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When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

"Sensitive" and "conventional" lung function tests were compared in a group of 114 males, aged 35-55 years, including healthy non-smokers, asymptomatic smokers with normal spirometry, and smokers with chronic bronchitis with or without mild airflow limitation. In non-smokers, with the exception of a MEF vs. FEV1 correlation, "sensitive" and "conventional" tests were independent of each other. In asymptomatic smokers the phase III slope and the closing volume were significantly related to FEV1, RV/TLC and CO transfer factor. In smokers with chronic bronchitis all the "sensitive" tests were related to the "conventional" tests (with the exception of the total lung capacity). Hyperinflation and CO transfer impairment suggest that early emphysema may accompany mucus hypersecretion in smokers.

'Conventional' (lung volumes, airway conductance, CO transfer factor) and 'small-airway dysfunction' (single-breath N2 washout, maximal expiratory flows with air and a helium-oxygen mixture) tests were performed in a group of asymptomatic male ex-smokers (n = 20) with normal spirometry and compared to those of a similar group of middle-aged nonsmokers (n = 41). The study group had a mean life-long consumption of 13.2 +/- (SD) 8.8 pack-years and had stopped smoking 1-21 years ago, mean 7.3 +/- (SD) 5.8 years. Among the conventional tests, a minimal increase in residual volume and residual volume/total lung capacity ratio was found. Ex-smokers had a steeper phase III slope, a higher closing volume/vital capacity ratio, lower forced flows with air and a higher volume of isoflow, but neither difference between the group means was significant. There was a trend to more abnormal small-airway tests as a function of increased smoking, but only the correlation between percent of predicted closing volume and pack-years reached significance (r = +0.51, p less than 0.05). We conclude that small-airway function normalizes in the long term in most ex-smokers if they become asymptomatic, with less than 10% still having abnormal results years after they stopped smoking.

Mechanical impedance of the respiratory system was measured at 5, 10, 15 and 20 Hz in 47 healthy non-smokers, 20 ex-smokers and 51 current smokers. Besides the resistance and its frequency dependence, the compliance, the inertance and the resonant frequency of the respiratory system were computed using the assumption of a second order linear system. The data were normalized for sex, age and body height on the basis of correlations observed in non-smokers. No significant difference was found in ex-smokers. In smokers the resistance was significantly increased at all frequencies. However, it was normal in a number of subjects with abnormally low maximal expiratory flows. unlike maximal flows, forced oscillations indices were not correlated to tobacco consumption expressed in pack-years. The results do not indicate that impedance measurements breathing air may be specially useful for early detection of airway abnormalities.

An increase in H+ ions concentration by infusion of hydrochloric acid produces a reduction in lactacidemia. This phenomenon is a result of the inhibitory effect of acidosis on phosphofructokinase producing a diminution of intracellular glycolysis.

Two mini-peak flow meters, the Airmed (mini-Wright) and the Medicheck (Pulmonary Monitor), were assessed against a reference electronic spirometer (Spiromatic, based on a pneumotachograph, integrator and an Apple II computer) in a series of 10 healthy subjects and 20 patients with chronic obstructive lung disease. The devices to be tested were mounted in series with the reference instrument; each subject did five trials. It was found that the Airmed instrument overestimated the flows up to 9 l X s-1 (i.e. in patients, average difference 0.86 l X s-1, p less than 0.001; in healthy subjects, average difference 0.35 l X s-1, p less than 0.001). The correlation with the results of the reference instrument was high (r = 0.992) in healthy subjects, whose regression slope was less than unity (0.763). In patients the correlation was satisfactory (r = 0.974), and the slope close to 1 (1.05). The Medicheck overestimated slightly the results of patients (difference 0.17 l X s-1, p less than 0.01); in normal subjects the overestimation was present only below 10 l X s-1 and the difference with the reference instrument nonsignificant (average 0.19 l X s-1). The results were closely related to those of the reference spirometer in both healthy subjects (r = 0.960) and patients (r = 0.936). As for the first instrument the slope of the regression was below 1 in healthy subjects (0.751) and practically one (1.01) in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the actual sensitivity of forced expiration indices to changes in the resistance of peripheral airways, maximal expiratory flow-volume curves were obtained in 30 normal subjects breathing air and breathing an O2-Ne-SF6 gas mixture having the same density as air but a 45% larger viscosity. The measurements were made using a bag-in-box system to circumvent calibration problems, and the data were processed digitally. Besides the usual forced expiration indices, slope ratios, as described by Mead (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 156-165, 1978), and transit time indices were also computed. Breathing the viscous mixture, the largest changes were seen with the slope ratio measured at 60% forced vital capacity, followed by other slope ratios, the standard deviation of transit times, and maximal flows at low lung volumes. However, when the data were compared using the t test for paired measurements, the most significant changes were found with the forced expiratory volumes at 1 and 2 s, due to their low within-subject variability. These indices may therefore by considered as the most suitable for detecting changes in individuals.

