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Triiodothyronine nuclear binding in fetal and adult rabbit lung and cultured lung cells.

To investigate the possible mechanism of thyroid hormone action in the lung, we examined fetal and adult rabbit lung, and cell lines derived from lung, for specific nuclear binding sites for T3. Using incubation of isolated nuclei with L-[125I]T3 at 37 C, we found approximately 2400 specific binding sites/cell in fetal lung and 1120 sites/cell in adult lung, with a similar dissociation constant (approximately 500 pm) for both tissues. The L-2 and A549 cell lines, which may have originated from pulmonary type II alveolar cells, contained 2280 and 1580 nuclear sites/cell, and the dissociation constants were 280 and 200 pm, respectively. In fetal lung, the ability of various analogs to compete for L-T3 (100%) binding was: 3,5-diiodo-3'-isopropylthyronine, 81%; D-T3, 73%; L-T4, 6.7%; 3,3'-diiodothyronine, 0.19%; 3,5-dimethyl-3'-isopropyl-L-thyronine, 0.15%; and rT3, 0.08%. These findings indicate that both fetal and adult lung, and cultured lung cells, contain specific nuclear binding sites for T3, suggesting that these tissues and their type II alveolar cells may be directly influenced by thyroid hormones.

Animals↗

Estimating the volume of lung irradiated during tangential breast irradiation using the central lung distance.

The aim of this study was to evaluate the central lung distance (CLD) as a surrogate for the volume of lung irradiated during tangential breast radiotherapy. 20 women underwent a planning computed tomography (CT) scan and three-dimensional (3D) treatment planning for both breasts. The field size was perturbed in a systematic manner to give a number of plans with the CLD increasing from 0 to 30 mm. The volume of lung irradiated was determined directly using dose-volume histograms of the lung and correlated with the known CLD. The results indicate that absolute and percentage lung volumes increase with increasing CLD according to a quadratic relationship which is different for both left and right lungs. It is concluded that while there is no substitute for a 3D plan and a lung dose-volume histogram calculation, CLD may be used as a guide to the volume of lung included within the tangential fields used for breast radiotherapy.

Breast Neoplasms↗

Use of Medicare claims data to evaluate outcomes in elderly patients undergoing lung resection for lung cancer.

OBJECTIVE: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. DESIGN: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (part A) claims records to identify patients who underwent lung resection for lung cancer; we assessed perioperative, one-year, and two-year survival using Medicare enrollment file data. PATIENTS: From a nationally random sample of 1,138,000 Medicare beneficiaries over 65 years of age, we identified 1,290 individuals who fulfilled our definition for lung resection for lung cancer. MEASUREMENTS AND MAIN RESULTS: Overall perioperative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced perioperative and one-year and two-year survival. The adverse effect of advanced age on one-year and two-year survival following lung resection was not explained by the lower life expectancy of older individuals. CONCLUSIONS: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected outcomes vary with the patient's age, sex, and the type of surgical procedure performed.

Aged↗

The senile lung. Comparison with normal and emphysematous lungs. 1. Structural aspects.

As part of a study of the structural-functional correlations of excised human lungs obtained at autopsy, the parenchyma and peripheral airways were examined by means of morphometric techniques. Among the 30 lungs characterized by the absence of fibrosis, ten differed from the normal and emphysematous lungs by a homogeneous dilatation of the airspaces, in excess of the dimensions predicted on the basis of age. Study of the standard deviations of the mean linear intercepts showed that the airspace dilatation was more regular than in emphysematous lungs; in addition, there was no clear-cut destruction, as estimated from the number of alveolar attachments. These lungs were characterized in addition by an increased thickening of alveolar septa, without inflammation or fibrosis, normal size of the diameter, and reduced density of the membranous bronchioles. Since these lungs were from people older than 60 years, it is assumed that they represent cases of exaggerated airspace enlargement of the aging lung, differing from emphysema by the absence of destruction of alveolar walls. The term "senile lung" is proposed or this condition.

Aged↗

Infection in the transplanted and native lung after single lung transplantation.

