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Biomedical subjects

N Zamel

Publications and source records attributed to N Zamel.

At least 91 records · Page 5Linked to original sources

Assessment of maximal expiratory pressure in healthy adults.

Maximal static expiratory pressure developed at the mouth (PEmax) provides a useful clinical index of expiratory muscle function; however, the range of normal values among laboratories shows considerable variation. We examined the hypothesis that the wide variability could be attributable to the differences in technique among laboratories. We measured PEmax at functional residual capacity (PEmax FRC) in 28 healthy subjects using the following five techniques: 1) using a scuba-type mouthpiece with the cheeks supported by the hands ("hands on"), 2) without supporting the cheeks ("no hands"), 3) using a rigid, circular mouthpiece (2.8 cm ID, "tube"), 4) using the scuba-type mouthpiece but with the cheeks supported by an observer ("other hands"), and 5) using a large-bore circular mouthpiece (4.1 cm ID, "new tube"). Mean PEmax FRC obtained with hands on was significantly higher than no-hands and tube methods. PEmax FRC values obtained by the other-hands and new-tube maneuvers were similar to the hands-on maneuver. We conclude that the technique used to measure PEmax FRC can significantly affect the results and suggest that it should be measured using a large-bore circular mouthpiece or a scuba-diving mouthpiece with the cheeks supported.

Adult↗

Relative hysteresis of the airways and lung parenchyma in normal subjects.

We evaluated the mechanical properties of the airways sequentially from the glottis toward the main bronchi in 10 normal subjects. Plots of airway cross-sectional area vs. lung volume, measured during inspiration and expiration, were used to determine the relative magnitude of the airways vs. parenchymal hysteresis. Airway cross-sectional area was measured by means of the acoustic reflection technique. We found that the hysteresis of the proximal part of the trachea was greater than that of the lung parenchyma, whereas the hysteresis of the distal trachea and subcarinal segments of the airways was smaller than that of the lung parenchyma. The transition zone between the proximal and the more distal airway properties occurred 8-26 cm distal to the glottis. This transition zone was reproducible in its location on repeated testing in each subject but varied among subjects. To the extent that relative hysteresis of the airways depends on bronchomotor tone, our findings suggest that the bronchomotor tone is inhomogeneous, being maximal at the proximal part of the trachea and gradually decreasing toward the more distal trachea and subcarinal airway segments.

Acoustics↗

Dichotomous airway response to exercise in asthmatic patients.

The extent and location of airway narrowing in asthmatic subjects are usually inferred from measurements of maximal expiratory flow rates and airway resistance. In the present study, we used the acoustic reflection technique to measure the airway cross-sectional area in 14 asthmatic subjects and 8 normal controls before and following treadmill exercise tests. In normal subjects, exercise caused no significant change in FEV1 and bronchial area, but did cause a significant increase in the intrathoracic tracheal area from 2.0 +/- 0.7 cm2 to 3.1 +/- 0.7 cm2 (p less than 0.002). In the asthmatics, exercise was followed by a 37 +/- 15% reduction in forced expiratory volume in 1 s(FEV1), and a 36% decrease in bronchial area from 8.5 +/- 2.8 cm2 to 5.4 +/- 1.1 cm2 (p less than 0.001); however, extra- and intrathoracic tracheal areas increased significantly. These findings provide direct and quantitative evidence that the bronchi are the main site of airway narrowing in exercise-induced asthma, and draw attention to the phenomenon of tracheal dilatation that occurs concomitant with bronchoconstriction in asthmatic patients.

Adult↗

Paradoxical glottic narrowing in patients with severe obstructive sleep apnea.

Most patients with obstructive sleep apnea have increased pharyngeal collapsibility (defined in the present study as an increased lung volume dependence of pharyngeal area), which predisposes them to upper airway occlusion during sleep. However, there are patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility. The factors leading to nocturnal upper airway obstruction in such patients have not been ascertained. We studied 10 overweight male patients with severe obstructive sleep apnea and low-normal pharyngeal collapsibility to determine the site of upper airway pathology in these patients. We found that all 10 patients exhibited paradoxical inspiratory narrowing of the glottis during quiet tidal breathing. This phenomenon was not observed in a matched group of 10 snoring, nonapneic male controls. We conclude that paradoxical glottic narrowing may be a contributing factor in the pathogenesis of upper airway obstruction in patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility.

Adult↗

Diagnosis and Nd-YAG laser treatment of unsuspected malignant tracheal obstruction.

