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At least 793 records · Page 44Linked to original sources
PubMed2004

Positive end-expiratory pressure applied to the dependent lung during one-lung ventilation improves oxygenation and respiratory mechanics in patients with high FEV1.

BACKGROUND AND OBJECTIVE: The aim of this study was to test the efficacy of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation, taking into consideration underlying lung function in order to select responders to PEEP. METHODS: Forty-six patients undergoing open-chest thoracic surgical procedures were studied in an operating room of a university hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP) or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral decubitus. The patients were stratified according to preoperative forced expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above 72%). Oxygenation was measured in the supine position, in the lateral decubitus with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system pressure-volume curve of the dependent hemithorax was measured in supine and open-chest lateral decubitus positions with a super-syringe. RESULTS: Application of 10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did not occur in ZEEP group, considered as a time matched control. PEEP improved oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P < 0.05). There was no significant change in the low FEV1 group. Dependent hemithorax compliance decreased in lateral decubitus, more in patients with high FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). CONCLUSIONS: During one-lung ventilation in lateral decubitus, PEEP applied to the dependent lung significantly improves oxygenation and respiratory mechanics in patients with rather normal lungs as assessed by high FEV1.

Analysis of Variance↗
PubMed2002

Assessment of regional lung ventilation in dog lungs with Gd-DTPA aerosol ventilation MR imaging.

PURPOSE: Gd-DTPA aerosol ventilation MR imaging was obtained using a modified aerosol delivery system with an aerosol reservoir to non-invasively assess regional lung ventilation in dogs. MATERIAL AND METHODS: Seven anesthetized, spontaneously breathing normal dogs inhaled 200 mmol Gd/l Gd-DTPA aerosol produced by an ultrasonic nebulizer, using an open-circuit aerosol delivery system with or without an aerosol reservoir. Fast gradient-echo MR images were sequentially acquired with an interval time of 1 min for 25 min before and after aerosol inhalation. The aerosol study was also performed using the aerosol delivery system with an aerosol reservoir in the same 7 dogs after airway obstruction with a balloon catheter, and in another 7 dogs after pulmonary arterial embolization with enbucrilate. An i.v. Gd-DTPA-enhanced dynamic MR study after i.v. bolus injection of a 0.1 mmol/kg dose of Gd-DTPA was combined to assess regional lung perfusion. Lung enhancement effect was evaluated by time-signal intensity curves and the subtracted ventilation- and perfusion-weighted images. RESULTS: With or without the aerosol reservoir, the normal dog lungs were gradually and gravity-dependently enhanced with time after aerosol inhalation. The use of the aerosol reservoir, however, showed significantly greater lung enhancement without a significant increase in breathing rate and with minimal reduction in PaO2 of less than 5 mm Hg in these animals. The enhancement effect of i.v. injection of Gd-DTPA at pulmonary arterial perfusion phase was significantly greater compared to that of Gd-DTPA aerosol throughout the normal lungs, and the subtracted ventilation-weighted and perfusion-weighted images showed homogeneous but gravity-dependent aerosol deposition and perfusion. These images clearly defined the regionally matched perfusion-ventilation deficits in the lung regions distal to bronchial obstruction in all the airway obstruction dogs, and the regionally mismatched perfusion-ventilation in the embolized regions of all the pulmonary arterial embolization animals. CONCLUSION: Gd-based aerosol can non-invasively image regional lung ventilation in spontaneously breathing animals, using an adequate aerosol delivery system. The combined use of Gd-DTPA perfusion MR imaging may be acceptable for defining regionally impaired lung function associated with acute airway obstruction and pulmonary arterial embolization.

Aerosols↗
PubMed2003

Lung injury severity scoring in the era of lung protective mechanical ventilation: the PaO2/FIO2 ratio.

