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PubMed1986

Nitrogen dioxide exposure and development of pulmonary emphysema.

This study assessed the relationship between nitrogen dioxide inhalation and the development of pulmonary emphysema and investigated how the severity of preexisting emphysema brought about by protease (elastase) instillation into the lung may be augmented by a subchronic exposure to a relatively high concentration of nitrogen dioxide. Lungs of adult Fischer-344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25-d exposure to 35 ppm nitrogen dioxide (NO2), and (3) elastase instillation followed by 25-d exposure to 35 ppm NO2 (E + NO2). Rats instilled with sterile normal saline and subsequently exposed to filtered air served as a control group (NS). Residual volumes (RV) of the NO2 and NS groups were virtually identical, whereas the RV of the E and E + NO2 lungs (2.3 and 2.3 ml, respectively) were significantly greater than those of the NS and NO2 lungs (1.3 and 1.4 ml, respectively). Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO2 groups; NO2 alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO2 exposed lungs were essentially identical with average values of approximately 62 micron. This morphometric parameter was substantially increased in the E- and E + NO2-exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO2 lungs (approximately 95 and approximately 97 micron, respectively). From these data, as well as histologic examinations of lung sections for evidence of emphysema, we conclude that (1) a subchronic, moderately high level of NO2 exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease-induced emphysema or bring about a progression in preexisting emphysema.

Animals↗

PubMed2000

Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis.

The simultaneous occurrence of pulmonary fibrosis and emphysema may present considerable problems in clinical assessment. Recent studies have shown that Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are changed in patients with pulmonary emphysema. This study was performed to assess the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and ABD. ADAM and ABD measurements were performed in 20 patients with lone high resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15 emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm; FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E showed a significantly higher bolus dispersion than patients with FE (724 +/- 122 cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus dispersion was still significantly higher than in previously published control groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The results of this study confirm that ADAM and ABD are powerful tools for identifying emphysema even in patients with superimposed pulmonary fibrosis.

Aerosols↗

PubMed2003

Vitamin A depletion induced by cigarette smoke is associated with the development of emphysema in rats.

We showed previously that vitamin A deficiency per se causes emphysema. Benzo(a)pyrene, a constituent in cigarette smoke, induces vitamin A depletion when administered to rats; therefore, we tested the hypothesis that cigarette smoke induces vitamin A depletion, which is associated with the development of emphysema. Male weanling rats were fed a purified AIN-93G diet and divided into two groups. The experimental group was exposed to cigarette smoke from 20 nonfiltered commercial cigarettes/d for 5 d/wk, whereas the control group was exposed to air. After 6 wk, tissues were collected for histological and biochemical analyses. Retinol levels were measured in serum, lung and liver. The trachea, lung and liver were examined for histological changes. Vitamin A levels decreased significantly in serum, lung and liver of smoke-treated rats. Histological examination revealed the presence of interstitial pneumonitis along with severe emphysema. There was a significant inverse relationship between vitamin A concentration in the lung and the severity of emphysema (r = -0.69 and P < 0.03). Detachment or hyperplasia (and metaplasia) of the tracheal epithelium and liver vacuole formation also were evident in the smoke-treated rats. The results of this research indicate that exposure to cigarette smoke induces vitamin A depletion in rats, which is associated with the development of emphysema.

Animals↗

PubMed1991

Sequential morphologic changes of elastase-induced pulmonary emphysema in pig lungs. Evaluation by high-resolution computed tomography.

The authors evaluated the early morphologic changes of elastase-induced pulmonary emphysema in the pig and correlated the findings with high-resolution computed tomography (HRCT). Nine Yorkshire pigs were included in this investigation; in seven, pulmonary emphysema was induced by 2 mg/kg body weight of elastase instilled selectively into the left lower lobe bronchus. Animals were studied by CT at 0, 1, 2, 3, 7, 14, and 21 days. At the completion of the experiment, the lungs were removed, inflated, fixed and dried, and subsequently sliced corresponding to the CT sections. The gross appearance, histologic appearance, and HRCT were correlated. On HRCT, sequential changes from early edema to development of emphysema were noted. Panlobular, centrilobular and paraseptal emphysema were observed. Elastase-induced pulmonary emphysema in the pig is a useful and reproducible animal model, and high-resolution computed tomography depicts the morphologic changes observed both by gross pathologic observations and histologic observations.

Animals↗

PubMedDate not supplied

Pulmonary function abnormalities in patients with CT-determined emphysema.

