Diagnostic value of gas exchange tests in patients with clinical suspicion of pulmonary embolism.

OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal scans who had normal P(A-a)O2, PaO2 and PaCO2 were 20, 25 and 37%, respectively. No differences were observed in the mean values of arterial blood gas data between patients with pulmonary embolism and those who had abnormal scans and negative angiograms. Among the 773 patients with suspected pulmonary embolism, 364 (47%) had prior cardiopulmonary disease. Pulmonary embolism was diagnosed in 151 (41%) of 364 patients with prior cardiopulmonary disease, and in 161 (39%) of 409 patients without prior cardiopulmonary disease. Among patients with pulmonary embolism, there was no difference in arterial blood gas data between patients with and those without prior CPD. CONCLUSION: These data indicate that arterial blood gas tests are of limited value in the diagnostic work-up of pulmonary embolism if they are not interpreted in conjunction with clinical and other laboratory tests.

Carbogen and nicotinamide combined with unconventional radiotherapy in glioblastoma multiforme: a new modality treatment.

PURPOSE: A new radiotherapy schedule to treat glioblastoma multiforme after surgery, combining nicotinamide and carbogen. METHODS AND MATERIALS: We analyzed 36 patients with glioblastoma multiforme treated after surgery with radiotherapy, Nicotinamide and Carbogen as follows: 7 patients were treated with accelerated fractionation: two fractions/day, 1.5 cGy/fraction, 6 h interval, 5 days/week, total dose 60 Gy in 4 weeks; 8 patients were treated with the same irradiation scheduling plus Nicotinamide at the dose of 4 g and 2 g in capsules, respectively, 1 h before the first and the second irradiation fraction; 21 patients were treated with accelerated radiotherapy, Nicotinamide, and Carbogen (inhaled 10 min before radiotherapy and during the whole course of irradiation). On the basis of surgical removal our patients were subdivided in three groups: totally resected, with residual tumor <50%, or >50%. Radiotherapy with accelerated fractionation was completed in the scheduled time without side effects on the whole group of patients and Carbogen inhalation did not cause significant change of cardiopulmonar parameters. The toxicity observed was predominant in the gastrointestinal tract and was related to Nicotinamide. RESULTS: The median survival time (M.S.T.) was 10 months, as reported by others authors with conventional treatment, but in patients without surgical residual tumor and submitted to the complete treatment schedule, the survival at 35 months was around 25%. CONCLUSIONS: We conclude that this method is feasible with acceptable toxicity; analyzing the survival curves appears to be a trend towards an improvement in survival in the subgroup of patients with gross total removal treated with the combination of Carbogen, Nicotinamide, and accelerated fractionation.

Carbogen breathing in patients with glioblastoma multiforme submitted to radiotherapy. Assessment of gas exchange parameters.

It has been reported that carbogen breathing yields a remarkable increase of radiosensitivity in murine tumour models. Hence, application of carbogen might be promising in radiotherapy of human tumours. We describe a method to increase arterial oxygenation and to ensure stability of O2 and CO2 during carbogen breathing in patients with malignant disease. We measured in 6 patients with histologically proven intracranial glioblastoma multiforme arterial blood gases, inspired and expired gas concentrations and vital signs either baseline and during carbogen breathing. The highest values of arterial oxygenation were achieved after 10 min of carbogen breathing and they remained stable up to 15 min. In none of our patients was N2 wash-out from the lungs completed in 15 min of carbogen breathing. In conclusion, carbogen breathing increased arterial oxygenation in patients with intracranial malignant diseases. The system used is reliable and of practical use. Monitoring of expired gas concentrations is highly recommended.

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure.

We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Stress failure in pulmonary capillaries.

