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PubMed2002

Lung volume reduction surgery as a bridge to lung transplantation.

Lung volume reduction surgery (LVRS) improves lung function, exercise capacity, and quality of life in patients with advanced emphysema. In some patients with emphysema who are candidates for lung transplantation, LVRS is an alternative treatment option to lung transplantation, or may be used as a bridge to lung transplantation. Generally accepted criteria for LVRS include severe non-reversible airflow obstruction due to emphysema associated with significant evidence of lung hyperinflation and air trapping. Both high resolution computed tomography (CT) scan of the chest and quantitative ventilation/perfusion scan are used to identify lung regions with severe emphysema which would be used as targets for lung resection. Bilateral LVRS is the preferred surgical approach compared with the unilateral procedure because of better functional outcome. Lung transplantation is the preferred surgical treatment in patients with emphysema with alpha1 antitrypsin deficiency and in patients with very severe disease who have homogeneous emphysema pattern on CT scan of the chest or very low diffusion capacity.

Emphysema↗
PubMed2001

Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients.

OBJECTIVE: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history. METHODS: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report "fibre years" of the German Berufsgenossenschaften. RESULTS: Median and maximum concentrations of fibres longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history. CONCLUSIONS: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R = 0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).

Adult↗
PubMed1995

Successful canine bilateral single-lung transplantation after 21-hour lung preservation.

A canine bilateral single-lung transplantation model was used to evaluate 21-hour lung preservation with low-potassium dextran glucose solution. Donor lungs were flushed with low-potassium dextran glucose solution (50 mL/kg), inflated with 100% oxygen (35 mL/kg), and preserved at 8 degrees C. Bilateral single-lung transplantation was performed without using cardiopulmonary bypass. The ischemic times to the right and left lungs were designed to be 3 and 6 hours, respectively, in group 1 (n = 5) and 18 and 21 hours in group 2 (n = 6). After bilateral single-lung transplantation, animals were maintained on a ventilator for 12 hours and lung function, including arterial blood gas and pulmonary hemodynamics, was measured. All 5 dogs in group 1 and 5 of 6 dogs in group 2 completed bilateral single-lung transplantation successfully and survived for 12 hours with excellent lung function. Arterial oxygen tension and mean pulmonary artery pressure were stable during the 12-hour assessment period in both groups and did not differ significantly from donor values. Twelve hours after reperfusion, mean arterial oxygen tension (inspired oxygen fraction = 1.0) was 590 +/- 18 mm Hg in group 1 and 604 +/- 8 mm Hg in group 2. After the 12-hour assessment period, the animals were extubated and immunosuppressed. Two dogs in group 2 survived for 7 and 8 days, respectively, with a mean arterial oxygen tension of 74 mm Hg on room air at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Distant organ procurement in clinical lung- and heart-lung transplantation. Cooling by extracorporeal circulation or hypothermic flush.

The scarcity of suitable donors for single lung and heart-lung transplantation calls for methods of medium-term pulmonary preservation to allow for distant organ procurement. At our institution, the first five grafts (four heart-lung, one single lung) were cooled by means of a transportable extracorporeal circulation unit, while the last eight grafts (four heart-lung, four single lung) were flush-perfused with modified cold Euro-Collins solution. The technique of extracorporated circulation included aortic and right atrial cannulation and cooling to 12 degrees-14 degrees C (rectal temperature) using a bubble oxygenator. Bypass times ranged between 41 and 52 min. Following excision, the organs were transported in ice-cold donor blood for ischemic times from 171 to 310 min. For cold flush preservation, simultaneous coronary (cold St. Thomas's solution) and pulmonary artery perfusion (Euro-Collins solution, 50 ml/kg over 4 min) were initiated simultaneously. The organs were transported in cold Euro-Collins solution for ischemic times of 175 to 270 min. In heart-lung transplantations the first postoperative arterial PO2 upon arrival at the intensive care unit was 120 +/- 38 Torr in the extracorporeal circulation and 140 +/- 38 Torr in the Euro-Collins solution group. Six of eight patients were extubated within 48 h after cardiopulmonary grafting. We conclude that pulmonary function following heart-lung or single lung preservation with simple hypothermic flush is as good or better than that following extracorporeal circulation. Since distant organ retrieval is much more convenient without the latter, preservation using Euro-Collins solution is preferred.