OBJECTIVE: To analyze a single-center experience with infectious complications of single lung transplantation (SLT) with special emphasis on risk factors for infection in the transplanted and native lung. DESIGN: Consecutive case series. SETTING: University teaching hospital. PATIENTS: Fifteen consecutive SLT recipients (mean age, 43 years; 9 men and 6 women). Mean follow-up was 337 days. RESULTS: Fifteen patients had 24 infectious episodes (1.6 per patient) of which 83 percent were life-threatening, 79 percent involved the lung, airway, or pleural space, and 79 percent occurred in the first 4 months after transplantation. Despite this high infectious morbidity, there were no infectious deaths. The most important infections were bacterial pneumonia (n = 10), cytomegalovirus (CMV) pneumonia (n = 5), and bronchial anastomotic infections (n = 3). Significant risk factors for bacterial pneumonia were a diagnosis of primary or secondary pulmonary hypertension (p < 0.05) and the presence of airway complications of stenosis or dehiscence (p < 0.05). No risk factors for overall lung infections were identified. The native lung was involved in 6 of 16 lung infections and was the exclusive site of infection in 4 cases. Underlying disease in the native lung may have predisposed to infection at that site by a mechanism of inadequate blood flow or impaired ventilation. Three bronchial anastomotic infections (Pseudomonas, Candida, Aspergillus) occurred, all with dehiscence of the anastomosis. These were highly morbid but resolved with antibiotics, stent placement, and surgical retention in two of the three cases. The five episodes of CMV pneumonia caused mild (four patients) or moderate (one patient) dysfunction and responded to antiviral agents without relapse. CONCLUSION: The frequency, complexity, and morbidity of infections after SLT were great, but most infections were manageable and good outcomes were achieved. A pretransplant diagnosis of pulmonary hypertension or posttransplant occurrence of bronchial stenosis or dehiscence were associated with a higher rate of bacterial pneumonia. The underlying disease in the native lung may predispose to infection at that site.

Adolescent↗

Aerosol-derived airway morphometry and aerosol bolus dispersion in patients with lung fibrosis and lung emphysema.

OBJECTIVE: Patients with lung emphysema show increased aerosol-derived dimensions of peripheral airspaces and increased aerosol bolus dispersion (AD). To apply these tests in epidemiologic studies, the objective of this pilot study was to investigate whether morphometric changes caused by lung fibrosis can be distinguished from those caused by emphysema. DESIGN: This study was designed as a cross-sectional study in which airspace dimensions and AD in patients with emphysema and in patients with fibrosis were compared. Forty patients participated in the study: 20 patients had high-resolution CT (HRCT)-proved lung emphysema and 20 patients had HRCT-proved lung fibrosis. All patients underwent conventional lung function tests, aerosol-derived airway morphometry (ADAM), and AD measurements. RESULTS: Patients with lung emphysema showed normal dimensions of small airways but enlarged airspace dimensions in the lung periphery. Patients with fibrosis showed in all lung depths increased airspace dimensions. AD was increased in patients with emphysema but was normal in patients with fibrosis. CONCLUSIONS: These results show that when using ADAM and AD, morphometric changes caused by emphysema can be distinguished from those caused by fibrosis with high sensitivity and specificity.

Adult↗

Using technetium-99m methoxyisobutylisonitrile lung single-photon-emission computed tomography to predict response to chemotherapy and compare with P-glycoprotein expression in patients with untreated small cell lung cancer.

The purpose of this study was to predict chemotherapy response by technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) lung single-photon-emission computed tomography (SPECT) and compare P-glycoprotein (Pgp) expression in patients with untreated small cell lung cancer (SCLC). Before chemotherapy, 40 patients with untreated SCLC underwent Tc-99m MIBI lung SPECT. Immunohistochemical analyses were performed using multiple nonconsecutive sections of the biopsy specimens to detect Pgp expression. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. Based on quantitative analyses, the tumor uptake ratios (TUR) of the 20 patients with good response (1.89 +/- 0.28) were significantly higher than that of the 20 patients with poor response (1.21 +/- 0.28) (p value < 0.05). Based on visual interpretation, all of the 20 patients (100%) with good response had positive Tc-99m TF lung SPECT findings and negative Pgp expression. Five of the other 20 patients (25%) with poor response had positive Tc-99m MIBI lung SPECT findings, and 12 of the other 20 patients (60%) with poor response had negative Pgp expression (p value < 0.05). Negative Tc-99m MIBI lung SPECT findings could predict poor response. Therefore, we concluded that Tc-99m MIBI lung SPECT can accurately predict the chemotherapy response, and Tc-99m MIBI lung SPECT findings can be partially compatible with Pgp expression in patients with untreated SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Role of lung maintenance program in the heterogeneity of lung destruction in emphysema.

