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.     

Use of CT morphometry to detect changes in lung weight and gas volume

STUDY OBJECTIVES: CT estimates of lung density have been used to estimate the extent and severity of emphysema. The present study was designed to test the hypothesis that quantitative CT can track the changes that occur in diffuse lung disease. DESIGN: The study was based on five patients with pulmonary alveolar proteinosis (PAP) who underwent lung lavage. Pulmonary function was measured before and after each individual lung lavage, and the CT scans before and after lavage were used to compare total lung volume, airspace volume, lung weight, and regional lung inflation. The dry weight of proteinaceous material lavaged from the lung was measured and compared to the change in CT lung weight. RESULTS: All the patients showed improvements in dyspnea, percentage of predicted diffusion capacity of the lung for carbon monoxide, and FVC. There was no change in CT-measured total lung volume or airspace volume, but there was a reduction in lung weight following lavage (p = 0.001), which correlated with the dry weight of the lavage effluent (R(2) = 0.73). Therefore, there was a shift in the regional lung inflation toward a more inflated lung with a corresponding increase in the mean lung inflation (p = 0.001). CONCLUSION: These data show that quantitative CT can objectively track the changes in lung weight and airspace inflation produced by a standard intervention in PAP, and we postulate that it can provide similar information about the progression of other diffuse lung diseases.     

Resolution of native lung pneumothorax by insertion of a nitinol stent for bronchostenosis in the transplanted lung

Following single lung transplantation, the native lung remains a potential source of morbidity from spontaneous pneumothorax, hyperinflation, bacterial and fungal infection and malignancy. The case of a single lung transplant recipient for idiopathic pulmonary fibrosis who developed a recurrent, non-resolving, spontaneous multiloculated pneumothorax in the native lung following thoracoscopic talc pleurodesis is reported. The pneumothorax ultimately resolved following insertion of a nitinol stent for coexisting bronchostenosis in the transplanted lung. In a single lung transplantation recipient in whom a native lung pneumothorax reoccurs or persists despite appropriate initial management, it may be useful to undertake bronchoscopy to exclude the possibility of bronchostenosis in the transplanted lung.     

Unexpandable lung from pleural disease

Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post‐procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment.     

Respiratory control during independent lung ventilation

We describe the case of a lung transplant patient with primary graft failure and an emphysematous native lung, who displayed different respiratory rates between the transplanted lung and the native lung. Inflation of the native lung delayed the next inspiratory effort relative to inflation of the denervated transplanted lung. Synchronous inflation of both lungs required more pressure in each lung than when that lung was inflated with the contralateral lung near functional residual capacity, suggesting the two lungs compete for space within the thoracic cavity.     

Lung cancer screening with CT

Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer accounts for 75% to 80% of all lung cancers. There is an impetus to find a screening test that can detect non-small cell lung cancer in its early preclinical stages, when surgical resection is most likely to reduce lung cancer mortality. Although earlier randomized controlled trials of lung cancer screening using chest radiography and sputum cytology failed to show reduced lung cancer mortality, CT is a much more sensitive test for detecting small lung nodules, and has generated considerable enthusiasm as a potential contemporary screening tool for lung cancer.     

改良床旁肺部超声评估方案对重症患者肺实变和肺不张的诊断价值

  目的 探讨改良床旁肺部超声评估方案（BLUE方案）对重症患者肺实变和肺不张的诊断价值。方法 选呼吸衰竭需机械通气超过48 h的患者,同时行床旁胸部X线、CT检查及BLUE方案、改良BLUE方案检查患者肺实变、肺不张情况,并与床旁胸部X线和CT对比,同时比较改良BLUE方案与BLUE方案评价肺实变与肺不张的差异。结果 最终78例患者纳入本研究。胸部CT发现70例（89.74%）患者存在不同程度的肺实变、肺不张。床旁胸部X线诊断肺实变、肺不张的敏感性为31.29%,特异性为75.00%,诊断准确率为38.46%。改良BLUE方案发现68例患者存在肺实变、肺不张,诊断肺实变、肺不张的敏感性为95.71%,特异性为87.50%,诊断准确率为94.87%,与胸部CT比差异无统计学意义（P>0.05）。BLUE方案发现48例患者存在肺实变、肺不张,诊断敏感性为65.71%,特异性为75.00%,诊断准确率为66.67%。BLUE方案未发现的肺实变、肺不张,胸部CT证实肺实变、肺不张部位主要位于双肺下叶后基底段。结论 重症机械通气患者肺实变、肺不张发生率高,改良BLUE方案可以发现绝大部分肺实变、肺不张,具有较高的敏感性、特异性及诊断准确率,由于其具有即时、床旁、无创、可重复的优越性,将成为床旁评价重症患者肺实变、肺不张的首选的、重要的安全检查手段。     

Metachronous lung cancer that presented as bilateral synchronous lung cancer

Every patient undergoing curative treatment for primary lung cancer is a candidate for metachronous lung cancer, with a reported risk of 5% per year. The majority of cases are stage I patients. Patients who undergo resection for lung cancer should be followed regularly. A metachronous lung cancer that develops as bilateral synchronous lung cancer is very rare.KEY WORDS : Synchronous lung cancer, metachronous lung cancer, surgery     

