Vertical distributions of pulmonary diffusing capacity and capillary blood flow in man.

In six normal upright subjects, a 100 mol bolus-composed of equal parts of neon, carbon monoxide, and acetylene (Ne, CO, and C(2)H(2))-was inspired from either residual volume (RV) or functional residual capacity (FRC) during a slow inspiration from RV to total lung capacity (TLC). After breath holding and subsequent collection of the exhalate, diffusing capacity and pulmonary capillary blood flow per liter of lung volume (D(L)/V(A) and Q(C)/V(A)) were calculated from the rates of CO and C(2)H(2) disappearances relative to Ne. The means: D(L)/V(A) = 5.26 ml/min x mm Hg per liter (bolus at RV), 6.54 ml/min x mm Hg per liter (at FRC); Q(C)/V(A) 0.537 liters/minute per liter (bolus at RV), 0.992 liters/minute per liter (at FRC). Similar maneuvers using Xenon-133 confirmed that, during inspiration, more of the bolus goes to the upper zone if introduced at RV and more to the lower, if at FRC. A lung model has been constructed which describes how D(L)/V(A) and Q(C)/V(A) must be distributed to satisfy the experimental data. According to this model, there is a steep gradient of Q(C)/V(A), increasing from apex to base, similar to that previously determined by other techniques-and also a gradient in the same direction, although not as steep, for D(L)/V(A). This more uniform distribution of D(L)/V(A) compared with Q(C)/V(A) indicates a vertical unevenness of diffusing capacity with respect to blood flow (D(L)/Q(C)). However, the relative degree of vertical unevenness of D(L)/V(A) compared with Q(C)/V(A) can account only in part for previous observations attributed to the inhomogeneity of D(L)/V(A) and Q(C)/V(A). Thus, a more generalized unevennes of these ratios must exist throughout the lung, independent of gravitation.

Relationship between frequency dependence of lung compliance and distribution of ventilation.

The previously demonstrated empirical association between frequency dependence of lung compliance and distribution of ventilation, the latter determined by the N(2) washout technique, was confirmed by establishing a mathematical link between the two tests. By assuming a two-compartment system with known compliances and making corrections for Pendelluft and common dead space mixing effects, the ratio of dynamic to static compliance (C(dyn)/C(st)) for any respiratory frequency can be calculated from the compartmental analysis of the N(2) washout at a single respiratory frequency. By using these equations, a good correlation was found between calculated and measured C(dyn)/C(st) in dogs with artificially induced bronchial obstruction and in young smokers or young nonsmokers after carbachol inhalation. A two-compartment N(2) washout was demonstrated in 10 young healthy smokers at one or two respiratory frequencies whereas all 10 normal controls showed a single exponential curve. These findings indicate that the non-invasive N(2) washout test is capable of predicting C(dyn)/C(st) and at the same time gives a direct measure of gas distribution. Further, it appears to be a highly sensitive method for the detection of "small airway disease."

Breathing abnormalities during sleep.

The purpose of this communication is to review obstructive and central breathing abnormalities that may occur during sleep, such as obstructive sleep apnea, and Cheyne-Stokes respiration. Emphasis is placed on noninvasive monitoring of the breathing pattern and intrapleural pressure swings by respiratory and surface inductive plethysmography, respectively, which establish the diagnosis of these abnormal breathing patterns.

Recent advances in the management of obstructive airways disease. Auxiliary MDI aerosol delivery systems.

Aerosol delivered through metered-dose inhalers (MDI) offers a potentially convenient way to deliver bronchodilator agents and corticosteroids to the lungs of patients with asthma and COPD. Unfortunately, most patients are unable to coordinate satisfactorily their actuation with inhalation, a problem overcome by using auxiliary MDI aerosol delivery systems. Left to their own judgment, patients often inhale the aerosol with a high inspiratory flow rather than slowly to produce optimal aerosol deposition within the airways. This problem has been corrected by one of the auxiliary MDI aerosol delivery systems (InspirEase) through auditory, visual, and tactile feedback mechanisms. MDI devices release aerosol at a high jet velocity in large particle sizes, depositing most of the aerosol in the oropharynx which can lead to potential systemic absorption of adrenergic agonists with CNS and cardiovascular side effects, oral thrush, and suppression of adrenocortical activity. All the auxiliary MDI aerosol systems promote delivery of small aerosol particles and markedly diminish oropharyngeal impaction. Of all the systems, only InspirEase provides volume and flow feedback controls to ensure an optimal inhalation maneuver. Auxiliary MDI aerosol systems should always be used for aerosolized corticosteroid administration because they minimize oropharyngeal deposition and improve aerosol delivery efficiency.