In the mammalian lung, alveolar gas and blood are separated by an extremely thin membrane, despite the fact that mechanical failure could be catastrophic for gas exchange. We raised the pulmonary capillary pressure in anesthetized rabbits until stress failure occurred. At capillary transmural pressures greater than or equal to 40 mmHg, disruption of the capillary endothelium and alveolar epithelium was seen in some locations. The three principal forces acting on the capillary wall were analyzed. 1) Circumferential wall tension caused by the transmural pressure. This is approximately 25 dyn/cm (25 mN/m) at failure where the radius of curvature of the capillary is 5 microns. This tension is small, being comparable with the tension in the alveolar wall associated with lung elastic recoil. 2) Surface tension of the alveolar lining layer. This contributes support to the capillaries that bulge into the alveolar spaces at these high pressures. When protein leakage into the alveolar spaces occurs because of stress failure, the increase in surface tension caused by surfactant inhibition could be a powerful force preventing further failure. 3) Tension of the tissue elements in the alveolar wall associated with lung inflation. This may be negligible at normal lung volumes but considerable at high volumes. Whereas circumferential wall tension is low, capillary wall stress at failure is very high at approximately 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2) where the thickness is only 0.3 microns. This is approximately the same as the wall stress of the normal aorta, which is predominantly composed of collagen and elastin. The strength of the thin part of the capillary wall is probably attributable to the collagen IV of the basement membranes. The safety factor is apparently small when the capillary pressure is raised during heavy exercise. Stress failure causes increased permeability with protein leakage, or frank hemorrhage, and probably has a role in several types of lung disease.

Respiratory effects of occupational exposure in a general population sample in north Italy.

We assessed the effects of occupational exposure in a general population sample living in an unpolluted rural area of North Italy. In the age range of 18 to 64 yr, there were 417 participants who reported any exposure to dusts, chemicals, or gases and 1,218 who reported no exposure. Each subject completed a standardized interviewer-administered questionnaire (CNR-questionnaire). A variable proportion of participants succeeded in performing flow-volume curves, diffusing capacity of carbon monoxide, and slope of alveolar plateau of nitrogen. There was no significant difference for symptom prevalence rates between exposed and nonexposed in men and women who smoke. In nonsmoking women, those exposed showed significantly higher prevalence rates for exertional dyspnea and asthma. Regarding lung function, in exposed male smokers there was a significantly higher slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced expiratory flows were significantly lower. Multiple logistic models in the overall group, accounting for age, smoking, and pack-years, showed that work exposure was associated significantly with higher risks for all symptoms in men (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64 for phlegm); in females, the association was significant for dyspnea (OR = 3.74) and asthma (OR = 3.29). Exposed men also had a significantly higher risk for %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other few epidemiologic surveys in general population samples and contribute to the suggestion of a causal association between occupational exposure and chronic obstructive pulmonary disease.

Carbon monoxide diffusing capacity, other indices of lung function, and respiratory symptoms in a general population sample.

To assess the relationships among single-breath diffusing capacity for CO (DLCOsb) (13), respiratory symptoms, and cigarette smoking in a general population sample, the data of 718 men and 894 women 20 yr of age or older were analyzed, and comparisons were performed with flow-volume curve (MEFV) variables and the slope of the alveolar plateau (DN2%/L) as well. Percent predicted DLCOsb and its correction for alveolar volume (DL/VA) were significantly lower in smokers than in nonsmokers. The relationship of presence/absence of respiratory symptoms and cigarette smoking with DLCOsb and DL/VA was significant. DLCO indices were almost always selected as discriminant variables in multivariate analysis between asymptomatic and symptomatic subjects. Poor concordance among lung function tests was evident: in men, 30% with abnormal (i.e., lower than 97.5% percentile) and 21% with normal DLCO indices also had abnormal MEFV parameters and/or DN2%/L. In women, the corresponding figures were 24 and 10%, respectively. In men, when considering only DLCO indices, the percentage of symptomatic subjects with abnormal lung function tests ranged from 33% in those with at least one symptom to 45% in those complaining of dyspnea. When the proportion of symptomatic subjects with DN2%/L and MEFV abnormalities were added, it increased to 56 and 66%, respectively. However, in women the proportion of symptomatic subjects with abnormal lung function indices was very small. These results indicate the usefulness of including CO diffusing capacity in epidemiologic surveys in the detection of abnormalities.

Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram.

Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional recovery of these patients, thus giving additional information about the effect of therapy.

Effects of childhood and adolescence-adulthood respiratory infections in a general population.

The role of childhood respiratory infections before 12 yrs of age (CRI) and during adolescence-adulthood (ARI) was studied in a general population sample (n = 3,289), living in an unpolluted area of Northern Italy. The presence of respiratory symptoms and diseases, as well as risk factors for obstructive airways disease (OAD), was assessed by a standardized questionnaire. Forced vital capacity and derived expiratory flows, and single-breath diffusing capacity were measured using computerized instrumentation. There were 1,185 (36.2%) subjects who reported pertussis (PT), 374 (11.4%) recurrent chest colds, pneumonia and croup, singly or in combination, with or without pertussis (CRI), and 1,718 (52.4%) reported no respiratory infections in childhood (NOCRI). Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects of the CRI group in all ages, and in older smokers. Wheeze and attacks of shortness of breath with wheeze were significantly higher in younger nonsmoking subjects with a history of CRI. Respiratory symptoms and diseases were not more prevalent in subjects of the PT group. Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects with a history of ARI, both in smokers and nonsmokers. Lung function parameters adjusted for sex, age and smoking were significantly lower in CRI subjects; PT subjects showed lower values than NOCRI subjects. A significantly higher prevalence rate of ARI was present in subjects who reported CRI, both in smokers and nonsmokers. Subjects with both CRI and ARI showed the highest prevalence of respiratory symptoms and diseases. In addition, they had the lowest lung function values regardless of smoking habit.

[Changes in pulmonary gas exchange in chronic obstructive bronchopneumopathies and their modifications induced by therapy]. / Le alterazioni degli scambi gassosi polmonari nelle broncopneumopatie croniche ostruttive e loro modificazioni indotte dalla terapia.

In order to assess the mechanisms of gas exchange disturbances (i.e. to what extent shunting and diffusion impairment contribute to hypoxemia) in chronic obstructive pulmonary disease (COPD) and respiratory failure, ventilation-perfusion relationships (V/Q) by the multiple inert gas elimination technique were obtained in 16 patients with respiratory failure breakthrough. In 6 instances the study was repeated after long-term treatment with the aim to analyze V/Q changes after therapy. Initially, patients showed severe hypoxemia and hypercapnia and they presented signs of marked bronchoconstriction. A great dispersion of V and Q distribution was present as indicated by the marked increase of the second moment of V and Q distributions. Interestingly, few patients presented a unimodal distribution of both V and Q, whereas most-patients had bimodal distributions where the ventilation was distributed in a mode such that high V/Q areas were present between 10 and 100 of V/Q ratio and blood flow was displaced leftward or toward lower V/Q values. No correlations were found between V and Q distribution and clinical types A or B of COPD. Significant relationships were found between measured and calculated arterial PO2 (r = 0.90, p less than 0.001) and between measured PO2 and the sum of the fractional perfusion to regions with V/Q ratio less than 0.1, suggesting that V/Q inequality and shunting, instead of the impairment of diffusion equilibration, can account for all the hypoxemia. Finally, the reduced inhomogeneity of ventilation after treatment, especially in the fraction located in high V/Q regions is mostly related to some functional and reversible damages in COPD.

Single breath nitrogen test in an epidemiologic survey in North Italy. Reliability, reference values and relationships with symptoms.

The usefulness of single breath nitrogen test (SBN2) was evaluated in a cross-sectional epidemiologic survey on a general population sample (n = 3,289) of North Italy. Each subject was submitted to CNR standardized questionnaire and to lung function testing using automated equipment (Hewlett-Packard 47804S). Acceptable closing volume (CV) and slope of alveolar plateau (DN2%/L) tracings were performed by only 1,370 and 1,982 subjects respectively, in comparison with the 2,638 diffusing capacity and the 3,079 forced vital capacity acceptable maneuvers. Prediction equations were computed on normal subjects for CV indices, with the exception of DN2%/L: they were similar to those found in other studies. Significant differences among smoking categories were found for all the SBN2 parameters in males, but only for DN2%/L in females. The latter was also able to distinguish either subjects with airway obstruction from those without it or symptomatic from asymptomatic individuals, but DN2%/L did not give more information than Vmax75, a sensitive index of flow volume curve. Our results suggest that the place of SBN2 in large scale epidemiologic testing has not been justified.

