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.     

Long-term effects of bicycle-ergometry training on exercise endurance and dyspnea in patients with chronic pulmonary emphysema]

OBJECTIVE: To evaluate prenatal diagnosis of limb-body wall complex (LBWC) by ultrasonography in eight cases. STUDY DESIGN: The diagnosis was based on two of the following: exencephaly/encephalocele with facial clefts, thoracoschisis and/or abdominoschisis and limb defect. The ultrasonographic findings were compared with the autopsy findings in each case. RESULTS: The average weeks of gestation at which malformations were diagnosed by ultrasonography was 21.7 +/- 4.7 (mean +/- SD, n = 8). All eight fetuses were diagnosed as having characteristic abnormalities and six of them as having scoliosis by ultrasonography. Four of the eight were examined for maternal serum alpha-fetoprotein (MSAFP); the levels exceeded 2.5 multiples of the mean according to the standard value at our hospital. Chromosomal analysis was performed for six cases and revealed that they were normal in karyotype. All eight cases showed abdominoschisis, scoliosis and abnormalities of the lower extremities. A single umbilical artery was present in seven cases (87.5%), and a short umbilical cord was present in seven (87.5%). CONCLUSION: Ultrasonographic detection of abdominoschisis, scoliosis abnormalities of the lower extremities, a single umbilical artery and a short umbilical cord is important for the prenatal diagnosis of LBWC. An extremely elevated level of MSAFP is also indicative of the complex.     

Bioelectrical impedance analysis of body composition in patients with pulmonary emphysema

In this study we utilized bioelectrical impedance analysis (BIA) to compare the body composition of 36 stable pulmonary emphysema (PE) patients with 19 healthy controls. We compared the PE patients and healthy controls in terms of fat-free mass (FFM) and body fat (BF) as percentages of ideal body weight (FFM/IBW, BF/IBW). FFM/IBW and BF/IBW were significantly lower in the PE patients than in the controls (75.0 +/- 9.8% vs. 85.2 +/- 7.3%, p < 0.001 and 11.8 +/- 6.4% vs. 16.7 +/- 7.7%, p < 0.05, respectively). We divided the PE patients into two subgroups according to FFM, then investigated the relationships between FFM and skeletal muscle strength, and between FFM and respiratory muscle strength. In patients with reduced FFM (FFM < 43.5 kg) grip strength as an index of skeletal muscle strength was significantly lower than in patients without reduced FFM (FFM > or = 43.5 kg) (25.7 +/- 7.8 kg vs. 36.2 +/- 7.2 kg, p < 0.005). As indexes of respiratory muscle strength, maximal expiratory pressure (PEmax) and maximal inspiratory pressure (PImax) were lower in the patients with reduced of FFM, but not to a statistically significant degree (49.6 +/- 20.8 cm H2O vs. 58.7 +/- 23.9 cm H2O and 40.5 +/- 19.2 cm H2O vs. 50.2 +/- 22.1 cm H2O, respectively). In the PE patients, FFM correlated closely with vital capacity (r = 0.528, p < 0.001), forced vital capacity (FVC) (r = 0.531, p < 0.001), FEV1.0 (r = 0.554, p < 0.001), FEV1.0/FVC (r = 0.467, p < 0.005), RV/TLC (r = -0.395, p < 0.05), DLco (r = 0.770, p < 0.001), and DLco/VA (r = 0.622, p < 0.001). However no correlation was observed between BF and any of the measures of lung function. The findings of our study suggest that FFM correlates with skeletal muscle strength, respiratory muscle strength and some measures of lung function in patients with PE, and that assessments of body composition are valuable to their clinical management.     

Diagnosis of emphysema in patients with chronic bronchitis: a new approach

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (D) are altered in patients or animal models with lung emphysema. This study was performed to examine the sensitivity and specificity of ADAM and D in the detection of emphysema in vivo compared with conventional lung function parameters. The study comprised patients with chronic obstructive bronchitis (COB) without emphysema (group COB; n=19, age 56+/-8 yrs, forced expiratory volume in one second (FEV1)/vital capacity (VC) 66+/-12% predicted) and patients with chronic bronchitis with high-resolution computed tomography-confirmed emphysema (group COB-E; n=20), age 65+/-7 yrs, FEV1/VC 44+/-16% pred). Using monodisperse aerosol particles ADAM assessed the calibres of peripheral airspaces, while D measured convective gas mixing. Among all lung function parameters, ADAM and D showed the highest sensitivity and specificity for separating patients with COB from those with COB-E (area under the receiver operating characteristics curve (pROC) 0.99 and 1.0, respectively). In patients with COB aerosol parameters did not differ from those found in the control group, whereas patients with COB-E exhibited a two-fold increase in peripheral airspace dimensions compared with subjects with COB (0.86+/-0.07 versus 0.37+/-0.02 mm, p=0.0001) and an increase in D by >50% (541+/-74 versus 345+/-42 cm3, p=0.0001). In conclusion, aerosol-derived airway morphometry and aerosol bolus dispersion are powerful tools in the differential diagnosis of chronic obstructive pulmonary disease.     

