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Due to the solubility of xenon-133 in blood and tissues, errors are introduced in the determination of regional pulmonary ventilation. We investigated these errors by comparing the results from ventilation measurements with Xe-133 and N-13 in five normal subjects (both at rest and during exercise) and in seven patients after a pneumonectomy. In the normal subjects at rest, the upper lung fields showed no significant difference in the uptake rates of the two gases. In the middle and lower lung fields, however, the uptake rate for Xe-133 was higher than for N-13. During exercise a significant increase of the specific ventilation was found in the upper lung fields for N-13 compared with Xe-133. In the pneumonectomy patients the overall uptake rate for Xe-133 in the intact hemithorax was 25% larger than for N-13. Over the pneumonectomized hemithorax the uptake of the fastest component of Xe-133 was (8.5 +/- 1.3)% of the total. The total chest-wall contribution of Xe-133 was (27 +/- 8)% of the total count rate.

To study subclinical pulmonary toxicity of bleomycin we measured the single-breath carbon monoxide transfer factor (TLCO) and its components, pulmonary capillary blood volume (Vc), diffusing capacity of the alveolar-capillary membrane (Dm), and vital capacity (VC) in a homogenous group of 18 patients with testicular nonseminomatous germ cell tumor treated with bleomycin, vinblastine, and cis-diammine-dichloroplatinum (DDP). The most prominent finding was a substantial decrease in Vc (p less than 0.001) with only minor, though significant, changes in the other parameters. No recovery of pulmonary function had taken place 4 months after the last dose of bleomycin. The importance of correcting TLCO for hemoglobin concentration is shown. We conclude that vascular damage may be an important feature of subclinical pulmonary injury caused by bleomycin given in combination with vinblastine and DDP. In the postbleomycin phase, other forms of potentially lung-toxic treatment should be instituted with care.

Esophageal and CVP changes were measured simultaneously during mechanical ventilation in 12 patients with acute respiratory failure (ARF). The results of these measurements were different and showed no correlation. Values of transpulmonary pressure changes and calculated lung compliances correlated well, because of the higher airway pressure changes. It is concluded, therefore, that measurements of esophageal and CVP changes are equally well suited for these calculations. For practical purposes, there is no need to measure a representant of intrapleural pressure changes, because during mechanical ventilation total static compliance calculations can be used to monitor changes in lung compliance, provided the thoracic cage compliance is not reduced substantially and does not change during the course of the studies. Clinical awareness of factors influencing thoracic cage compliance is important. The difference in transpulmonary and transthoracic pressure relationships during mechanical ventilation and during spontaneous breathing is emphasized. In spontaneous breathing, intrapleural pressure changes are determined primarily by the elastic properties of the lungs; in mechanical ventilation, on the other hand, by the elastic properties of the thoracic cage.

In 24 patients with a cadaveric renal allograft, serial measurements after transplantation were made of the diffusing capacity for carbon monoxide (DLCO) together with serial measurements of C3d, the stable conversion product of the complement factor C3, and determinations of the anaphylatoxin C3a. Twelve patients were studied during an active cytomegalovirus (CMV) infection, and 12 patients were studied during allograft rejection or during a stable phase after renal transplantation (control subjects). No patients had pulmonary symptoms nor abnormal chest radiographs or arterial blood gas determinations. During an active CMV infection, DLCO was significantly reduced compared with the measurements made during allograft rejection or during a stable phase after renal transplantation. This was true both with (p less than 0.01) and without (p less than 0.01) correction for the hemoglobin concentration. Serum C3d levels were increased in 8 of the 12 patients with a CMV infection, but not in any of the patients in the control group. In 8 patients with a CMV infection, measurements were made of the anaphylatoxin C3a, and were found to be significantly higher than the levels in the control population (p less than 0.01). We conclude that our data are consistent with pulmonary dysfunction in every patient with an active CMV infection. The concomitant findings of complement activation and formation of anaphylatoxins suggest a causal relationship of the complement activation and a decreased DLCO, although further studies are warranted to determine the exact role of complement in the pulmonary events during an active CMV infection after renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each, we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity. The patients were randomly allocated to treatment with either 200 or 800 micrograms budesonide per day for a period of 8 wk. The active treatment period was preceded by a selection period of 3 wk, and a single-blind placebo period of 2 wk. During these initial 5 wk the maintenance treatment of the patients, including cromolyn sodium and inhaled corticosteroids, was withheld. Spirometry and inhalation provocation tests with methacholine were carried out, and the symptom score was recorded every 2 wk. The methacholine provocation concentrations (geometric mean) causing a decrease in FEV1 of 20% (PC20) in the 200 and 800 micrograms/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml, respectively. These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment (p less than 0.05 and p less than 0.001, respectively) and to 1.55 and 2.74 mg/ml after 8 wk of treatment (p less than 0.01 and p less than 0.001). During the whole study period budesonide in a dosage of 800 micrograms/day induced a significantly larger change in PC20 than in a dosage of 200 micrograms/day. The FEV1 before treatment was 91 +/- 3% (SEM) and 84 +/- 2% of the predicted value in the 200 and 800 micrograms/day treatment groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary function tests, including the transfer factor for carbon monoxide of the lungs (T1CO) and pulmonary capillary blood volume (Vc), were measured in 43 patients with disseminated testicular carcinoma and in eight patients with disseminated malignant melanoma before the start of a bleomycin-containing cytostatic combination. Their relation to the development of bleomycin-induced pulmonary toxicity was evaluated. We found two subgroups of patients, one group with and one group without an abnormal pretreatment T1CO and Vc. In the latter group the risk of bleomycin-induced pulmonary toxicity is not increased. Reduction in bleomycin dose during treatment is not necessary. The hypothesis is formulated that tumor embolism could be the explanation for this phenomenon.

