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Biomedical subjects

N Zamel

Publications and source records attributed to N Zamel.

At least 19 recordsLinked to original sources

Heterogeneous airway tone in asthmatic subjects.

We examined the effect of volume history on the dynamic relationship between airways and lung parenchyma (relative hysteresis) in 20 asthmatic subjects. The acoustic reflection technique was employed to evaluate changes in airway cross-sectional areas during a slow continuous expiration from total lung capacity to residual volume and inspiration back to total lung capacity. Lung volume was measured continuously during this quasi-static maneuver. We studied three anatomic airway segments: extra- and intrathoracic tracheal and main bronchial segments. Plots of airway area vs. lung volume were obtained for each segment to assess the relative magnitude and direction of the airway and parenchymal hysteresis. We also performed maximal expiratory flow-volume and partial expiratory flow-volume curves and calculated the ratio of maximal to partial flow rates (M/P) at 30% of the vital capacity. We found that 10 subjects (group I) showed a significant predominance of airway over parenchymal hysteresis (P < 0.005) at the extra- and intrathoracic tracheal and main bronchial segments; these subjects had high M/P ratios [1.53 +/- 0.27 (SD)]. The other 10 subjects (group II) showed similar airway and parenchymal hysteresis for all three segments and significantly lower M/P ratios (1.16 +/- 0.20, P < 0.01). We conclude that the effect of volume history on the relative hysteresis of airway and lung parenchyma and M/P ratio at 30% of vital capacity in nonprovoked asthmatic subjects is variable. We suggest that our findings may result from heterogeneous airway tone in asthmatic subjects.

Adolescent

Maximal exercise testing in single and double lung transplant recipients.

Patients with end-stage pulmonary and pulmonary vascular disease can now be offered single-lung (SLT), double-lung (DLT), or heart-lung (HLT) transplantation. Long-term survival with greatly improved pulmonary function has been reported with all three procedures. Little has been reported of the exercise capacity after transplantation. This report documents Stage 1 exercise test results in six SLT (five males and one female; age 50.7 +/- 4.4; FEV1.0 75.5 +/- 6.7% of predicted) and seven DLT (three males and four females; age 37.3 +/- 6.7; FEV1.0 85.1 +/- 10.3% of predicted) recipients, early (3 months) and late (1 to 2 yr) following transplantation. The results show low work rates and VO2max in both SLT and DLT recipients at 3 months after transplant. Heart rate and minute ventilation did not appear limiting. There was no significant improvement when retested 1 to 2 yr after transplant. At 3 months, VO2max was 46% of predicted for SLT and 50% of predicted for DLT recipients. It is concluded that considerable exercise limitation persists after transplantation and does not appear to improve with time. These limitations are similar for both SLT and DLT and are not related to ventilation. The results may suggest chronic muscle deconditioning after long-term pretransplant debilitation.

Adult

Changes in cross-sectional airway areas induced by methacholine, histamine, and LTC4 in asthmatic subjects.

To examine whether leukotrienes, histamine, and methacholine have different sites of bronchoconstrictor action, we studied 8 stable asthmatic subjects (mean age +/- SD, 26 +/- 5 yr) on 3 different days. On each day, a randomized challenge with LTC4, methacholine, or histamine was performed until the dose that provoked a fall of 20% in FEV1 (PC20) was obtained. Complete and partial flow-volume curves as well as area-distance profiles generated by the acoustic reflection technique (ART) at a fixed lung volume were obtained in all subjects before and after each inhalation challenge. No significant differences were found in pulmonary function or baseline cross-sectional airway areas for the different study days. The three agonists provoked significant (p less than 0.05) bronchoconstriction at the level of the main bronchi when identical falls of FEV1 were achieved. Similarly, equal reductions of V30p were elicited by the three agonists. However, LTC4 and methacholine induced additional tracheal constriction but histamine inhalation did not. These differences in the degree of tracheal constriction were statistically significant (p less than 0.05; ANOVA). These results may be explained by distinct pharmacologic properties of the agents used and may have relevance in the understanding of the pathophysiology of asthma.

Analysis of Variance

Physiologic studies of tracheobronchial stents in airway obstruction.

