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PubMed1994

Correlation of quantitative CT with selective alveolobronchogram and pulmonary function tests in emphysema.

BACKGROUND: Emphysema diagnosed by computed tomography (CT) has been reported to be correlated with morphologic data from autopsied lungs or resected lobes. However, autopsied lungs or resected lobes are quite different from lungs in vivo. We examined the correlation between a quantitative analysis of CT and the in vivo morphologic degree of emphysema (selective alveolobronchography [SAB]) in patients with COPD. METHODS: We measured the mean attenuation value (MAV) of the lung fields between -700 HU and -1,024 HU to exclude the effect of high-density structures in 21 patients with COPD. Low attenuation, greater than 2 SD below the mean value of five normal healthy subjects, was used as an index of emphysema. To quantitate the amount of emphysema, the relative area of low attenuation to the area of the entire lung field (2SD percent) was measured. The morphologic degree of emphysema was determined from the diameter of ring shadow (DR) of SAB. We also examined the relationship between CT data and pulmonary function tests. RESULTS: The DR was highly correlated with the CT indexes of MAV and 2SD percent; (r = -0.894, p < 0.001, and r = 0.890, p < 0.001). Both MAV and 2SD percent were correlated with pulmonary function tests such as Dco, FEV1, and residual volume (r > 0.60). CONCLUSIONS: The MAV and relative area of emphysema obtained from CT density measurements accurately assess the severity of emphysema in patients with COPD as well as SAB.

Adult↗
PubMed1995

Do radiographic criteria for emphysema predict physiologic impairment?

OBJECTIVE: The functional consequences of pulmonary emphysema have been estimated from autopsy studies. This antemortem study correlates structure as assessed by criteria applied to chest radiographs and function in earlier disease. SUBJECTS AND METHODS: Four thousand one hundred seven male shipyard and construction workers had chest radiographs scored for asbestosis using International Labour Office criteria and for emphysema using five criteria: hyperlucent lung fields, low flat diaphragms on posteroanterior views, low flat diaphragms on lateral radiographs, a wide retrosternal space, and bullae. Total lung capacity (TLC) was measured by planimetry of radiographs and forced vital capacity (FVC) and flows by spirometry: TLC minus FVC equaled residual volume (RV). All were expressed as percentage of predicted (% pred) adjusted for height, age, and duration of cigarette smoking. Linear regression modeling examined the influence of each emphysema criterion on function measurements. RESULTS: Four hundred three (10.1%) of 4,107 men had two or more emphysema criteria and 24.5% had asbestosis. Prevalence of 2 criteria varied by smoking status and was present in 20% of current smokers, 7.5% of ex-smokers, and 2% of never smokers. The TLC % pred and RV/TLC increased and % pred of FEV1/FVC and FEF25-75, FEV1, and FVC decreased with increasing radiographic emphysema criteria. Forty-four (10%) had normal results of spirometry with two or more radiographic emphysema criteria. CONCLUSION: Impairment of airway function worsened with each additional radiographic criteria of emphysema. These criteria were more strongly associated with an increase in RV/TLC than an increase in TLC.

Asbestosis↗
PubMed1999

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

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

Adult↗
PubMed1988

Hyperinflation in asthma and emphysema. Assessment by pulmonary function testing and computed tomography.

To assess the role of emphysema on the hyperinflation in chronic asthma, we studied 20 subjects with irreversible airflow limitation. Ten of the subjects had asthma and had never smoked; the other ten were cigarette smokers. Pulmonary function testing and chest computed tomography (CT) scans were performed on all subjects. Emphysema was graded using a score based on the percentage of lung involved on CT scan. There was good inter- and intra-observer agreement for the emphysema scores. The median emphysema score was 0 percent in the nonsmoking group and 10 percent in the smoking group. All smokers with a total lung capacity (TLC) of greater than 120 percent predicted had evidence of emphysema on the CT scan. None of the asthmatic subjects with a TLC greater than 120 percent predicted had emphysema identifiable on CT scan. We conclude that chronic asthma with severe hyperinflation does not result in emphysema.

Adult↗
PubMed1990

Quantitation of emphysema by computed tomography using a "density mask" program and correlation with pulmonary function tests.