Effects of terbutaline aerosol in reversible airway obstruction.

Aerosol terbutaline is an effective bronchodilator agent with at least a seven-hour duration of action in patients with reversible obstruction of the airways. Inhalation of up to 1.5 mg of this drug is not associated with significant alterations of pulse rate and blood pressure. Although a dose-related improvement of specific airway conductance was demonstrated 30 minutes after administration of the drug, no such effect was observed in measurements of the forced expiratory volume in one second.

Oronasal distribution of ventilation during exercise in normal subjects and patients with asthma and rhinitis.

This study was undertaken to determine whether the resistance to nasal airflow and differences in oronasal distribution of ventilation at rest and during exercise alter the pattern of breathing. We observed six normal subjects, six patients with symptomatic allergic rhinitis, and six patients with asymptomatic bronchial asthma (three men and three women in each group), all of whom had normal pulmonary function. At rest, five of the six normal subjects breathed nasally but 11 of the 12 patients breathed with an oronasal distribution. Five normal subjects who breathed nasally at rest breathed with an oronasal distribution of ventilation during exercise, and one normal subject who breathed oronasally at rest had slightly less oral ventilation during exercise. In the patients, the change in oral distribution of ventilation during exercise was variable. Among the three groups, there were no significant differences from the resting oronasal distribution for ventilation during exercise, and all subjects breathed oronasally during exercise. The oronasal distribution of ventilation did not correlate with the level of nasal airflow resistance. Analysis of the timing, volume, and flow components of breathing showed no statistically significant differences among the three groups at rest and exercise. Thus, neither the level of resistance to nasal airflow, even up to moderately high values, nor the nasal distribution of ventilation at rest and with moderate exercise appears to have a major role in the pattern of breathing.

Periodic breathing triggered by hypoxia in normal awake adults. Modification by naloxone.

Breathing patterns in six normal awake subjects were monitored noninvasively during progressive hypoxia accomplished with the administration of nitrogen at 2, 4, 6, and 8 L/min by nasal cannula. The lowest value of arterial oxygen saturation (SaO2) of 88 +/- 4 percent (mean +/- SD) was achieved with nitrogen at 8 L/min. At baseline, tidal volume (VT) and frequency were fairly regular; with nitrogen at 2 and 4 L/min, some subjects showed minor fluctuations of VT. At 6 and 8 L/min, periodic breathing with marked oscillations of VT, apneas, hypopneas, and intermittent large tidal breaths were consistently observed. Inspired oxygen concentration fluctuated because of the variations of tidal breaths provoked when periodic breathing took place and enhanced fluctuation in SaO2. A randomized, double-blind crossover design was used to assess the effect of pretreatment with naloxone on this periodicity. In contrast to the irregular breathing pattern observed with pretreatment with placebo, the breathing pattern after pretreatment with naloxone was regular during nasal administration of nitrogen except at 8 L/min, when minor fluctuations in VT with occasional hypopneas and large tidal breaths occurred. On another day, irregular and periodic breathing with apneas or hypopneas (or both) produced by nasal nitrogen at 8 L/min was eliminated or blunted by short-term intravenous administration of naloxone. On another day, electroencephalographic monitoring corroborated visual observations made in the previous studies that the hypoxic subjects were awake during the breathing alterations. Thus, awake adults develop irregular and periodic breathing during induction of mild hypoxia produced by nasal administration of nitrogen. The irregularity in breathing appears to be mediated through release of endorphins, since the effect is blunted or eliminated by pretreatment or short-term treatment with naloxone.