BACKGROUND: Lung protective ventilatory strategies using low tidal volume and high positive end-expiratory pressure (PEEP) have become standard practice. Such strategies, however, may invalidate measurement of lung injury severity by traditional methods that are based on plain chest radiograph findings, oxygenation, minute ventilation, lung compliance, and PEEP level, such as the Murray lung injury score (LIS). Many of these criteria are potentially therapy dependent and may change with different ventilatory strategies. The purpose of this study was to determine whether measurement of lung injury severity based simply on oxygenation criteria (PaO(2)/FIO(2)) was as accurate as the Murray LIS currently used in multiple organ failure (MOF) scoring. METHODS: Since 1992, trauma patients at high risk for developing MOF have been prospectively identified and MOF scores calculated daily. Pulmonary dysfunction is graded from 0 to 3 on the basis of a modified Murray LIS incorporating the aforementioned parameters. Lung injury severity was redefined using the PaO(2)/FIO(2) (P/F score): Grade 0 = >250; 1 = 175 to 250; 2 = 100 to 174; and 3 = <100. The maximum (worst) score using each was compared using logistic regression and receiver operating characteristic curve analysis. RESULTS: Five hundred thirty-nine trauma patients had lung injury severity assessed using both LIS and P/F score. The mean P/F score was over twice the mean LIS (1.9 +/-.04 vs. 0.9+/-.04, p < 0.0001). In 28% of patients, the LIS and P/F score were identical, whereas in 71%, the P/F score was greater than the LIS. Both scores were significant predictors of mortality; however, receiver operating characteristic curve analysis showed that the P/F score was superior in predicting mortality (area under the curve, 0.74+/-.03 vs. 0.67+/-.04). CONCLUSION: The P/F score is a simple method of quantifying lung injury severity in trauma patients that better predicts mortality compared with the more complicated modified Murray lung injury score currently in use. The P/F score should replace more complex and potentially therapy-dependent scores.

Adult↗
PubMed2001

The infant lung function model: a mechanical analogue to test infant lung function equipment.

To facilitate international multicentre studies and quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society (ERS-ATS) working group for infant lung function testing aims to develop specifications for standardized infant lung function equipment and software. However, a standardized test device is also needed to test whether existing infant lung function equipment is able to meet these requirements. The authors have built a "mechanical model baby" consisting of a linear pump which can reproduce prerecorded tidal flow waveforms with a precision of 0.5% (full stroke), enabling the simulation of tidal and forced flow patterns. This linear pump can be connected to a series of copper lung volumes (range 50-300 mL) with known time constants, so that lung volumes can be reproduced with a precision of +/-1% at frequencies 10-120bpm. Five airflow resistors were built using sinter material. When assessed using flows 0-300 mL.s(-1) all resistors showed a quasilinear pressure/ flow relationship, with slopes 1.0-5.6 kPa.L(-1).s. These resistances could be reproduced with a precision of +/-2.5%. The infant lung model can also be used to assess frequency responses of infant lung function equipment, since the pump is capable of delivering low amplitude volumes up to 20 Hz in a pseudorandom noise manner. In summary, based on error estimations, this infant lung model is able to test whether or not infant lung function equipment meets the requirements suggested by the European Respiratory Society-American Thoracic Society standardization group, that is: flow measurements within +/-2.5%, volume and resistance measurements within +/-5%, frequency response: magnitude attenuation <+/-10% and phase shift <+/-3 degrees at 10 Hz.

Airway Resistance↗
PubMed2005

The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung.

BACKGROUND: Translocation of ultrafine particles (UFP) into the blood that returns from the lungs to the heart has been forwarded as a mechanism for particle-induced cardiovascular effects. The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. METHODS: The isolated perfused rat lung (IPRL) was used under negative pressure ventilation, and radioactive iridium particles (18 nm, CMD, 192Ir-UFP) were inhaled during 60 minutes to achieve a lung burden of 100-200 microg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 microM) in perfusate, iii) luminal histamine instillation (1 mM), and iv) luminal instillation of H2O2. Particle translocation to the perfusate was assessed by the radioactivity of 192Ir isotope. Lung permeability by the use of Tc99m-labeled diethylene triamine pentaacetic acid (DTPA). In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate were measured to assess epithelial and endothelial integrity. RESULTS: Particle distribution in the lung was homogenous and similar to in vivo conditions. No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine (1 microM) in the perfusate or with luminal H2O2 (0.5 mM) showed small amounts of radioactivity (2-3 % dose) in the single pass perfusate starting at 60 min of perfusion. Although the kinetics of particle translocation were different from permeability for 99mTc-DTPA, the pretreatments (H2O2, vascular histamine) caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage. CONCLUSION: Permeability of the lung barrier to UFP or nanoparticles is controlled both at the epithelial and endothelial level. Conditions that affect this barrier function such as inflammation may affect translocation of NP.

Journal Article↗
PubMed2006

Spirometrically gated high-resolution CT findings in COPD: lung attenuation vs lung function and dyspnea severity.

