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Display of the alveolar plateau of single-breath tests in "dilution index" format.

In 1949, Fowler (J. Appl. Physiol. 2: 283-299) advocated calculation of a "dilution index" from data of the alveolar plateau of single-breath tests; the calculation provides an estimate of the dilution of resident gas in the lung that gave rise to the observed concentrations. In this communication, we show that the calculation can be applied to conventional single-breath tests where O2 is inhaled by air-breathing persons, and we illustrate the principle with vital capacity breaths of a mixture that contained a low concentration of neon. The dilution was approximately 3:1 in young subjects (20-30 yr), as if a vital capacity of 6 liters were mixed with a residual volume of 2 liters. The dilution was less, 2:1, in older subjects (56 yr) and tended to become as low as 1:1 during emptying of the closing volume. In addition to being more informative, the dilution index format allows common sense comparison of alveolar plateau levels and slopes when single-breath tests are done by various methods.

Adult↗

[Effect of low lung volume ventilation on the relative proportions of carbon monoxide partial ductances (author's transl)].

Lacoste has shown the interest of determination of overall ductance of CO and partial expired alveolar ductance and arterio-alveolar partial ductances in the assessment of the efficacy of gaseous exchanges in the lung. DuCO was, by definition, the product : DuACO X DuaCO, the increase in partial ductance may theoretically compensate reduction in the other, the overall ductance then remains normal. This theory was verified studying the effects of low lung volume ventilation. Under these conditions, the dead space series becomes reduced and the DuACO should increase at the same rate, for ventilation occurs at the level of the closing volume. The inspired air is then directed preferentially towards the lung apices. These artificial changes in distribution of ventilation should produce a reduction in DuaCO. The measurements carried out confirmed these theories during low lung volume ventilation ; whereas the differences observed in overall ductance were not significant, those observed on partial ductance were very definitely significant. It appears that isolated measurement of overall ductance is insufficient and may lead to misdiagnosis of a change in the lung exchanges.

Adult↗

Mucus secretion by tracheas of ferret and dog.

Mucus secretion, stimulated by nerve excitation or drugs, was measured from the ferret trachea in vitro by two methods: from the whole trachea, and compared with the volume of submucosal glands estimated from histological sections; and from mounted segments of trachea, by displacement of tantalum dust applied to the epithelium and compared with changes in tissue volume estimated by probing the epithelial surface between hillocks. Maximal secretion rates (2-3 microliters X min-1 X cm-2) with tracheal segments were 5-6 times greater per unit area than those with the whole trachea. During secretion the tissue shrank by a volume close to that of the secretion. Similar experiments with the hillock method and dog trachea in vivo gave variable results. Although the ferret submucosal glands can secrete 0.7-5.4 times their volume per minute, any change in tracheal resistance to airflow would be rather small.

Animals↗

Lung volumes in man immersed to the neck: dilution and plethysmographic techniques.

Previous studies of lung volumes during immersion have utilized dilution techniques for residual volume. We have compared lung volumes obtained by the use of a dual inert gas dilution technique with those determined by the Boyle's law technique in a plethysmograph designed to allow measurements in air and submersed to the neck in water. Both techniques gave similar results dry, but during immersion the dilution residual volume (RV) was 0.200 liter (16%) lower than the plethysmographic value (P greater than 0.001), which suggests that there is a significant amount of gas trapping during immersion due to breathing at low lung volumes and the central shift of blood. The unchanged RV due to hydrostatic force on the chest wall is balanced by the tendency to increase RV due to vascular congestion, which increases closing volume and stiffens the lung to compression.

Adult↗

Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats.