In order to define the minimal frequency response requirements for spirometric measurements, the harmonic content of forced expiratory flow has been assessed in 63 healthy subjects. The amplitude of the harmonics has been found to decrease almost exponentially with increasing frequency. On the average, the cumulated frequency content beyond 10 Hz represented less than 5% of the total frequency content in men, and less than 3% in women. No significant difference has been observed between male smokers and non-smokers. The harmonic content per unit frequency has been found to be correlated to maximal flows at middle and low lung volumes and to maximal mid-expiratory flow up to 4 Hz. For FEV1, maximal flow at 75% of the vital capacity and, particularly, peak expiratory flow rate (PEFR), the correlations were still significant at quite higher frequencies. The data suggest that, except for PEFR, all these indices may be obtained with a good accuracy when the frequency response of the equipment is flat up to 5-7 Hz.

Using an integrated flow pressure-corrected body plethysmograph we obtained total lung capacities (TLC) derived from thoracic gas volumes measured at low, medium, and high panting frequencies in 10 healthy men and in 13 patients with chronic airflow obstruction before and after an aerosol of albuterol. Using a gastric balloon we also assessed gastric-to-mouth pressure ratios (delta Pga/delta Pm). In patients before albuterol, estimated TLC remained unchanged from low to medium and increased (not significantly) from medium to high frequency. Healthy subjects and patients after albuterol showed a significant decrease in TLC from low to medium panting frequencies, which persisted after correcting the data for abdominal gas compression using observed delta Pga/delta Pm. In patients after albuterol the results may be explained, at least in part, by intrathoracic airway compliance and mechanical inhomogeneity of the lung. In healthy subjects a remote possibility is the association of mechanical inhomogeneity and nonuniform pleural pressure.

We investigated two methods of decreasing the error on plethysmographic determinations of thoracic gas volume (TGV) related to cheeks movements during panting maneuvers: lowering gas density in the airways with an 80% He-20% O2 mixture and computing TGV from the in-phase component of the plethysmographic signal (TGVr). The methods were tested by measuring how TGV estimates varied when panting frequency was raised from 0.8 to 2.5 Hz during the same occlusion. The measurements were performed in 6 normal subjects and 12 patients with chronic bronchitis with and without cheeks support and when the airway was connected to an external device simulating an increased cheeks compliance. A small negative frequency dependence of TGV (delta TGV/delta f = -1.2 +/- 0.8%/Hz with cheeks support), most probably unrelated to upper airway walls, was found in normal subjects. Delta TGV/delta f was positive and algebraically larger in patients than in normals, reaching 2.2 +/- 3.4%/Hz without cheeks support and 11.8 +/- 8.0%/Hz with the additional cheeks. The latter value was only 20% smaller when computed on the basis of TGVr, demonstrating the limited usefulness of the phase-based correction. In contrast, breathing He-O2 decreased delta TGV/delta f to approximately 50% of its air value (P less than 0.01) and appears as an effective way to diminish the error in obstructive patients.