Breathlessness and blood oxygen tension in patients with chronic bronchitis and emphysema

A method is described whereby about 100 litres of plasma containing 10-50 IU/ml tetanus antitixin was obtained, from which were prepared 5000 X 250 IU doses of human antitetanus immunoglobulin. Of 40 blood donors who received a booster injection of tetanus vaccine BP, 33 were plasmapheresed each week over a 10-12 week period starting three weeks after the injection. Twenty-two of these donors provided 90% of the total plasma, the antitoxin content of which averaged 23.6 IU/ml over the 10-12 week period.     

Estimation of respiratory muscle endurance using an inspiratory threshold loading device in patients with chronic pulmonary emphysema and in elderly subjects

We studied respiratory muscle endurance with an inspiratory threshold loading (ITL) device using Martyn's method (2-min incremental loading test) in 9 patients with chronic pulmonary emphysema (CPE patients) and in 9 elderly subjects with no lung disease (NE subjects), and their endurance was compared with that of 9 normal young subjects (NY subjects). In 11 cases (8 CPE patients and 3 NE subjects) a treadmill exercise test was performed and cardiopulmonary parameters obtained from the ITL and treadmill tests were compared. The maximum weight tolerated for 2 minutes (Wmax) and the mean peak inspiratory mouth pressure/maximum inspiratory mouth pressure ratio at the maximum load (Ppk/MIP at Max Load) were used as indices of respiratory muscle endurance. CPE patients had significantly decreased Wmax compared with those of NE and NY subjects. Wmax in all cases positively correlated with Ppk/MIP at Max Load, and endurance time of both the ITL and treadmill tests. During both tests, SaO2 significantly decreased, and heart rate and mean blood pressure significantly increased. There was less change in SaO2 and heart rate during the ITL test than during the treadmill test, and neither arrhythmias nor ST changes on ECG were observed during the ITL test. These results indicate that the ITL test can be easily and safely employed in CPE patients and elderly subjects to estimate respiratory muscle endurance.     

Arterial carbon dioxide tension and dyspnea in chronic bronchitis and pulmonary emphysema

The severity of dyspnea (MRC scale) was confronted to the blood carbon dioxide tension (PaCO2) in 45 patients with chronic nonspecific lung disease having moderate or severe airway obstruction (FEV1.0 of less than 1.5 liters). The patients were classified as "bronchitic", "emphysematous" and "intermediate" using a 10- criterion (clinical, roentgenologic and biological) "emphysema score". No correlation between dyspnea grade and PaCO2 was found in "bronchitic" and "intermediate" patients; in the "emphysematous" subgroup PaCO2 tended to rise as dyspnea was more severe, but the linear correlation coefficient (r= +0.37) did not reach the significance threshold, which is high (0.468) for such a limited number of observations.     

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.     

Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.     

Treatment of patients with chronic pulmonary tuberculosis with expectoration--evaluation of effectiveness

Two patients with multidrug-resistant pulmonary tuberculosis were surgically treated after 3 and 7 years of unsuccessful chemotherapy. There was pneumonectomy in one case and lobectomy with segmentectomy in the second. Pneumonectomy was complicated by bronchopleural fistula. Both patients become sputum culture negative after surgical treatment but first patient died 5 months after surgery because of acute hepatitis.     

Predictors of functioning of patients with chronic obstructive pulmonary disease

The subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide-hydrolyzing activities was studied in the left and right rat brain during development and aging. During development, the soluble activity was heterogeneous, whereas adult animals showed the highest activity in the synaptosomal fraction. However, except in fetuses, membrane-bound activity was greatest in the microsomal fraction. Except in microsomal and myelin fractions, soluble and membrane-bound activities showed a decrease in 1-wk-old rats compared with fetuses and a subsequent increase to adult levels in 1-mo-old rats. This profile differed in the microsomal fraction, which increased steadily throughout development. In the synaptosomal fraction, both activities were lower in 24-mo-old rats than in 5-mo-old animals. No differences between the hemispheres were observed in soluble or membrane-bound fractions at any age tested.     