The CT quantification of both the extent and severity of emphysema was undertaken in 30 subjects. The CT scans at five preselected anatomic levels were analyzed using two methods. Correlation of the results of the CT methods were with pulmonary function results of airway obstruction and alveolar diffusion for carbon monoxide. Analysis by direct observation of the CT scans gave insignificantly different results for a complex grid method of analysis. The emphysema score with the observational method had a positive correlation with airflow obstruction (r = -0.817) as did the score with the grid method (r = -0.873). The diffusing capacity for carbon monoxide also correlated with both emphysema scores. The CT methods for quantifying emphysema correlate closely with functional abnormalities. As previously demonstrated with pathological assessment of lung slices for emphysema, direct observation of CT scans is as precise as a more complex grid method.

Aged↗

PubMed1998

Posterior inferior junction line and left pleuroesophageal stripe: their association with emphysema.

In an effort to define the posterior inferior junction line (PIJL) and its clinical associations more precisely, 64 posteroanterior radiographs demonstrating the PIJL or left pleuroesophageal stripe (LPES) were analyzed for the presence of emphysema, kyphosis, air-filled esophagus, and/or tortuous aorta. Pursuant to the possible association of a PIJL or LPES with an air-filled esophagus, posteroanterior radiographs of 66 patients with achalasia were evaluated for the presence of a PIJL or LPES. To determine the components of the PIJL or LPES, 50 randomly selected computed tomographs (CT) of the chest were reviewed. Finally, 118 posteroanterior radiographs of patients with emphysema were analyzed for the presence of a PIJL and/or LPES to determine the sensitivity of the line/stripe for emphysema. The finding of a PIJL and/or LPES had a combined sensitivity of 23% for emphysema. Although certain other anatomic constructs lead to the presence of a line or stripe, emphysema is the most commonly associated clinical entity with a positive predictive value of 65.8%. The line and/or stripe is formed by interfaces between lung/lung, lung/esophagus, or both at different levels.

Aorta↗

PubMed1996

Bullous emphysema.

Bullae are usually associated with varying degrees of emphysema, and bullous emphysema may be an appropriate term for bullous diseases. Recent advances in high-resolution computed tomography and thoracoscopic surgery allow us to improve both our knowledge of as well as the surgical outcomes for bullous emphysema. However, the etiology and pathogenesis of bullae and their association with emphysema are not yet elucidated. Further investigation, including animal studies, may be helpful in solving the questions from the perspectives of etiology, pathology, and function in bullous emphysema.

Animals↗

PubMed2004

Implication of differences in the incidence of orbital emphysema in ethmoidal and maxillary sinus fractures.

This study investigated the incidence of orbital emphysema in patients with fractures of the ethmoidal cells or maxillary sinus. We noted that mucosal destruction is essential for orbital emphysema to occur. Computed tomographic examination and intraoperative studies of 58 patients with orbital bone fracture were performed with the patients divided into 2 groups according to the location of the fracture lines. The incidences of orbital emphysema and of intrasinus hematoma were significantly higher in the group with medial orbital bone fracture of ethmoidal cells than in the group with maxillary sinus fracture, which indicates mucosal tear was significantly higher in the former group. Fractured lamina papyracea and intrasinus hematoma were observed in all cases with ethmoidal sinus fracture. On the other hand, intrasinus hematoma was not found in some cases with maxillary sinus fracture, blowout fracture of the orbital floor, or zygomatic bone fracture, while all cases with orbital emphysema were included in the cases with intrasinus hematoma. This suggests that the incidence of orbital emphysema depends on the occurrence of tearing of the mucosa of the paranasal sinus.

Emphysema↗

PubMed2005

Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema.

Inflammation, protease/anti-protease imbalance and oxidative stress play important roles in the pathogenesis of emphysema. Nrf2 counteracts oxidative tissue damage and inflammation through transcriptional activation via the anti-oxidant responsive element (ARE). To clarify the protective role of Nrf2 in the development of emphysema, the susceptibility of Nrf2-knockout mice to cigarette smoke (CS)-induced emphysema was examined. In Nrf2-knockout mice, emphysema was first observed at 8 weeks and exacerbated by 16 weeks following CS-exposure, whereas no pathological abnormalities were observed in wild-type mice. Neutrophilic lung inflammation and permeability lung damage were significantly enhanced in Nrf2-knockout mice 8 weeks after CS-exposure. Importantly, neutrophil elastase activity in bronchoalveolar lavage fluids was markedly higher in Nrf2-knockout mice preceding the pronounced neutrophil accumulation. The expression of secretory leukoprotease inhibitor, a potent inhibitor of neutrophil elastase, was inducible in wild-type, but not in Nrf2-knockout mice. This protease/anti-protease imbalance, together with the lack of inducible expression of ARE-regulated anti-oxidant/anti-inflammatory genes, may explain the predisposition of Nrf2-knockout mice to neutrophilic inflammation. Indeed, specific activators of Nrf2 induced the expression of the SLPI gene in macrophages. These results indicate that Nrf2 protects against the development of emphysema by regulating not only the oxidant/anti-oxidant balance, but also inflammation and the protease/anti-protease balance.