Deliberately lowering blood pressure facilitates middle ear surgery. However, bleeding can persist in spite of hypotension in some tachypneic patients. Fentanyl is a powerful morphinomimetic which decreases ventilatory frequency. This work studies the respiratory effects of fentanyl during spontaneous ventilation in 16 anesthetized patients. Their systemic blood pressure was decreased 40 per cent by trimetaphan. One single injection of fentanyl (0.0125 mg) reduced minute ventilation by 26 per cent, mean inspiratory flow rate (VT/T1) and T1/TTOT, but did not modify the pulmonary dynamic compliance. The acid-base balance parameters changed little toward respiratory alkalosis by trimetaphan and returned to their control values after the injection of fentanyl. Thus, a small dose of fentanyl can be combined with controlled hypotension during anesthesia and spontaneous ventilation without respiratory risk or an acid-base inbalance. With this dose, it has an efficient central influence to reduce the breathing frequency and can be used to lessen bleeding.

A model was developed to interpret the difference between volume variations at the mouth and at the chest observed by body plethysmography during inspiration in normal subjects breathing ambient air. The mechanical phenomena were characterized, as usual, by a time constant alpha, the product of airway resistance and alveolar gas compressibility. In contrast to other models, the change in temperature and water vapor pressure of the inspired gaswas not considered to be instantaneous but rather a first-order process characterized by a thermal time constant tau. Experimental curves obtained in eight subjects were analyzed by use of parameter estimation techniques. Thevalues of alpha were in agreement with those obtained by conventional plethysmography and tau averaged 63+/-24 ms. The results of additional experiments devised to test the physical meaning of the coefficients and the influence of neglected factors support the validity of the model. It was shown that tau cannot be neglected when breathing air at room temperature.

This study was aimed at determining the haemodynamic effects of various flow resistances in the anaesthetic breathing system in 15 patients under induced hypotension. The breathing pattern, arterial blood gases and haemodynamics were analysed during spontaneous breathing with three systems with different flow resistance as compared with a low-resistance control system. One was made up of a Digby-Leigh valve with an inspiratory resistance of 7 cmH2O l-1s and a high expiratory resistance of 25 cmH2O l-1s (DLS); the other two had an added inspiratory resistive load of 12 cmH2O l-1s (IRS1) and 25 cmH2O l-1s (IRS2) respectively. Whichever system was used, blood gases did not change. With DLS, pulmonary arterial and wedge pressures increased. With the two high inspiratory resistance systems, stroke volume (SV) increased and heart rate (HR) decreased. In six patients, SV was increased only with IRS2, whereas the increase seen with IRS1 in the other nine subjects disappeared with IRS2. It is concluded that the expiratory resistance should be as low as possible in order to avoid pulmonary haemodynamic consequences. An inspiratory resistive load, carefully adapted to each individual case, produced an increase in SV probably by enhancing the venous return. This latter effect could be beneficial in reducing bleeding during middle ear micro-surgery.

Ten mongrel dogs (mean weight: 27 kg) awake and with an implanted femoral catheter have been maintained for three days in a controlled chamber (10% CO2 and 21% O2). Arterial blood samples, taken before admission and after one, two, four, six, 24, 48 and 72 hours of exposure, allowed to study blood gases and acid-base equilibrium. Glycemia, phosphatemia, erythrocyte concentration of glucose-6-phosphate (G-6-P), fructose-6-phosphate (F-6-P), fructose-1,6-diphosphate (F-1,6-DP), 2,3-diphosphoglycerate (2,3-DPG), pyruvate, lactate and ATP were also titrated by various enzymatic methods. In addition, nine reference subjects were studied in air (without CO2). During the hypercapnia, [H+] rapidly increases to 70 nmol/1, then progressively decreases after 24 hours, while [HCO3-] slowly rises. The glycemia stays high during the whole exposure. There is also an increase in inorganic phosphate, G-6-P and F-6-P, but during the first 24 hours only. F-1,6-DP, pyruvate and lactate remain lowered during the whole exposure. The 2,3-DPG diminishes after the sixth hour. These phenomena, related to the acidosis and probably to the phosphofructokinase inhibition don't arise in the reference subjects. However the latter present after a two and four hour-stay in the chamber a small decrease in pyruvicemia and lactacidemia.

