Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images

RATIONALE AND OBJECTIVES: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images. METHODS: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours. RESULTS: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1. CONCLUSIONS: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.     

Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery

Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.     

Stress test blood gas analysis in chronic obstructive lung diseases

This study was conducted to investigate the clinical value of blood gas analysis during exercise in patients with COPD and healthy controls using the new criteria of the Deutsche Gesellschaft für Pneumologie (DGP) for performance and interpretation of blood gas analysis during exercise. A total of 64 patients with COPD (age: 63.7 +/- 10.1 years) and 35 healthy controls (age: 35.0 +/- 14.3 years) exercised on a bicycle ergometer to their submaximal capacity under steady state conditions (patients: 44.4 +/- 24.6 watt vs. 102.4 +/- 32.1 watt; p < 0.01). A pathological response for PaO2 occurred in 3 of 35 controls (8.6%) and 14 of 64 patients (21.9%; p < 0.01). A decrease in PaO2 yielded a sensitivity of 28% and a specificity of 92% in respect of patients with emphysema. Significant associations of lung function parameters at rest and blood gases under exercise were found by linear regression analysis (airway resistance (Rt): beta = -0.48; p < 0.001) and PaCO2 (FEV1: beta = -0.27; p < 0.05). This study demonstrates that in patients with COPD parameters of lung function and blood gas analysis at rest are already good predictors of gas exchange under exercise conditions. In individual cases, however, prediction may not be possible. This underlines the importance of the exercise test to investigate gas exchange under diagnostic (i.e. dyspnoea, medical opinion) and therapeutic aspects (i.e. therapy control). For COPD patients, the rule of the DGP yielded a poor sensitivity, but an excellent specificity in the diagnosis of emphysema, which yields confirmation of the diagnosis only in conjunction with, and complementary to, other methods.     

Pathophysiology and treatment of alpha 1-antitrypsin deficiency

The pathophysiology of alpha 1-antitrypsin (AAT) deficiency and the use of alpha 1-proteinase inhibitor therapy in the management of emphysema caused by AAT deficiency are described. AAT deficiency is the most common genetic cause of liver disease in children and emphysema in adults. However, not all patients with AAT deficiency develop hepatic or pulmonary involvement. Changes in the composition of the AAT molecule have been associated with AAT dysfunction in liver disease, whereas lung disease occurs when AAT concentrations are reduced. A definitive diagnosis can be made through serum AAT phenotype determination. Therapy for liver disease induced by AAT deficiency consists of supportive measures. Therapy for pulmonary disease due to AAT deficiency includes AAT augmentation therapy along with supportive measures. The available product, alpha 1-proteinase inhibitor, is derived from fractionated plasma and has similar biological activity to native serum AAT. Clinical trials have demonstrated a positive effect on serum and lung concentrations of AAT with few adverse events. Two recombinant forms of AAT have also been developed; however, few trials have been published evaluating their safety and efficacy in AAT-deficient patients. Many questions remain unanswered concerning AAT deficiency and replacement therapy. AAT augmentation therapy appears to reduce the progression of emphysema in some AAT-deficient patients.     

Lactulose and neomycin attenuate leukocyte-endothelial cell adhesion in an animal model of inflammatory bowel disease

OBJECTIVE AND SIGNIFICANCE: To examine functional performance in people with emphysema because of alpha-1 antitrypsin (AAT) deficiency. A severe deficiency of AAT affects 1:3,500 to 1:1,670 Americans who can develop debilitating emphysema in the third to fifth decades of life. DESIGN: Exploratory. POPULATION: People with a severe deficiency of AAT. SAMPLE AND DEMOGRAPHICS: Thirty-three patients (21 men) with a mean age of 47 (SD = 7) years. YEARS: Data were collected 1993-1996. METHODS: Activities patients identified as important on the dyspnea subscale of the Chronic Respiratory Disease Questionnaire were categorized and interpreted within the context of an integrity framework (i.e., effectiveness--or connectedness-related). FINDINGS: Patients identified over 25 activities. Effectiveness activities, such as bathing, were mentioned most frequently (78%). Connectedness activities, such as playing with children, were mentioned less often (22%) but were ranked more important. Two patients reviewed and supported the content validity of the framework. CONCLUSIONS: Results offer insight into the activities patients with genetic emphysema choose to perform and the factors that influence the decision that "the dyspnea is worth it." IMPLICATIONS: Identifying the activities people with AAT deficiency choose to perform and understanding why these activities are meaningful can guide interventions to help patients maintain a sense of integrity.     