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between high-resolution CT (HRCT) lung attenuation measurements, acquired under spirometric control of inspiratory and expiratory lung volume, and pulmonary dysfunction as well as dyspnea severity in patients with COPD. PATIENTS AND DESIGN: In 51 patients with COPD, we compared by linear regression, univariate and multivariate logistic regression airflow limitation (FEV(1)/vital capacity [VC]), hyperinflation (percentage of predicted residual volume [RV%]), parenchymal loss (percentage of predicted diffusing capacity of the lung for carbon monoxide [Dlco%]), and Medical Research Council (MRC) dyspnea scale with relative area with attenuation values < - 950 HU at 90% of VC [RAI(950)] and < - 910 HU at 10% of VC, respectively, and with mean lung attenuation measured at the same levels of VC (mean CT lung density at 10% of VC, and mean CT lung density at 90% of VC [MeanCTEXP]). RESULTS: All HRCT attenuation measurements were significantly related with functional abnormalities and dyspnea severity. In multivariate logistic models, with 1 indicating worse changes in dichotomous outcome variables, MeanCTEXP independently predicted FEV(1)/VC (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11 to 0.56), RV% (OR, 0.57; 95% CI, 0.42 to 0.77), and MRC dyspnea scale (OR, 0.63; 95% CI, 0.48 to 0.82), while RAI(950) independently predicted Dlco% (OR, 1.90; 95% CI, 1.37 to 2.65). CONCLUSIONS: Spirometrically gated measurements of HRCT lung attenuation reflect differently functional changes and dyspnea perception in COPD. Inspiratory measurements assess the extent of emphysematous tissue loss, and expiratory measurements may reflect airflow limitation and lung hyperinflation with attendant dyspnea perception. Pulmonary dysfunction in COPD cannot be assessed by a single modality of lung attenuation measurement.

Adult↗
PubMed2000

Obstructive lung disease and low lung function in adults in the United States: data from the National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Obstructive lung disease (OLD) is an important cause of morbidity and mortality in the US adult population. Potentially treatable mild cases of OLD often go undetected. This analysis determines the national estimates of reported OLD and low lung function in the US adult population. METHODS: We examined data from the Third National Health and Nutrition Examination Survey (NHANES III), a multistage probability representative sample of the US population. A total of 20,050 US adults participated in NHANES III from 1988 to 1994. Our main outcome measures were low lung function (a condition determined to be present if the forced expiratory volume in 1 second-forced vital capacity ratio was less than 0.7 and the forced expiratory volume in 1 second was less than 80% of the predicted value), a physician diagnosis of OLD (chronic bronchitis, asthma, or emphysema), and respiratory symptoms. RESULTS: Overall a mean (SE) of 6.8% (0.3%) of the population had low lung function, and 8.5% (0.3%) of the population reported OLD. Obstructive lung disease (age-adjusted to study population) was currently reported among 12.5% (0.7%) of current smokers, 9.4% (0.6%) of former smokers, 3.1% (1.1%) of pipe or cigar smokers, and 5.8% (0.4%) of never smokers. Surprisingly, 63.3% (0.2%) of the subjects with documented low lung function had no prior or current reported diagnosis of any OLD. CONCLUSIONS: This study demonstrates that OLD is present in a substantive number of US adults. In addition, many US adults have low lung function but no reported OLD diagnosis, which may indicate the presence of undiagnosed lung disease.

Adolescent↗
PubMed1976

A normal adult and fetal lung antigen present at different quantitative levels in different histologic types of human lung cancer.

Rabbits were immunized with extract of either an adenocarcinoma of the lung, or one of three oat cell carcinomas of the lung. Unabsorbed and variously absorbed antisera, and various extracts, were analyzed by double and radial immunodiffusion. The adenocarcinomas-antisera identified an antigen subsequently quantitated at high concentration in seven adenocarcinomas of the lung, but a low concentration in five normal adult and four fetal lungs. Three of four epidermoid carcinomas of the lung contained the antigen at low concentration, however only trace amounts were detected in four of five oat cell carcinomas of the lung. The oat cell carcinoma-antisera failed to identify a significant antigen. Quantitatively, the above antigen appeared to distinguish adenocarcinomas and to a lesser extent epidermoid carcinomas from oat cell carcinomas of the lung, and to be consistent with the concept that oat cell carcinomas arise from a different cell type than the other lung tumors.

ABO Blood-Group System↗
PubMed1987

Aryl hydrocarbon hydroxylase in lymphocytes and lung tissue from lung cancer patients and controls.