Thoracocardiographic-derived left ventricular systolic time intervals.

Thoracocardiography noninvasively estimates left ventricular performance by recording ventricular volume curves with inductive plethysmography. We studied timing of these curves to evaluate their potential to accurately track systolic time intervals in comparison with standard methods. Thoracocardiographic left ventricular volume curves, carotid pressure pulses determined by applanation tonometry, the phonocardiogram and ECG were recorded simultaneously in ten normal subjects at various body positions achieved with a tilt table. An equation was derived to predict preejection period from onset of ejection in thoracocardiographic curves. Ventricular ejection time was calculated as total electromechanical systole obtained by phonocardiography minus preejection period. The equation was validated prospectively in 31 measurements in critically ill patients. In normal subjects, the interval ECG Q wave to ejection onset in thoracocardiographic curves correlated well with preejection period from applanation tonometry and phonocardiography (r = 0.92; standard error of estimate (SEE), 8 ms; p < 0.001). Thoracocardiographic curves showed a delay that varied with body position according to the regression equation: delay = 40 ms + 10 x sine (tilt angle) (where r = 0.62; SEE, 7 ms; p < 0.001). Application of this equation in the prospective study in patients revealed close agreement in systolic time intervals from thoracocardiography and simultaneous applanation tonometry plus phonocardiography, respectively. The mean difference +/- SD between methods in preejection periods was 3 +/- 7 ms and in the ratios of preejection period to left ventricular ejection time, 0.02 +/- 0.05. Trends of changes in systolic time intervals were identical for the two methods. We conclude that thoracocardiography combined with phonocardiography provides accurate systolic time intervals when corrected for a position-dependent delay of its waveforms.

Effect of beta-adrenergic agonists aerosolized by freon propellant on tracheal mucous velocity and cardiac output.

The present study was designed to assess the effects of two beta-adrenergic agonists, isoproterenol sulfate and carbuterol hydrochloride, and aerosolized Freon propellant (a mixture of Freon II, Freon 12, and Freon 114) on tracheal mucous velocity and cardiac output in anesthetized dogs. Five groups of ten animals each received the following dosages of aerosols: Freon, 20 puffs; isoproterenol, four puffs; carbuterol, four puffs; isoproterenol, 20 puffs; and carbuterol, 20 puffs. The puff was delivered by a standard metered aerosol; each puff of isoproterenol spray contained 75 mug of isoproterenol sulfate, and each puff of carbuterol spray contained 100 mug of carbuterol hydrochloride. Tracheal mucous velocity was not changed by receiving Freon, but administration of both isoproterenol and carbuterol caused a significant increase in this measurement, with peak increases ranging from 74 to 111 percent above control values. The duration of action for four and 20 puffs of isoproterenol and for four puffs of carbuterol was two hours. Twenty puffs of carbuterol increased tracheal mucous velocity for three hours. Administration of carbuterol effected a slightly larger increase in cardiac output than isoproterenol. The duration of action for the increased cardiac output was shorter than the duration of action for the increased tracheal mucous velocity. These studies indicate that beta-adrenergic agonists may have an important role in improving mucous transport in patients with chronic obstructive pulmonary disease in whom mucociliary clearance is depressed.

Effect of cuffed endotracheal tubes on tracheal mucous velocity.

The inflated cuffed endotracheal tube produces a significant depression of tracheal mucous velocity in anesthetized dogs after one hour. This effect occurs with bot low and high compliance cuffs but is not observed with an uncuffed tube. This phenomenon is another factor that must be considered in establishing criteria for the frequency of cuff deflation in patients supported by mechanical ventilators.

Effects of drinking hot water, cold water, and chicken soup on nasal mucus velocity and nasal airflow resistance.