Bounds on null functions of linear digital imaging systems

OBJECTIVE: The purpose of this investigation was to quantitatively assess abnormally low attenuation of the lung by use of three-dimensional volumetric reconstructions from routine helical CT and to assess their correlation with pulmonary function tests. MATERIALS AND METHODS: Helical CT was performed in 100 patients in full inspiration. Examination was also performed in full expiration in 53 of these patients. Three-dimensional volumetric reconstructions were performed for total lung volumes at inspiration and at expiration, with a threshold of -896 H on inspiratory CT and -790 H on expiratory CT, to quantify emphysematous change. Correlation was made with pulmonary function tests in 79 patients. RESULTS: CT volumetric assessments of abnormally low attenuation of the lung at inspiration and expiration had a high correlation (r2 = .84, p < or = .0001). In comparison with pulmonary function tests, both inspiratory low attenuation of the lung and expiratory low attenuation of the lung correlated well with the logarithm of the ratio of the forced expiratory volume in 1 sec (FEV1) to the forced vital capacity (r2 = .74, p < or = .0001 and r2 = .74, p < or = .0001, respectively) and with the percentage of predicted ratio of the FEV1 to the forced vital capacity (r2 = .69, p < or = .0001 and r2 = .69, p < or = .0001, respectively). Linear correlations were also seen with FEV1, residual volume, and forced residual capacity. CONCLUSION: Three-dimensional volumetric reconstructions of hypoattenuating lung correlate well with pulmonary function tests. In addition, inspiratory and expiratory data are also correlative, suggesting that a dedicated expiratory examination is not needed. This easily obtainable information will prove useful for patients with obstructive lung disease from emphysema, providing a measure of pulmonary function status in this population.     

MR analysis of lung volume and thoracic dimensions in patients with emphysema before and after lung volume reduction surgery

OBJECTIVE: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery. SUBJECTS AND METHODS: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery. RESULTS: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration. CONCLUSION: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.     

Response to symptom-limited exercise in patients with the hepatopulmonary syndrome