Changes in acid-base equilibrium and blood lactate and pyruvate concentrations were studied during recovery (breathing room air) after three days hypercapnia (FICO2 = 0.10) in awake dogs. Fast return to FICO2 = 0 produced a slight alkalosis in arterial blood and an increase in lactate and pyruvate concentrations which seemed to be maximum at the 15th minute. These changes were inhibited by previous injection of acetazolamide (50 mg/kg body weight). During progressive return to FICO2 = 0, over 1 hour, the peak value of blood lactate and pyruvate was delayed until the end of that hour, at the same time as a slight blood alkalosis appeared. These phenomen are most probably explained by a stimulation, due to alkalosis, of glycolysis at the level of phosphofructokinase.

The clinical usefulness of lung compliance calculated indirectly was reassessed in a large number of healthy subjects and patients with chronic airflow obstruction or restrictive lung disorders. Indirect compliance was calculated from maximal expiratory flow-volume (MEFV) curve and airway resistance measured plethysmographically according to two approaches. In the first (approach A) all calculations were done at the functional residual capacity, whereas in the second (approach B) they were obtained over the 50-75% volume range of the forced vital capacity; values were compared to those of direct compliance measured concurrently. For the group as a whole, the correlations between indirect and direct values were poor regardless of the approach. Examined separately, the best correlations were found for the healthy group using approach A (r = 0.501) and for the obstructive group using approach B (r = 0.312). Failure to derive a valuable indirect compliance is due to the fact that there is a very poor correlation between upstream resistance and airway resistance measured by body plethysmography.U

Summary. The variability, short-term (1 hour) and long-term (2 weeks) reproducibility of the variables derived from the single-breath N2 test were evaluated in a group of 56 healthy children aged 10 to 16 years with a computerized system. The variability was low for vital capacity and total lung capacity (coefficient of variation less than 3%), moderate for residual volume and phase III N2 slope (9 and 13%) and very high for closing volume (more than 50%). A closing volume could not be identified by the computer algorithm in 18.3% of the trials. The reproducibility of the variables was satisfactory both at 1 hour and at 2 weeks, with the exception of the closing volume, whose increase at 2 weeks seemed to be due to methodological factors. We conclude that reliable results of static lung volumes and phase III N2 slope, but not of closing volume, may be obtained in children by a computerized system in epidemiological studies.

To determine the best procedure for reading maximal expiratory flow-volume curves 2 sets of 5 curves were obtained one hour apart in 89 subjects and processed digitally according to 8 different methods. Four indices were considered: the forced expiratory flows at 25, 50, and 75 per cent of the forced vital capacity, and the maximal mid-expiratory flow. When selecting the curve yielding the largest forced vital capacity or the largest sum of forced vital capacity and forced expiratory volume in 1 sec, flow values were significantly lower (P less than 0.001) and were often less reproducible than those obtained with most of the other methods. Computing the mean of the indices among the curves with the 2 largest forced vital capacities also provided comparatively low values, but with with better reproducibility. In contrast, maximal flows were probably overestimated by using the highest values among the curves having forced vital capacity or a surface area within 5 per cent of the largest, or when reading the indices on a composite curve obtained by superimposing individual breaths at residual volume. More reproducible and, probably, unbiased data may be drawn from the composite curves obtained by superimposing the breaths either at total lung capacity or on the descending limb.