Nasal mucus velocity and nasal airflow resistance were measured in 15 healthy subjects before and at 5 and 30 minutes after drinking hot water by sip or straw, hot chicken soup by sip or straw, and cold water by sip. A sham drinking procedure with straw was also employed. Hot water by sip increased nasal mucus velocity from 6.2 to 8.4 mm per min, hot chicken soup by sip from 6.9 to 9.2 mm per min, and chicken soup by straw from 6.4 to 7.8 mm per min five minutes after administration. These increases were statistically significant compared to cold water, hot water by straw and sham. All values returned to their baseline at 30 minutes except cold water which significantly decreased the nasal mucus velocity from 7.3 to 4.5 mm per min. There were no significant changes from baseline in nasal airflow resistance 5 and 30 minutes following the above treatments. We conclude that drinking hot fluids transiently increases nasal mucus velocity in part or totally through the nasal inhalation of water vapor. Hot chicken soup, either through the aroma sensed at the posterior nares or through a mechanism related to taste, appears to possess an additional substance for increasing nasal mucus velocity. Finally, hot liquid might be superior to cold liquids in the management of fluids in upper respiratory tract infections.

Hemodynamic effects of smoking cigarettes of high and low nicotine content.

We studied the hemodynamic effects of smoking cigarettes with high and low contents of nicotine in young smokers free of coronary arterial disease. The smoking of one cigarette with a high content of nicotine produced a peak rise in cardiac output of 32 percent above baseline values, and the effect persisted for one hour. Smoking a cigarette with a low content of nicotine produced a peak rise of 13 percent above baseline values, with a duration of five minutes. The rise in cardiac output was almost entirely attributable to tachycardia, since stroke volume remained relatively constant. The smoking of a cigarette with high nicotine content also caused greater and more sustained elevation in systemic blood pressure than smoking a cigarette with low nicotine content. Thus, there was a responsiveness to the dose of nicotine in cigarettes smoked by young smokers free of coronary arterial disease.

Subjective and objective measurement of cigarette smoke inhalation.

The pattern of cigarette smoke inhalation was studied in 19 smokers with respiratory inductive plethysmography, a reliable unobtrusive ventilatory monitoring device. The mean volumes inhaled varied widely from 0.27 to 1.97 L, with a group mean (+/- SD) of 0.79 +/- 0.45 L. Mean duration of smoke inhalation varied from 2.0 to 6.8 seconds, with a group mean of 4.5 +/- 1.3 seconds. An inhalation fraction was derived by dividing the inhaled volume by the vital capacity; this fraction varied from 0.09 to 0.47, with a group mean of 0.20 +/- 0.10. Subjects rated the depth that they inhaled smoke into their lungs on a visual analog scale and on a grading system. Correlation between visual analog scale and inhalation fraction was poor (r = -0.15). Also, inhalation fraction bore no relationship to smoking pack-years or current pulmonary function. The smokers' inaccurate assessment of their inhalation pattern may help to explain the poor correlation reported between cigarette smoke inhalation and severity of obstructive lung disease.

Periodic sleep apnea: chronic sleep deprivation related to intermittent upper airway obstruction and central nervous system disturbance.

Periodic sleep apnea may be due to repeated episodes of upper airway obstruction in patients who have a short thick neck and/or large jowls. Apnea due to complete cessation of breathing may occur to a lesser extent. Anaylsis of the sleep electroencephalogram shows that these patients rarely achieve deep sleep and have less stage 1-REM sleep than normal subjects of comparable age. They are chronically sleep-deprived, a manifestation expressed by daytime somnolence, chronic fatigue and often by personality disturbances marked by paranoia, agitated depression and hostility. The definitive diagnosis of this syndrome may be established by monitoring during sleep, the electroencephalogram, measuring abdominal excursions through a mercury-in-Silastic-strain gauge and recording air flow at the nose by means of a thermocouple. As demonstrated by other investigators, chronic hypoventilation during sleep leads to both pulmonary and systemic arterial hypertension, which may produce generalized cardiac enlargement and congestive heart failure. The abnormalities in the periodic sleep apnea syndrome are abolished by establishing a patent airway either through tracheostomy or weight reduction.

Respiratory drive in nonsmokers and smokers assessed by passive tilt and mouth occlusion pressure. Response to rebreathing carbon dioxide.