We used a CT program "density mask" outlining areas with attenuation values less than -910 HU, to indicate areas of emphysema on a chest CT and to provide an overall percentage of lung involvement by emphysema. The "density mask" quantitation of emphysema was previously shown to correlate well with the pathologic assessment of emphysema in patients undergoing lung resection. We compared the CT quantitation of emphysema with mean lung density, overall lung volume on CT and pulmonary function tests in 85 patients. There was a significant correlation between the extent of emphysema on CT and FEV/FVC percent of predicted, functional residual capacity percent predicted and Dsb percent predicted. Determination of the percentage of lung with areas of low attenuation by CT provides a useful method for quantitating emphysema in life and correlates significantly with pulmonary function tests.

Adult↗
PubMed2006

Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?

The alveolar destruction leading to airspace enlargement in patients with end-stage chronic obstructive pulmonary disease (COPD) is frequently progressive, despite smoking cessation. Several laboratories have accumulated data demonstrating the presence of immune cells in bronchial biopsy specimens and lung tissue sections from patients with COPD. Recently, the accumulation of T and B lymphocytes, often forming follicles, in the lung parenchyma from patients with severe COPD has been reported. In addition, it has been postulated that there might be an autoimmune component to COPD. T-cell receptor analysis has provided data consistent with the concept of T-cell clones in the lung tissue from patients with COPD. Against this background, we developed a model of autoimmune emphysema in adult rats. Based on published data showing that immunization of mice with human umbilical vein endothelial cells (HUVECs) causes production of anti-vascular endothelial growth factor (VEGF) receptor II (KDR) antibodies, and our own data indicating that administration of a VEGF receptor blocker in adult rats causes emphysema, we reasoned that intraperitoneal injection of HUVECs in rats would generate both anti-VEGF receptor antibodies and emphysema. Indeed, intraperitoneal injection of HUVECs caused emphysema. We further explored the autoimmune nature of this model, identified KDR antibodies in the serum of HUVEC-immunized rats, and injected serum from the emphysematous rats into naive rats and mice, which resulted in emphysema. Presently, we are in the process of investigating whether cigarette smoke extract causes emphysema. We recently identified anti-endothelial cell antibodies in the serum of patients with end-stage emphysema.

Animals↗
PubMed2006

Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa.

We have recently established a new bone marrow transplantation (BMT) method in which bone marrow cells are injected into the intrabone marrow (IBM). In the present study, we used an animal model for emphysema (tight-skin [Tsk] mouse) to examine whether IBM-BMT could be used to treat emphysema in Tsk mice. IBM-BMT was carried out from C3H mice into Tsk mice (8-10 weeks old) that had already shown emphysema. Six months after transplantation, the lungs of all the Tsk mice treated with IBM-BMT [C3H-->Tsk] showed similar structures to those of normal mice, whereas the [Tsk-->Tsk] mice showed emphysema, as seen in age-matched Tsk mice. Next, we attempted to transfer emphysema from Tsk mice to C3H mice by IBM-BMT. Six months after IBM-BMT, the [Tsk-->C3H] mice showed emphysema. These results strongly suggest that emphysema in Tsk mice originates from defects of stem cells in the bone marrow.

Animals↗
PubMed1994

Panlobular pulmonary emphysema caused by i.v. injection of methylphenidate (Ritalin): findings on chest radiographs and CT scans.

OBJECTIVE: Recent reports have described severe precocious pulmonary emphysema in persons who inject methylphenidate (crushed Ritalin tablets) i.v. We retrospectively evaluated the plain radiographic and CT features in 21 such patients. MATERIALS AND METHODS: The chest radiographs, available CT scans, and clinical and pathologic data were reviewed in 21 cases of i.v. Ritalin use. The patients were from 35 to 54 years old. Twelve patients were men, and nine were women. Emphysema was graded on the basis of findings on chest radiographs, by consensus, on a four-point scale as absent, mild, moderate, or severe. CT scans were available for three patients, including one imaged after a single lung transplantation. Autopsy results were available for four patients. Fixed inflated lung specimens and corresponding high-resolution CT scans were available in three cases. RESULTS: Radiographs showed pulmonary emphysema in all cases. The distribution of disease was basilar and symmetric. Small apical bullae were suggested in only one case. Basilar emphysema was rated as mild in four patients, moderate in three patients, and severe in 14 patients. In 11 patients who had serial chest radiographs, the basilar emphysema was noted to progress over a 2- to 7-year period. No evidence of progressive massive fibrosis was seen in any patient. CT scans confirmed emphysema, most severe at the lung bases. CONCLUSION: The plain radiographic and CT findings in patients who inject Ritalin are similar to those found in patients with alpha 1-antitrypsin deficiency and different from the findings seen in other types of i.v. drug use. The finding of basilar pulmonary emphysema should alert the radiologist to the possibility of i.v. injection of Ritalin.

