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Measurement of temporal changes in DLSBCO-3EQ from small alveolar samples in normal subjects.

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of the single-breath diffusing capacity in asthma and cystic fibrosis.

To explain why the single-breath carbon monoxide diffusing capacity (Dsb) was, on the average, elevated in 163 asthmatic subjects and 175 patients with cystic fibrosis, we simulated this elevation in ten normal subjects by having them perform the test for Dsb through an inspiratory obstruction. This resulted in an 18 percent increase in Dsb corrected for pulmonary volume. Inhalation of a bronchodilator drug was associated with relief of obstruction and a fall in the corrected Dsb in 31 asthmatic subjects but did not change either the obstruction or the corrected Dsb in 17 patients with cystic fibrosis. We suggest that elevated Dsb in asthma and cystic fibrosis is partly due to maximal inspiration against obstructed airways. This requires abnormally negative intrathoracic pressures, increasing the pulmonary capillary blood volume, and, thereby, increasing the Dsb.

Adolescent↗

Time-related decrease in diffusion capacity in HIV-infected patients with impaired immune function.

The purpose of this study was to investigate acute and time-related changes in lung function, i.e. forced expiratory volume in 1 second (FEV1), vital capacity (VC) and transfer factor (KCO) in HIV-infected patients with CD4 cell counts less than 400 x 10(6)/l. 66 males with no history of HIV-related pulmonary symptoms participated in a prospective lung function study for 9 months with 3-month intervals between examinations. 15/66 patients (23%) developed acute pulmonary symptoms, i.e. dyspnea (n = 12), cough (n = 13), fever greater than 38 degrees C (n = 13) and interstitial infiltrates on the X-ray (n = 9). Among the 51 asymptomatic patients, a significant time-related decrease in KCO (median decrease of 7%) was found, whereas no significant change in FEV1 or VC was observed during the study. Baseline KCO, i.e. KCO at entry, was found to be significantly higher in the asymptomatic patients (102% predicted (pred.) than in those patients who developed pneumonia (88% pred.). Development of pulmonary symptoms was both followed by a significant decrease in KCO (median decrease 17%), FEV1 and VC. We therefore conclude that HIV-infected patients with impaired immune function have in the absence of pulmonary symptoms a decrease in KCO. In case of pneumonia an acute decrease in both KCO, FEV1 and VC occurs.

Adult↗

High resolution computed tomography and lung function in asbestos-exposed workers with normal chest radiographs.

Asbestos-exposed persons with normal chest radiographs can demonstrate parenchymal abnormalities on high resolution computed tomography (HRCT). We reviewed the HRCT, clinical presentation, and results of pulmonary function tests in 169 asbestos-exposed workers with normal chest radiographs (ILO less than 1/0). The HRCT was normal or near normal in 76 subjects (Group 1), abnormal but indeterminate for asbestosis in 36, and abnormal and suggestive of asbestosis in 57 (Group 2). The indeterminate subjects were excluded from further analysis. The subjects in Groups 1 and 2 were not significantly different in their duration of asbestos exposure, latency, smoking history, or in measurements of airflow obstruction (FEV1/FVC% and %FEV1). Both the vital capacity percent predicted and diffusing capacity percent predicted were significantly lower in the abnormal subjects (Group 2) than in the normal subjects (Group 1) (79.0 versus 86.2, p = 0.005; 78.2 versus 87.1, p = 0.024; independent t test). We conclude that in asbestos-exposed subjects with normal chest radiographs, HRCT can identify a group of subjects with significantly reduced lung function indicative of restrictive lung disease when compared with a group with normal or near-normal HRCT.

Adult↗

Pulmonary function evaluation of the lung resection candidate: a prospective study.