Centrilobular emphysema caused by chronic cigarette smoking is a heterogeneous disease with a predominance of upper lobe involvement. It is presumed that this heterogeneity indicates a particular susceptibility to cigarette smoke or the fact that the inhaled smoke distributes preferentially to upper lung zones. The less involved areas might therefore retain the capacity for lung regeneration and gain of pulmonary function in terminally ill patients. We propose that the interplay between molecular and cellular switches involved in the lung response to environmental injuries determines the heterogeneous pattern of emphysema due to cigarette smoke. Regional activation of alveolar destruction by apoptosis and oxidative stress coupled with regional failure of defense mechanisms may account for the irregular pattern of lung destruction in cigarette smoke-induced emphysema. Protection afforded by the key antioxidant transcription factor Nrf-2 and the antiproteolytic and antiapoptotic actions of alpha(1)-antitrypsin is central to maintain lung homeostasis and lung structure. As the lung is injured by environmental pollutants, including cigarette smoke, molecular sensors of cellular stress, such as the mTOR/protein translation regulator RTP-801, may engage both inflammation and alveolar cell apoptosis. As injury prevails during the course of this chronic disease, it leads to a more homogeneous pattern of lung disease.

Apoptosis↗

Validity of bronchoalveolar lavage in acute lung injury: recovered cells accurately reflect changes in the lung parenchyma.

Bronchoalveolar lavage (BAL) has come into widespread use as a tool to diagnose and manage various lung diseases. However, the usefulness of BAL is based on the assumption that the cells recovered in BAL fluid accurately reflect cellular populations in the lung parenchyma. To test this hypothesis, random source (n = 16) dogs were given intravenous phorbol myristate acetate (PMA) to produce acute, diffuse lung inflammation. Dogs were divided into three groups. Group I animals (n = 2) underwent BAL and open lung biopsy at time zero. Group II (n = 7) animals underwent hourly BAL after PMA with open lung biopsy at 3 h. Group III (n = 7) animals underwent hourly BAL after PMA with open lung biopsy at 6 h. When BAL cell populations were compared with the corresponding biopsies, there was a direct correlation (r = 0.67) between BAL neutrophil percentages and neutrophils present in histologic sections. These findings suggest BAL accurately reflects changes in the lung parenchyma in acute lung disease.

Acute Disease↗

Effect of lung airway branching pattern and gas composition on particle deposition. II. Experimental studies in human and canine lungs.

The recovery of monodisperse inhaled particles from humans in vivo and from excised human and canine lungs was measured after a single breath for particles suspended in air and in mixtures of He or SF6 with O2. Comparisons were made using the unique particle sizes for which the intrinsic particle motions in air and each mixture were identical, so that differences in recovery could be associated with differences in convective flow. For the in vivo tests, only mixtures with 20% O2 were used, while for the excised lungs, mixtures with 10% O2 were also used. In humans in vivo and in excised human lungs, there was significantly greater deposition from He-O2 mixtures and less deposition from SF6-O2 mixtures, with no differences between the in vivo and the excised lung results for the 80-20 mixtures. For the canine lungs, there were no differences in deposition between air and any He or SF6 mixture. The interspecies differences are consistent with the hypothesis that particle exchange between tidal and residual lung gas is dependent on the distance into each airway that is needed to establish a stable flow profile. The more symmetrical branching of human lung airways causes the entry flow into daughter airways to be highly asymmetric, and flow profile rearrangement is greater than that in the monopodal canine lung.

Adult↗

Tyrosine kinase activation during lung injury, fibrosis, and compensatory lung growth.

Endobronchial instillation of paraquat into left lungs of rats resulted in ipsilateral fibrosis (evaluated by light and electron microscopy) and compensatory growth of the contralateral lung. Tyrosine kinase (Tyr-K) activity rose early in the fibrotic lung, peaked to a value 4 times the controls on day 3, and remained elevated on day 14. In the right lung, slight increase in activity occurred only on day 5. Cellular proliferative activity was inhibited in both lungs early after injury. In the right lung, however, DNA synthesis increased to levels 10 times the controls by day 7. In the left lung, the inhibition decreased gradually after day 7, indicating increased cellular proliferation. We conclude that activation of some cellular Tyr-K may play a role in regulating early cellular proliferation during lung injury, fibrosis, and compensatory growth.