Water-free Na+ storage may buffer extracellular volume and mean arterial pressure (MAP) in spite of Na+ retention. We studied the relationship among internal Na+, K+, water balance, and MAP in Sprague-Dawley rats, with or without deoxycorticosterone-acetate (DOCA) salt, with or without ovariectomy (OVX). The rats were fed a low-salt (0.1% NaCl) or high-salt (8% NaCl) diet for 5 weeks. DOCA salt increased MAP (161+/-14 versus 123+/-4 mm Hg; P<0.05), and DOCA-OVX salt increased MAP further (181+/-22 mm Hg; P<0.05). DOCA salt increased the total body Na+ by &40% to 45%; however, water-free Na+ retention by osmotically inactive Na+ storage and by osmotically neutral Na+/K+ exchange allowed the rats to maintain the extracellular volume close to normal. DOCA-OVX salt rats showed similar Na+ retention. However, their osmotically inactive Na+ storage capacity was greatly reduced and only partially compensated by neutral Na+/K+ exchange, resulting in greater volume retention despite similar Na+ retention. For every 1% wet weight total body water gain, MAP increased by 2.3+/-0.2 mm Hg in DOCA salt rats and 2.5+/-0.3 mm Hg in DOCA-OVX salt rats. Because water-free Na+ retention buffered total body water content by 8% to 11% wet weight, we conclude that this internal Na+ escape buffered MAP. Extrarenal Na+ and volume balance seem to play an important role in long-term volume and MAP control.

Animals↗

[Study of lung symptomatology and lung function in steelworkers].

We have examined 272 steelworkers, aged 45 to 55 years, by means of the ECSC-questionnaire and the following lung function tests: vital capacity (VC) and forced expiratory volume in one second (FEV1), residual volume (RV) and total lung capacity (TLC); maximal expiratory flow rates (Vmax, Vmax 50, Vmax 75); specific airways conductance (SGaw); slope of the N2 alveolar plateau after oxygen inhalation (delta N2) and the bolus closing volume (CV). The influence of smoking on respiratory symptoms and lung function was confirmed. In order to assess the influence of occupational pollution a sample of 163 workers was classified according to smoking habits and workplace (either LD-steelplant and continuous casting department, or sheet rolling mill). In the nonsmokers group we found that the workers from the steelplant and continuous casting department (n = 12) had a significantly lower SGaw value (delta = 0.065 cm H2O-1 . s-1, p less than 0.01) and a significantly higher CV value (delta = 4.5% VC, p less than 0.05) than the workers from the sheet rolling mill (n = 11). Differences in FEV1/VC, Vmax 50 and Vmax 75 were not significant, but were also consistent with a slight airflow obstruction in the steelplant workers. In the smokers (n = 99) and exsmokers (n = 41) groups no differences existed between both working categories. Our results suggest that nonsmoking workers from the steelplant and the continuous casting department have undergone moderate, but detectable effects from industrial pollution. These effects are probably masked by those of tobacco in smokers and exsmokers.

Air Pollutants, Occupational↗

"Sensitive tests" are poor predictors of the decline in forced expiratory volume in one second in middle-aged smokers.

In 1978, we studied 3 groups of steelworkers 45 to 55 yr of age who were all smokers: "obstructive" smokers (OS) with a FEV1/VC less than 66.6% (59.8% in average) (n = 37), smokers with "small airways disease" (SAD) and an abnormal closing capacity and/or slope of phase III (delta N2) but normal FEV1/VC (n = 32), and "resistant" smokers (RS) with normal functional indices (n = 36). Smokers with SAD had a lower (p less than 0.05) FEV1/VC (71.7%) than did RS (74.9%). We studied again 6 yr later about 85% of survivors in each group. Analysis of variance showed that FEV1 decreased significantly (p less than 0.001) only in OS (from 2.67 to 2.46 L). In RS and smokers with SAD, FEV1 declined from 3.34 to 3.26 L and from 2.95 to 2.85 L, respectively (p greater than 0.05). In all 3 groups, delta N2 increased (p less than 0.001) from 0.77 to 1.30% N2/L in RS, 1.41 to 2.43% N2/L in smokers with SAD, and 2.22 to 4.20% N2/L in OS. A multivariate analysis showed that the initial N2 explained about 30% (p less than 0.001) of the decline in FEV1 in OS, but only 10% (p less than 0.001) in the 3 groups together. In fact, the link between delta N2 and fall in FEV1 was restricted to OS. Closing volume and maximal expiratory flow rates were not related to decline in FEV1. The link between uneveness of ventilation and subsequent loss of FEV1 is of physiopathologic interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Forced Expiratory Volume↗

Assessment of time-volume and flow-volume components of forced vital capacity. Measurement with spirometry, body plethysmography and respiratory inductive plethysmography in nonsmokers and smokers.

