CT fluoroscopy guidance for transbronchial needle aspiration: an experience in 35 patients.

OBJECTIVE: To demonstrate the usefulness of real-time guidance with CT fluoroscopy to improve the yield of transbronchial needle aspiration (TBNA). DESIGN: Prospective, observational. SETTING: A tertiary-care, university-affiliated medical center. METHODS: From December 1998 to April 2000, 35 patients underwent CT fluoroscopy-guided TBNA. Patients with subcarinal and precarinal lymph nodes were only included if a previous attempt was nondiagnostic, as the initial yield in this setting with conventional TBNA is high. TBNA was performed using standard technique in a CT-scan suite. Needle location was confirmed with fluoroscopy without IV contrast being used. Specimens were evaluated on-site for adequacy. RESULTS: The procedure had to be aborted in three patients before TBNA could be performed. Samples were obtained in 32 patients. Samples were nondiagnostic in four patients. Adequate tissue was obtained in 28 of 32 patients (87.5%). Twenty-two patients had a specific benign or malignant diagnosis made, and 6 patients had lymphocytes only on the specimen. In follow-up, only one of these six patients proved to have a malignancy. All procedures were performed within a regular interventional CT time slot of 1 h. No TBNA side effects were noted. CONCLUSION: TBNA under CT fluoroscopic guidance is easy to perform. The yield in all accessible lymph node stations is high.

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance imaging is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Cardiovascular morbidity in obstructive sleep apnea.

The repetitive respiratory events that characterize obstructive sleep apnea (OSA) are each followed by abrupt increases in heart rate and in pulmonary and systemic artery pressure and by sudden decreases in right and left ventricular stroke volume. The changes in systemic pressure may be profound, with patients who are normotensive while awake having systolic pressures approaching 300 mm Hg after apnea termination. Because of these dramatic hemodynamic oscillations during sleep, many clinicians and investigators have postulated a connection between sleep-disordered breathing and cardiovascular morbidity and even mortality. This review critically examines the evidence for such a causal relationship. We begin, however, by reviewing the normal hemodynamic changes that occur during sleep. We then describe the acute hemodynamic events associated with OSA. Finally, we summarize the evidence for and against a causal connection between sleep apnea and cardiovascular morbidity.

MR imaging of pulmonary parenchyma with a half-Fourier single-shot turbo spin-echo (HASTE) sequence.

OBJECTIVE: To evaluate the utility of a half-Fourier single-shot turbo spin-echo sequence (HASTE) at depicting lung parenchyma and lung pathology. METHODS AND PATIENTS: A HASTE sequence was applied to five normal volunteers and 20 patients with various pulmonary disorders to depict the lung parenchyma. Images were acquired with ECG-triggering and breath-holding. In three volunteers, signal intensity measurements from lung parenchyma were performed using four sequences: (a) HASTE; (b) conventional spin echo; (c) fast spin echo; and (d) gradient echo. T2 maps were produced using the HASTE acquisition. RESULTS: Minimal respiratory or cardiac motion artifacts were observed. The signal-to-noise ratios from lung parenchyma were 27.8 +/- 5.4, 22.0 +/- 3.0, 15.3 +/- 0.9, and 6.0 +/- 1.9 for HASTE, spin-echo, fast spin-echo, and gradient echo sequences, respectively. The scan time for HASTE was 302 ms for each slice. The T2 values in the right lung and the left lung were 61.2 +/- 4.1 and 79.1 +/- 8.9 ms in systole and 92.6 +/- 5.8 and 97.5 +/- 12.2 ms in diastole, respectively (P < 0.05 diastole versus systole). The HASTE sequence demonstrated clearly various pulmonary disorders, including lung cancer, hilar lymphadenopathy, metastatic pulmonary nodules as small as 3 mm, pulmonary hemorrhage, pulmonary edema and bronchial wall thickening in bronchiectasis. CONCLUSION: Our preliminary results indicate that the HASTE sequence provides a practical means for breath-hold MR imaging of lung parenchyma.

Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast.

CONTEXT: Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident. OBJECTIVE: To describe a clinical syndrome associated with zafirlukast therapy. DESIGN: Case series. PATIENTS: Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast. MAIN OUTCOME MEASURES: Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment. RESULTS: The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6 x 10(9)/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5 degrees C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment. COMMENT: Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast.

Hemodynamic consequences of obstructive sleep apnea.