Animals↗

PubMed2005

133Xenon ventilation scintigraphy applied to bronchoscopic lung volume reduction techniques for emphysema: relevance of interlobar collaterals.

BACKGROUND: 133Xenon ventilation scintigraphy and (99m)Tc-MAA perfusion scintigraphy can be used to assess dynamic ventilation patterns in patients with severe emphysema. AIM: To describe the scintigraphic features of attempted bronchoscopic lung volume reduction (BLVR), exploring mechanisms that might explain the unexpected lack of postoperative atelectasis. METHODS: Five patients with heterogenous severe upper lobe emphysema were evaluated with 133Xenon ventilation and (99m)Tc-MAA perfusion scintigraphy, chest radiography, bronchoscopy and high resolution computed tomography before and up to 1 month after endoscopic placement of bronchial prostheses (BLVR). Ex vivo assessment of the lungs of two further patients with severe upper lobe emphysema was performed. RESULTS: No significant subsegmental or lobar collapse was evident on post-procedure chest radiography or high resolution computed tomography, despite bronchoscopic confirmation of adequate position and functioning of prostheses. 133Xenon ventilation scintigraphy confirms significantly decreased upper lobe wash-in (P < 0.023), unchanged lower lobe wash-in and significantly increased lower lobe wash-out rates (P < 0.005) after BLVR. Significant redistribution of perfusion to the lower lobes occurred after BLVR (P < 0.025). Ex vivo experiments on explanted emphysematous lungs demonstrated that these findings could best be explained by collateral interlobar ventilation, which was calculated in one specimen to be as high as 15% of total lower lobe ventilation. Peri-valvular leak is a much less likely possibility. CONCLUSION: 133Xenon ventilation scintigraphy indicated the presence of significant interlobar collateral ventilation in patients with severe emphysema that may have major relevance to these novel alternative techniques to lung volume reduction surgery. 133Xenon scintigraphy can be used in the evaluation of severe emphysema before and after novel therapeutic interventions.

Bronchoscopy↗

PubMed1986

Comparison of right ventricular weight at necropsy in interstitial pulmonary fibrosis and in chronic bronchitis and emphysema.

The ventricular weights in 43 patients with interstitial pulmonary fibrosis were retrospectively compared with those in 172 patients with emphysema and chronic bronchitis. The mean right ventricular weight of patients with interstitial pulmonary fibrosis and those with emphysema and chronic bronchitis was 85.5 g (SD 23.2) and 88.8 g (34.3), respectively. Thirty five patients (81%) with interstitial pulmonary fibrosis had a right ventricular weight over 65 g compared with 124 (72%) of those with emphysema. Fifty three per cent of both those with interstitial pulmonary fibrosis and those with chronic bronchitis and emphysema had a right ventricular weight greater than 80 g. Differences between the two groups were not significant. These results suggest that the prevalence of right ventricular hypertrophy and pulmonary hypertension in interstitial pulmonary fibrosis is similar to that found in chronic bronchitis and emphysema.

Aged↗

PubMed1992

A new high resolution computed tomography scoring system for pulmonary fibrosis, pleural disease, and emphysema in patients with asbestos related disease.

The aim of this study was to describe a scoring system for high resolution computed tomographic (HRCT) scans analogous to the International Labour Office (ILO) scoring system for plain chest radiographs in patients with asbestos related disease. Interstitial fibrosis, pleural disease, and emphysema were scored, the reproducibility and the interobserver agreement using this scoring system were examined, and the extent of the various types of disease was correlated with measurements of lung function. Sixty asbestos workers (five women and 55 men) mean age 59 (range 34-78) were studied. The lungs were divided into upper, middle, and lower thirds. An HRCT score for the extent of pleural disease and pulmonary disease in each third was recorded in a way analogous to the International Labour Office (ILO) method of scoring pleural and parenchymal disease on chest radiographs. A CT score for the extent of emphysema was also recorded. Pleural disease and interstitial fibrosis on the plain chest radiographs were assessed according to the ILO scoring system. A chest radiographic score for emphysema analogous to that used for HRCT was also recorded. Two independent readers assigned HRCT scores that differed by two categories or less in 96%, 92%, and 85% compared with 90%, 78%, and 79% of cases for chest radiographs for fibrosis, emphysema, and pleural disease respectively. There was better intraobserver repeatability for the HRCT scores than for the chest radiograph scores for all disorders. Multiple regression analysis showed that scores for interstitial fibrosis, emphysema, and pleural disease on chest radiographs and HRCT correlated to a similar degree with impairment of lung function.

Adult↗

PubMed2002

Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.

BACKGROUND: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. METHODS: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B(4) (LTB(4)) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) which are predominantly chemotactic for mononuclear leucocytes. RESULTS: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-alpha(1) protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. CONCLUSION: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.