Adult↗
PubMed2005

Transcription factor Nrf2 plays a pivotal role in protection against elastase-induced pulmonary inflammation and emphysema.

Emphysema is one of the major pathological abnormalities associated with chronic obstructive pulmonary disease. The protease/antiprotease imbalance and inflammation resulting from oxidative stress have been attributed to the pathogenesis of emphysema. Nrf2 is believed to protect against oxidative tissue damage through the transcriptional activation of a battery of antioxidant enzymes. In this study, we investigated the protective role of Nrf2 in the development of emphysema using elastase-induced emphysema as our model system. We found that elastase-provoked emphysema was markedly exacerbated in Nrf2-knockout (KO) mice compared with wild-type mice. The severity of emphysema in Nrf2-KO mice correlated intimately with the degree of lung inflammation in the initial stage of elastase treatment. The highly inducible expression of antioxidant and antiprotease genes observed in wild-type alveolar macrophages was significantly attenuated in the lungs of Nrf2-KO mice. Interestingly, transplantation of wild-type bone marrow cells into Nrf2-KO mice retarded the development of initial lung inflammation and subsequent emphysema, and this improvement correlated well with the appearance of macrophages expressing Nrf2-regulated antiprotease and antioxidant genes. Thus, Nrf2 appears to exert its protective effects through the transcriptional activation of antiprotease and antioxidant genes in alveolar macrophages.

Animals↗
PubMed2000

Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers.

BACKGROUND: Previous uncontrolled reports have suggested that HIV-seropositive persons develop an accelerated form of emphysema. OBJECTIVE: To characterize the risk for emphysema in a stable HIV-seropositive outpatient population. DESIGN: Controlled, cross-sectional analysis. SETTING: Midwestern urban community. PARTICIPANTS: HIV-seropositive persons (n = 114) without AIDS-related pulmonary complications and HIV-seronegative controls (n = 44), matched for age and smoking history. MEASUREMENTS: Measurement of pulmonary function, bronchoalveolar lavage, and high-resolution computed tomography of the chest. RESULTS: The incidence of emphysema was 15% (17 of 114) in the HIV-seropositive group compared with 2% (1 of 44) in the HIV-seronegative group (P = 0.025). The incidence of emphysema in participants with a smoking history of 12 pack-years or greater was 37% (14 of 38 persons) in the HIV-seropositive group compared with 0% (0 of 14 persons) in the HIV-seronegative group (P = 0.011). The percentage of cytotoxic lymphocytes in lavage fluid was much higher in HIV-seropositive smokers with emphysema. CONCLUSIONS: Infection with HIV accelerates the onset of smoking-induced emphysema. The results of this study support the emerging concept that cytotoxic lymphocytes may have an important role in emphysema pathogenesis.

Adult↗
PubMed1999

Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema.

To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied collagens, laminin, fibronectin, proteoglycans (PGs), and beta1-integrins. The majority of the patients with severe emphysema showed diminished staining for the interstitial PGs, decorin and biglycan, in the peribronchiolar area, compared with patients in the control and fibrosis groups. Only a minority of patients with mild emphysema showed this diminished staining. In contrast, decorin and biglycan were well preserved in the perivascular area of all of the specimens from the emphysema group. Heparan sulfate PG staining was diminished in the respiratory airspace walls of patients with emphysema and fibrosis. Staining for Types I, III, and IV collagen, as well as for laminin, fibronectin, and the integrins, showed no differences between the four groups. The specific loss of interstitial PGs may be crucial for elastic recoil loss and subsequent bronchiolar obstruction, as seen in patients with smoking-related emphysema.

Adolescent↗
PubMed2001

[Effect of dietary protein on the function and morphology of diaphragm in rats with experimental emphysema].