The inducibility of aryl hydrocarbon hydroxylase (AHH) activity in peripheral mitogen-treated lymphocytes, and of AHH and other monoxygenase activities in lung samples, was studied in 41 patients--34 with pulmonary carcinoma, 4 with a benign lung tumour and 3 with chronic obstructive pulmonary disease. Lymphocyte AHH induction alone was studied in 43 non-smoking and 37 smoking surgical patients. Absolute induced and non-induced AHH activities were at about the same level in the lymphocytes from the lung cancer patients as in those from the non-smoking controls, whereas the activities in smoking controls were about 100% higher. The mean inducibility ratios were very similar in all groups, ranging from 4.4 in the benign tumour patients to 5.4 in both control groups. Thymidine incorporation was on average about 40% lower in the lymphocytes from the lung cancer patients. AHH activity was detectable in all the peripheral lung samples, both normal or tumorous tissue, and its inter-individual variation was more than 67-fold. ECDE activity was also detectable in all the samples studied and its correlation with AHH activity was statistically significant (r = 0.888), suggesting that the same enzyme metabolizes both substrates. ERDE was detectable only in the samples with the highest AHH and ECDE activities. There was no correlation between basal or induced lymphocyte AHH activities and lung tissue AHH activity, but there were statistically significant correlations between lung AHH activity and the inducibility ratio with (r = 0.618) or without correction by thymidine incorporation (r = 0.442). These correlations suggest that there are common regulatory factors for AHH inducibility in different tissues. No significant difference in any drug metabolism parameter measured was observed between the lung cancer patients and the controls.

Animals↗
PubMed2002

Characterization of bleomycin lung injury by nuclear magnetic resonance: correlation between NMR relaxation times and lung water and collagen content.

The response of the NMR relaxation times (T(1), CPMG T(2), and Hahn T(2)) to bleomycin-induced lung injury was studied in excised, unperfused rat lungs. NMR, histologic, and biochemical (collagen content measurement) analyses were performed 1, 2, 4, and 8 weeks after intratracheal instillation of saline (control lungs) or 10 U/kg bleomycin sulfate. The control lungs showed no important NMR, water content, histologic, or collagen content changes. The spin-spin relaxation times for the fast and intermediate components of the CPMG decay (T(2f) and T(2i), respectively) increased 1 week after bleomycin injury (acute inflammatory stage) and then progressively decreased during the following 2-8 weeks (i.e., with the development of the chronic, fibrotic stage of the injury). The slow component (T(2s)) showed no significant changes. The response of T(1) and the slow component of the Hahn T(2) was, on the whole, similar to that of CPMG T(2f) and T(2i). T(1) changes were very small. Lung water content increased 1 week after injury. Histologic and biochemical assessment of collagen showed that collagen content was close to control at 1 week, but markedly increased at 2, 4, and 8 weeks. T(1) and T(2) data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T(2)) reflect the structural changes associated with bleomycin injury. The prolonged T(2) relaxation times observed in the acute stage are related to the presence of edema, whereas the subsequent decrease in these values marks the stage of the collagen deposition (fibrotic stage). CPMG-T(2) and Hahn-T(2) measurements can be valuable as a potentially noninvasive method for characterizing bleomycin-induced lung injury and pathologically related lung disorders.

Animals↗
PubMed2004

[Laser-induced thermotherapy of lung metastases and primary lung tumors].

We present laser-induced thermotherapy (LITT) of primary and secondary lung tumors analysing indications and technical concepts. Thirty patients with lung metastases of different primary tumors (n=24) as well as localized lung tumors (n=6) were prospectively treated in 41 sessions using laser-induced thermotherapy (LITT). An MR-compatible puncture system was used with direct puncture technique. The puncture was performed via CT guidance in care vision technique. Eight patients were thermoablated using MR tomographical monitoring, 22 patients using CT monitoring. Local therapy effects, tumor control rate, side effects, complications, and survival were evaluated. In 74% of cases (28/38 lesions) of 24 patients with lung metastases and in all cases of the 6 patients with lung carcinoma a complete local ablation could be achieved. The complication rate (pneumothorax) was 9,8%. One patient with bronchial carcinoma had to be thoracotomized and resected. 93% of the patients are still alive. Percutaneous LITT of lung tumors permits a complete ablation of lung metastases and lung carcinomas with a low complication rate. Indications for the procedure were defined for patients with no more than 5 metastases up to 3 cm in size.