In the past, preoperative pulmonary function abnormalities have identified a group of patients in danger of postoperative cardiorespiratory morbidity and mortality. We selected a group of 56 patients, each of whom had a lung mass and had demonstrated significant abnormalities in screening pulmonary function. By using temporary unilateral pulmonary artery occlusion and quantitative macroaggregate lung scanning, we then studied these patients for split pulmonary function. Those patients whose noncancerous lung had a calculated forced expiratory volume in 1 sec greater than 800 ml and a circulation that could accommodate all of the cardiac output without producing hypertension or arterial hypoxemia were offered thoracotomy. Of the 56 patients, we judged 6 to be physiologically inoperable and did not offer surgery. Another 4 patients were not offered surgery, and 4 refused surgery. Forty-two patients underwent surgical exploration-of these, 17 then had a pneumonectomy and 13, a lobectomy. Of the 30 patients resected, 6 died in surgery (4 from respiratory insufficiency). These cardiorespiratory mortality rates (neumonectomy, 17.6 per cent; lobectomy, 7.7 per cent) are lower than those reported previously when patients had equivalent pulmonary function abnormality. A follow-up of 49 of 56 patients revealed that 59 per cent of the patients undergoing either pneumonectomy or lobectomy were still living 1 to 3 years after the resection. Our results suggested that the preoperative testing of split pulmonary function permitted an attempt at surgery in patients who might otherwise be considered inoperable by history, physical examination, screening pulmonary function tests alone.

Aged↗

Compensatory lung growth occurs in adult dogs after right pneumonectomy.

We investigated the structural changes in the left lung of five adult male foxhounds 5 mo (n = 2) or 16 mo (n = 3) after right pneumonectomy (approximately 54% of lung resected) and five sex- and age-matched foxhounds 15-16 mo after right thoracotomy without pneumonectomy. Lungs were fixed by intratracheal instillation of glutaraldehyde and analyzed by standard morphometric techniques. After right pneumonectomy, volume of the left lung increased by 72%. Volumes of all septal structures increased significantly and were more pronounced at 5 than at 16 mo after pneumonectomy. At 16 mo, the relative increases in volume with respect to the control left lung were as follows: epithelium 73%, interstitium 100%, endothelium 55%, and capillary blood volume 43%. Surface areas of alveoli and capillary increased significantly by 52% and 34%, respectively. At 5 mo after pneumonectomy, harmonic mean thickness of the tissue-plasma barrier was significantly greater but at 16 mo it was not different from controls. There was a significant increase in diffusing capacity for oxygen (33% above controls) at 16 mo after pneumonectomy. These data suggest that, in contrast to previous findings after left pneumonectomy, compensatory lung growth does occur in adult dogs after resection of > 50% of lung.

Animals↗

[The value of lung perfusion scintigraphy in radiation pneumonitis in comparison with the diffusing capacity DLCO].

The value of lung perfusion scintigraphy (Tc99m) and lung diffusing capacity are compared with references to early detection of radiogenic pneumonitis. Perfusion scintigraphy completed by diffusing capacity is excellent suitable for early detection. Risk cases are recognized up to 40 days earlier than by X-ray. Severity of radiogenic pneumonitis can be diminished remarkable by prevention therapy.

Breast Neoplasms↗

Genomewide linkage analysis identifies novel genetic Loci for lung function in mice.

RATIONALE: Pulmonary function, including lung volumes and compliance, may be genetically determined, but few genetic polymorphisms have been identified that control these traits. We used an experimental approach and performed the first whole genome scan for pulmonary function in mice. OBJECTIVES AND METHODS: To identify novel chromosomal regions contributing to lung function, quantitative trait locus linkage analysis was applied in N(2) backcross and F(2) intercross mice derived from two inbred strains-C3H/HeJ and JF1/Msf-with extremely divergent phenotypes. MAIN RESULTS: Significant linkages to total lung capacity with LOD (logarithm of the odds) scores up to 6.0 were detected on chromosomes 15 and 17, to dead space volume and lung compliance on chromosomes 5 and 15 (LOD scores higher than 4.0), to lung compliance also on chromosome 19 (LOD score of 5.8), and to diffusing capacity on chromosomes 15 and 17 (LOD scores up to 5.0). The region of interest on chromosome 17 near D17Mit133 contains a syntenic region to human chromosome 6q27, which was recently identified to be linked to lung function in humans. The identified intervals harbor valuable candidate genes, such as the relaxin1 and transforming growth factor beta receptor 3 gene, which revealed missense polymorphisms between the parental strains. CONCLUSION: The study provides evidence for linkage of different measures of lung function on murine chromosomes 5, 15, 17, and 19 and suggests novel candidate genes that may also affect the expression of human pulmonary function.