The effects of dietary protein on the function and morphology of diaphragm of rats with emphysema were observed in 50 SD rats, 10 rats in each group. The emphysema in groups E(emphysema control), HP(emphysema with high protein diet) and LP(emphysema with low protein diet) was induced by intra-tracheal instillation of elastase (750 U/kg BW). The control rat (C1, C2) were instilled with normal saline. After 6 weeks of experiment, the total lung volume and the average area of alveolus was significantly increased in the group E compared with group C1 (P < 0.05) and the number of alveolus per unit area was also reduced obviously (P < 0.05). The average contractile force of diaphragm at a stimulus rate of 20 Hz expressed as a ratio of the maximal contractile force (F20/Fmax) was increased significantly in group E compared with group C (P < 0.01). The cross-sectional area of slow-twitch fibers increased significantly in group E. After 10 weeks of oral supplementation with 24% casein(HP) or 8% casein (LP) to the rats with emphysema, the contractility of the diaphragm in group LP was lower than that in the control group and the HP group. It was concluded that high protein diet might be beneficial to maintain the function of diaphragm in patients with emphysema.

Animals↗
PubMed2003

Diagnosis of emphysema and air-trapping in high resolution computed tomography.

Conventional computed tomography has several limitations, connected with long scanning time, and using 1cm thick collimation. Improvement in quality of images of lung parenchyma led to the development of high resolution computed tomography (HRCT). It optimizes the morphological images of the lung parenchyma at the level of the lung lobule, becoming the modality of choice in evaluating the lung interstitium. The aim of the study was assessment of the usefulness of HRCT in diagnosis of emphysema, determining its character and presence of air-trapping. The emphysema and air-trapping are interstitial changes, causing inhomogeneous lung density on HRCT sections. Emphysema is usually a permanent destruction of lung parenchyma, while in the case of air-trapping the pathology may be potentially reversible. HRCT is considered to be the most accurate diagnostic modality in emphysema. The focal areas of low attenuation are clearly seen among the areas of normal lung parenchyma of higher density, provided sufficiently low window level is established (-600 to -800 H.U.). The HRCT sections statistically significantly increased the frequency of diagnosis of emphysema on inspiratory sections, and air-trapping on expiratory scans. In revealing of air-trapping HRCT is diagnostic modality of choice. The expiratory sections reveal presence of air-trapping invisible on expiratory scans. The HRCT section enables differentiation of different kinds of emphysema that were invisible on plain radiograms, sensitivity of which in revealing small emphysematous changes is very poor. HRCT makes it possible to quantify emphysematous changes, the degree of parenchymal destruction, secondary functional disorders. It is more sensitive and specific in determining the type and extension of emphysema.

Adult↗
PubMed2004

[Emphysema].

The term emphysema refers both to abnormal enlargement and destruction of distal spaces of the lung. Diagnosis of emphysema is achieved by high resolution CT-scan of the thorax. Advanced forms of emphysema are associated with severe respiratory insufficiency. Isolated forms of emphysema may present as giant bullae with normal surrounding parenchyma. Diffuse panlobular emphysema is frequently associated with a genetic disease characterized by a severe deficit in alpha1-antitrypsin (AAT). Common forms of emphysema are observed in the distal lung of patients with COPD, or around fibrous and retractile lesions of the lung. Apart from the possible beneficial effect of augmentation therapy in case of severe deficit in AAT, there is no medical therapy currently active on the emphysematous process. Surgical approaches include bullaectomy which may be indicated in some cases of giant bullae, and lung transplantation and lung volume reduction surgery whose indications are both restricted to selected cases of advanced emphysema.

Diagnosis, Differential↗
PubMed1991

In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects.

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.

Glucuronidase↗
PubMed2005

Effects of strain and treatment with inhaled aII-trans-retinoic acid on cigarette smoke-induced pulmonary emphysema in mice.