Adolescent↗
PubMed2005

Evaluation of automated lung nodule detection on low-dose computed tomography scans from a lung cancer screening program(1).

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the performance of a fully automated lung nodule detection method in a large database of low-dose computed tomography (CT) scans from a lung cancer screening program. Because nodules demonstrate a spectrum of radiologic appearances, the performance of the automated method was evaluated on the basis of nodule malignancy status, size, subtlety, and radiographic opacity. MATERIALS AND METHODS: A database of 393 thick-section (10 mm) low-dose CT scans was collected. Automated lung nodule detection proceeds in two phases: gray-level thresholding for the initial identification of nodule candidates, followed by the application of a rule-based classifier and linear discriminant analysis to distinguish between candidates that correspond to actual lung nodules and candidates that correspond to non-nodules. Free-response receiver operating characteristic analysis was used to evaluate the performance of the method based on a jackknife training/testing approach. RESULTS: An overall nodule detection sensitivity of 70% (330 of 470) was attained with an average of 1.6 false-positive detections per section. At the same false-positive rate, 83% (57 of 69) of the malignant lung nodules in the database were detected. When the method was trained specifically for malignant nodules, a sensitivity of 80% (55 of 69) was attained with 0.85 false-positives per section. CONCLUSION: We have evaluated an automated lung nodule detection method with a large number of low-dose CT scans from a lung cancer screening program. An overall sensitivity of 80% for malignant nodules was achieved with 0.85 false-positive detections per section. Such a computerized lung nodule detection method is expected to become an important part of CT-based lung cancer screening programs.

Adult↗
PubMed2005

Polyphenol associated-DNA adducts in lung and blood mononuclear cells from lung cancer patients.

The formation of smoking induced-DNA adducts is a critical factor in the induction of human lung cancer. As derivates of benzene and polyaromatic hydrocarbons (PAHs) are important compounds of tobacco smoke, in DNA isolated from human lung and blood mononuclear cells (MNCs) from 38 lung cancer patients, we used the (32)P-postlabeling assay to detect polyphenol associated DNA adducts. Two DNA adducts were detected in blood MNCs and lung tissue that co-chromatographed with DNA modifications from HL60 cells treated with combinations of benzene metabolites (e.g., hydroquinone and benzenetriol). These adducts were designated polyphenol-associated DNA adducts. Relative adduct levels for polyphenolic adducts were five-fold higher than aromatic adducts in both lung and MNCs. A significant correlation was observed between levels of polyphenol adducts and total duration of cigarette smoking in lung (r=0.34; P<0.04) and MNCs (r=0.7; P<0.04), but no correlation between levels of polyphenol adducts and pack-years consumption of cigarettes nor time since quitting smoking in former smokers. Long term former smokers and the one non-smoker in the study had detectable levels of polyphenol adducts. Surprisingly, the levels of polyphenol adducts in MNCs were highly correlated with aromatic adduct levels (r=0.84; P<0.001). Individual aromatic adducts in MNCs also correlated with polyphenol adducts. Total polyphenol adduct levels had a correlation with aromatic DNA adduct levels in lung tissue (r=0.46; P<0.01). To our knowledge these results are the only comparison of adducts in MNCs with lung tissue, and the only data set indicating that blood MNCs are a valid surrogate for lung adduct DNA burden.

Adenocarcinoma↗
PubMed2004

Expression of glutaredoxin is highly cell specific in human lung and is decreased by transforming growth factor-beta in vitro and in interstitial lung diseases in vivo.

