predicted), forced expiratory flow 25%-75% was 72.6 +/- 14.5 (percent predicted), and arterial oxygen tension was 82.8 +/- 10.06 mm Hg when measured at annual follow-up in a group of eight patients without obliterative bronchiolitis. Pulmonary artery pressures of systemic level or greater in the group with pulmonary vascular disease were normal at annual catheterization. Most patients had at least one episode of allograft rejection. Actuarial freedom from rejection at the end of 3 months was 30%. Three of the 17 single lung patients receiving lung lobes were children. Two children received living-related lobe transplants and one neonate received a lobe from a 2-year-old cadaver donor. Single lung transplantation is an effective therapeutic option for selected patients with vascular or parenchymal lung disease. Expanding indications will permit more individuals to receive transplants from the existing donor pool. Living-related and cadaver lobe transplantation will also increase the options available to children in need of lung transplantation.

Adolescent↗

Ventilation-perfusion lung scanning and the diagnosis of pulmonary embolism: improvement of observer agreement by the use of a lung segment reference chart.

OBJECTIVE: To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans. DESIGN: A randomized trial. STUDY POPULATION: Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism. INTERVENTION: Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme. MEASUREMENTS: Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic. RESULTS: Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P less than 0.01), whereas intra-observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09). CONCLUSION: Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism.

Humans↗

Intrapulmonary spread of established B16 melanoma lung metastases and lung colonies.

Spontaneous metastasis of subcutaneous B16 melanoma transplants proceeds in two distinct stages: initially to the lungs, and secondarily, following tumor removal, from established lung metastases to extrapulmonary systemic sites. Coincident with extrapulmonary metastasis, there is a dramatic amplification of visible lung metastases, with death generally resulting from extensive lung metastasis. The progression of lung metastasis, and lung colonization initiated by intravenous injection of tumor cells, was investigated using B16 melanoma clone G3.12. Analysis of the growth of invisible metastases in organ culture explants of lung revealed that tumors continually disseminated relatively small numbers of lung metastases after reaching a size of about 6 mm in diameter. However, most terminal-stage lung metastases, along with all extrapulmonary metastases, apparently arise from a secondary spread of tumor cells from tumor-derived lung metastases 1-2 mm in size. Individual lung colonies, initiated with G3.12 cells bound to single microbeads, also disseminated large numbers of secondary lung colonies, as well as extrapulmonary colonies, at a 1- to 2-mm size. The mechanism for intrapulmonary spread of secondary metastases and colonies is unclear, but the consequence appears to be a secondary stage of intrapulmonary and extrapulmonary metastasis with selection for tumor cells with rapid growth rates.

Animals↗

Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Université Paris-Sud Lung Transplant Group.

BACKGROUND: Pentoxifylline attenuates neutrophil-mediated lung injury in several models of acute lung inflammation. METHODS: Because pulmonary neutrophil sequestration is the main determinant of lung reperfusion injury, we sought to determine whether pentoxifylline prevented reperfusion injury in isolated perfused rat lung (4-hour cold ischemia, 1-hour reperfusion; pentoxifylline intravenously 40 mg) and in pigs after left lung allotransplantation (24-hour cold ischemia, 4-hour reperfusion; pentoxifylline 1.5 mg/kg/hr intravenously). In the pigs, inflatable cuffs placed around each pulmonary artery enabled us to evaluate each lung separately. RESULTS: In rat lungs, the coefficient of lung permeability increased by 75% +/- 10% in controls and by 3% +/- 2% (p < 0.01) in pentoxifylline-treated lungs. In the pigs, with blood flow to the transplanted lung alone and ventilation with an inspired oxygen fraction of 1, the arterial oxygen tension was greater in the pentoxifylline group than in the control group (423 +/- 49 versus 265 +/- 43 mm Hg, p < 0.05), whereas the total pulmonary vascular resistance was lower (15 +/- 1 versus 30 +/- 9 mm Hg/L/min, p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell by 35% +/- 3% in the control group and remained unchanged in the pentoxifylline group, and the leukocytes count per microscopic field in the transplanted lung was lower in the pentoxifylline group than in the control group (15 +/- 2 versus 140 +/- 50, p < 0.02). CONCLUSIONS: These data suggest that pentoxifylline prevented reperfusion injury by decreasing neutrophil lung sequestration.

Animals↗

Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures.

Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation.

Animals↗

A comparison of the effects of paraquat and diquat on lung compliance, lung volumes and single breath diffusing capacity in the rat.

Paraquat intoxication in its initial stage is characterized histologically in the lungs by atelectasis, hyaline membrane formation, alveolar edema and vascular hemorrhage often into the interstitium or air spaces. Information on the functional modification of paraquat-damaged lungs has been lacking. We evaluated lung volumes, single breath diffusing capacity of the lungs for carbon monoxide (DLCO) and static lung compliance (Cst(L)) in rats treated with paraquat or diquat. Measurements were made 12, 24, 48, and 72 h after treatment. Paraquat by intratracheal (i.t.) instillation 0.5 mg/kg or by intraperitoneal injection (i.p.) 27 mg/kg significantly decreased (P less than 0.01) the body weight, total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC), residual volume (RV), DLCO, apparent alveolar volume (VA) and Cst(L). At a lower dose level (13.5 mg/kg), the effects of paraquat peaked at about 24 h following treatment, causing a significantly decreased (P less than 0.01) VC and TLC. Diquat i.t. or i.p. had little effect on the lungs. However, diquat i.p. decreased body weight (P less than 0.01) and caused a slight increase (P less than 0.05) in VC. The data obtained are consistent with the known pathological changes seen in paraquat-damaged lungs in that, by both routes, paraquat caused severe lung damage associated with decreased elasticity of the lungs and thorax, destruction of gas exchanging alveolar surfaces, and edema. These changes were detected reliably by lung function measurements.

