Degree Of Emphysema Research Articles

Alpha1-antitrypsin determines the pattern of emphysema and function in tobacco smoke-exposed mice: parallels with human disease.

Cigarette smoking in humans is associated with various patterns of emphysema and functional consequences. We tested the hypothesis that variations in alpha1-antitrypsin expression modulate the pattern of emphysema and functional consequences in cigarette smoke-exposed mice. We compared the effects of up to 6 months of cigarette smoke exposure in C57BL/6J (C57) mice and in low-alpha1-antitrypsin, C57BL/6J pa+/pa+ (pallid) mice. At the end of the experiment, we determined lung mechanical properties, the extent (mean linear intercept) and type of emphysema, and the cellular inflammatory response. After 4 months of cigarette smoking, pallid smoking mice, but not C57 smoking mice, had a significant increase in mean linear intercept. After 6 months of smoke exposure, C57 smoking mice and pallid smoking mice had similar degrees of emphysema. The pattern of emphysema in pallid smoking mice was more diffuse than in C57 smoking mice, affecting all airspaces. Pallid mice, but not C57 mice, developed a T cell inflammation in the alveolar wall after 6 months of smoking (p < 0.01). Although lung compliance was not changed in C57 smoking mice after smoke exposure, it increased significantly in pallid smoking mice over the 6 months of exposure (p < 0.0082). In summary, cigarette smoking induces emphysema in C57 and pallid mice, but the emphysema, inflammatory infiltrate, and resulting physiologic abnormalities were substantially different in the two strains, with the C57 and pallid mice exhibiting features similar to centrilobular and panlobular emphysema, respectively.

Visual grading of emphysema severity in candidates for lung volume reduction surgery. Comparison between HRCT, spiral CT and "density-masked" images

Purpose: To investigate which of three types of CT imaging yielded the best results in estimating the degree of emphysema in patients undergoing evaluation for lung volume reduction surgery (LVRS), whether there was any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema had an impact on the estimation. Material and Methods: Four radiologists visually classified different degrees of emphysema on three different types of CT images into four groups. The degree of emphysema was calculated by a computer. The three types of images were as follows: HRCT images (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density-masked images (spiral CT images printed with pixels below −960 HU, depicted in white). Results: The conventionally presented images from HRCT and spiral CT yielded the same results (60% respective 62% correct classifications) in assessing the degree of emphysema irrespective of localisation. Significantly improved results were obtained when the spiral CT images were presented as density-masked images (74%). Conclusion: There was no difference between HRCT and spiral CT in assessing the degree of emphysema in candidates for LVRS. Improvement can be achieved by the use of density-masked images.

Effects of a Novel Implantable Elastomer Device for Lung Volume Reduction Surgery in a Rabbit Model of Elastase-Induced Emphysema

There is intense interest in lung volume reduction surgery (LVRS) for treatment of severe symptomatic emphysema. LVRS results in objective and subjective improvement in lung function in selected patients. However, LVRS is complicated by substantial morbidity, including prolonged pulmonary air leak associated with resection of emphysematous lung tissue. In this study, we investigated the use of a novel implanted silicone elastomer device that reduces lung volume without surgical resection, in a previously reported emphysematous animal model. The purpose of this investigation was to determine the applicability, physiologic effects, complications, and air-leak results of this lung volume reducer (LVR) approach. Controlled, randomized, prospective animal study. Emphysema was induced in 20 New Zealand white rabbits with three nebulizations of 10,000 U of porcine elastase. After 6 weeks, the animals were randomized to control sham surgery (n = 10) vs implanted silicone elastomer LVR (n = 10) treatment groups. Lung function, including helium-dilution lung volumes, static respiratory system compliance curves, and diffusion capacity of the lung for carbon monoxide (DLCO), was measured at baseline, following emphysema induction (week 6), and when the animals were killed (1 week after LVR or sham surgery). Histologic evaluation was performed in all lung specimens after fixation. Moderate emphysema developed after elastase nebulization, assessed by lung function and postmortem histology. Functional residual capacity (FRC) and an upward shift of lung compliance curves was observed with development of emphysema at 6 weeks (p < 0.05). Following LVR, FRC decreased (p = 0.005) and compliance curves shifted back downward (p = 0.002), without reduction in DLCO. There was no change in control sham animals. DLCO did not change in either group. In this short-term, randomized, controlled animal model study, the implantable LVR approach produced safe and effective lung volume reduction without tissue resection in the treated animals. The implant procedure produced minimal morbidity, no mortality, and no observed air-leak complications in the treated animals. Limitations include the short-term follow-up and moderate degree of emphysema in this animal model. Further research is required to assess long-term effects and complications of this method for lung volume reduction.