Models of emphysema produced by exposing animals to cigarette smoke (CS) have potential for use in testing treatments of this disease. To better characterize development of emphysema in an animal model, male and female mice of the B6C3F1 and A/J strains were exposed to CS at 250 mg total particulate material (TPM)/m3 for 15 weeks. Emphysema was evident in both strains of mice to differing degrees of severity. The CS-induced increase in the mean linear intercept (normalized to BW) of A/J mice was 51% greater than the control value, while CS-exposed B6C3F1 had an increase of 38% in this morphometric measurement of alveolar air space enlargement. In separate experiments, female B6C3F1 mice and male A/J mice were exposed to CS for 32 weeks and 15 weeks, respectively, and were then used to test the efficacy of all trans-retinoic acid (ATRA) treatments to ameliorate emphysema lesions. Following CS exposure, the B6C3F1 mice were treated once daily for 14 days in a 3-week period by nose-only inhalation exposure to aerosols of 180 or 1,800 mg-minutes ATRA/m3. The A/J mice were treated once daily, 4 days/week, for three weeks by either intraperitoneal injection of ATRA (0.5 or 2.5 mg/kg) or inhalation exposure to ATRA (3,600 or 18,000 mg-minutes/m3). Neither the injections nor inhalation exposures of ATRA in either strain of mouse caused reversal of the emphysema. In summary, CS-induced emphysema was more severe in A/J mice than in B6C3F1 mice. Treatment with ATRA did not reverse emphysema in either strain of CS-exposed mice.

Administration, Inhalation↗
PubMed1977

[The differential diagnosis of chronic bronchitis and emphysema from mutually supplemental functional and radiographic criteria].

In a retrospective study in 91 patients an attempt was made to differentiate the primary and/or predominating disorder "emphysema" or/and "chronic bronchitis" by independent evaluation of a number of X-ray signs and lung function criteria in routine diagnosis. Good congruency of the diagnosis from these two different aspects, could be established. Patients with 3 or more X-ray signs of emphysema were found to have larger lung volume and smaller diffusing capacities than those without. Vice versa, patients with functional diagnosis of predominant emphysema more often showed the full X-ray pattern of emphysema, than those with predominant "chronic bronchitis". In either method of diagnostic procedure, the occurence of the "small heart of emphysema" was obviously much more frequent in patients believed to have predominant or primary emphysema. Assessment of X-ray signs of changes of the lesser circulation can be obtained in a stage of the disease, when structural changes have become irreversible. Considering the different pathophysiologic pattern of predominant panacinar emphysema, the destruction of alveolar walls and, consequently of the capillary bed, is more likely to reduce DCO as well as cardiac output before pulmonary hypertension can develop. The X-ray signs resulting from this effect on the lesser circulation, exist in widened right hilar branch and abrupt narrowing of peripheral vessels, with a small heart and lack of prominence of the pulmonary trunk. In chronic bronchitis, however, signs of pulmonary hypertension are expected to occur early in the disease. The relevance of the X-ray changes of the heart size and the pulmonary circulation in both types of lung disease, could be confirmed by lung function data.

Bronchitis↗
PubMed1994

[High-resolution computed tomography study (HRCT) in so-called emphysema B. The correlations between the radiogram, the anatomical findings yielded by high-resolution computed tomography and the clinico-functional assessment].

The results are reported of a prospective study on 28 emphysematous patients with clinical, functional and radiologic correlations. Thirteen of 28 patients had type-B, the clinical "blue and bloater", emphysema. The grade of emphysema was investigated on conventional chest films and on HRCT scans, with a visual scoring system. Hyperinflation was assessed on conventional chest films and correlated with the extent of emphysema on HRCT images and with functional impairment. In our series, the extent of emphysema in B-type patients was markedly lower than in other patients of the same age, with the same smoking habits, dyspnea and functional impairment. Moreover, the incidence of centrilobular involvement was higher, though not statistically significant. The B-type exhibited more severe dilatation of subsegmental pulmonary arteries (76.9% vs. 20% p < 0.001) and a striking incidence of small airway disease (84.6% vs. 26.6%, p < 0.002). This findings may explain the radiographic pattern of "increased vascularity" seen on chest films. Bronchiolectasis and small airway wall thickening are much more frequent in type-B emphysema, together with patchy areas of ground-glass opacity and small peripheral nodules. A close correlation was observed between signs of small airway disease on HRCT images and functional clinical impairment. Thus, the small airway disease might eventually prove to be a more critical factor in causing functional and hemodynamic impairment in B-type emphysema than the actual extent of centrilobular emphysema.

Adult↗