Animals↗

Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue.

BACKGROUND AND PURPOSE: The low density of lung tissue causes a reduced attenuation of photons and an increased range of secondary electrons, which is inaccurately predicted by the algorithms incorporated in some commonly available treatment planning systems (TPSs). This study evaluates the differences in dose in normal lung tissue computed using a simple and a more correct algorithm. We also studied the consequences of these differences on the dose-effect relations for radiation-induced lung injury. MATERIALS AND METHODS: The treatment plans of 68 lung cancer patients initially produced in a TPS using a calculation model that incorporates the equivalent-path length (EPL) inhomogeneity-correction algorithm, were recalculated in a TPS with the convolution-superposition (CS) algorithm. The higher accuracy of the CS algorithm is well-established. Dose distributions in lung were compared using isodoses, dose-volume histograms (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy (V20). Published dose-effect relations for local perfusion changes and radiation pneumonitis were re-evaluated. RESULTS: Evaluation of isodoses showed a consistent overestimation of the dose at the lung/tumor boundary by the EPL algorithm of about 10%. This overprediction of dose was also reflected in a consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/-1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both parameters, a strong correlation was found between the EPL and CS algorithms yielding a straightforward conversion procedure. Re-evaluation of the dose-effect relations showed that lung complications occur at a 12-14% lower dose. The values of the TD(50) parameter for local perfusion reduction and radiation pneumonitis changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively. CONCLUSIONS: A simple tissue inhomogeneity-correction algorithm like the EPL overestimates the dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20) computed using both algorithms are strongly correlated making an easy conversion feasible. Dose-effect relations should be refitted when more accurate dose data is available.

Algorithms↗

Does interstitial lung disease predispose to lung cancer?

PURPOSE OF REVIEW: This review examines the evidence for the causality and pathogenesis of lung cancer associated with interstitial lung disease. RECENT FINDINGS: Although cigarette smoking is the leading cause of lung cancer, several other conditions either predispose to lung cancer or increase the risk of lung cancer in smokers. The evidence supports an increased risk of lung cancer due to specific fibrotic and inflammatory lung diseases (termed interstitial lung diseases), including idiopathic pulmonary fibrosis, systemic sclerosis, and certain pneumoconioses. The potential pathogenetic mechanisms indicate that recurrent injury and inflammation result in genetic alterations that predispose to lung cancer. SUMMARY: Idiopathic pulmonary fibrosis, systemic sclerosis, and certain pneumoconioses are associated with an independent increased risk of lung cancer; however, a unifying pathogenetic mechanism to explain the causality of this association has not been described. In addition, the inconsistently reported lung cancer frequencies call attention to the need for prospective studies of good quality.

Causality↗

Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice.

Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly (P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant (P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.

Aging↗

Using 99mTc-DTPA radioaerosol inhalation lung scintigraphies to detect the lung injury induced by consuming Sauropus androgynus vegetable and comparison with conventional pulmonary function tests.

Consuming Sauropus androgynus, a Malaysian plant, to reduce body weight began to become fashionable in Taiwan in 1994. According to some reports, people consuming this vegetable developed lung injuries. From July to November 1995, there were 81 nonsmoking women admitted to our hospital. Thirty-six cases had respiratory symptoms/signs and the remaining 45 had no symptoms/signs. We investigated these patients with pulmonary function tests (PFT) and technetium-99m DTPA radioaerosol inhalation lung scintigraphies (DTPA lung scan), a test to evaluate the lung ventilation and alveolar epithelial permeability. Eighteen patients had abnormal results in PFT, including obstructive type (n = 17), restrictive type (n = 5), and both (n = 4). There were 33 patients with abnormalities in DTPA lung scans, including unhomogeneous deposition of DTPA radioaerosols (n = 19), faster clearance of radioaerosols from lung (n = 26), and both (n = 12). Analyzing the results, we found that the patients with respiratory symptoms had a higher incidence of abnormal results of PFT and DTPA lung scans than the patients without respiratory symptoms (p < 0.05). Besides, we found that the DTPA lung scan was more sensitive than chest x-ray and PFT in detecting the lung injuries related to the consumption of S. androgynus (p < 0.05). Consuming S. androgynus can result in symptomatic or asymptomatic lung injuries, manifested as obstructive or restrictive ventilatory impairment, unhomogeneous radioaerosol distribution, and increased alveolar epithelial permeability. In addition, measurement of the 99mTc-DTPA clearance is the most sensitive test to detect the lung injuries caused by consuming S. androgynus.

Adolescent↗

Lung volumes before and after lung volume reduction surgery: quantitative CT analysis.

The volume and severity of pulmonary emphysema in individual lungs were measured by means of quantitative computed tomography (CT) studies in 28 patients (14 women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body plethysmographic, and CT data (at TLC and RV) were correlated before and after LVRS. Lung volumes determined by CT correlated well with volumes obtained by total body plethysmography (p < 0.0001). For individual lungs after LVRS, CT-derived mean lung capacity decreased 13% and residual volume 20% (p < 0.00001 for each), while mean total functional lung volume (TFLV, defined as the volume of lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p < 0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS)) decreased more at RV (23%) than at TLC (14%) (p < 0.0005 for each). In contrast, unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV, TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the contralateral lung. Moreover, postoperative alterations in TFLV and FEV1 correlated significantly (r = 0.80, p < 0.0001), which suggests that the expansion of functioning tissue may contribute to the mechanism by which LVRS palliates airway obstruction.

Aged↗