Thirteen adult patients underwent palliative Nd-YAG laser treatment for relief of severe dyspnea due to malignant endotracheal obstruction. Three of the 13 patients had underlying chronic airflow obstruction (CAO) due to diffuse obstructive pulmonary disease. Despite dyspnea, cough, wheezing, stridor and/or hemoptysis, the diagnosis was delayed because of a normal chest roentgenogram in eight patients and nondiagnostic pulmonary function studies (including maximal expiratory and inspiratory flow-volume loops) in all three patients with CAO and in four of ten patients without CAO. The location of the tumor was extrathoracic in two patients, including one with CAO; intrathoracic in seven patients, including two with CAO; and combined extra- and intrathoracic in four. Tracheal diameter increased from 3.5 +/- 1.0 mm before, and to 9.8 +/- 2.0 mm after single or multiple laser treatments. Increased patency of the trachea after laser surgery was associated with improvement in expiratory and/or inspiratory flow rates and with symptomatic relief in all patients which persisted for 14.1 +/- 8.7 months (range four to 48 months). These results indicate that severe symptomatic narrowing of the extra- and/or intrathoracic trachea to a diameter of 2 to 5 mm may not be detected by conventional chest radiography or even by sensitive physiologic tests, especially in patients with underlying CAO. The resultant delay in diagnosis defers possible relief of disabling symptoms with palliative therapy, including Nd-YAG laser photocoagulation.

Adult↗

Immediate and delayed bronchoconstriction after exercise in patients with asthma.

Although an immediate asthmatic response after exercise is known to occur in some patients with asthma, the existence of a delayed asthmatic response after exercise is controversial. Accordingly, we studied 53 patients who had an immediate mean (+/- SD) decrease in forced expiratory volume at one second (FEV1) of 36 +/- 13 percent, which was maximal 13 +/- 12 minutes after the completion of treadmill exercise. Eight of these patients also had a delayed asthmatic response (a 32 +/- 5 percent decrease in FEV1 occurring 5.0 +/- 1.8 hours after exercise). During a control day, on which the FEV1 was measured serially but no exercise was performed, the same delayed asthmatic response was observed in all but one patient. This finding suggests that the delayed asthmatic response observed in these patients after exercise was not specifically related to the performance of exercise. We conclude that in patients who have bronchoconstriction immediately after exercise, a second asthmatic response occurring later after the exercise is uncommon.

Adolescent↗

An isovolume method for analysis of density dependence of maximal expiratory flows.

The usual method of measuring density dependence of maximum expiratory flows is superimposition at total lung capacity or residual volume of maximum expiratory flow volume (MEFV) curves obtained breathing air and a mixture of 80% He plus 20% O2 (HeO2). A major problem with this technique is the large variability in results, which has been thought to be due to errors in matching lung volumes on both gases. Accordingly, we obtained MEFV curves breathing air and HeO2 using a bag-in-the-box system so that the curves breathing the two gas mixtures could be directly superimposed without removing the mouthpiece (isovolume). Ten healthy, nonsmoking subjects performed MEFV curves on each gas mixture for six consecutive experiments. We compared the increase in flow at 50% of vital capacity (delta Vmax50) and volume of isoflow (Viso) by superimposing and matching the MEFV curves at total lung capacity, at residual volume, and using the isovolume method. The variability of each method was assessed by the mean intersubject and intrasubject coefficients of variation. In all subjects, the mean delta Vmax50 and Viso as well as their corresponding coefficients of variation were not significantly different among the three methods. We conclude that, in healthy nonsmoking young adults, the method chosen for superimposing and matching MEFV curves has no effect on the variability of delta Vmax50 and Viso.

Adult↗

Effect of mouthpiece, noseclips, and head position on airway area measured by acoustic reflections.

To investigate whether it is possible to simplify the methodology of measuring airway area by acoustic reflections, we measured upper airway area in 10 healthy subjects during tidal breathing according to seven different protocols. Three protocols employed custom-made bulky mouthpiece with or without nose-clips, two protocols used a scuba-diving mouthpiece and cotton balls placed in the nostrils instead of noseclips, and two protocols employed neck flexion and extension. We found no significant difference in average pharyngeal, glottic, and tracheal areas for any of the protocols except for neck flexion, which was associated with a significantly lower mean pharyngeal area. Intraindividual variabilities were comparable for all protocols, except for protocol employing the customary bulky mouthpiece and no noseclips, which consistently resulted in the most variable measurements of area for all three airway segments: pharynx, glottis, and trachea. Furthermore, we found that the protocol employing the scuba-diving mouthpiece with or without cotton balls in the nostrils resulted in the lowest number of unacceptable measurements. We conclude that measurements of airway area by acoustic reflections may be further simplified by using a scuba-diving mouthpiece without noseclips; furthermore, control of head position during measurements is not critical provided there is no obvious neck flexion.

Acoustics↗

Changes in pharyngeal cross-sectional area with posture and application of continuous positive airway pressure in patients with obstructive sleep apnea.