We have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances. Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml.h-1.kg-1 respectively. Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml.h-1.kg-1 respectively. There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance. It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.

Pulmonary function tests, including T1CO, and renal function tests were performed and GFR and ERPF measured in 18 patients with disseminated testicular non-seminoma before and after remission induction according to the Einhorn regimen. We found a significant positive correlation between delta GFR and delta T1CO (p less than 0.05). No significance could be demonstrated between delta ERPF and delta T1CO. It is concluded that caution should be exercised in administrating bleomycin to patients with severely impaired renal function.

We performed a double-blind crossover study to compare the effects of long-term treatment of inhaled budesonide and terbutaline on bronchial hyperreactivity in 17 patients with allergic asthma. Both drugs were administered for 4 weeks with a placebo-treatment period before and after each active-treatment period. To assess bronchial hyperreactivity, standardized inhalation provocation tests with histamine and propranolol were performed every 2 weeks. Before each inhalation provocation the drugs were withheld for at least 12 hours. Before the budesonide treatment the FEV1 value (percent predicted) was 85.3 +/- 4.1% (mean +/- SEM). After 2 and 4 weeks of treatment with this drug, the value increased significantly to 89.4 +/- 4.1% and 96.2 +/- 3.8%, respectively (p less than 0.05 and p less than 0.005). The histamine provocation concentrations causing a decrease in FEV1 of 20% (PC20) on the same days were 4.0, 7.2, and 9.5 mg/ml, respectively (both p less than 0.001). The PC20 values for propranolol, which were measured 1 hour after the histamine provocation, were 11.7, 13.3, and 14.0 mg/ml (ns). The FEV1 values before and after 2 and 4 weeks of treatment with terbutaline were 86.2 +/- 4.0%, 84.8 +/- 4.1%, and 87.0 +/- 4.6%, respectively. The histamine PC20 values on the same days were 4.7, 3.1 (p less than 0.05), and 3.8 mg/ml, respectively. The propranolol PC20 values were 14.2, 8.7, and 10.1 mg/ml (p less than 0.001 and p less than 0.05, respectively. We conclude that budesonide improves bronchial hyperreactivity, possibly by a dampening of late allergic reactions, whereas treatment with terbutaline may lead to a temporary increase of bronchial hyperreactivity, possibly as a result of beta-receptor desensitization.

Forty-eight patients with a history of exercise-induced asthma were exercised on ambient breathing (T = 18-20 degrees C, relative humidity = 45-55%). There were 19 responders and 29 non-responders according to post-exercise spirometry. During the first minutes of exercise at a workload of 25-50 W, the functional residual capacity (FRC) was measured by a rebreathing technique. There was a significant increase in FRC in responders (p less than 0.025). A loose though significant correlation was found between the rise in FRC during exercise and the fall in forced expiratory volume in one second (FEV1) after exercise (r = -0.429, p less than 0.005). The effects of a sympathomimetic drug were studied in five responders submitted to a second exercise test 4 h after the first one. Spirometry returned to normal but FRC remained high between both tests. During the second test neither spirometry nor FRC changed. The results suggest that different mechanisms may be responsible for changes in FRC and in maximal expiratory flow in exercise-induced broncho constriction.

In this study, long-term pulmonary complications of bleomycin were evaluated in 8 patients with bleomycin-induced pneumonitis (BIP). The lung function parameters: VC, alveolar volume, transfer factor for carbon monoxide of the lungs, diffusing capacity of the alveolocapillary membrane, and pulmonary capillary blood volume were studied in all patients for as long as 2 yr after the development of BIP. Perfusion scans with 133Xe and 99mTc were performed in these patients 2 yr after BIP developed. We concluded that if a patient survives the acute event of BIP, the pulmonary symptoms and the changes in these lung function parameters are completely reversible.

Five pulmonary function tests (transfer factor for carbon monoxide, diffusing capacity of the alveolar-capillary membrane, pulmonary capillary blood volume, alveolar volume, vital capacity) were performed, and creatinine clearance was measured in 39 patients with disseminated testicular nonseminomatous tumor treated with a combination chemotherapy containing bleomycin. Eight of these patients (20.5%) developed bleomycin-induced pneumonitis (BIP). To investigate which parameter has value in predicting BIP, a discriminant analysis was performed. The combination of a low normal creatinine clearance, a decrease in vital capacity and alveolar volume without a decrease in pulmonary capillary blood volume, pointed to an increased risk. We concluded that it is worthwhile to monitor these parameters and, if necessary, to adapt the chemotherapy of a patient at risk.

Forty-two patients presenting with Raynaud's phenomenon (RP) were prospectively evaluated for pulmonary function changes over a 6-year followup period. Fifteen patients had secondary RP at presentation, 27 patients had nonsecondary RP. In the latter group, decreased pulmonary diffusing capacity (Tlco) was observed in only 2 patients (7%) whereas 9 patients with secondary RP (60%) had decreased Tlco. In the group of patients with nonsecondary RP exhibiting one or more autoantibodies, Tlco values were lower than in the group without autoantibodies (p less than 0.01). In patients with nonsecondary RP the duration of disease was correlated with the level of Tlco (r = 0.55), probably explained by a higher prevalence of truly primary RP in patients with longstanding nonsecondary RP. During followup no significant changes in pulmonary function were observed in the group with nonsecondary RP. We conclude that pulmonary function testing in patients presenting with nonsecondary RP without autoantibodies does not appear of clinical value.