When airway obstruction is due to extraluminal compression and/or dynamic collapse, metal and silicone rubber prosthetic stents may stabilize the affected airway. Through a rigid bronchoscope, we inserted three metal stents in two patients and 18 silicone stents in 15 adult patients with symptomatic tracheobronchial compression and dynamic airway collapse. The underlying cause was malignancy in three patients; benign tracheobronchial malacia in three patients, two of whom refused surgical resection; and tracheobronchial stenosis that developed at the anastomotic site following lung transplantation in 11 patients. Clinical status and lung function studies were analyzed before and after stent insertion. Following stent insertion, airway diameter at least doubled and near normal patency of the affected tracheobronchial tree was achieved in every patient using stents of axial length 4 to 5 cm. The stents were well tolerated clinically, and all patients noted immediate relief of dyspnea. Following stent insertion, the forced vital capacity (FVC) increased from 64 +/- 21% predicted (mean +/- 1 SD) to 73 +/- 19% predicted, p less than 0.1; the forced expiratory volume in 1 s (FEV1) from 49 +/- 25% predicted to 72 +/- 26% predicted, p less than 0.02; the ratio of the FEV1/FVC from 59 +/- 16% to 78 +/- 15%, p less than 0.01; and the maximum flow at 50% expired FVC from 38 +/- 26% predicted to 72 +/- 31% predicted, p less than 0.01.

Adult

Hypercapnic ventilatory response in recipients of double-lung transplants.

Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR.

Carbon Dioxide

Effect of low concentrations of ozone on inhaled allergen responses in asthmatic subjects.

The relation between inhalation of ambient concentrations of ozone and airway reactivity to inhaled allergens may be important in asthma, since both agents can produce inflammatory changes in the airways. Seven asthmatic patients (mean age 40 [SD 13] years), with seasonal symptoms of asthma and positive skin tests for ragweed or grass, took part in a study to investigate whether exposure to low concentrations of ozone potentiates the airway allergic response. The patients were studied during 4 separate weeks in the winter. In each week there were 3 study days: on days 1 and 3 methacholine challenges were carried out; and on day 2 the subject received one of four combined challenges in a single-blind design--air breathing followed by inhalation of allergen diluent (placebo); ozone followed by inhalation of allergen diluent; air followed by allergen; or ozone followed by allergen. The ozone concentration was 0.12 ppm during 1 h of tidal breathing at rest, and allergens were inhaled until the forced expiratory volume in 1 s (FEV1) had fallen by 15% (PC15). There were no significant differences in baseline FEV1 after exposure to ozone but PC15 was significantly reduced when allergen was preceded by ozone inhalation: the mean PC15 after air was 0.013 (SD 0.017) mg/ml compared with 0.0056 (0.0062) mg/ml after ozone (p = 0.042). Thus, low ozone concentrations, similar to those commonly occurring in urban areas, can increase the bronchial responsiveness to allergen in atopic asthmatic subjects. This effect does not seem to be the result of changes in baseline airway function.

Adult

Pharyngeal function and snoring characteristics in apneic and nonapneic snorers.

Abnormalities in pharyngeal function, manifested even when the patients are awake, are thought to play an important role in the pathogenesis of sleep apnea. Tests of awake pharyngeal function continue to stimulate interest because it is hoped that they may allow physicians to distinguish patients with sleep apnea from those without it, and therefore reduce the number of unnecessary sleep studies. We elected to study two measures of pharyngeal function: changes in pharyngeal area with lung volume (PLVD) and changes in pharyngeal area in response to externally applied positive pressure, i.e., pharyngeal distensibility (Cph). Both measurements have been employed for assessment of pharyngeal function, and both are thought to reflect pharyngeal "floppiness." Measurement of PLVD is technically very simple, whereas the measurement of Cph is technically more complex. If the two measurements are highly correlated, it might be possible to replace the technically more difficult one by the simpler one. Consequently, the purpose of this study was two-fold: first, to examine the relationship between pharyngeal distensibility and lung volume dependence of pharyngeal area, and second, to compare these parameters in a large group of confirmed snorers with and without obstructive sleep apnea (OSA). We studied 75 unselected patients referred for the investigation of snoring and suspected sleep apnea. All patients had nocturnal polysomnography, pulmonary function tests, and measurement of pharyngeal areas at TLC, FRC, and residual volume (RV) employing the acoustic reflection technique. The area measurement at FRC was performed at zero and at 4.1 cm H2O positive airway pressure to calculate pharyngeal distensibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Airflow limitation in morbidly obese, nonsmoking men.