CT Assessment of Subtypes of Pulmonary Emphysema in Smokers

ObjectiveTo determine the incidence of subtypes of pulmonary emphysema (PE) identified by CT imaging in male patients who have a significant smoking history. Patients and settingWe reviewed 945 subjects (619 men and 326 women) who had undergone CT scanning. However, only the data for male subjects were analyzed due to there being too few female subjects. The male subjects were divided into the following two age groups: group A (age, ≤ 50 years) and group B (> 50 years). There were two subtypes of PE found: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Based on these subtypes, PE was divided into the following three categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). ResultsPE was found in 270 of 516 male smokers (10 of 38 female smokers had PE). Among male subjects, in age group A there were 53 subjects with some degree of PE (category I, 12 subjects [22.6%]; category II, 7 subjects[13.2%]; and category III, 34 subjects [64.2%]). Among men in age group B, there were 217 subjects with some degree of PE (category I, 109 subjects [50.2%]; category II, 23 subjects [10.6%]; and category III, 85 subjects [39.2%]). ConclusionIn age group A, men < 50 years of age who were in category III (PSE or PSE-predominant PE) predominated (34 of 53 subjects; 64.2%). In age group B, men > 50 years of age who were in category I (CLE or CLE-predominant PE) predominated (109 of 217 subjects; 50.2%).

Increased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke.

Epidemiological evidence suggests that smoking is a major cause of human lung cancer. However, the mechanism by which cigarette smoke induces the cancer remains unestablished. To evaluate the effects of cigarette smoke on the expression of inducible nitric oxide synthase (iNOS), nuclear protooncogenes and related mitogen-activated protein kinases (MAPKs) in rat lung tissue, a histopathological study of the effects of gas-phase cigarette smoke on rat lung tissue were carried out. The terminal bronchioles were found to be infiltrated predominantly by lymphocytes in the peribronchiolar region and a mild to moderate degree of emphysema was noted in the alveolar spaces. The terminal bronchioles also showed marked lipid peroxidation, dilatation, and peribronchiolar fibrosis. Immunohistochemical evaluation showed that the expression of iNOS, NF-kappa B, MAPKs (MEK1, ERK2), phosphotyrosine protein and c-fos was increased in the terminal bronchioles but protein kinase C (PKC), MEKK-1, c-jun, p38 and c-myc showed no change. These results provide evidence to suggest that exposure to cigarette smoke results in oxidant stress which leads to the stimulation of iNOS and c-fos together with the induction of protein tyrosine phosphorylation and MEK1/ERK2 which in turn may promote lung pathogenesis.

Thin-section CT vs spiral CT in candidates for lung volume reduction surgery: a comparison based on radiologists' subjective preferences

The aim of this study was to investigate whether high-resolution (HRCT) or spiral CT was preferred in evaluating severe emphysema in patients undergoing lung volume reduction surgery (LVRS), whether there is any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema has an impact on the radiologists' preference. The study was performed by letting four radiologists compare images obtained with the two techniques (film pairs) and decide which technique they preferred or if the techniques were considered as equal in evaluating emphysema. In evaluation of 188 film pairs, the HRCT images were preferred in 56 %, spiral CT in 19 % and the techniques considered as equal in 25 %. Spiral CT images were preferred more often in the caudal part of the lung and in more advanced emphysema compared with the HRCT images. The study confirms our clinical assumption that use of both CT techniques are valuable in evaluating advanced emphysema and there may be technical as well as histopathological reasons for this.