Adult↗
PubMed2005

LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0+/-8.1) than in normal lung tissues (1.0+/-0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2002

Cytokeratin typing as an aid in the differential diagnosis of primary versus metastatic lung carcinomas, and comparison with normal lung.

Due to more efficient chemotherapy protocols, the number of second and even third primary carcinomas is steadily increasing. To denominate the possible origin of a carcinoma, different markers are available as an aid, e.g. hormones, proteins and lipoproteins, secretion products and cytoskeletal proteins. Cytokeratins (CKs) have gained new popularity; however, they have not been extensively evaluated in lung tumours. In our study we evaluated the staining patterns of CK polypeptides 4-8, 10, 13, 14, and 17-20 and high molecular weight (HMW) CK polypeptides in routinely processed primary lung carcinomas and lung metastases of diverse origin. As expected, immunohistochemical investigation gave no clear-cut results, but, with statistical analysis, lung adenocarcinomas could be separated from metastatic adenocarcinomas using CK 5 and 18 and HMW CK (specificity 92.5%, sensitivity 62.5%). The different origin of the metastases could often be detected using CK 18 and CK 20. Lung clear cell carcinomas and large cell carcinomas with clear cell areas could be distinguished from metastatic renal clear cell carcinomas by the CK 7 staining reaction. Squamous cell carcinomas of the lung and metastatic squamous cell carcinomas of the larynx, pharynx and oesophagus could not reliably be separated in part due to the few number of cases available. CK polypeptide typing is thus an additional aid in the differential diagnosis of lung carcinomas versus carcinomas metastatic to the lung.

Adenocarcinoma↗
PubMed1994

Liberalization of donor criteria in lung and heart-lung transplantation.

Since March 1986, we have performed 26 heart-lung transplantations, 42 single-lung transplantations, 9 bilateral single-lung transplantations, and 1 double-lung transplantation. The original lung donor requirements were as follows: age less than 40 years, no smoking history; no gram-negative rods or fungus on sputum Gram stain; arterial oxygen tension greater than 140 mm Hg on an inspired oxygen fraction of 0.40; no infiltrate or pneumothorax on the chest radiograph; and donor height within 15 cm (6 inches) of recipient height. As the number of potential recipients increased, so did the waiting time. To counter this delay, during the past year we have liberalized our donor criteria. We now accept lung donors up to age 60 years. Any kind of smoking history is acceptable unless there is chronic obstructive pulmonary disease or pulmonary fibrosis on the chest radiograph. Sputum must be free from fungus, but gram-negative rods are treated with appropriate antibiotics. The arterial oxygen tension on an inspired oxygen fraction of 0.40 should be greater than 100 mm Hg, and a small pulmonary infiltrate is not worrisome. This liberalization of the donor pool for lung and heart-lung transplantation has not adversely affected early outcome.

Adult↗
PubMed1975

Studies on lung tumours. III. Oxidative metabolism of dimethylnitrosamine by rodent and human lung tissue.

The oxidative metabolism of the carcinogen dimethylnitrosamine (DMN) was studied in mouse, rat, hamster and human respiratory tissue. [14C]DMN was purified by Dowex-1-bisulfite column chromatography to remove a contaminant (probably [14C]formaldehyde) interfering with the enzyme assay. Since formaldehyde and methyl carbonium ions - yielding methanol with water - are considered to be the primary products of DMN metabolism, tissue slices were assayed for the production of [14C]CO2 from 14C-labelled methanol, formaldehyde, formate, and DMN. Oxidation of formaldehyde to formate was not, but oxidation of formate to CO2 was very much rate-limiting. This rate-limiting step was circumvented by introducing quantitative chemical oxidation of formate to CO2 by mercury(II)chloride following the enzymic reaction. Since oxidation of methanol to CO2 proved to be insignificant, production of CO2 from DMN by lung tissue enzymes and HgCl2 may serve as a parameter for N-demethylating activity and the production of the suspected carcinogenically active methyl carbonium ions. The DMN-N-demethylating activities of lung tissue slices of two mouse strains with widely different susceptibilities to formation of lung adenomas by DMN differed significantly, but the difference seemed too small to explain the divergence in tumourigenic response. The enzymatic activities decreased in hamster bronchus, hamster trachea, hamster lung, GRS/A mouse lung, C3Hf/A mouse lung, human lung, Sprague-Dawley rat lung, in that order. The reported resistance of the hamster respiratory system to tumour induction by DMN may therefore not be due to poor DMN-N-demethylating capacity.