Patients with obstructive sleep apnea demonstrate both acute and chronic hemodynamic changes attributable to their disease. Acutely, these patients experience repetitive nocturnal hemodynamic oscillations. Sudden increases in heart rate and arterial pressure occur in association with decreases in left ventricular stroke volume immediately following apnea termination. These hemodynamic changes are likely attributable primarily to the effects of oxygen desaturation and arousal, an abrupt change in state. These acute changes occur against a background of altered cardiovascular control. Patients with sleep apnea, even when sleeping without obstructions, fail to display the normal nocturnal decline in arterial pressure of 10-15% from the waking value. The absence of a nocturnal decline may have chronic consequences, such as development of left ventricular hypertrophy. Another chronic hemodynamic consequence of sleep apnea may be sustained diurnal hypertension. Epidemiologic studies suggest individuals with sleep disordered breathing are at greater risk of daytime hypertension, even after controlling for other risk factors. Although sleep apnea may contribute to pulmonary, as well as systemic hypertension, sleep apnea alone does not appear to be a cause of decompensated right heart failure. Although knowledge of the hemodynamic consequences of sleep apnea has grown in recent years, much remains to be learned.

Effects of beta adrenergic receptor blockade on hemodynamic changes associated with obstructive sleep apnea.

To study the effects of airway obstruction (AWO) and arousal on coronary blood flow, mean arterial pressure (MAP) and heart rate (HR), pigs were chronically instrumented with arterial catheters, Doppler flow probes on the left circumflex coronary artery, and electrodes for determination of sleep stages. A modified balloon catheter was placed in the trachea to obstruct the upper airway during sleep. Following control studies, the role of beta adrenergic receptors in hemodynamic responses to AWO was assessed by administering propranolol, a beta adrenoreceptor blocking agent. In control studies, during nonrapid eye movement sleep (NREM), MAP was 85 +/- 2 mmHg before AWO and increased by 8 +/- 2 mmHg upon arousal. Mean arterial pressure was lower during rapid eye movement (REM) sleep (64 +/- 2 mmHg) and the increase upon arousal was threefold greater (22 +/- 2 mmHg). Heart rate was similar in both sleep stages (NREM 123 +/- 5 bpm; REM 125 +/- 6 bpm) and increased significantly upon arousal (NREM, 11 +/- 2 bpm; REM, 18 +/- 3 bpm increase). Coronary blood flow was similar during both stages (NREM 44 +/- 5 ml/min; REM 44 +/- 6 ml/min) and increased by 13% (NREM) and 22% (REM) during arousal. Coronary vascular resistance increased significantly by 17% during arousal from AWO during REM sleep. All changes were significant at p < 0.05. Following beta adrenergic receptor blockade studies using propranolol, baseline HR was reduced in NREM sleep and HR and coronary blood flow increases during arousal from apnea were eliminated. Adrenoreceptor blockade studies suggest that these effects were mediated by the beta adrenergic component of the sympathetic nervous system.

Sleep stage influences the hemodynamic response to obstructive apneas.

Blood pressure (BP) rises at the termination of obstructive episodes in patients with sleep apnea. Although the relationship of these BP elevations to oxygen saturation (SaO2) and arousal has been explored, the influence of sleep stage is undefined. To examine the effects of sleep stage on the postapnea BP elevation, we enrolled 12 patients with obstructive sleep apnea (OSA), and successfully collected data from seven of these (all male). Subjects slept overnight in the sleep laboratory, with full sleep and respiratory monitoring. Arterial pressure was assessed continuously with a radial artery catheter (six patients) or with digital photoplethysmography (one patient). Apneas occurring in both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep were matched for duration and degree of desaturation. When mean arterial pressure (MAP) at termination of apneas during NREM sleep associated with SaO2 nadirs 78 to 82% (NREM 80%) was compared with MAP following apneas in REM with the same SaO2 nadir (REM 80%), there was a significant difference (NREM 80% 122 +/- 15.3 mm Hg, REM 80% 132 +/- 11.0; p = 0.0109). We also analyzed the effect of oxygen desaturation on MAP during REM sleep, by comparing events with SaO2 nadirs of 78 to 82% with events with nadirs of < 75% (REM < 75%). In REM, further desaturation was associated with significant lengthening of the obstructive episodes and significantly higher postapnea BP increases (REM 75% 143 +/- 19.9 mm Hg, p = 0.0392). We conclude that sleep stage alters the hemodynamic response to obstructive apneas during sleep.

Decrease in ventricular stroke volume at apnea termination is independent of oxygen desaturation.

Patients with obstructive sleep apnea experience nocturnal hemodynamic oscillations in association with repetitive respiratory events. Apnea termination (recovery) is accompanied by the nadir of arterial O2 saturation (SaO2), changes in intrathoracic pressure, and arousal from sleep. To investigate separately the contributions of hypoxemia and of arousal from sleep to changes in cardiac function, we continuously measured left ventricular stroke volume (LVSV) and mean arterial pressure (MAP) in eight subjects with severe obstructive sleep apnea (apnea-hypopnea index > 30 events/h associated with SaO2 < or = 82%) during two experimental conditions: 1) subjects slept without intervention for 1-2 h and then supplemental O2 was administered to maintain SaO2 > or = 90% (mean SaO2 nadir 92.7%) throughout the apnea-recovery cycle and 2) upper airway obstructions were abolished using nasal continuous positive airway pressure and subjects were aroused from sleep by an auditory signal. Recovery was associated with an increase in MAP and a decrease in LVSV both with and without supplemental O2. Arousal from sleep on nasal continuous positive airway pressure reproduced the postapneic elevation of MAP but not a decrease in cardiac function of the magnitude that occurred at apnea termination. We conclude that elevation of blood pressure and reduction of LVSV that occurred at apnea termination may be due to different physiological mechanisms.