Distribution of Lung Density and Mass in Patients With Emphysema as Assessed by Quantitative Analysis of CT

To assess the effects of emphysema on the apex-to-base gradient of lung density (D) and lung mass (M) and to explore the relationship between M and lung function. CT scans of whole lungs were performed in 12 healthy subjects and 29 patients who were breathing at functional residual capacity, after which lung function tests were performed. Whole D and M and regional D (RLD) and M (RLM) were calculated. The degree of emphysema was scored. The RLM for each height did not differ significantly between patients with disease and healthy subjects, while RLD was significantly lower in the patients with disease. A less marked nonlinear, increasing, craniocaudal gradient of D was observed in the group with disease, suggesting that the distension increases progressively from the apex to the base. RLD and RLM in the 40 to 90% lung height differed significantly among patients in the emphysema group with normal, high, and low M compared to the healthy subjects. M did not differ significantly between patients with centrilobular and panlobular emphysema, which was thought to stem from the marked variations in the results. Vital capacity was lower in the patients with low M. The lower RLD in the group with low M was due to both lung overinflation and to tissue loss, while in the groups with high or normal M, it was due only to lung overinflation.

Pulmonary vascular pressures increase after lung volume reduction surgery in rabbits with more severe emphysema.

Emphysema is a chronic disease of the lungs with destruction of terminal alveoli and airway obstruction. Lung volume reduction surgery (LVRS) is being investigated for the treatment of emphysema. Increasing resection volumes with LVRS may lead to worsening of carbon monoxide diffusing capacity (Dlco) despite improvement in compliance and flow. We hypothesized that the pulmonary circulation-related parameters, pulmonary artery pressure (PAP) and diffusing capacity (Dlco), may be used as indicators of the maximally tolerated LVRS resection volume. Emphysema was induced in 55 rabbits by endotracheal nebulization, with either single 15,000-unit (mild emphysema) or three 11,000-unit (moderate emphysema) doses of elastase. At Week 6, bilateral LVRS was performed via median sternotomy with an endoscopic stapler. Single-breath Dlco, static compliance, and PAP were measured prior to emphysema induction, preoperatively, and 1 week following LVRS. Animals were divided into the following groups: Group I (mild emphysema, <3 g resected), group II (mild emphysema, >3 g resected), group III (moderate emphysema, <3 g resected), group IV (moderate emphysema, >3 g resected). All animals having LVRS had immediate postoperative increase in pulmonary vascular resistance (PVR) following lung resection. Mean PAP, however, remained elevated when measured 1 week after LVRS (sacrifice) in animals with moderate emphysema. This is in contrast to animals with mild emphysema, in which follow-up PAPs approached preoperative baseline. These finding suggests that sustained increased PVR, denoted by elevated PAP, is more likely to occur after LVRS in animals with more severe emphysema and larger volume resection. The spirometric and compliance benefits of greater resection volumes have to be weighed against the compromise in pulmonary vasculature in the effort to determine the ideal resection volume for various degrees of emphysema.

Tumour necrosis factor-alpha gene promoter polymorphism in chronic obstructive pulmonary disease.

Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.

Does hyperexpansion of the native lung adversely affect outcome after single lung transplantation for emphysema? Preliminary findings

The authors evaluated the effect of the native emphysematous lung on graft function after single lung transplantation. Thirty-two patients who underwent single lung transplantation were examined with radiography preoperatively for degree of emphysema and postoperatively for hyperexpansion of the native lung. All patients underwent ventilation-perfusion scanning before transplantation and ventilation scanning after transplantation. Pulmonary function tests and measurement of arterial partial pressure of oxygen were also measured before and after surgery. The postoperative course was graded on a subjective scale. Hyperexpansion of the native lung was seen in 16 of the 32 patients in the postoperative period. On the basis of serial measurements of forced expiratory volume in 1 minute, these patients fared poorly in the postoperative period compared with patients without hyperexpansion. Pulmonary blood flow to the native lung, as measured with perfusion scintigraphy, paradoxically increased in 11 patients after transplantation. Nine of these 11 patients demonstrated hyperinflation of the native lung, suggesting that graft compression adversely affects blood flow to the transplanted lung. Hyperexpansion of the native lung after single lung transplantation for emphysema may have a deleterious effect on graft function and possibly on clinical outcome.