In an attempt to elucidate whether changes in posture (from sitting to supine) result in reduction in pharyngeal area, thus promoting pharyngeal occlusion during sleep in so predisposed persons, we studied 12 snoring apneic patients and 6 snoring nonapneic control subjects. in all subjects, we employed acoustic reflection technique to measure pharyngeal area at FRC sitting and supine. We also examined changes in pharyngeal area resulting from the application of positive intrapharyngeal pressure in sitting and supine posture. We found that (1) pharyngeal cross-sectional area at FRC was similar in both groups, (2) decrease in pharyngeal area with assumption of supine posture was also similar in both groups (21 +/- 11% in patients with OSA versus 15 +/- 13% in nonapneic control subjects), and (3) pharyngeal distensibility was significantly higher in apneic snorers than in nonapneic control subjects (0.090 +/- 0.039 cm H2O-1 in apneic snorers versus 0.032 +/- 0.027 cm H2O-1 in nonapneic control subjects; p less than 0.005). We conclude that changes in posture alone are not sufficient to convert a snorer into a patient with OSA; however, when physiologic abnormalities ("floppy" pharynx) are superimposed on postural reduction in pharyngeal area, airway occlusion results.

Humans↗

Differences in pharyngeal properties between snorers with predominantly central sleep apnea and those without sleep apnea.

The underlying cause of idiopathic central sleep apnea syndrome is not well understood. We therefore examined the possibility that patients with idiopathic central sleep apnea may have abnormalities of upper airway mechanics that might contribute to the pathogenesis of central apneas. The acoustic reflection technique was used to assess pharyngeal size, lung volume dependence, and pharyngeal "compliance" in 8 patients with idiopathic central sleep apnea, all of whom were snorers, and in 8 weight-matched, snoring control subjects with normal sleep studies. Patients with central sleep apnea when compared with control subjects exhibited markedly increased specific pharyngeal "compliance" (0.12 +/- 0.05 versus 0.03 +/- 0.01 cm H2O-1; p less than 0.001), increased change in pharyngeal area from FRC to RV (0.8 +/- 0.5 versus 0.03 +/- 0.3 cm2; p less than 0.05), and a larger pharyngeal area at FRC (4.7 +/- 0.9 versus 3.8 +/- 0.8 cm2; p less than 0.03). We conclude that increased pharyngeal "compliance" and lung volume dependence may play a role in the etiology of central apneas in this syndrome.

Brain Diseases↗

Nd-YAG laser surgery for severe tracheal stenosis physiologically and clinically masked by severe diffuse obstructive pulmonary disease.

Nd-YAG laser surgery was performed on six patients with tracheal stenosis complicating severe diffuse intrathoracic airways obstruction due to emphysema, chronic obstructive bronchitis and/or asthma. Tracheal stenosis was extrathoracic in four patients and both extrathoracic and intrathoracic in two patients. Results suggest that patients with severe chronic obstructive pulmonary disease and asthma have maximal expiratory and inspiratory flow volume patterns that may completely mask extrathoracic and intrathoracic tracheal stenosis. Following relief of tracheal obstruction with laser therapy, substantial improvement can occur both clinically and physiologically, as reflected by symptomatic relief and large increases in Vmax 50I and FVC.

Adult↗

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea.

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.

Adult↗

Changes in tracheal cross-sectional area during Mueller and Valsalva maneuvers in humans.

Pressure-area behavior of the excised trachea is well documented, but little is known of tracheal compliance in vivo. Extratracheal tissue pressures are not directly measurable, but transmural pressure for the intrathoracic trachea is inferred from intra-airway and pleural pressure differences. Extramural pressure of the cervical trachea is assumed to be atmospheric. The difference in transmural pressure between the intra- and extrathoracic tracheal segments should be exaggerated during Mueller and Valsalva maneuvers. We used the acoustic reflection technique to measure tracheal areas above and below the thoracic inlet during these isovolume-pressure maneuvers. We found that 10 cmH2O positive pressure increased tracheal area in the extrathoracic segment by 34 +/- 16% (mean +/- SD) and in the intrathoracic segment by 35 +/- 15%. There was a reduction in area of 27 +/- 16 and 24 +/- 14%, respectively, for the extra- and intrathoracic segments with 10 cmH2O negative pressure. We conclude that the effective transmural pressure gradients do not vary significantly between intra- and extrathoracic tracheal segments.

Adult↗

Pharyngeal cross-sectional area in normal men and women.