STUDY OBJECTIVE: To determine the effect of obesity on pulmonary function. DESIGN: Case-control study, using nonobese, age- and height-matched [corrected] nonsmokers. SETTING: Metabolic and obesity clinics of two major teaching hospitals. PATIENTS: One hundred and three obese, lifelong nonsmokers without cardiopulmonary disease. CONTROLS: One hundred and ninety healthy, nonobese nonsmokers recruited from among hospital personnel. MEASUREMENTS AND MAIN RESULTS: Complete pulmonary function measurements in all patients and controls. These measurements included maximum expiratory flow-volume curve, lung volumes and airway resistance using body plethysmograph, single-breath diffusing capacity for carbon monoxide, and total lung capacity using the helium dilution technique. Obese persons were found to have lower functional residual capacity, expiratory reserve volume, and total lung capacity by helium dilution than nonobese controls. In addition, residual volume and diffusing capacity were higher in the obese group. Finally, we found that obese men, but not women, had reduced maximum expiratory flow rates at 50% and 75% of exhaled vital capacity. CONCLUSION: Obesity may contribute independently of smoking habits to chronic airflow limitation in men.

Adult

Results of single-lung transplantation for bilateral pulmonary fibrosis. The Toronto Lung Transplant Group.

Between November 1983 and August 1989, we performed single-lung transplantation for end-stage pulmonary fibrosis in 20 patients. Nine patients (45 percent) who survived for more than one year form the basis of this report. Before surgery, the nine survivors had severe restrictive lung disease, with a mean (+/- SD) vital capacity (VC) of 43 +/- 9 percent, a forced expiratory volume in one second (FEV1) of 50 +/- 9 percent, and a single-breath diffusing capacity (DLCO) of 36 +/- 9 percent of predicted values. One year after transplantation, the patients' VC had reached 69 +/- 10 percent, FEV1 79 +/- 15 percent, and DLCO 62 +/- 16 percent of predicted values. Relative perfusion to the transplanted lung rose from 63 +/- 14 percent (three days after surgery) to 77 +/- 7 percent within three months and stayed constant or increased slightly thereafter. Before surgery, despite supplemental oxygen at flow rates varying from 1 to 9 liters per minute, none of the patients could exercise beyond stage 1/2 (2.7 km [1.7 miles] per hour, 5 percent grade) on a modified Bruce treadmill-exercise protocol. All eight patients tested one year or more after transplantation achieved at least stage 1 (2.7 km [1.7 miles] per hour, 10 percent grade), and usually a higher stage, without supplemental oxygen. Arterial oxygen tension returned to normal values in most patients (87 +/- 13 mm Hg), and supplemental oxygen, which all patients required before surgery, was no longer needed by any patient after transplantation. We conclude that in carefully selected patients with end-stage pulmonary fibrosis, single-lung transplantation is an effective treatment.

Adolescent

Mechanisms of gas exchange with different gases during constant-flow ventilation.

To investigate the mechanisms responsible for the difference in gas exchange during constant-flow ventilation (CFV) when using gases with different physical properties, we used mixtures of 70% N2-30% O2 (N2-O2) and 70% He-30% O2 (He-O2) as the insufflating gases in 12 dogs. All dogs but one had higher arterial PCO2 (PaCO2) with He-O2 compared with N2-O2. At a flow of 0.37 +/- 0.12 l/s, the mean PaCO2's with N2-O2 and He-O2 were 41.3 +/- 13.9 and 53.7 +/- 20.3 Torr, respectively (P less than 0.01); at a flow rate of 0.84 +/- 0.17 l/s, the mean PaCO2's were 29.1 +/- 11.3 and 35.3 +/- 13.6 Torr, respectively (P less than 0.01). The chest was then opened to alter the apposition between heart and the lungs, thereby reducing the extent of cardiogenic oscillations by 58.4 +/- 18.4%. This intervention did not significantly alter the difference in PaCO2 between N2-O2 and He-O2 from that observed in the intact animals, although the individual PaCO2 values for each gas mixture did increase. When the PaCO2 was plotted against stagnation pressure (rho V2), the difference in PaCO2 between N2-O2 and He-O2 was nearly abolished in both the closed- and open-chest animals. These findings suggest that the different PaCO2's obtained by insufflating gases with different physical properties at a fixed flow rate, catheter position, and lung volume result mainly from a difference in the properties of the jet.

Animals

Do patients with obstructive sleep apnea have thick necks?