Animals↗

Pulmonary effect of amiodarone in patients with heart failure. The Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) Investigators (Veterans Affairs Cooperative Study No. 320).

OBJECTIVES: The purpose of this study was to evaluate the pulmonary effects of amiodarone in patients with heart failure, in those with chronic obstructive pulmonary disease (COPD) and in those undergoing a surgical procedure. BACKGROUND: Amiodarone has been known to cause pulmonary complications; especially in those with COPD and in those undergoing a surgical procedure. METHODS: Patients receiving vasodilator therapy for congestive heart failure were prospectively randomized to placebo or amiodarone at 800 mg/day for 14 days, 400 mg/day for 50 weeks and then 300 mg/day thereafter. Chest X-ray film and pulmonary function tests with diffuse capacity of carbon monoxide (DLCO) were obtained at baseline and annually. The power to detect a 20% difference in DLCO at 1 year exceeded 90% in all patients and in those with COPD (two-sided alpha = 0.05). The sample allowed a 75% power to detect pulmonary complications (1% vs. 5%) between the two treatment groups. RESULTS: There was no difference in baseline characteristics between patients randomized to amiodarone (n = 269) or placebo (n = 250). The DLCO measurements at randomization were 18.3 +/- 6.9 and 17.7 +/- 7.6 ml/min per mm Hg for the amiodarone and placebo groups, respectively (p = 0.3). At 1 and 2 years, DLCO measurements were 17.7 +/- 7.0 and 18.3 +/- 7.7 ml/min per mm Hg for the amiodarone group and 17.9 +/- 7.2 and 18.2 +/- 7.2 for the placebo group, respectively. There were no significant differences between the groups, with corresponding p values of 0.73 ad 0.96 at years 1 and 2, respectively. Among patients with COPD, DLCO measurements at randomization were 17.9 +/- 6.7 and 15.8 +/- 6.8 ml/min per mm Hg for the amiodarone and placebo groups, respectively. At years 1 and 2, DLCO measurements were 16.6 +/- 7.8 and 17.8 +/- 9.5 ml/min per mm Hg for the amiodarone group and 16.5 +/- 6.6 and 16.3 +/- 7.0 ml/min per mm Hg for the placebo group, with corresponding p values of 0.95 and 0.48, respectively. There was no difference in survival free of noncardiac or perioperative deaths between patients assigned to amiodarone or placebo. Pulmonary fibrosis was diagnosed in four patients (1.1%) treated with amiodarone and in three patients (0.8%) receiving placebo. CONCLUSIONS: Our study shows that amiodarone can be safely used, with an acceptable pulmonary toxicity, in patients with heart failure.

Aged↗

Hemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans.

OBJECTIVE: The objective of this study was to evaluate the exercise capacity of subjects given an autologous transfusion or a polymerized bovine hemoglobin solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin-based oxygen carrier (HBOC-201). METHODS: Six normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery catheter was inserted in each subject before serial cardiac output and pulmonary function tests and phlebotomy of 15% blood volume (750 ml plus another 250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin). This was followed by isovolemic hemodilution with Ringer's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity) were done before phlebotomy and at approximately 45 minutes after the autologous transfusion or HBOC-201 infusion. RESULTS: Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201 (which paralleled plasma HBOC-201 levels) than during autologous transfusion periods. Oxygen use (uptake) and carbon dioxide production at rest were greater during the HBOC-201 infusion than during the autologous transfusion period. The half-life of HBOC-201 was about 23 hours. CONCLUSIONS: Exercise capacity and diffusion capacity were similar after HBOC-201 and autologous transfusion. HBOC-201 resulted in greater oxygen (or uptake) and carbon dioxide production and lower lactate levels compared with autologous transfusion. Under the conditions of the study, the physiologic effects of 1 gm bovine hemoglobin of HBOC-201 were similar to 3 gm human hemoglobin from autologous transfusion.