Mediastinal lung herniation associated with pulmonary sequestration

Mediastinal lung herniation is a rare condition characterized by protrusion of 1 lower lung through behind the heart into the opposite side of the chest, usually from right to left. We present a case of mediastinal lung herniation associated with pulmonary sequestration, which was confirmed both surgically and pathologically in a 13-year-old girl initially admitted with a diagnosis of pneumonia. Contrast-enhanced computed tomographic images using a multidetector-row computed tomography clearly demonstrated the right lung herniation toward the left and 2 aberrant systemic arteries supplying the sequestered lung mass. These arteries run through the herniated lung from right to left. Additionally, on the basis of pleural anatomy, we discuss herein the difference between a mediastinal lung herniation and horseshoe lung.     

Ex vivo lung perfusion

Lung transplantation is a life-saving treatment for patients with end stage lung disease. The imbalance between lung graft supply and recipients has been a serious issue and barrier to successful lung transplantation. Ex vivo lung perfusion is a strategy wherein lungs are perfused and ventilated outside of the body. This technology has emerged as a safe preservation method that also enables the reassessment and reconditioning of marginal lung grafts. Ex vivo lung perfusion has successfully expanded the donor pool and led to greater lung transplant activity worldwide. Furthermore, ex vivo lung perfusion can be used as a platform for advanced diagnostics that enable specific targeted or personalized treatments that can be developed along a bench to bedside pathway leading to safe ex vivo intervention. Recent findings have shown that ex vivo lung perfusion could significantly and safely extend the preservation period, which enables transplant programs further optimization of the logistics around transplantation surgeries, and create a new paradigm whereby donor lungs are assessed at a centralized ex vivo lung perfusion center prior to delivery to a transplant clinic in need. The introduction of ex vivo lung perfusion to clinical lung transplantation has been a major step in the evolution and practice of lung transplantation.     

Recruitment of antibody-forming cells in the lung after local immunization is nonspecific

The deposition of particulate antigen into the dog lung induces a large accumulation of antigen-specific-forming cells in immunized lung lobes. The results of our previous studies with dogs indicate that these cells are recruited to the immunized lung lobes from the blood. The present study was designed to determine if the recruitment of immune cells to the lung is antigen-specific, or if changes occur in the lung after immunization that allow immune cells to enter the lung nonspecifically. Dogs were immunized in the left and right cardiac lung lobes with antigenically different particulate antigens. The number of lymphoid cells producing antibody to each antigen and the concentrations of antigen-specific antibody were measured in the immunized lung lobes and in a control lung lobe at 5 through 14 days after immunization. Similar numbers of antibody-forming cells and concentrations of antibody to both antigens were found in each immunized lung lobe, regardless of which antigen was used for immunization. These results indicate that antigen exposure alters the lung to allow a nonspecific recruitment of immune cells from the blood into the immunized lung lobes, regardless of antigen specificity. These data also provide further evidence that the antibody-forming cells found in the lung lavage fluid after localized immunization are produced in the thoracic lymph nodes or other systemic lymphoid tissues, rather than locally in lymphoid tissues in the deep lung.     

Radiological imaging in acute lung injury and acute respiratory distress syndrome

Computed tomography (CT) has been utilized to study acute respiratory distress syndrome (ARDS) since the middle 1980s, when it revealed the inhomogeneous pattern of the lung lesion. Its advantages rely on the strict correlation between CT density and the lung physical density, allowing a quantification of lung compartments with different degrees of aeration. By CT scans, ARDS lung appeared to be "small" rather than "stiff," leading to the "baby lung" concept. The regional analysis revealed that this appearance derives from an evenly distributed lung edema, which tends, because of gravitational forces, to lie predominantly in the most dependent regions, leading to alveolar collapse. New data suggest that such a "sponge lung" is made by a "core," consolidated, lung portion, from which, through an inflammatory reaction, lung edema will spread, determining the collapsed and recruitable lung portion. The amount of recruitable lung varies among ARDS patients. This knowledge is necessary for a rational positive end-expiratory pressure (PEEP) setting because the amount of tissue maintained aerated by PEEP is closely associated with the amount of recruitable lung. CT scans may also help to diagnose ARDS because CT provides a good estimate of the high-permeability lung edema, the characteristic lesion of this syndrome.     