Decreased C4 Complement Component Serum Levels Correlate With the Degree of Emphysema in Patients With Chronic Bronchitis

Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.

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.

Does phase 2 of the expiratory PCO2 versus volume curve have diagnostic value in emphysema patients?

It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relationships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most discriminating in the separation between healthy controls and severely obstructed emphysema patients. Separating healthy controls and severely obstructed emphysema patients on the basis of the discriminant line for V25-50, 9 of the 12 asthma patients in exacerbation were classified as normal, and only 5 of the 9 moderately obstructed emphysema patients as emphysematous. For V25-75 involvement of phase 3 of the curve (alveolar plateau) in asthma patients in exacerbation caused a marked overlap with the severely obstructed emphysema patients. In the healthy controls, a fixed breathing frequency of 20 breaths.min-1 led to an increase of both volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of Quantitative CT With Selective Alveolobronchogram and Pulmonary Function Tests in Emphysema

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. 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. 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). 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.

Emphysema and airway obstruction in non-smoking South African gold miners with long exposure to silica dust.

Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. 242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease.

Relationship of pulmonary arterial pressure and airflow obstruction to emphysema

Guinea pigs were exposed to cigarette smoke for 6 mo, after which lung and cardiac function and lung morphology were examined. The smoke-exposed animals were divided into two groups on the basis of final pulmonary arterial pressure. We found that the smoke-exposed animals with increased pulmonary arterial pressure had a moderate degree of airflow obstruction compared with the normotensive smoke group, which showed only mild airflow obstruction, and with the control group. Both smoke groups had similar degrees of emphysema. Although both smoke groups had an increased percentage of muscularized small arterioles, only the group with increased pulmonary arterial pressure had an altered flow-pressure response to dobutamine. We conclude that although cigarette smoke appears to induce changes in the vascular structure and to produce emphysematous lung destruction, the increased pulmonary arterial pressure in guinea pigs chronically exposed to smoke is not directly related to either of these findings. Instead, it appears that there is a dynamic alteration of both the airways, producing airflow obstruction, and the vasculature, producing increased pulmonary arterial pressure.

Regional distribution of emphysema: correlation of high-resolution CT with pulmonary function tests in unselected smokers.

High-resolution computed tomography (CT) was correlated with pulmonary function tests in the evaluation of regional emphysema in 59 smokers. The lung was divided into upper (above the carina tracheae) and lower (below the carina tracheae) zones, and the degree of emphysema was graded with a subjective and an objective measurement. Functional emphysema was defined as a diffusion capacity less than 75% of predicted and forced expiratory volume in 1 second less than 80% of predicted. Three of 15 (20%) subjects with functional emphysema had no subjective evidence of emphysema at high-resolution CT, and 10 of 25 (40%) with emphysema at high-resolution CT had no functional abnormalities consistent with emphysema. Even though the upper lung zones were more severely affected by emphysema, the degree of emphysema in the lower zones had a stronger correlation with pulmonary function abnormalities. The upper lung zones are a relatively silent region where extensive destruction may occur before functional abnormalities become known.