Glutaredoxins (Grx) are thiol-disulfide oxidoreductases with antioxidant capacity and catalytic functions closely associated with glutathione, an antioxidant abundantly present in human lung. The present study investigated the expression of both human glutaredoxins in cultured human lung cells and lung homogenates by reverse-transcription polymerase chain reaction and Western blotting. Immunohistochemical studies were conducted with 38 human lung specimens, including healthy lung, parenchymal sarcoidosis, extrinsic allergic alveolitis, and usual interstitial pneumonia (UIP). The ultrastructural localization of Grx1 was assessed by immunoelectron microscopy. In addition, cultured airway epithelial cells were exposed to tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Both Grx1 and Grx2 could be detected at the mRNA and protein level in cultured human lung cells, but only Grx1 was prominently expressed in lung homogenates and alveolar macrophages. Immunohistochemically, Grx1 was highly concentrated to alveolar macrophages and weakly positive in the bronchial epithelium. Grx1 was ultrastructurally localized to the plasma membrane, cytoplasmic vacuoles, and nucleus. The expression of Grx1 decreased in alveolar macrophages of sarcoidosis and allergic alveolitis compared with the case for controls (P < 0.001), and bronchial epithelium of these diseases revealed no Grx1 immunoreactivity. Fibroblast foci and other fibrotic areas in UIP were mainly negative. In A549 cells, Grx1 was down-regulated by TGF-beta, whereas TNF-alpha caused no clear effect. Overall, high expression of Grx1 in alveolar macrophages suggests its importance in the primary defense of human lung. Decreased expression of Grx1 further suggests the impairment of this system both in inflammatory and fibrotic lung diseases, consistent with the down-regulation of Grx1 by TGF-beta in vitro.

Blotting, Western↗
PubMed2005

Postnatal lung mechanics, lung composition, and surfactant synthesis after tracheal occlusion vs prenatal intrapulmonary instillation of perfluorocarbon in fetal rabbits.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO. METHODS: In each of 18 pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1) intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9% NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control). Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were mechanically ventilated for 15 minutes to evaluate lung compliance and airway resistance. Pulmonary surfactant protein B (SP-B) was quantified by immunohistochemistry in fetuses of the remaining 6 rabbits. RESULTS: Compliance was decreased in the TO group after cesarean delivery (0.33 +/- 0.13 mL/cm H2O) compared with PFOB (0.59 +/- 0.12 mL/cm H2O), saline (0.50 +/- 0.12 mL/cm H2O), and control (0.52 +/- 0.10 mL/cm H2O) fetuses. Mean fetal lung to body weight ratio was higher in TO and PFOB fetuses compared with saline and control. Higher water content and lower numbers of surfactant protein B-positive cells were found in the TO-treated fetuses. CONCLUSIONS: Both prenatal intrapulmonary instillation of PFOB and TO accelerate lung growth, but TO is associated with decreased postnatal lung compliance, possibly influenced by decreased surfactant production and increased fluid retention. Conversely, instillation of PFOB preserved lung compliance and surfactant synthesis.

Administration, Inhalation↗
PubMed2004

Experimental study of extracorporeal lung resection in dogs: ex situ sleeve resection and autotransplantation of the pulmonary lobe after extended pneumonectomy for central lung cancer.

OBJECTIVE: Extracorporeal lung resection as an alternative to pneumonectomy for central lung cancer is a procedure in which the unilateral lung is extirpated, removing the pulmonary lobe with the cancers and replanting the residual pulmonary lobe. The aim of this study was to investigate whether extracorporeal lung resection for lung cancer can be performed safely. METHODS: Nineteen dogs were divided into the control and extracorporeal lung resection groups. The former (n = 5) underwent lung autotransplantion, and the latter was subdivided into ND1 (n = 7) and ND2 (n = 7) groups on the basis of the manner of lymph node dissection. By comparing the 3 groups, the adverse effects of lymph node dissection were examined. RESULTS: All dogs in the control group had no complications. Four dogs in the ND1 group survived for 90 to 630 days after the operation. In the ND2 group 5 dogs succumbed within 30 days after the operation, although the other 2 dogs survived for 391 and 573 days, respectively. Bronchopulmonary fistulas were seen in 1 of the ND1 dogs and 3 of the ND2 dogs. Two of the latter were free of thrombus formation in the pulmonary arteries and veins of the autografts. In the ND2 group, compared with the control and ND1 group, the tissue blood flow at the bronchial anastomotic site indicated reduction between the 3rd and 14th postoperative days. CONCLUSION: The extensive lymph node dissection had severe adverse effects on bronchial anastomotic healing in extracorporeal lung resection. Therefore extracorporeal lung resection can be applied to only a very limited number of patients with N0 or N1 disease.