Prevalence of respiratory symptoms in an unpolluted area of northern Italy.

Using a multistage stratified geographic cluster sample of households living in an unpolluted area of Northern Italy (near Venice), we enrolled 3289 inhabitants (aged 8-64 yr) for a longitudinal respiratory study. During the first cross-sectional survey, before the start of operation of a large oil-burning thermoelectric power plant, they completed a standardized administered questionnaire and performed several lung function tests. In the whole sample, dyspnoea grade 1 (11%), chronic cough and chronic phlegm (9%) were the most frequent respiratory symptoms; all the symptoms except dyspnoea were more prevalent in males than in females. Smokers (S) showed higher prevalence rates than ex-smokers (ES) and nonsmokers (NS), especially in males. In both sexes, the frequency of respiratory symptoms increased with increasing smoking as assessed by pack-years. An inverse relationship between prevalence of symptoms and socio-economic status was also observed. All tests of lung function were significantly impaired in S compared with NS in males; single-breath CO diffusing capacity and slope of alveolar plateau but not spirometric indices were significantly impaired in female S compared to female ES and NS. Finally, our prevalence rates were lower than in other epidemiological surveys: this result may be ascribed to the low levels of air pollution measured in the area.

Ventilation-perfusion heterogeneity and gas exchange variables in acute pulmonary embolism evaluated by two different computerized techniques.

The mechanisms by which the disturbances of gas exchange develop in human pulmonary embolism are unknown. We investigated whether the inequality of ventilation-perfusion ratio is associated with the abnormalities of pulmonary gas exchange as evaluated by two different computerized techniques. We measured the alveolar to arterial gradients of oxygen and carbon dioxide by means of a computer based system with a mass spectrometer and the ventilation-perfusion distributions by the multiple inert gas technique in 5 patients with acute pulmonary embolism. In these subjects there was a marked ventilation-perfusion inhomogeneity, as detected from inert gases and this finding was in agreement with the impairment of the alveolar to arterial gradients and of their derived indexes. Consideration on the responsible mechanisms for the disturbances of gas exchange are also reported. In conclusion these two computerized techniques provide a useful assessment of the ventilation-perfusion relationships in order to explain the disturbances of gas exchange in critically ill patients.

The assessment of gas exchange by automated analysis of O2 and CO2 alveolar to arterial differences.

A computer program to measure breath by breath alveolar pressure (PA) and alveolar to arterial difference (AaD) for O2 and CO2, by a mass-spectrometer has been implemented. The program allows the determination of alveolar gas by different methods: 1. Bohr's equation (BE); 2. ideal alveolar air equation for O2 (IDO2); 3. end-tidal (ET); 4. by the Rahn's definition of 'mean alveolar gas', i.e., alveolar pressures are defined when instantaneous respiratory exchange ratio (IRQ) equals mean respiratory exchange ratio (MRQ). This automated technique has been used in 16 patients with chronic obstructive lung disease (COLD) and 15 patients with pulmonary embolism (APE). In both groups of patients it was always possible to find in each breath the point where IRQ = MRQ and therefore to measure AaD by RD. IDO2 was significantly lower than PAO2 by the other methods. Also ET values of O2 and CO2 were significantly different from RD and BE in both groups of patients, however the difference was consistently higher in COLD patients. The different shape of the expirograms (steeper expirograms in COLD) is responsible for this different result. RD and BE AaD characterize gas exchange more precisely than ET, because the contribution of high VA/Q units is also evaluated. This is particularly important in COLD patients. Consideration on dead space measurements are also reported both for COLD and APE patients. In conclusion this automated technique provides the assessment of gas exchange for the use in clinical respiratory physiology and for the monitoring of gas-exchange in critically ill patients.