Adult↗

Reduction of lung diffusion for carbon monoxide in patients with lung carcinoma.

A retrospective study to investigate the prevalence and severity of impairment of the lung diffusing capacity for carbon monoxide (DCO) in patients with lung carcinoma was done using a case-control matched design. A group of 70 patients with the histologic diagnosis of lung carcinoma was matched on a one-to-one basis with a group of patients with chronic bronchitis and/or pulmonary emphysema (COPD); the matching was done based on the FEV1 within 10 percent of each other for all pairs. The groups of lung carcinoma and COPD had similar history of smoking consumption and pulmonary function, except that the Dco was reduced in the carcinoma group (mean +/- SD: 56.4 +/- 12.8 percent of predicted) compared with the control group (64.4 +/- 20.1 percent of predicted; p = 0.0027). Among the carcinoma group, only one patient had a Dco above 75 percent of the predicted value, while in the control group, 22 patients had a Dco above 75 percent of predicted values. It appears that Dco is more frequently reduced in patients with lung carcinoma than in a group of patients with similar FEV1 and smoking history who have chronic bronchitis and/or emphysema but had no evidence of lung carcinoma. We speculate that the reduction of Dco in patients with lung carcinoma could be due to the concurrent presence of pulmonary emphysema.

Aged↗

A small amount of inhaled nitric oxide does not increase lung diffusing capacity.

The aim of the present study was to determine: 1) whether 40-50 ppm nitric oxide (NO) increases diffusing capacity of the lung for NO (D(L,NO)) and carbon monoxide (D(L,CO)), membrane diffusing capacity for CO (D(m,CO)) and pulmonary capillary blood volume (V(c)); 2) the actual number of tests required to provide a reasonable estimate of D(L,NO), D(L,CO), D(m,CO) and V(c); and 3) repeatability of these parameters using the single-breath D(L,NO)-D(L,CO) method. In total, 31 subjects performed five single-breath hold manoeuvres at rest, inhaling 43+/-3 ppm NO together with a standard diffusion mixture. D(L,NO) (D(m,CO)) remained unchanged from the first to fifth trial. However, compared with the first trial, D(L,CO) and V(c) had decreased by the fourth (-4+/-5%; 95% confidence interval (CI) = -5- -2%) and third trial (-5+/-7%; 95% CI = -7- -2%), respectively. Repeatability over five trials was 17, 3 and 7 mL.min(-1).mmHg(-1) for D(L,NO), D(L,CO) and D(m,CO), respectively, and 13 mL for V(c) when D(m,CO) = D(L,NO)/2.42. In conclusion, nitric oxide inhaled during sequential single-breath manoeuvres has no effect on diffusing capacity of the lung for nitric oxide and, thus, membrane diffusing capacity for carbon monoxide. Since more than two and three trials will lower pulmonary capillary blood volume and diffusing capacity of the lung for carbon monoxide, respectively, the average value of only two properly performed trials is suggested.

Administration, Inhalation↗

A clinical evaluation of the Terumo Capiox SX18R hollow fiber oxygenator.