During physical examination of patients with suspected obstructive sleep apnea (OSA), a comment is frequently made that they appear to have a short and fat neck. To confirm this subjective impression by objective measurements, we studied a group of 123 patients referred to us because of snoring and suspected OSA, all of whom had nocturnal polysomnography and measurements of external and internal neck circumference. The external neck circumference was measured at the level of the superior border of the cricothyroid cartilage. Internal neck circumferences were calculated from the measurements of pharyngeal, glottic, and tracheal areas obtained by the acoustic reflection technique. Internal pharyngeal circumference was further subdivided into the proximal, middle, and distal thirds. The acoustic technique also permitted us to measure the distance between the teeth and the glottic minimum, which reflects the length of the upper airway. Stepwise multiple linear regression analysis revealed that the apnea/hypopnea index (AHI) correlated only with the external neck circumference, the body mass index, and the internal circumference of the distal pharynx; these three variables accounted for 39% of the variability in AHI. We conclude that the external and internal neck circumferences and the degree of obesity are important predictors of sleep apnea; it is possible that obesity produces its effect via fat in the neck. We speculate that the static pharyngeal size modulated by the dynamic loading of the airway due to the weight of fatty tissue of the neck may contribute to the pathogenesis of OSA.

Adult

An evaluation of flow-volume curves as a screening test for obstructive sleep apnea.

We examined flow-volume curves for their potential as screening tests for obstructive sleep apnea (OSA) in 401 patients referred for investigation of snoring. In all patients, we performed nocturnal polysomnography, maximum inspiratory and maximum expiratory flow-volume curves. The curves were examined for two features: 1) presence of flow oscillations (the "saw-tooth" sign), and 2) changes in their configuration that might suggest upper airway obstruction as documented by the expiratory/inspiratory flow ratios calculated at 50 and 75 percent of exhaled vital capacity (FR50 and FR25, respectively). Based on the results of nocturnal polysomnography, the patients were stratified according to severity into apnea groups, and the flow ratios and flow oscillations were compared among these groups. We found that neither the FR50 nor FR25 were significantly different among the groups. Inspiratory and expiratory flow oscillations were seen infrequently (32 patients) and tended to occur in patients with more severe sleep apnea. Neither the flow ratios nor the flow oscillations had good predictive values for snoring or sleep apnea. The sensitivity of the flow volume curve abnormalities ranged between 0 and 14 percent, but the specificity was high, ranging between 93 and 95 percent. We conclude that because of low sensitivity, flow-volume loops are not a useful screening test for the diagnosis of OSA in snoring patients.

Adult

Glottic dimensions in healthy men and women.

Glottic aperture is important in modulating respiratory system resistance. Male patients with obstructive sleep apnea (OSA) have a smaller glottic cross-sectional area compared to controls. Since OSA has a strong male predominance, we reasoned that glottic dimensions may differ between healthy men and women. Therefore, we utilized the acoustic reflection to measure glottic cross-sectional area in 44 non-smoking, non-obese, healthy subjects, 25 men and 19 women. Glottic area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared glottic areas in men and women at three lung volumes: TLC, 50% of vital capacity (VC), and RV. We found that in all but 2 subjects, glottic areas at TLC was greater than at 50% VC or RV. At any given lung volume, there was no significant difference in glottic area between men and women. The reduction in glottic area between TLC and RV was also similar between men and women (36 +/- 24% and 33 +/- 21%, respectively). However, this reduction in glottic area occurred mainly at low lung volumes in women, and more uniformly throughout the vital capacity range in men. We conclude that changes in glottic dimensions are dependent on lung volume, that healthy men and women have similar glottic areas, and that the glottic aperture shows similar variation with lung volume among both sexes.

Adult

Tracheal hysteresis in sleep apnea.

The collapsibility of pharyngeal walls, characteristic of patients with obstructive sleep apnea, likely results from reduced tone of the pharyngeal muscles. This reduction in the upper airway muscle tone may not end at the pharynx but may extend further distally, e.g., into the trachea. Because tracheal tone cannot be measured directly in conscious humans, we inferred the tone from the relative hysteresis of the tracheal area compared with the lung. Relative hysteresis was measured by plotting the cross-sectional area of a tracheal segment obtained by the acoustic reflection technique vs. lung volume. All measurements were performed during wakefulness. We found that in 42 patients with obstructive sleep apnea (apnea/hypopnea index greater than 10), relative hysteresis of the proximal trachea was predominantly clockwise, i.e., smaller than that of the lung parenchyma; in the 33 nonapneic patients (apnea/hypopnea index less than or equal to 10), it was predominantly counter-clockwise, i.e., larger than that of the lung parenchyma. For the distal trachea all patients, apneic and nonapneic, had similar, clockwise, relative hysteresis. We conclude that reduction in the upper airway muscle tone in patients with obstructive sleep apnea extends into the trachea.

Adolescent