The purpose of this investigation was to assess the effectiveness of the time-volume and flow-volume components of the forced vital capacity measured by simultaneous spirometry, respiratory inductive plethysmography, and body plethysmography in detecting small airway disease. Spirometry measured the exit of gas from the lungs, whereas body plethysmography measured both the exit of gas and alveolar gas compression. Respiratory inductive plethysmography, which reflected change in thoracic volume, provided semi-quantitative data f both gas exit and alveolar gas compression which generally lay between spirometry and body plethysmography. In nine nonsmokers and 12 smokers (six with small airway disease as defined by abnormal closing volumes and alveolar uniformity), analysis of forced vital capacity revealed that the only test which differentiated nonsmokers from smokers was the higher spirometric estimation of maximum expiratory flow measured at 25 percent VC in nonsmokers. Combining flow measure at the mouth with volume referenced to change in alveolar gas volume as measured by body or respiratory inductive plethysmography did not differentiate nonsmokers from smokers. Moment analysis performed of forced vital capacity with all of the three devices did not distinguish nonsmokers from smokers. The data in this study and a review of other investigations indicate that the time-volume and flow-volume components of the forced vital capacity on air breathing are not very sensitive in detecting early lung disease in smokers.

Adolescent↗

Effects of immersion in water and changes in intrathoracic blood volume on lung function in man.

1. In healthy, normal subjects simultaneous peripheral venous occlusion of all four limbs caused a small but significant increase in vital capacity (VC) and single-breath carbon monoxide transfer factor (DLCO) without significantly changing total lung capacity (TLC), residual volume (RV), pulmonary gas flow or pulmonary compliance. 2. Immersion in water to the neck resulted in a small but significant fall in VC, FEV 1.0/FVC and TLC, and a rise in DLCO, but flow/volume curves and 'closing volume' were unchanged. Peripheral venous occlusion during immersion only significantly increased VC and DLCO; pulmonary compliance and flow/volume curves did not alter significantly. 3. It is concluded that peripheral venous occlusion produces these effects by altering intrathoracic blood volume. Water immersion reduces TLC, mainly from the hydrostatic pressure, and VC is reduced from both the hydrostatic pressure and the increase in intrathoracic blood volume consequent on immersion. The increase in DLCO is due, almost entirely, to the increase in intrathoracic blood volume.

Adult↗

Small airways function and molecular markers in exhaled air in mild asthma.

BACKGROUND: Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (Feno) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of Feno and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test. METHODS: Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second >80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. Feno was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (deltaN2) and the closing volume (CV) were assessed from the single breath washout curve. RESULTS: The median Feno level was 30.4 ppb (range 10.1-82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6-2.7), and the mean (SD) deltaN2 value was 1.1 (0.4)% N2/l. Feno was positively associated with deltaN2 (r(s) = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV1% predicted (rs= -0.58; p = 0.017) and CV as a percentage of vital capacity (rs= 0.58; p = 0.019). CONCLUSIONS: Feno and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.

Adult↗

Automatisation of the single-breath nitrogen washout test.

The paper presents a computer-based system for performance and analysis of the single-breath nitrogen washout test (Sb-N2 test). A pneumotachometer and a rapid gas analyser are used for volume flow rate and nitrogen fraction measurements. The data are acquired and analysed by a PDP-11/34 computer. Several sources of measurement errors are considered. An algorithm is proposed to reduce errors in flow measurements due to viscosity variation in respired air. The algorithm for closing volume (CV) detection and calculation of other Sb-N2 parameters is developed from 50 tracings of 18 subjects. The CV is obtained by an iterative linear fitting of the later half of the Sb-N2 curve. Comparisons between computer and hand measurements of three trained readers show good correlations (r = 0.87, 0.93, 0.91). The variability of computer CV measurements was comparable with that of the hand reader with the lowest variance. The coefficient of variation of residual volume and slope of alveolar plateau measurements are apparently reduced. The results demonstrate the adequacy and convenience of using the computer to analyse the Sb-N2 test and indicate that the automation allows for reduction of experimental errors and of test parameter variabilities.