The Terumo Capiox SX18R is a commercially available, low prime, reverse phase, hollow fiber membrane oxygenator. The oxygenator consists of a 1.8 m2 microporous polypropylene hollow fiber bundle, a 2200 cm2 tubular stainless steel heat exchanger, and an open hard shell venous reservoir with integral cardiotomy filter. The Terumo Capiox SX18R oxygenator was evaluated to determine its clinical oxygenating performance. Blood samples were drawn from 25 patients yielding 114 data points. The following parameters were recorded: blood flow, cardiac index, gas flow, gas to blood flow ratio, and oxygen fraction. Samples were assayed for hematocrit, hemoglobin, arterial and venous blood gas values, and venous oxygen saturation. The data and assay results were used to calculate arterial, venous, and membrane gas oxygen content, oxygen transfer, shunt fraction, and oxygen diffusion capacity. The Terumo Capiox SX18R oxygenator performed adequately with sufficient oxygen transfer reserve and carbon dioxide clearance under a variety of clinical conditions for the tested population.

Adult↗

Influence of ventilation, exercise, and body position on techniques for determining steady state diffusing capacity.

Three different methods of measuring steady state diffusing capacity were analysed regarding the effect of using either the physiological dead space for CO2 (DLCOss1), the measured anatomical dead space (DLCOss2), or an assumed anatomical dead space of the lungs (DLCOss3) for the determination of alveolar CO. The material consisted of 28 healthy men and 91 patients with various pulmonary diseases. DLCOss1 and DLCOss2 were compared in the total material (Section 1) using determinations both at rest and during exercise. As was expected DLCOss1 was almost always higher than DLCOss2. The difference between the two methods followed the curve that could be predicted from the mathematically obtained relation between DL, VD/VT, and fractional CO uptake, published by West in a diagram 1962. In determinations with a large sum of the latter two variables, DLCOss1 was highly dependent on the validity of the PaCO2 used. The validity of an end-tidal sample under different ventilatory patterns is investigated in Section 2 and the relation between DLCOss and alveolar ventilation in Section 3. Relative hypoventilation gave low values for DLCOss regardless of method. There was a rapid increase in DLCOss with increasing alveolar ventilation in the normal ventilation range. During hyperventilation DLCOss1, like FuCO, decreased with increasing ventilation. The composition of the end-tidal sample was frequently distorted under forced breathing with large VT so that erroneously high VDa and DLCOss2 were computed. Consequently, DLCOss2 appeared positively correlated to VE and VT over the whole ventilation range. On the other hand, the uncertainty of the size of the anatomical dead space--assumed in DLCOss3--at high flow rates in the bronchial tree reduces the usefulness of this method during pronounced hyperventilation.

Adult↗

A modeling approach to the estimation of CO diffusing capacity.

Standard methods of measuring the diffusing capacity of the lung for CO are susceptible to inhomogeneity and to errors in the performance of a breathing maneuver by the subject. A mathematical model of CO uptake from a single alveolar lung is developed and used as the basis for an estimation procedure to measure both lung volume and diffusing capacity during a rebreathing maneuver. Because this estimator-model uses the exact flow generated by the subject, errors in such factors as breath-hold times or depth of inspiration do not result. The estimator-model was tested using simulated data from uniformly and nonuniformly ventilated models and was found to be insensitive to noise and inhomogeneity, in contrast to the diffusing capacity of the lungs for CO (exhaled). The estimator-model makes greater use of the available data than traditional methods by utilizing both the slope of the alveolar plateaus for CO and the relative heights of such plateaus in a rebreathing experiment.

Capillaries↗

[Pulmonary gas exchange after myocardial infarction in the late period of recovery. I. Investigation at rest].

In the late period of recovery after myocardial infarction (13-25 months p. infarctum) lung function of 23 patients was examined at rest. Spirometric values and parameters of pulmonary gas exchange showed alterations caused by pathological left ventricular function. Arterial Po2 was slightly decreased (chi=74.5 +/- 5.9 Torr), AaDo2 (chi=33.6 +/- 7.7 Torr) and aADco2 (chi=8.6 +/- 3.7 Torr) were increased. Pathological changes of arterial Pco2 (chi=40.6 +/- 2.5 Torr) were not observed. Mixed venous Po2 and cardiac output in 9 patients suggested cardiac failure. In a number of pulmonary parameters measured at rest correlations could prove a dependence on the patients physical work capacity.

Carbon Dioxide↗