Bronchoalveolar Lavage Fluid↗

PubMed2006

Relation of interlobar collaterals to radiological heterogeneity in severe emphysema.

BACKGROUND: A study was undertaken to assess the prevalence of interlobar collateral ventilation in patients with severe emphysema to identify factors that may help to predict patients with significant collateral ventilation. METHODS: Between April 2002 and August 2003, ex vivo assessment of the lungs 17 consecutive patients with smoking related severe emphysema was performed. To assess collateral flow, all lobes of explanted specimens were selectively intubated using a wedged cuffed microlaryngeal intubation tube and then manually ventilated using a bagging circuit. Interlobar collateral ventilation was defined as the ability to easily inflate a non-intubated lobe at physiological pressures. Pre-transplant demographic characteristics, physiological data, radiological results, and explant histology were assessed for retrospective relationships with the degree of interlobar collateral ventilation in the explanted lung. RESULTS: A total of 23 lungs were evaluated, 15 of which (66%) had significant collateral interlobar airflow. There were no significant differences in any demographic, physiological, or pathological variables between patients with collateral ventilation and those with no collateral ventilation. However, there was a significant relationship between the presence of interlobar collateral ventilation and radiological scores (p<0.05). CONCLUSIONS: Interlobar collateral ventilation occurs to a much greater extent in patients with radiologically homogeneous emphysema than in those with heterogeneous emphysema. Heterogeneity of emphysema may predict patients with a significantly reduced risk of interlobar collateral ventilation.

Female↗

PubMed1981

Volume of emphysema.

A method of determining the volume of emphysema in excised lungs is presented, with its validation. This method is based on macroscopic point counting using a perforated grid but only the holes (points) overlying emphysema need be counted to produce results within a percentage standard error of 5%. Application of the method shows that an adequate assessment of emphysema cannot be made from one lung slice alone, and that the amount of emphysema found in one lung cannot be used to predict the amount of emphysema in the other lung.

Emphysema↗

PubMed1983

Assessment by radionuclide angiography of right and left ventricular function in chronic bronchitis and emphysema.

Non-invasive measurements of right and left ventricular ejection fraction (RVEF, LVEF) by multiple-gated equilibrium radionuclide ventriculography were performed in 18 control subjects, 16 patients with angina pectoris, and 45 patients with hypoxic chronic bronchitis and emphysema. The mean RVEF in the control subjects was 0.62 +/- 0.09 (SD), which was not significantly different from the mean RVEF in the patients with angina (0.60 +/- 0.09), but was significantly higher (p less than 0.01) than the mean value in patients with chronic bronchitis and emphysema (0.45 +/- 0.11). LVEF was not significantly different in the groups studied. There was a significant correlation between LVEF and RVEF only in patients with chronic bronchitis and emphysema (p less than 0.001). Those patients with chronic bronchitis and emphysema who had clinical evidence of cor pulmonale at the time of the study had significantly lower values of RVEF and LVEF (p less than 0.001) than patients with no previous cor pulmonale or those who had had cor pulmonale in the past. There was a significant correlation between RVEF and arterial oxygen (p less than 0.01) and carbon dioxide tensions (p less than 0.05). Reduced RVEF in patients with chronic bronchitis and emphysema may be an early indicator of the development of cor pulmonale and may be useful as a non-invasive method of assessing the effects of therapeutic interventions.

Adult↗

PubMed1992

Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows.

BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation.

Aged↗

PubMed1996

Pulmonary emphysema: quantitative CT during expiration.

PURPOSE: To determine whether measurement of the relative area of lung with attenuation coefficients lower than a certain threshold on thin-section computed tomographic (CT) scans obtained during expiration is a valuable method of quantifying the extent of pulmonary emphysema. MATERIALS AND METHODS: Eighty-nine patients underwent CT (with 1-mm collimation) preoperatively during inspiration and expiration. Relative areas of lung with attenuation coefficients lower than various thresholds were calculated. These relative areas were compared with areas found macroscopically to have emphysema (59 patients [51 men, eight women; aged 40-77 years]) and with two microscopic indices (35 patients [29 men, six women; aged 42-77 years]) assessed on the resected specimens. RESULTS: The valid expiratory CT thresholds were found to be -820 and 910 HU for microscopic and macroscopic emphysema, respectively. However, results of stepwise multiple regression analyses showed that the inspiratory threshold of -950 HU was superior for both macroscopically and microscopically quantified emphysema. The correlation coefficients in expiratory CT were higher for the pulmonary volumes but similar for the diffusing capacity. CONCLUSION: Expiratory quantitative CT is not as accurate as inspiratory CT for quantifying pulmonary emphysema and probably reflects air trapping more than reduction in the alveolar wall surface.

Adult↗