OBJECTIVE: To study the response to symptom-limited exercise in patients with the hepatopulmonary syndrome (HPS). DESIGN: The response to maximal cardiopulmonary exercise (CPX) was studied in 5 patients with HPS and compared with 10 case control (normoxemic, NC) cirrhotics (matched for age, gender, etiology and severity of liver disease, tobacco use, and beta-blocker therapy) and 9 hypoxemic control cirrhotics (HC) without clinical evidence of HPS. SETTING: Cardiopulmonary exercise physiology laboratory in a tertiary care referral center. PATIENTS: Cirrhotics referred for CPX as part of their preliver transplantation evaluation. MEASUREMENTS: Standard pulmonary function tests and echocardiography were performed to assess resting pulmonary and cardiac function. Peak oxygen consumption (VO2), minute ventilation, arterial blood gases, and dead space (VD/VT) were determined during symptom-limited maximal CPX. RESULTS: Resting spirometry and lung volumes were similar between HPS and NC subjects, while HC subjects had restrictive physiology. Differences existed in diffusing capacity corrected for hemoglobin and alveolar volume percent predicted (HPS, 45+/-2 vs NC, 68+/-3, p<0.05; vs HC, 70+/-4, p<0.05), PaO2 (HPS, 70+/-5 mm Hg; HC, 79+/-3 mm Hg, vs NC, 102+/-3 mm Hg, p<0.05) and alveolar-arterial (A-a) O2 gradient (HPS, 42+/-8 mm Hg vs HC, 27+/-2 mm Hg, p<0.05; vs NC, 6+/-2 mm Hg, p<0.05). During CPX, HPS patients achieved a lower peak VO2 percent predicted (HPS, 55+/-6 vs NC, 73+/-3, p<0.05; vs HC, 71+/-5, p<0.05) and VO2 at the ventilatory threshold as percent predicted peak VO2 (HPS, 36+/-2 vs NC, 55+/-4, p<0.05; vs HC 55+/-5, p<0.05). While no differences existed in heart rate and breathing reserve, HPS patients had significantly lower PaO2 (HPS, 50+/-5 mm Hg vs NC, 97+/-4 mm Hg, p<0.05; vs HC, 87+/-6 mm Hg, p<0.05), wider A-a O2 gradient (HPS, 73+/-5 mm Hg vs NC, 13+/-3 mm Hg, p<0.05; vs HC, 31+/-5 mm Hg, p<0.05) and higher VD/VT (HPS, 0.36+/-.03 vs NC, 0.18+/-.02, p<0.05; vs HC, 0.28+/-.02, p<0.05) at peak exercise. For HPS patients, VO2 was negatively correlated with VD/VT (r2=0.9) and positively correlated with PaO2 (r2=0.41) at peak exercise. Conclusions: Patients with HPS demonstrate a severe reduction in aerobic capacity, beyond that found in cirrhotics without syndrome. The significant hypoxemia and elevated VD/VT at peak exercise suggest that an abnormal pulmonary circulation contributes to further exercise limitation in patients with HPS.     

Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer

STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). RESULTS: All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). CONCLUSIONS: Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.     

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves'' disease (GD)

OBJECTIVE: This study was performed to assess the usefulness of preoperative thin-section CT alone and in combination with physiologic measurements in emphysema patients being evaluated for lung volume reduction surgery. SUBJECTS AND METHODS: Six 1-mm collimation sections through the chest were obtained in 20 patients being evaluated for lung volume reduction surgery. Extent and severity of emphysema were assessed by visually scoring the images. CT scores ranged from 0 to 144. Inspiratory resistance was measured in 12 of 20 patients and was also used to discriminate between responders (change in forced expiratory volume in 1 sec, > or = 150 ml after surgery) and nonresponders (change in forced expiratory volume in 1 sec, < 150 ml after surgery). RESULTS: Four of 20 patients with mild emphysema as revealed by thin-section CT (scores of < 50) did not improve lung function after lung volume reduction surgery. Eight of the remaining 16 patients with moderate to severe emphysema as revealed by thin-section CT (scores of > 50) underwent inspiratory resistance measurement. Those seven patients whose inspiratory resistance measurement exceeded 8.5 cm H2O/l per second did not respond favorably to lung volume reduction surgery (change in forced expiratory volume in 1 sec, < 150 ml). The remaining five patients whose inspiratory resistance measurement was less than 8.5 cm H2O/l per second responded favorably to lung volume reduction surgery. Thus, only five of the 20 patients showed improvement in forced expiratory volume in 1 sec after surgery. CONCLUSION: Our data suggest that among patients with moderate to severe emphysema who are being examined for lung volume reduction surgery, the combination of radiologic and physiologic assessment is more accurate for predicting a favorable response to lung volume reduction surgery than radiologic assessment alone. However, in patients with chronic obstructive pulmonary disease by the American Thoracic Society criteria, mild emphysema as revealed on thin-section CT virtually precludes further workup because these patients are unlikely to respond favorably to lung volume reduction surgery.     

Two distinct anti-allergic drugs, amlexanox and cromolyn, bind to the same kinds of calcium binding proteins, except calmodulin, in bovine lung extract

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.     

Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function

The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.     

Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin

alpha 1-antitrypsin (alpha 1-AT) deficiency is a genetic disorder characterized by low serum levels of alpha 1-AT and a high risk of pulmonary emphysema at a young age. The resulting surplus of proteases, mainly of neutrophil elastase, can be balanced by i.v. augmentation with alpha 1-AT. However, it is not clear if affected patients benefit from long-term augmentation therapy and no long-term safety data are available. We examined 443 patients with severe alpha 1-AT deficiency and pulmonary emphysema receiving weekly i.v. infusions of 60 mg/kg body weight alpha 1-AT in addition to their regular medication. The progression of the disease was assessed by repeated lung function measurements, particularly the decline in forced expiratory volume in 1 second (delta FEV1). 443 patients with alpha 1-AT deficiency tolerated augmentation therapy well with few adverse reactions. The delta FEV1 in 287 patients with available follow-up data was 57.1 +/- 31.1 ml per year. Stratified for baseline FEV1, the decline was 35.6 +/- 21.3 ml in the 108 patients with an initial FEV1 < 30% and 64.0 +/- 26.4 ml in the 164 with 30% < FEV1 < or = 65% of predicted normal (p = 0.0008). The remaining 15 patients had an initial FEV1 > 65%. Long-term treatment with i.v. alpha 1-antitrypsin in patients with severe alpha 1-Pi deficiency is feasible and safe. The decline in forced expiratory volume in one second is related to the initial forced expiratory volume in one second as in alpha 1-antitrypsin deficient patients not receiving augmentation therapy.     

Short stature due to a partial idiopathic deficiency of the growth hormone. The role of the TW2 method in assessing treatment with r-hGH

The purposes of this study were: (1) to determine whether peripheral arterial occlusive disease (PAOD) patients who smoked had more severe claudication pain, reduced peripheral circulation, and poorer cardiopulmonary measurements at peak exercise than non-smoking patients, and (2) to determine whether the differences between the smoking and non-smoking patients persisted after controlling for the resting ankle/brachial systolic pressure index (ABI). Thirty-eight PAOD patients (ABI = 0.59 +/- 0.15, mean +/- SD) who smoked an average of 1.5 packs of cigarettes per day over 42 years and 100 PAOD patients (ABI = 0.74 +/- 26) who had quit smoking for an average of 7 years were recruited. Smokers refrained from smoking on the day of testing. Claudication pain times, oxygen uptake, ventilation, leg oximetry, and ankle systolic pressure responses to peak exercise were recorded. The smoking group had more severe claudication pain, as maximal pain occurred 1:37 min:s sooner during exercise (p < 0.05), and the pain took 2:21 min:s longer to subside (p < 0.01) compared to the non-smoking group. Additionally, at peak exercise the smoking group had a lower oxygen uptake (12.8 +/- 2.6 vs 13.9 +/- 2.4 ml/kg/min, p < 0.01), a higher ventilation (31.7 +/- 9.2 vs 27.9 +/- 7.1 liters/min, p < 0.05), and a higher oximeter electrode power (409 +/- 55 vs 385 +/- 37 mW, p < 0.01) than the non-smoking group. Differences between the groups persisted (p < 0.05) after adjusting for resting ABI. It is concluded that cigarette smokers with PAOD had more severe claudication pain, reduced peripheral circulation, and poorer cardiopulmonary measurements at peak exercise than non-smoking patients. These differences were independent of resting ABI. Thus, cigarette smoking reduces the exercise capacity of claudicants, placing patients who smoke at an even greater risk of living a functionally dependent lifestyle.     

Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.     

Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.     

Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique

The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.     