Centrilobular and Panlobular Emphysema in Smokers: Two Distinct Morphologic and Functional Entities

In order to investigate the hypothesis that different morphologic patterns of disease might correspond to different mechanical properties of the lung in emphysema, pulmonary function tests and lung mechanics were measured in 34 subjects undergoing lung resection for peripheral lung tumors. Using standard microscopic criteria, pure or predominant centrilobular (n = 18) or panlobular (n = 16) emphysema was diagnosed in lungs. The degree of emphysema measured by the mean linear intercept (Lm) was not significantly different between the two groups. However, the coefficient of variation of the interalveolar wall distance (CV) was significantly higher for the same Lm in CLE than in PLE. This indicates that CLE has an uneven pattern of destruction, whereas PLE is more homogeneous. CLE had a higher degree of abnormalities in the small airways (SAD) than did PLE (p less than 0.05) mainly because of significantly higher muscle score (p less than 0.001) and fibrosis. CLE also had a higher proportion of airways less than 400 microns in diameter than did PLE (p less than 0.05). Static compliance, specific compliance, and the exponential constant (K) were significantly lower (p less than 0.005, p less than 0.001, and p less than 0.05, respectively) in CLE than in PLE. FEV1/FVC was significantly correlated with SAD in CLE (r = -0.69, p less than 0.01) but not in PLE (r = 0.29 p greater than 0.05); conversely, FEV1/FVC was significantly correlated with elasticity (K) in PLE (r = -0.72, p less than 0.01) but not in CLE (r = 0.08, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The Radiographic Diagnosis of Emphysema

There are many findings of emphysema by conventional radiography, but the most reliable and reproducible is that of overinflation, which is best judged by the height and contour of the hemidiaphragm. Even in expert hands, the diagnosis of emphysema by conventional radiography is 65% to 80% accurate, depending to a large degree on the clinical population studied. Although most patients with severe emphysema are diagnosed correctly, only half of those patients with mild-to-moderate levels of parenchymal destruction are detected. Emphysema is identified by CT as focal, unmarginated, hypodense areas unassociated with fibrosis. Emphysema also may be detected by computer programs selecting pixels with abnormally low attenuation values. By either method, CT is superior to chest radiography in detection of mild and moderate degrees of emphysema and has detection rates of more than 90% and correlation with extent and severity of disease in more than 80% of patients. CT may be more sensitive to the presence of mild emphysema than pulmonary function tests, which are global indications of lung function. HRCT appears to offer a small, but real, advantage over 10-mm collimation in identification of small areas of emphysema, but areas of emphysema smaller than 0.5 cm in diameter are commonly missed, even with HRCT. Wider use of CT for investigation of relatively asymptomatic smokers may allow early diagnosis of emphysema and provide more information of the natural history of this disease, information that is sorely lacking at this time. Assessment of potential therapy such as smoking cessation or antioxidants will only be possible with widespread use of a method that is of relatively low risk, easy to duplicate, and accurate.

Gas Exchange during Exercise in Mild Chronic Obstructive Pulmonary Disease: Correlation with Lung Structure

To investigate whether or not the pathologic features in the lungs of patients with chronic obstructive pulmonary disease (COPD) are related to the gas exchange response during exercise, we studied 17 patients (15 men, two women) with mild-to-moderate airflow obstruction (FEV1/FVC ratio, 59 +/- 3%), undergoing resective lung surgery, at rest and during submaximal exercise (71 +/- 5% predicted VO2max). During exercise, arterial PO2 increased (from 81 +/- 3 to 86 +/- 3 mm Hg, p less than 0.05) as a result of an overall improvement in VA/Q relationships. This improvement included an increase in the mean VA/Q ratios of both ventilation and blood flow distributions, and a more homogeneous ventilation distribution (logSD V, from 0.66 +/- 0.06 to 0.50 +/- 0.03; p less than 0.01; normal value, less than or equal to 0.6). The morphologic evaluation of the resected specimens disclosed a moderate degree of emphysema (emphysema score, 16 +/- 4) and mild abnormalities in membranous bronchioles (total pathology score, 107 +/- 8). At rest, significant correlations were found between the severity of the pathologic findings and both the degree of hypoxemia and the extent of VA/Q mismatching. During exercise, no relationship between bronchiolar abnormalities and gas exchange measurements was observed, whereas the severity of emphysema was correlated with PaO2 (r = -0.54, p less than 0.05). Both the overall increase in and the more efficient distribution of ventilation accounted for the improvement in VA/Q distributions during exercise. These changes were more pronounced in patients with a greater degree of bronchiolar abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)