Anastomosis, Surgical↗
PubMed2006

Distinguishing lung tumours from normal lung based on a small set of genes.

Identifying specific molecular markers and developing sensitive detection methods are two of the fundamental requirements for detection and differential diagnosis of cancer. Toward this goal, we first performed cDNA array analysis using 65 non-small cell lung cancer and non-involved normal lung tissues. We then used several complementary statistical and analytical methods to examine gene expression profiles generated by us and others from four independent sets of normal and neoplastic lung tissues. We report here that several sets of roughly 20 genes were sufficient to provide a robust distinction between normal and neoplastic tissues of the lung. Next we assessed the predictive ability of these gene sets by using Flow-Thru Chips (FTC) (MetriGenix, Baltimore, MD) containing 20 genes to screen 48 primary lung tumours and normal lung tissues. Gene expression changes detected by FTC distinguished lung cancers from the normal lung tissues using an RNA amount equivalent to that present in as few as 300 cells. We also used an independent set of 24 genes and showed that their expression profile was equally effective when measured by quantitative polymerase chain reaction (Q-PCR). Our results demonstrate that lung cancers can be identified based on the expression patterns of just 20 genes and that this approach is applicable for cancer diagnosis, prognosis, and monitoring using small amount of tumour or biopsy samples.

Biomarkers, Tumor↗
PubMed1993

Parenchymal emphysema measured by CT lung density correlates with lung function in patients with bullous disease.

In subjects with chronic obstructive pulmonary disease (COPD) computed tomographic (CT) lung density correlates with direct pathological measurements of the size of the distal airspaces, as well as with measurements of airflow limitation and impairment of the diffusing capacity. Thus, CT lung density can be used to quantify emphysema in life. We wanted to assess the use of CT scanning to detect and measure the extent of bullous lung, and to quantify the severity of emphysema in the non-bullous areas of the lungs. In patients with bullous emphysema (21 males and 2 females; aged 31-69 yrs; forced expiratory volume in one second (FEV1) 14-84% predicted; volume corrected diffusing capacity of the lungs for carbon monoxide (DLCO/VA) 17-114% predicted). CT lung density was measured in electromagnetic imaging (EMI) units. The extent of bullous emphysema correlated poorly with all respiratory function measurements. In contrast, the severity of emphysema in the non-bullous parts of the lungs, expressed as either the mean EMI number, or the EMI number of the lowest 5th percentile of the CT lung density histogram, correlated well with measurements of airflow limitation and diffusing capacity. Our findings, thus, suggest that in patients with bullae the major determinant of respiratory function is the severity of the emphysema in non-bullous lung, and that the extent of the bullae has less functional importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Lung growth after transplantation of an adult lobe of lung into a juvenile rat.

OBJECTIVE: Shortage of donor organs for children has led to the use of living related adult lung lobar transplants. It is not known how these lobes or the recipient remaining lung grow after such transplants. The purpose of the present study was to assess lung growth in rat lungs up to 6 months after adult lobe transplantation into a juvenile recipient. METHODS: Right cardiac lung lobes from adult male Lewis rats were transplanted into the left hemithorax of juvenile (6-week-old) male Lewis rats after left pneumonectomy. Animals with appropriate controls were put to death 14 days and 6 months after transplantation. The lungs were fixed inflated and studied by means of quantitative morphometric techniques. RESULTS: By 6 months after transplantation both the recipient right lung and the transplanted cardiac lobe were significantly larger than normal (p = 0.005; p = 0.001). In the recipient right lung this increase was due to an increase in the number of alveoli (p = 0.004) and in the transplanted cardiac lobe to an increase in size of the alveoli (p = 0.008). CONCLUSIONS: An adult lobe transplanted into a young recipient is still viable and has normal architecture after 6 months, and growth of the recipients' own lung continues. The outlook for comparable transplants in children is promising, although the human condition can be complicated by rejection, infection, and treatment strategies.

Age Factors↗
PubMed2001

Early hilar lung cancer--risk for multiple lung cancers and clinical outcome.