Adult↗

Regulation of end-expiratory lung volume during exercise.

We determined the effects of exercise on active expiration and end-expiratory lung volume (EELV) during steady-state exercise in 13 healthy subjects. We also addressed the questions of what affects active expiration during exercise. Exercise effects on EELV were determined by a He-dilution technique and verified by changes in end-expiratory esophageal pressure. We also used abdominal pressure-volume loops to determine active expiration. EELV was reduced with increasing exercise intensity. EELV was reduced significantly during even mild steady-state exercise and during heavy exercise decreased an average of 0.71 +/- 0.3 liter. Dynamic lung compliance was reduced 30-50%; EELV remained greater than closing volume. Changing the resistance to airflow (via SF6-O2 or He-O2 breathing) during steady-state exercise changed the peak gastric and esophageal pressure generation during expiration but did not alter EELV; breathing through the mouthpiece produced similar effects during exercise. EELV was significantly reduced in the supine position. With supine exercise active expiration was not elicited, and EELV remained the same as in supine rest. With CO2-driven hyperpnea (7-70 l/min), EELV remained unchanged from resting levels, whereas during exercise, at similar minute ventilation (VE) values EELV was consistently decreased. At the same VE, treadmill running caused an increase in tonic gastric pressure and greater reductions in EELV than either walking or cycling. We conclude that both the exercise stimulus and the resultant hyperpnea stimulate active expiration and a reduced FRC. This new EELV is preserved in the face of moderate changes in mechanical time constants of the lung. This reduced EELV during exercise aids inspiration by optimizing diaphragmatic length and permitting elastic recoil of the chest wall.

Adult↗

High-frequency jet ventilation during oleic-acid induced pulmonary oedema.

In oleic acid-induced pulmonary oedema (OAPO) sequential intrapulmonary fluid accumulation occurs leading to different expiratory flow pattern in dependent lung regions. The potential effects on efficacy of high-frequency jet ventilation (HFJV, f = 3 Hz, I: E = 0.43, FiO2 = 0.4) were studied and compared with continuous positive pressure ventilation (CPPV, f = 12-18/min, I:E = 0.5, TV = 12 ml/kg, PEEP = 0.5 kPa, FiO2 = 0.4) in a dog model of OAPO. In the control state (lung-healthy dogs), 15 min after oleic acid lung injury (interstitial oedema, period I) and 60 min after onset of OAPO (alveolar oedema, period II), gas exchange, lung volumes, compliance, resistance and haemodynamics were measured. The course of lung oedema was determined indirectly by means of washout curves of helium (foreign gas bolus-test, FGB) and nitrogen (single breath-test for oxygen, SBO2). During control, there were no significant differences between the HFJV-group (n = 7) and the CPPV-group (n = 6) by virtue of gas exchange, lung volumes and haemodynamics. During period I, PaO2 decreased significantly both with HFJV (p less than 0.01) and CPPV (p less than 0.05), being lower in the HFJV-group (p less than 0.05). PaCO2, pulmonary and haemodynamic parameters were unchanged. Onset of phase IV of the alveolar plateau (closing volume CV) occurred significantly earlier (p less than 0.05) in all animals. Impaired ventilation of dependent lung regions, increased maldistribution of intrapulmonary gas and VA/Q-mismatching may be the underlying mechanisms for lower efficacy of HFJV during interstitial lung oedema. In period II, pulmonary and cardiocirculatory parameters had changed significantly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pulmonary function in obese patients scheduled for jejuno-ileostomy.