Adaptation, Physiological↗

Effect of lung airway branching pattern and gas composition on particle deposition in bronchial airways: III. Experimental studies with radioactively tagged aerosol in human and canine lungs.

Particle penetration into lung airways during normal respiration is affected by the exchange of inspired air and residual gas. In this study, particle penetration during the inspiratory phase was investigated using gamma-tagged monodisperse particles (0.70, 0.90, 0.96, and 1.44 microns) suspended in various carrier gases having a wide range of kinematic viscosity. A 40-mL bolus of tagged aerosol was drawn into excised human and dog lungs at the end of a tidal breath, followed by a long breathhold to allow for complete particle deposition by sedimentation. The lungs were then fixed, sectioned, and autoradiographed to determine tidal front locations. In human lungs, particles suspended in He-O2 penetrated deeper than particles suspended in air; particles penetrated least in SF6-O2. Dog lungs, which have more asymmetrical airway branching patterns than human lungs, had no significant particle penetration differences associated with carrier gas composition. It is concluded that particle penetration during the inspiratory phase is dependent on factors that determine flow profile development, such as branching pattern and the Reynolds number of the carrier gas. The bolus front at the end of an air inspiration extended into about 10% of human lung airways of 1 mm diameter, and into about 0.1% of 0.5-mm airways. It is concluded that rapid particle penetration to 1-mm airways during high-frequency oscillatory ventilation of lung casts is due to cumulative axial core transport during multiple breathing cycles. Similarly, the dispersion of an aerosol bolus from large airways to small airways during in vivo breathholding studies appears to be due to oscillatory flow created by the heartbeat.

Aerosols↗

Paired Whole-Genome Sequencing of Scalp Angiosarcoma and Matched Lung Metastasis Reveals Common Clonal Origin and Lung-Specific Evolution.

Background and Clinical Significance: Cutaneous angiosarcoma frequently metastasizes to the lungs, where it may rarely present as diffuse cystic lung disease with recurrent pneumothorax, resulting in substantial diagnostic difficulty. We report a case of pulmonary metastatic cutaneous angiosarcoma in which paired whole-genome sequencing (WGS) of the primary and metastatic lesions was performed to clarify clonal origin and characterize metastatic evolution. Case Presentation: A 65-year-old man with recurrent right-sided pneumothorax and progressive bilateral cystic lung lesions underwent skin and lung biopsies. Histopathological examination and immunohistochemistry established the diagnosis of cutaneous angiosarcoma with pulmonary metastases. Paired WGS was performed on matched scalp and lung tumor specimens to evaluate shared and lesion-specific genomic alterations, pathway enrichment, and copy-number changes. Histopathology confirmed metastatic angiosarcoma involving the lungs. WGS identified 128 shared somatic alterations, supporting a common clonal origin, together with lung-specific and skin-specific mutations indicative of continued genomic divergence. Recurrent alterations involving POT1 and FLT4 were preserved in both lesions, whereas additional POT1 and TP53 alterations were detected only in the pulmonary metastasis. Pathway analysis demonstrated preferential enrichment of IGF1-mTOR, RAS, and WNT/LRP6 signaling in the metastatic lesion, while Gene Ontology analysis suggested functional divergence associated with metastatic progression. Conclusions: Pulmonary metastatic angiosarcoma should be considered in patients presenting with unexplained diffuse cystic lung disease and recurrent pneumothorax, particularly when pathological findings are inconclusive. Paired WGS complemented conventional histopathology by confirming the metastatic origin and providing insights into clonal evolution and lesion-specific molecular alterations, highlighting its potential value in the investigation of rare metastatic malignancies.

angiosarcoma↗

Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001) higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001) attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