The purpose of the present investigation was to assess respiratory center function in smokers using (1) measurement of mouth occlusion pressure during carbon dioxide rebreathing and (2) noninvasive measurement of breathing pattern during passive upright tilt. The breathing patterns of 20 normal nonsmokers and 20 smokers without major obstruction of the airways were monitored noninvasively with respiratory inductive plethysmography for 15 minutes in the supine position and then after 90 degrees head-up passive tilt to the standing position. In nonsmokers, significant increases from supine to standing positions included the following: (1) minute ventilation from 6.22 +/- 1.47 to 7.32 +/- 1.16 L/min (p less than 0.05); (2) tidal volume from 368 +/- 93 to 462 +/- 108 ml (p less than 0.01); and (3) mean inspiratory flow from 263 +/- 61 to 320 +/- 43 ml/sec (p less than 0.01). Responses of smokers to tilt were variable; 14 showed changes similar to nonsmokers, but six showed no increase of ventilation and respiratory drive upon tilting. The latter also showed blunted response to rebreathing carbon dioxide in the supine position as estimated by plotting mouth occlusion pressures against end-tidal carbon dioxide tension. These data suggest that disturbances of respiratory center control are common in smokers without major obstruction of the airways.

Effect of InspirEase on the deposition of metered-dose aerosols in the human respiratory tract.

A radiotracer technique has been used to assess the effects of a 700-ml collapsible holding chamber (InspirEase, Key Pharmaceuticals Inc.) on the deposition of metered-dose aerosols in ten patients with obstructive airways disease (mean forced expiratory volume in one second [FEV1], 64.5 percent of predicted). Patterns of deposition obtained by patients' usual techniques with the metered-dose inhaler (MDI) were compared with those by correct MDI technique (actuation coordinated with slow deep inhalation and followed by ten seconds of breath-holding) and with those by InspirEase. Deposition of aerosol was assessed by placing Teflon particles labelled with 99mTc inside placebo canisters, and inhaling maneuvers were monitored by respiratory inductive plethysmography (Respitrace). Nine of the ten patients had imperfect technique with the MDI, the most prevalent errors being rapid inhalation and failure to hold their breath adequately. With patients' usual MDI techniques, 6.5 +/- 1.2 percent (mean +/- SE) of the dose reached the lungs. This was increased to 11.2 +/- 1.3 percent (p less than 0.02) with correct technique and increased further to 14.8 +/- 1.4 percent (p less than 0.05) with InspirEase. Oropharyngeal deposition exceeded 80 percent of the dose for the MDI alone but was only 9.5 +/- 0.9 percent with InspirEase (p less than 0.01); 59.2 +/- 2.1 percent of the dose was retained within InspirEase itself. It is concluded that InspirEase gives whole lung deposition of metered-dose aerosols greater than that from a correctly used MDI, while oropharyngeal deposition is reduced approximately nine times.

Noninvasive measurement of central venous pressure by neck inductive plethysmography.

Bedside estimation of the height at which the internal jugular veins collapse, referenced to a standard hemodynamic location, theoretically reflects central venous pressure. This method has never been demonstrated as accurate when compared to invasive CVP measurements because of the great clinical skills and time required to visually identify the internal jugular venous waveform. Since the principles of the bedside method are sound, we utilized them in conjunction with the neck inductive plethysmograph, a device which has the capability of recording internal jugular venous and carotid arterial waveforms. The respiratory distortion of these vascular waveforms was eliminated by employing a digital bandpass filter, making it easy to identify the venous and arterial waveforms on the videoscreen of a personal computer. The upper torso was positioned while observing the videoscreen until the vascular waveform was seen as a mixed arteriovenous waveform, signifying intermittent internal jugular venous collapse. The height of the internal jugular vein above the phlebostatic axis was obtained by external measurement and recorded as CVPni in cm H2O. In 43 patients, 86 percent of CVPni (NIP) values fell within 20 percent CVPi (invasive catheter measurements) over a range of CVP from 0 to 19 cm H2O. In an additional seven patients, CVPi was greater than the height that the upper torso could be elevated and an arterial waveform could not be obtained. Here, CVPni was recorded as the value at least exceeding the value measured. In two other patients, obstruction of an internal jugular vein gave spuriously low values of CVPni. Our study indicates that this new neck inductive plethysmographic method is accurate compared to invasive catheter measurements of CVP and should serve as a safe, noninvasive alternative in situations where such measurements are required.