Evaluation of emphysema progression as measured by computed tomography in patients with chronic obstructive pulmonary disease

It has been difficult to assess the progression of pulmonary emphysema since accurate quantification of the extent of this condition has only previously been possible on post mortem or resected lungs. Previously we have shown that measurements of CT lung density correlated with the degree of emphysema, measured morphometrically in resected lungs. We have therefore employed this technique to assess the progression of emphysema in 17 patients (12M, 5F) with wide range of chronic airflow limitation (FEV1 15-68% predicted). There was little change in the degree of airflow limitation, hyperinflation or arterial blood gas values over 30 +/- 4 months of follow up (p > 0.05). However during this period there was a significant decrease in the lowest 5th percentile of CT density, which fell from -920 +/- 32 to -940 +/- 36 Hounsfield units (p < 0.005) associated with significant fall in the diffusing capacity for carbon monoxide. We believe that these data show the ability of CT scanning to assess the progression of emphysema in patients with chronic obstructive pulmonary disease.     

Oxygen uptake kinetics during low level exercise in patients with heart failure: relation to neurohormones, peak oxygen consumption, and clinical findings

OBJECTIVE: To investigate whether oxygen uptake (VO2) kinetics during low intensity exercise are related to clinical signs, symptoms, and neurohumoral activation independently of peak oxygen consumption in chronic heart failure. DESIGN: Comparison of VO2 kinetics with peak VO2, neurohormones, and clinical signs of chronic heart failure. SETTING: Tertiary care centre. PATIENTS: 48 patients with mild to moderate chronic heart failure. INTERVENTIONS: Treadmill exercise testing with "breath by breath" gas exchange monitoring. Measurement of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and noradrenaline. Assessment of clinical findings by questionnaire. MAIN OUTCOME MEASURES: O2 kinetics were defined as O2 deficit (time [rest to steady state] x DeltaVO2 -sigmaVO2 [rest to steady state]; normalised to body weight) and mean response time of oxygen consumption (MRT; O2 deficit/DeltaVO2). RESULTS: VO2 kinetics were weakly to moderately correlated to the peak VO2 (O2 deficit, r = -0.37, p < 0.05; MRT, r = -0.49, p < 0.001). Natriuretic peptides were more closely correlated with MRT (ANF, r = 0.58; BNP, r = 0.53, p < 0.001) than with O2 deficit (ANF, r = 0.48, p = 0.001; BNP, r = 0.37, p < 0.01) or peak VO2 (ANF, r = -0.40; BNP, r = -0.31, p < 0.05). Noradrenaline was correlated with MRT (r = 0. 33, p < 0.05) and O2 deficit (r = 0.39, p < 0.01) but not with peak VO2 (r = -0.20, NS). Symptoms of chronic heart failure were correlated with all indices of oxygen consumption (MRT, r = 0.47, p < 0.01; O2 deficit, r = 0.39, p < 0.01; peak VO2, r = -0.48, p < 0. 01). Multivariate analysis showed that the correlation of VO2 kinetics with neurohormones and symptoms of chronic heart failure was independent of peak VO2 and other variables. CONCLUSIONS: Oxygen kinetics during low intensity exercise may provide additional information over peak VO2 in patients with chronic heart failure, given the better correlation with neurohormones which represent an index of homeostasis of the cardiovascular system.     

Correlation between echocardiographic changes and parameters of pulmonary function in patients with arterial hypertension

This study comprised 30 patients with mild or moderate arterial hypertension (according to classification of the World Health Organization) in whom some echocardiogram and parameters of the lung function were studied in order to establish correlation between them. A good correlation exists between LV (left ventricle) mass index and vital capacity (r = 0.562, p < 0.01), ejection fraction and forced mid expiratory flow (r = 0.717, p < 0.01), LV mass index and Tiffenau index (r = 0.620, p < 0.01), shortening fraction and forced mid expiratory flow (r = 0.591, p < 0.01), airways resistance and posterior wall thickness (r = 0.591), p < 0.01) and between LV mass index and total lung capacity (r = 0.821, p < 0.01). There was not a good correlation or it was not significant (p > 0.05) between other echocardiographic changes and lung function tests.