In early hilar lung cancer patients, multiple lung cancers frequently develop. The clinical outcome of such patients were studied. A total of 91 patients, 88 men and three women, who were endoscopically diagnosed with early hilar lung cancer were studied retrospectively. Surgery was performed in 46 patients, while organ-sparing treatment, including photodynamic therapy (PDT), Nd-YAG (neodymium-yttrium, argon, garnet) laser vaporization, and radiotherapy, were done for 45 patients. During follow-up, newly developed lung cancers and/or malignancies in other organs were recorded. The average smoking index (cigarettes per day x years) was 1040. Synchronous and/or metachronous multiple lung cancers developed in 26/91 patients (28.6%). Malignancies in other organs were found in 12/91 (13.2%). The smoking index of patients with multiple lung cancers was significantly higher than for other patients. The overall 5 year survival rate was 70.7% in all patients, 76.0% in the surgery group, and 64.4% in the nonsurgery group. The lung cancer-specific 5 year survival rate was 89.8% in all patients, 89.3% in the surgery group, and 90.5% in the nonsurgery group. Early hilar lung cancer frequently accompanies other lung cancers or malignancies in other organs. A favorable prognosis can be obtained with organ-sparing treatment.

Adult↗
PubMed2001

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.

Adolescent↗
PubMed2001

Lung and heart-lung transplant practice patterns in pulmonary hypertension centers.

BACKGROUND: Transplant practice patterns for pulmonary hypertension in the epoprostenol era are unknown. METHODS: Thirty-five centers in North America, Europe, and Israel were surveyed regarding practice patterns for lung and heart-lung transplant. RESULTS: New York Heart Association class and distance on a 6-minute walk were considered most useful for deciding who to refer for listing. Patients with New York Heart Association class I to II were referred for listing in 26% of centers, while 57% were classified as New York Heart Association class III or greater after epoprostenol failure. Twenty-nine of the 35 centers had transplant programs that performed approximately 75% of the International Registry volume annually. A double lung transplant was preferred by 83% of centers and heart-lung transplant in the remaining centers. The wait time for lung transplant averaged 16.8 months (range 4-36) and for heart-lung transplant averaged 21.3 months (range 6-36) and was significantly longer in the United States. The mean maximum age for heart-lung transplant was 51.4 years (range 35-65), double lung transplant 58.3 years (range 45-65), and single lung transplant 63.1 years (range 50-70). Fifty-three percent of centers transplant New York Heart Association class III or IV patients, 26% class IIIb-IV, and 21% only class IV. Eighty percent of centers use a transplant hold status. Major unqualified exclusions were hepatitis in 38%, 1 or more hepatic (90%) or renal (100%) criteria, smoking 97%, and obesity in 93%. CONCLUSIONS: Physicians and patients should be aware of the considerable variability in practice patterns for transplantation in pulmonary hypertension, despite published guidelines.

Adult↗
PubMed1999

Pulmonary fibrosis and lung carcinoma: a comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma.

Usual interstitial pneumonia (UIP), or idiopathic pulmonary fibrosis, has been considered to be associated with a high risk for lung carcinoma. To investigate this well-known but still equivocal relationship, we reviewed the clinical features of UIP autopsy cases with or without lung carcinoma (n = 32 and 38, respectively), and compared the morphology and cell kinetics of metaplastic epithelia in the honeycombed areas (n = 11, each group). Thirty-two of 70 UIP autopsy cases showed lung carcinomas. Clinically, UIP with lung carcinoma showed a male predominance (P = 0.001), a higher rate of smoking history (P = 0.001) and a later onset of UIP (P = 0.02), compared with UIP without lung carcinoma. Most of the carcinomas were peripheral in origin (90%), and 65% were topographically associated with honeycombed areas or the border between honeycombing and non-fibrotic areas. Quantitative assessment of the metaplastic epithelia in the honeycombed areas revealed that squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, occurred more frequently in UIP with lung carcinoma than in UIP without lung carcinoma (P = 0.02). There were no significant differences between the two groups with regard to the labeling indexes of Ki-67 and p53 in the metaplastic epithelia, including squamous metaplasia. The degree of atypical squamous metaplasia was not different between the two groups. The quantitative predominance of squamous metaplasia in the honeycombed areas may not be a precursor for lung carcinoma, but might reflect a constitutional susceptibility of UIP patients to develop a lung carcinoma.