Thoracocardiography. Part 1: Noninvasive measurement of changes in stroke volume comparisons to thermodilution.

The thoracocardiograph (TCG) is a new noninvasive monitoring device that measures cardiac oscillations transmitted to the external surface of the thorax. It consists of 2.5 cm in height, elastic inductive plethysmographic transducers placed transversely in the proximity of the xiphoid process to provide changes in cross-sectional area on a transverse plane across the minor ventricular axis. Cardiac oscillations synchronous with each heart beat are extracted from the respiratory signal during breathing with an ensemble-averaging technique using the electrocardiograph as a trigger pulse. The average cardiac waveform at locations near the xiphoid process in normal humans has the appearance of a ventricular volume curve. The latter is also found in the majority of patients with heart disease although in some, outward (dyskinetic) rather than inward motion during systole occurs at one or more locations of the TCG transducers. As in echocardiography, such findings are consistent with ischemic or scarred myocardium invalidating computation of changes in stroke volume from such sites. In anesthetized dogs and critically ill patients with normal ventricular wall motion, changes in TCG derived ventricular volume waveform amplitudes agreed well with changes of thermodilution estimates of stroke volume during atrial pacing and fluid loading in the dogs on the one hand and with application of extrinsic positive end-expiratory pressure (PEEP) in patients on the other hand. Thoracocardiography has the potential for noninvasive, continuous monitoring of stroke volume and cardiac output as well as for detection of ischemic or scarred myocardium.

Effect of oxygen in graded concentrations upon tracheal mucous velocity. A study in anesthetized dogs.

Graded concentrations of oxygen were used to establish dose-duration relations for the effect of oxygen on tracheal mucous velocity and tracheobronchial histologic findings in the anesthetized dog. Observations of tracheal mucous velocity were made during 30-hour periods of breathing air (100-percent humidified and warmed to 38 degrees C) and oxygen mixtures (also 100-percent humidified and warmed to 38 degrees C). In animals breathing oxygen mixtures, the baseline tracheal mucous velocity was taken as the value while breathing room air at the experiment's start. No statistically significant differences in tracheal mucous velocity occurred during air breathing. Tracheal mucous velocity fell 45 percent from the baseline value after breathing 100-percent oxygen for two hours (P less than 0.01), fell 42 percent after 75-percent oxygen for nine hours (P less than 0.01) and fell 51 percent after 50-percent oxygen for 30 hours (P less than 0.001). Histologic examination of the trachea and major bronchi after six hours of 100-percent oxygen and 12 hours of 75-percent oxygen revealed signs of acute tracheobronchitis. Minor histologic alterations in the tracheobronchial tree occurred both in animals breathing air and 50-percent oxygen for 30 hours; therefore, histologic evidence of oxygen toxicity could not be established at 30 hours. These findings indicate that in the anesthetized dog, oxygen depresses mucous transport as a function of inspired oxygen concentration (FIO2) and that even FIO2 as low as 0.05 might be deleterious.

Effects of S-carboxymethylcysteine on tracheal mucus velocity.

The effects of S-carboxymethylcysteine on tracheal mucus velocity were assessed in a double blind crossover study between 2 grams S-carboxymethylcysteine and placebo. Subjects included six healthy non-smokers, eight smokers with small airway disease and chronic simple bronchitis, and eight subjects with chronic obstructive bronchitis. Tracheal mucus velocity was measured prior to and two and three hours after each subject had ingested S-carboxymethylcysteine or placebo. No significant change in tracheal mucus velocity occurred after placebo or S-carboxymethylcysteine in any of the groups, indicating that the drug has no acute effect on mucus transport.