Preoperative pulmonary parameters were evaluated in 37 extremely obese but otherwise healthy patients. They were on average 100.9% overweight. X-ray of the chest, electrocardiograms, and residual volume, vital capacity, total lung capacity, maximum breathing capacity, forced expired volume in 1 second, and related ratios were all within the normal range. The alveolar-arterial oxygen gradient and the arterial carbon dioxide tension were also within the normal range. The only abnormal finding was a substantially reduced arterial oxygen tension. It is suggested that the measurement of functional residual capacity, closing volume, and the slope of the alveolar plateau (phase III in the single breath nitrogen washout technique) might give more valuable information.

Adult↗

Automated gamma knife radiosurgery treatment planning with image registration, data-mining, and Nelder-Mead simplex optimization.

Gamma knife treatments are usually planned manually, requiring much expertise and time. We describe a new, fully automatic method of treatment planning. The treatment volume to be planned is first compared with a database of past treatments to find volumes closely matching in size and shape. The treatment parameters of the closest matches are used as starting points for the new treatment plan. Further optimization is performed with the Nelder-Mead simplex method: the coordinates and weight of the isocenters are allowed to vary until a maximally conformal plan specific to the new treatment volume is found. The method was tested on a randomly selected set of 10 acoustic neuromas and 10 meningiomas. Typically, matching a new volume took under 30 seconds. The time for simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and 8/10 meningiomas, the automatic method found plans with conformation number equal or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10 meningiomas, both overtreatment and undertreatment ratios were equal or better in automated plans. In conclusion, data-mining of past treatments can be used to derive starting parameters for treatment planning. These parameters can then be computer optimized to give good plans automatically.

Automation↗

Lung recoil and gas trapping during oxygen breathing at low lung volumes.

If airways are closed at lung volumes less than the closing volume (CV), there should be correlations among 1) the volume of trapped N2 (VTN) during N2-washout performed below CV, 2) the increase in static lung recoil pressure (delta P) while breathing below CV after denitrogenation compared with breathing air (due to absorption atelectasis distal to closed airways), and 3) the CV. Static inspiratory pressure-volume (PV) curves and CV were measured in 18 seated normal volunteers (ages 24-48 yr). Subjects then breathed air for 30 s and O2 for 2.5 min at RV + 0.6 liter (LVB-air), and an inspiratory PV curve and VTN were determined. While still breathing O2, the subjects repeated the 3 min of low-volume breathing (LVB-O2). There was a significant (P less than 0.001) delta P with LVB but no difference between delta P (LVB-air) and delta P (LVB-O2). CV was not related to VTN or to either delta P. VTN was not related to delta P (LVB-O2)--delta P (LVB-air) nor to delta P (LVB-air), but was related to delta P (LVB-O2). Evidence of airway closure could not be demonstrated in all subjects by LVB and when present showed no correlation with CV.

Adult↗

Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function.

We have assessed the uniformity of regional ventilation during tidal breathing using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

Adult↗

Airway closure, atelectasis and gas exchange during general anaesthesia.

Airway closure and the formation of atelectasis have been proposed as important contributors to impairment of gas exchange during general anaesthesia. We have elucidated the relationships between each of these two mechanisms and gas exchange. We studied 35 adults with healthy lungs, undergoing elective surgery. Airway closure was measured using the foreign gas bolus technique, atelectasis was estimated by analysis of computed x-ray tomography, and ventilation-perfusion distribution (VA/Q) was assessed by the multiple inert gas elimination technique. The difference between closing volume and expiratory reserve volume (CV-ERV) increased from the awake to the anaesthetized state. Linear correlations were found between atelectasis and shunt (r = 0.68, P < 0.001), and between CV-ERV and the amount of perfusion to poorly ventilated lung units ("low Va/Q", r = 0.57, P = 0.001). Taken together, the amount of atelectasis and airway closure may explain 75% of the deterioration in PaO2. There was no significant correlation between CV-ERV and atelectasis. We conclude that in anaesthetized adults with healthy lungs, undergoing mechanical ventilation, both airway closure and atelectasis contributed to impairment of gas exchange. Atelectasis and airway closure do not seem to be closely related.

Adult↗