Animals↗

Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

BACKGROUND: Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously. OBJECTIVE: To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak. DESIGN: Case-finding survey and retrospective cohort study. SETTING: Academic occupational medicine program. PATIENTS: All workers employed at the Rhode Island plant on or after 15 June 1990. MEASUREMENTS: Symptomatic employees had chest radiography, pulmonary function tests, high-resolution computed tomography, and serologic testing. Those with unexplained radiographic or pulmonary function abnormalities underwent bronchoalveolar lavage, lung biopsy, or both. The case definition of "flock worker's lung" required histologic evidence of interstitial lung disease (or lavage evidence of lung inflammation) not explained by another condition. RESULTS: Eight cases of flock worker's lung were identified at the Rhode Island plant. Three cases were characterized by a high proportion of eosinophils (25% to 40%) in lavage fluid. Six of the seven patients who had biopsy had histologic findings of nonspecific interstitial pneumonia, and the seventh had bronchiolitis obliterans organizing pneumonia. All seven of these patients had peribronchovascular interstitial lymphoid nodules, usually with germinal centers, and most had lymphocytic bronchiolitis and interstitial fibrosis. All improved after leaving work. Review of the Canadian tissue specimens showed many similar histologic findings. Among the 165-member study cohort, a 48-fold or greater increase was seen in the sex-adjusted incidence rate of all interstitial lung disease. CONCLUSIONS: Work in the nylon flocking industry poses substantial risk for a previously unrecognized occupational interstitial lung disease. Nylon fiber is the suspected cause of this condition.

Adult↗

[Changes of thromboxane A2 receptors and their mRNA expression and effects of their antagonist phenol red in the lung of acute lung injury of rats].

OBJECTIVE: To investigate the changes of thromboxane A2 receptors and the influence of their antagonist phenol red, and to study in molecular level the mechanism of action of thromboxane A2 in acute lung injury. METHODS: Acute lung injury model of rats was produced by oleic acid, and phenol red (5 mg/kg, 50 mg/kg) was injected via vein 5 minutes before oleic acid injection. Changes of thromboxane A2 receptors and their mRNA expression in the lung were determined at 6 hours after oleic acid injection. RESULTS: Down-regulation of thromboxane A2 receptors were observed, but their mRNA transcription increased significantly in the lung after oleic acid injection. The injection of phenol red before oleic acid could induce down-regulation of thromboxane A2 receptors and abolish the increase of their mRNA transcription after oleic acid injection. Phenol red could reduce LBI, RLW and improve PaO2. Histological examination of lung tissues demonstrated that the degree of lung injury had been reduced significantly. CONCLUSION: Thromboxane A2 plays an important role plays in pathological processes of acute lung injury. Phenol red in vivo could effectively reduce severity of acute lung injury by blocking thromboxane A2 receptors and regulating the expression of thromboxane A2 receptors.

Animals↗

Progressive changes in arterial oxygenation during one-lung anaesthesia are related to the response to compression of the non-dependent lung.

BACKGROUND: Arterial oxygenation can change during one-lung ventilation for reasons that are not fully understood. METHODS: We studied patients during anaesthesia and one-lung ventilation, with an inspiratory oxygen fraction of 0.8. Arterial blood gas values were recorded every 10 s with a continuous intra-arterial sensor. The non-dependent lung was compressed several times during the surgical procedure, using a retractor. The change in Pa(O(2)) during and after compression of the non-dependent lung was measured. RESULTS: Pa(O(2)) increased significantly when the non-dependent lung was compressed, and decreased when the compression was released. The first compression of the non-dependent lung transiently increased Pa(O(2)), but the effect of the second compression on oxygenation was more marked and persistent. Pa(O(2)) increased by more than 13 kPa at 10 min after the second compression in four patients (responder group). Arterial oxygenation improved markedly in patients in this group during the surgical procedure. CONCLUSION: Oxygenation can improve during one-lung ventilation in some patients. This improvement is partly related to a marked increase in Pa(O(2)) during compression of the non-dependent lung.

Aged↗

[A case of re-expansion pulmonary edema after one lung ventilation for the radical operation of lung cancer].

A 64-yr-old man was admitted to our hospital for the examination of the abnormal shadow in his left lung field, which was diagnosed later as lung cancer. Radical operation was scheduled under combined epidural/general anesthesia. One lung ventilation was performed to facilitate the operative procedure for two hours and fifteen minutes. About two hours after the re-expansion of his left lung, he complained of dyspnea. He was hypoxic and moist rale was audible in his left lung. Cloudy shadow emerged in the left field of his chest X-P. Under bronchofiberoptic observation, excessive serous secretions was seen, but no obstructive lesions were found in his bronchial tree. Re-expansion pulmonary edema was suspected for these findings. It was improved with mechanical ventilation with PEEP. Re-expansion pulmonary edema seldom occurs in one lung anesthesia. Although radical operation of esophageal cancer performed six years before might have induced the development of re-expansion pulmonary edema in our case, complete collapse with quick re-expansion of the lung is clearly a potential risk of re-expansion pulmonary edema. Careful management is necessary after one lung ventilation.

Anesthesia, Epidural↗