Measurements of membrane diffusing capacity and pulmonary capillary blood volume in normal subjects and patients with mild emphysema

OBJECTIVE: To establish predicted values of membrane diffusing capacity (Dm) and pulmonary capacity blood volume (Vc), to compare the predicted values from our equations with those for Caucasians, to determine whether there are changes initially in Dm or Vc in patients with mild emphysema. PATIENTS AND METHODS: Diffusing capacity for carbon monoxide (DLco), Dm and Vc were determined in 86 normal subjects and 16 patients using the single-breath diffusing capacity for carbon monoxide (DLcosB) with two different alveolar concentrations of oxygen. RESULTS: The predicted equations are as follows. For males, DLco (ml/min/mm Hg) = 0.37H-0.19A-27.8; Dm (ml/min/mm Hg) = 0.65H-0.24A-53.7; Vc(ml) = 0.88H-78.9. For females, DLco = 0.28H-22.7; Dm = 0.59H-53.6; Vc = 66.6-0.36A. DLco and Vc are lower in Chinese than Caucasians while Dm is similar in Chinese and Caucasians. Eleven of 16 patients had a low DLco (< 80% predicted value), 12 had a low Dm and 5 had a low Vc. Eight of 12 patients with a low Dm also had a low DLco, but in 4 the DLco was normal. Nine of 12 with low Dm had a normal Vc. CONCLUSIONS: This study provides prediction equations of Dm and Vc. Chinese have a low DLco because their Vc is lower than Caucasians. The DLco and Dm are abnormal in a comparable percentage of patients. In patients with mild emphysema, the Dm becomes abnormal before the Vc.     

Surgical options for patients with advanced emphysema

Since the early 1900s, a variety of operations have been suggested for emphysema but, with the exception of giant bullectomy, an option in only a small fraction of patients, none has proven effective. Data collected by a number of academic medical centers indicate that LVRS may ameliorate symptoms and improve pulmonary physiology, function, and quality of life in appropriately selected patients with emphysema. Accordingly, LVRS may provide an opportunity to intervene in a rapid, effective, and, possibly, cost-effective manner in a debilitating, chronic disease. That is an extraordinarily attractive proposition for both patients and physicians alike. But a number of questions remain: (1) What is the effect of LVRS compared with maximal medical therapy? (2) What is the duration of any beneficial effect of LVRS? (3) What is the best operative approach? (4) What patient characteristics predict good and bad outcomes? (5) What is the role of pre- and, possibly, postoperative pulmonary rehabilitation? (6) Does LVRS adversely affect the rate of loss of lung function over time, as some have suggested? (7) What is the cost of LVRS compared with standard medical therapy? (8) Can the procedure be performed safely in nontransplant centers? (9) What is the effect on disease-specific quality of life? (10) Does it affect mortality? A prospective, randomized controlled trial involving 18 selected centers will begin in the fall of 1997 under the sponsorship of the Health Care Financing Corporation (the administrators of Medicare) and the National Institutes of Health. We strongly support the creative, collaborative approach that has been taken by those two government agencies to stimulate this study. The need for controlled trials of new therapies cannot be overstated; only with such trials can the questions enumerated above be answered with certainty.     

Evolution of nocturnal pulse-oximetry results in patients with chronic obstructive pulmonary disease

The aim of this study was to evaluate if results of overnight pulse-oximetry (PO) change with time and progression of the disease. We studied 39 COPD patients. Majority of them (33 pts) were treated with long-term oxygen therapy (LTOT). Fifty pairs of PO were performed in the whole group separated from 1 to more than 3 years. Pulmonary function tests were performed at the same time as PO. Results of these tests showed progressive deterioration in the lung function-decrease of FEV1 and PaO2. Despite of that there were no statistically significant changes in any variable of PO in any studied group. This phenomenon is difficult to explain. It may resulted from the improvement in the cardiac output observed in COPD patient undergoing LTOT. May be that studied groups were not large enough or time of observation was too short to reveal differences. Stabilization of PO results in spite of deterioration in the lung function in COPD patients needs more studies.     

Measurement of respiratory muscle performance in patients with chronic obstructive pulmonary disease

Respiratory muscle performance is measured in terms of strength and endurance. A RMSE-1 type measuring system for evaluation of respiratory muscle strength (RMS) and endurance (RME) has been developed and tested in normal subjects and patients with stable chronic obstructive pulmonary disease (COPD). The results showed that there was no significant difference between normal subjects and stable COPD patients in RMS measured as maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP). The maximum load (Load(m)), mean mouth pressure at maximum load (Pmean), and the maximum sustainable inspiratory pressure (SIP(m)) as % MIP (SIP(m)/MIP) were taken as measure of RME. All measures of RME in COPD group were much lower than those in the normal. The measurement of RME can be used to evaluate the effect of respiratory muscle training and direct the respiratory rehabilitation in COPD patients.