The relationship between diurnal pulmonary arterial pressure (Ppa) measured in steady state and nocturnal level of oxyhaemoglobin saturation (Sao2) measured continuously was studied in fourteen patients with chronic obstructive lung disease. A right heart catheterization was carried out in the morning in each patient. The nocturnal polygraphic study included a continuous recording of transcutaneous Sao2. The behaviour of oxygenation state during sleep was closely linked with the mean level of Sao2 during nocturnal wakefulness. Whatever the nocturnal period (wakefulness, non-rapid-eye-movement sleep, rapid-eye-movement sleep), the mean value of Sao2, which is an integration of variations of the oxygenation state, was more closely linked with diurnal Ppa than a single measure of Sao2 carried out during the catheterization. Ppa seemed independent of the amplitude and frequency of desaturation episodes. In patients with chronic obstructive lung disease, the measurement of mean Sao2 at rest is an easier investigation to carry out during diurnal wakefulness than during nocturnal wakefulness. Thus, this might allow the evaluation of the risk of developing permanent arterial hypertension in chronic obstructive patients.

The purpose of this study was to assess the relationship between the breathing pattern response to CO2 and the severity of mechanical impairment in twenty patients with COLD. The CO2 response was compared to that of a control group of twelve normal subjects. All patients had airway obstruction (FEV1 = 40 +/- 14% of predicted; means +/- SD) and hyperinflation (FRC = 154 +/- 23% of predicted). Tidal volume (VT), inspiratory and total cycle duration (TI, TT), occlusion pressure (P0.1) and endtidal PCO2 were measured at rest and during hyperoxic CO2 rebreathing. On the same day, in all patients, arterial blood gas analysis, spirometric and plethysmographic measurements were made. The slope (S) of the P0.1 response (SP 0.1) to increasing endtidal PCO2 was negatively correlated with airway resistance (r = -0.59; p less than 0.01). Although the flow response, S(VT/TI), was positively and closely correlated with SP 0.1 (r = 0.88; p less than 0.001), it also appeared to be independently influenced by obstruction (p less than 0.01). The tidal volume response, SVT, was principally correlated with inspiratory capacity (r = 0.90; p less than 0.001) and also, independently, with Vmax50 (p less than 0.01). SVT was diminished in seventeen patients, ten of whom only had a decreased S(VT/TI). The shortening in TI during hypercapnia was most marked in patients with the greatest S(P0.1), who did not have arterial hypercapnia at rest. These results suggest: that the poor VT response to CO2 in COLD patients is principally caused by a limitation in inspiratory volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

During light slow-wave sleep, ventilation is principally regulated by automatic metabolic control system. An instability in the respiratory control may be the predominant disturbance leading to very irregular or periodic breathing. During deep sleep, ventilation is progressively more stable. During REM sleep, automatic regulation is abolished and ventilation is particularly dependent on the compartmental control system. The reduction in airways and respiratory muscles tone favors the occurrence of obstructive apneas. The elevation in arousal threshold leads prolongation of the obstructive events.

A synthetic approach to lung and chest mechanics is to apply pressure variations to the respiratory system over a range of frequencies and to study the amplitude and phase relationships between applied pressure and resulting gas or tissue flow. Such impedance measurements may be performed in different ways, which are not equivalent: the most usual are to measure gas flow at the mouth while pressure is varied either at the same place (input impedance) or around the chest (transfer impedance). Transfer impedance measurements were performed in healthy subjects from 3 to 70 Hz and tentatively interpreted with a model featuring tissue elasticity, resistance and inertance, gas compressibility, and airway gas resistance and inertance. The pressure-flow ratio was minimum at 5-10 Hz and increased very fast above 50 Hz. The phase angle was nil around 7 Hz, of + 90 degrees at 30-40 Hz and close to 180 degrees at 70 Hz. The validity of the model is supported by the quality of the fit to the data up to 50 Hz, the values of the coefficients and the results of experiments where the subject's mechanical properties were varied.