Systemic blood pressure elevation after airway occlusion during NREM sleep.

Increases in arterial pressure follow obstructive sleep apneas even in the absence of hypoxemia. These blood pressure (BP) elevations could be caused by arousal from sleep, resumption of ventilation, or abrupt changes of intrathoracic pressure (ITP). To better define the relative contributions of each of these factors to the BP elevations, we designed two protocols employing six normal subjects isolating the effects of arousal from those of ventilation and ITP. BP (Penaz method), sleep stage, air flow, and esophageal pressure (Pes) were monitored. Episodically, a stopcock was closed, occluding the inspiratory circuit. In Experiment 1, data were recorded on tape. Occlusions were initiated during Stage 2 NREM sleep and released coincident with arousal. Subjects were than awakened and instructed to trace the displayed, taped Pes profile creating occlusions of identical duration to those recorded during sleep. In five subjects, the mean BP elevation (preocclusion to peak) associated with occlusion release upon arousal was 19.0 +/- 5.1 mm Hg, whereas the analogous rise for matched awake occlusions was 5.4 +/- 4.8 mm Hg (p = 0.027). In Experiment 2, occlusion release was delayed 6 to 12 s after arousal. In five subjects, these occlusions were associated with BP elevations that peaked coincident with arousal, not with resumption of ventilation (mean increase, 18.0 +/- 10.4 mm Hg). We conclude that under the conditions of these experiments, BP elevations after airway occlusion during sleep are attributable more to arousal than to resumption of ventilation.

Hemodynamic changes associated with obstructive sleep apnea followed by arousal in a porcine model.

To study the effects of airway obstruction (AWO) and arousal on coronary blood flow, mean arterial pressure (MAP), and heart rate, pigs were chronically instrumented with arterial catheters, Doppler flow probes on the left circumflex coronary artery, and electrodes for determination of sleep stages. A modified tracheostomy tube was placed in the trachea to obstruct the upper airway during sleep sessions. In control studies, during non-rapid-eye-movement (NREM) sleep, MAP was 84 +/- 2 mmHg before AWO and increased by 5 +/- 2 mmHg on arousal. MAP was lower during rapid-eye-movement (REM) sleep (62 +/- 2 mmHg), and the increase on arousal was fourfold greater (22 +/- 2 mmHg). Heart rate was similar in both sleep stages (NREM: 120 +/- 4 beats/min; REM: 124 +/- 5 beats/min) and increased significantly on arousal (NREM: 12 +/- 2 beats/min; REM: 18 +/- 1 beats/min). Coronary blood flow was similar during both stages (NREM: 43 +/- 4 ml/min; REM: 46 +/- 8 ml/min) and increased by 12-15% on arousal. Coronary vascular resistance index increased significantly by 24% on arousal from AWO during REM sleep. All increases and decreases were significant at P < 0.05. Receptor blockade studies were performed to assess alpha-adrenergic receptor involvement.

Stroke volume and cardiac output decrease at termination of obstructive apneas.

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenylephrine-induced hypertension acutely decreases genioglossus EMG activity in awake humans.

To investigate the relationship between systemic blood pressure (BP) and upper airway dilator muscle activity, we recorded genioglossus electromyograms (EMGgg) during pharmacologically induced acute increases in BP in five healthy humans (ages 27-40 yr). EMGgg was measured with perorally placed fine-wire electrodes; phasic EMGgg was expressed as percentage of baseline activity. Subjects were studied supine, awake, and breathing through a face mask with their mouths taped. End-tidal PCO2 was monitored with a mass spectrometer; minute ventilation was measured with a pneumotachograph. Digital BP was monitored continuously with the Penaz method (Finapres, Ohmeda). Mean arterial pressure (MAP) at baseline was 89 +/- 6 (SD) mmHg. Phenylephrine was infused until MAP reached 15-25 mmHg above baseline (107 +/- 7 mmHg). Recording was continued until MAP returned to baseline (90 +/- 7 mmHg). Elevated BP was associated with a significantly decreased phasic EMGgg (P less than 0.005). With return of MAP to baseline, phasic EMGgg returned toward normal (P less than 0.01). Minute ventilation and end-tidal PCO2 did not differ among conditions. Genioglossus activity appears to be influenced by acute changes in systemic BP. We speculate that BP elevations accompanying obstructive apneas during sleep may decrease upper airway tone and facilitate subsequent apneas.