Aged↗
PubMed1979

Studies on lung tumours. IV. Correlation between [3H]thymidine labelling of lung and liver cells and tumour formation in GRS/A and C3Hf/A male mice following administration of dimethylnitrosamine.

Male mice of the inbred strain GRS/A are highly susceptible to lung tumour but refractory to liver tumour formation, whereas the opposite relation holds for C3Hf/A male mice. Liver and lung cells of these 2 mouse strains were studied autoradiographically after intraperitoneal injection of [3H]dimethylnitrosamine (DMN) and of [3H]thymidine at days 1--14 after administration of unlabelled DMN. Corresponding cell types in the lungs or livers of these 2 mouse strains bound similar amount of [3H]DMN. Among the various types of lung cells only the alveolar Type II cells, from which the lung adenomas derive, showed a strain-specific difference in [3H]thymidine labelling indices, much more cells becoming labelled in the case of the GRS/A than of the C3Hf/A strain at days 3--7 after carcinogen administration. Opposite thymidine labelling indices were exhibited by the parenchymal liver cells of the 2 strains, with C3Hf/A now showing a greater response than did GRS/A males. Thus thymidine-labelling and tumourigenic responses of target lung and liver cells to carcinogen in the 2 strains coincided. Sulphur dioxide and carbon tetrachloride mimicked the effects of DMN on the thymidine labelling indices of, respectively, the lung alveolar Type II and the thymidine labelling indices of, respectively, the lung alveolar Type II and the liver parenchymal cells of the 2 strains. The nature of the differential effect of carcinogen on the [3H]thymidine labelling of the cells and the correlation of these patterns with susceptibility to tumour formation, are briefly discussed.

Animals↗
PubMed1983

Possible effects on occupational lung cancer from smoking related changes in the mucus content of the lung.

A number of recent epidemiological studies of lung cancer among occupations that expose workers to dusts or toxic aerosols have reported a larger prevalence of lung cancer among non-smoking than among smoking workers. One recent study using Beagle dogs has also reported significantly fewer respiratory tumors among animals exposed to radon, radon daughters, uranium dust and tobacco smoke than among animals exposed similarly except for tobacco smoke. The evidence is summarized here that the increased mucus in the lungs of smokers may help in the elimination of dust and toxic substances by facilitating migration of particles and aerosols and possibly also adding protection by thickening of the mucus layer. Recent developments in use of in vivo magnetometric measurements of dust content of workers' lungs in fact indicate that lungs of chronically exposed miners and millers contain less dust if they smoke than if they do not. The hypothesis that increasing mucus in the lung of exposed workers may protect them against lung disease now needs experimental verification in appropriate animal studies. If protective qualities of lung mucus are verified, means need to be explored that will increase mucus flow in non-smoking (and smoking) workers exposed to respiratory hazards.

Aerosols↗
PubMed1994

Changes in lung function and perfusion after irradiation in patients with lung cancer.

The changes in lung function were prospectively studied for patients with lung carcinoma who were treated with relatively high doses of irradiation. Their dyspnoea score, lung volume spirometry, diffusion capacity and ipsilateral hemithorax perfusion were measured at presentation, again between 5 and 6 months after irradiation (Group 1, 36 evaluable patients), and once more between 11 and 12 months (Group 2, 16 evaluable patients). There was a worsening of the dyspnoea score from 1 to 2, in a large percentage of patients, but only 6% developed a dyspnoea score of 3. The largest change in lung function tests was a decrease in the diffusion capacity (DLCO) to 14% at 6 months and 12% at 12 months (statistically significant, P < 0.0001 paired t-test). The forced vital capacity (FVC) and the total lung capacity (TLC) showed a lesser decrease at 6 and 12 months, and the smallest decrease, which was not statistically significant, was in the forced expiratory volume in 1 s (FEV1). There was also a statistically significant decrease in the ipsilateral hemithorax lung perfusion of 16% at 6 months and 20% at 12 months. There was a weak correlation between the decrease in the DLCO and the FEV1 at follow-up. There was no statistically significant correlation between initial perfusion or decreased perfusion and the decrease in lung function. Lung irradiation should be regarded as an ablative form of therapy, analogous to surgery, in patients with a projected survival of 6 months or more. The DLCO is the most sensitive indicator of clinical damage and its pretreatment assessment should be useful in predicting clinical tolerance to irradiation.

Dyspnea↗