Pharyngeal size and the dynamic behavior of the upper airway may be important factors in modulating respiratory airflow. Patients with obstructive sleep apnea are known to have reduced pharyngeal cross-sectional area. However, no systematic measurements of pharyngeal area in healthy asymptomatic subjects are available, in part due to the lack of simple, rapid, and noninvasive measurement techniques. We utilized the acoustic reflection technique to measure pharyngeal cross-sectional area in 24 healthy volunteers (14 males, 10 females). Pharyngeal area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared pharyngeal cross-sectional areas in males and females at three lung volumes: TLC, 50% of vital capacity (VC), and RV. In males, pharyngeal areas (means +/- SD) were 6.4 +/- 1.3 cm2 at TLC, 5.4 +/- 0.9 cm2 at 50% VC, and 4.1 +/- 0.8 cm2 at RV. In females, pharyngeal areas were 4.8 +/- 0.6 cm2 at TLC, 4.2 +/- 0.5 cm2 at 50% VC, and 3.7 +/- 0.6 cm2 at RV. The difference in area between males and females was statistically significant at TLC and 50% VC but not at RV. However, when the pharyngeal cross-sectional area was normalized for body surface area, this difference was not significant. In males there was a negative correlation of pharyngeal area with age. We conclude that sex differences in pharyngeal area are related to body size, pharyngeal area shows a similar variation with lung volumes in males and females, and in males pharyngeal area reduces with age.

Adult↗

Total lung capacity does not change during methacholine-stimulated airway narrowing.

The accurate measurement of changes in flow rates from partial flow-volume curves depends on their measurement at the same lung volume. This lung volume can be standardized from total lung capacity (TLC) if this does not change at the same time. We examined the effect of methacholine-stimulated maximal airway narrowing [change in mean forced expiratory volume in 1 s (delta FEV1) = 26.4%] on TLC, measured by whole-body plethysmography, in 10 normal subjects and of moderate airway narrowing (mean delta FEV1 = 34.9%) in 10 asthmatics. The TLC changed from 5.88 to 6.03 liters in normal subjects (P greater than 0.05) and from 6.92 to 6.95 liters (P greater than 0.5) in asthmatics. The results of this study suggest that TLC does not change significantly after methacholine-stimulated maximal airway narrowing in normal subjects and after moderate narrowing in asthmatics.

Adult↗

Clinical and physiologic heterogeneity of the central sleep apnea syndrome.

We examined the clinical and respiratory physiologic characteristics of 18 patients in whom a diagnosis of central sleep apnea syndrome was established by overnight polysomnographic studies. The patients could be readily divided into 2 groups on the basis of physiologic and clinical criteria. Five patients had an awake arterial PCO2 (PaCO2) of 53 +/- 4 (SEM) mmHg in the absence of intrinsic bronchopulmonary disease, a ventilatory response to CO2 of 0.6 +/- 0.2 L/min/mmHg, and a hemoglobin concentration of 180 +/- 6 g/L. Their clinical course was dominated by recurrent episodes of respiratory failure. In contrast, the other 13 patients had an awake PaCO2 of 35 +/- 1 mmHg (p less than 0.001), a CO2 response of 2.9 +/- 0.4 L/min/mmHg (p less than 0.005), and a hemoglobin concentration of 150 +/- 5 g/L (p less than 0.005). Clinically, they presented with features typical of sleep apnea; none had a history of respiratory failure. Despite the clinical and physiologic differences between the 2 groups, there were no differences between them in the frequency or duration of nocturnal apneic events or in sleep architecture. The findings indicate that the central sleep apnea syndrome is not a homogeneous disease entity. Rather, it includes 2 groups of patients that are clinically and physiologically distinct, with 1 group chronically hypoventilating and the other group either chronically hyperventilating or ventilating normally.

Adult↗

Role of diffuse airway obstruction in the hypercapnia of obstructive sleep apnea.

The mechanisms responsible for the development of chronic hypercapnia in patients with obstructive sleep apnea (OSA) are not well defined. Therefore, we tested the hypothesis that diffuse airway obstruction may be involved by studying 50 patients with a well-documented OSA syndrome. Seven patients had daytime hypercapnia with a mean PaCO2 of 51 +/- 2 (SEM) mm Hg, compared to a PaCO2 of 35 +/- 1 in the other 43 patients. There were no differences between the 2 groups in the number or duration of nocturnal obstructive events. In contrast, the hypercapnic patients were significantly heavier than the normocapnic patients (body weight, 189 +/- 11 versus 148 +/- 6% of ideal; p less than 0.005) and had evidence of diffuse airway obstruction, as indicated by an increased residual volume and a reduction in all expiratory flow rates. When the hypercapnic patients were compared with a weight-matched group of 9 normocapnic patients (body weight, 196 +/- 8% of ideal), there were still no differences in nocturnal obstructive events, but the differences in tests of airway mechanics persisted. Multiple regression analysis of PaCO2 against several anthropometric, respiratory physiologic, and polysomnographic variables revealed that only 2 variables (expiratory reserve volume and FEV1/FVC), both of which are influenced by airway mechanics, were significantly correlated with PaCO2 (multiple r = 0.78; p = 0.0001). The findings suggest that OSA alone does not produce daytime hypercapnia even in obese patients, and that the presence of diffuse airway obstruction is an important predisposing factor to the development of chronic CO2 retention in such patients.

Adult↗