Adenocarcinoma↗
PubMed2005

Lung fibre burden in lung cancer cases employed in the rock and slag wool industry.

OBJECTIVES: To evaluate the relationship between estimated exposure to man-made vitreous fibres (MMVF) and to asbestos fibres and their concentration in the lung tissue of lung cancer cases amongst MMVF production workers. METHODS: Retrospective retrieval of available lung tissue specimens was conducted following a case-control study that assessed estimated occupational exposures of MMVF workers. Fibre recovery and analysis by transmission electron microscopy (TEM) were conducted to determine fibre type, fibre dimension and numbers per gram of dry lung tissue. For cases with detailed exposure data, geometric mean (GM) concentrations were compared across the exposure categories, and regression models were used to investigate the relationship between the lung fibres and the variables of estimated exposure, with and without additional variables that may affect fibre retention. RESULTS: A total of 24 samples from 17 cases of lung cancer were available for analysis: MMVF were detected in all cases. Asbestos fibres were detected in 16. No difference or trend in GM MMVF concentration was observed across the estimated exposure categories. Odds ratio (OR) for MMVF g(-1) dry lung was 0.5 (95% confidence interval: 0.1-2.4) for the second, and 3.5 (0.6-18.9) for the third quartile of index of average exposure to MMVF in industry, compared with the first (lowest exposed) quartile (no cases in the highest quartile). CONCLUSIONS: No observable relationship existed between estimated exposure and directly-measured lung fibres among this sample of cases. Retrospective specimen collection, intra-individual variability in fibre concentration, effect of unknown factors on fibre retention and small sample size militated against this study providing evidence for or against a relationship between estimated exposure and lung fibre concentrations.

Adult↗
PubMed1993

The presence of mutagens/carcinogens in the excised lung and analysis of lung cancer induction.

To elucidate a relationship between lung cancer and tumor induction of environmental chemicals, the presence of 1-nitropyrene (1-NP) and benzo[a]pyrene (B[a]P) in 137 Japanese (97 male and 40 female), and 21 Chinese lung specimens was examined by HPLC, and GC-MS and environmental exposure discussed. Mortality due to lung cancer in Fuyuan County, China, is much higher than that of other cancers. We investigated 21 patients who were residents of Fuyuan County. All were female aged 28-64 years and were non-smoking farmers and cooks. The histological features of the tumors were adenocarcinoma, squamous cell carcinoma and small cell carcinoma. The incidence of cancer was due to inhaling soot from the combustion of coal used for cooking and indoor heating. The polycyclic aromatic hydrocarbons, chrysene, benzo[k]fluoranthene, B[a]P, benzo[g,h,i]perylene and pyrene, but not their nitrated derivatives, were detected in substantial amounts in the resected lungs. These mutagens and carcinogens normally originate in combustion products of coal, and are discussed as the possible initiators of the tumors in the lungs of these patients. All the Japanese lung specimens were also obtained from non-smokers. The concentrations of 1-NP averaged 21.3 +/- 12.4 and 5.9 +/- 2.4 pg/g of Japanese and Chinese samples respectively. The concentrations of B[a]P averaged 180.2 +/- 103.7 and 608.7 +/- 477.1 pg/g of Japanese and Chinese samples respectively. Thus, Japanese and Chinese lung specimens were mainly contaminated by 1-NP and B[a]P, respectively. Typical tissues from a carcinomatous human lung were examined. The patient was a 64-year-old Japanese male non-smoker and farmer who had raised chickens over a period of 40 years. The histological features of the tumor were those of keratinizing squamous cell carcinoma. 1-Nitropyrene, 1-nitro-3-hydroxypyrene, 1,3-dinitropyrene and chrysene were detected at concentrations of 0.11, 0.036, 0.095 and 0.16 ng respectively per gram of lung tissue. This cancer was due to long-term exposure to the combustion products of heavy oil used in a chicken house.

Adenocarcinoma↗