Serum anti-p53 autoantibodies from patients with idiopathic pulmonary fibrosis associated with lung cancer

Mutations of the tumour suppressor gene p53 lead to accumulation of the mutated p53 protein and subsequent production of antoantibodies against p53 proteins, which are also detected in lung cancer. Lung cancer is frequently associated with idiopathic pulmonary fibrosis (IPF). Therefore, we hypothesized that there might be a relationship between the p53 mutation and high prevalence of lung cancer in IPF. To test this hypothesis, we measured serum p53 antibody levels by an ELISA in various lung diseases including lung cancer (n=98), IPF (n=46; with lung cancer, n=14 and without lung cancer, n=32), pulmonary emphysema (PE, n=23) and healthy controls (HC, n=93). The median values of the serum anti-p53 antibody in each group were 8.78, 9.18, 8.08 and 4.95 for patients with lung cancer, IPF with lung cancer, IPF without lung cancer and PE, respectively, and 2.2 for the healthy control group. The groups of IPF (with and without lung cancer) showed a similar level of median values to the lung cancer group and a tendency for a higher level than the PE group. When the cut-off value was set at 7.7 according to the 95% specificity level for normal control, the incidence of positive anti-p53 antibody was significantly higher in lung cancer (61.2%), IPF with lung cancer (57.1%) and IPF without lung cancer (53.1%) than PE (21.7%). These results suggest that p53 mutations occur frequently and substantially in IPF, resulting in a high prevalence of lung cancer.     

Relationship between maternal and fetal lung growth

This study analyzes the relationship between the maternal and fetal lungs, in rats in relation to litter size, to determine whether the enlargement of maternal lung during pregnancy is concurrent with that of the fetal lung. Pregnant albino rats were sacrificed on gestation day 21 (term 22 days). Maternal lung growth was assessed by measuring the lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. The findings were as follows: (1) no differences were noted between the lungs of non-pregnant rats and pregnant rats with small litter size (1-4); (2) pregnant rats with large litter size (10-18) had larger lungs than rats with small litter size; (3) there was a direct relationship between cellularity (DNA content) of the fetal lung and maternal lung when the latter underwent a growth change during pregnancy; (4) no relationship in cellularity was found between the maternal lung and placenta nor between the fetal lung and placenta. The results suggest that factors or processes which regulate the growth and dictate the size of the maternal lung during pregnancy similarly influence the fetal lung.     

Regional compliance and bronchial pressure-diameter relationships in excised pig lungs.

We estimated the magnitude of parenchymal interdependence in excised pig lungs by measuring small airway diameter during homogeneous and nonhomogeneous lung inflation, by comparing the ratio of the specific compliance of the lung (Cl) to the specific compliance of a single lung region (Cs) and by using a continuum mechanics analysis to estimate the pressure at the interface between a single lung region and the surrounding lung. We found that the diameter of airways in a single lung region increased when the lung was held at a transpulmonary pressure (Ptp) of 5, 10 or 15 cmH2O and pressure in the region was increased by up to Ptp + 15 cmH2O, indicating that the surrounding lung offered little resistance to expansion of the lung region. The ratio of Cl to Cs averaged 1.22 (n = 5 lungs), indicating that the parenchyma surrounding the lung region caused a small reduction in its distensibility. When the lung was held at a Ptp of 5 cmH2O, pressure at the interface was estimated to be 1.1, 0.8 and -1.9 cmH2O when pressure in the single lung region was 15, 10 and O cmH2O, respectively. The relatively small change in boundary pressure from pleural pressure as the region was inflated or deflated indicated that the mechanical interaction between adjacent lung regions was small. Taken together, these results confirm the prediction of a small interdependence effect as determined by measurements of the distensibility and distortability of the pulmonary parenchyma.     

Histopathologic approach to the surgical lung biopsy in interstitial lung disease

Interpretation of lung biopsy specimens is an integral part in the diagnosis of interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy for disease involves answering several questions. Unlike much of surgical pathology of neoplastic lung disease, arriving at the correct diagnosis in nonneoplastic lung disease often requires correlation with clinical and radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers several hundred entities. This article is meant to be a launching point in the clinician's approach to the histologic evaluation of lung disease.     

Lung cysts in chronic paracoccidioidomycosis

On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.     

Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis

Chromosome 3p and 1p deletions are among the most frequent genetic changes in human lung cancer and although candidate tumor suppressor genes have been identified in these regions, no causative correlations have been drawn between deletion or mutation of these and lung carcinogenesis. We identify XPC and Gadd45a as genes within each of these regions involved in lung tumor initiation and progression, respectively. One hundred percent of XPC-/- mice develop multiple spontaneous lung tumors with a minority progressing to non-small cell lung adenocarcinoma, occasionally with metastasis to adjacent lymph nodes. Deletion of Gadd45a alone does not lead to increased lung tumors in mice, but coupled with an XPC deletion, it results in lung tumor progression. Analysis of published data indicated allelic loss of XPC in most human lung tumors and allelic loss of Gadd45a in some human lung and other cancer types. Because DNA repair capacity is compromised in XPC+/- cells, it is possible that the loss of a single XPC allele in the human lung might confer a mutator phenotype. Coupled with cigarette carcinogens, decreased DNA repair would lead to additional mutations in genes such as p53 that are frequent targets in lung cancer.     

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.     

实验动物肺癌模型的建立方法

建立肺癌的动物模型是肺癌研究的最常用的方法之一,但肺癌动物模型与人类肺癌的结果一直存在差距,很多研究人员一直在试图建立与人类肺癌最为接近的动物肺癌模型。根据制备方法及研究目的的不同,肺癌动物模型可分为自发性、诱发性、移植性和基因改造型动物模型。每种肺癌动物模型的制作方法是一个肺癌模型评定的重要方面之一。