Comparative effects of transdermal clonidine and oral atenolol on acute exercise performance and response to aerobic conditioning in subjects with hypertension.

We compared the effects of transdermal clonidine and oral atenolol on acute exercise performance and on conditioning response to an 8-week program of regular aerobic exercise in young, otherwise healthy subjects with mild hypertension. The study was a double-blind, randomized, parallel-group study with placebo control. Twenty-seven subjects (11 receiving transdermal clonidine, 8 receiving oral atenolol, and 8 receiving placebo) completed the study. Atenolol controlled blood pressure in all 8 subjects, vs 6 of 11 in the transdermal clonidine group and 0 of 8 in the placebo group. Both active drugs lowered systolic blood pressure during exercise. With clonidine treatment, the antihypertensive effect during exercise was smaller and was observed only at low and moderate workloads. Acute exercise performance (subjects receiving drug but still unconditioned) was assessed by endurance time at a constant workload equal to the highest workload completed on a previous 2-minute incremental exercise test. Endurance time was reduced 35% by atenolol but not by transdermal clonidine or placebo. Neither active drug interfered with the progress of the conditioning program, as measured by gradual lengthening of exercise time. However, as assessed by change in oxygen uptake standardized to a heart rate of 170 beats per minute, the improvement in conditioning was twice as great in subjects receiving transdermal clonidine and placebo (+20%, +18%) as it was in those receiving atenolol (+8%). Subjects receiving placebo and transdermal clonidine lost weight; subjects receiving oral atenolol gained weight. The changes in weight were small.

Nocturnal rocking bed therapy: improvement in sleep fragmentation in patients with respiratory muscle weakness.

Three patients with respiratory muscle weakness developed sleep fragmentation due to nonobstructive apnea and hypopnea. In two patients in whom inspiratory muscle electromyogram was recorded, the apneas and hypopneas were terminated only by arousal and excessive recruitment of accessory muscles. Nocturnal rocking bed ventilatory support resulted in immediate improvement in sleep fragmentation and inhibited arousal-associated phasic accessory muscle activation, resulting in improvement in daytime hypercapnia and subjective sleepiness. Sleep fragmentation may occur more commonly than generally appreciated in neuromuscular disease patients who are independent of daytime ventilatory support. The use of nocturnal rocking bed is an effective noninvasive method of reversing sleep fragmentation and daytime sequelae when obstructive apnea is absent.

Single night studies in obstructive sleep apnea.

The role of single night studies and the determinants of effective nasal continuous positive airway (CPAP) pressures were determined in 412 consecutive patients between 1984 and 1989. Patients chosen for analysis had an apnea index (AI) of greater than or equal to 20 hr-1 prior to CPAP. The AI was 67 +/- 30 hr-1, the body mass index (BMI) was 36 +/- 9 kg/m2, the age was 51 +/- 13 yr and the lowest oxygen saturation was 72 +/- 14%. Effective CPAP (9 +/- 3 cm H2O) was documented in 320 patients on single night studies and resulted in a 99% reduction in the frequency of obstructive events and improvement in the lowest O2 saturation to 94 +/- 5%. Only 18% of the variability in effective CPAP could be explained by AI and BMI. Single night studies are sufficient to establish effective CPAP in 78% of patients and offer considerable conservation of resources compared to routine multiple night studies. Effective CPAP pressures are variable and must be determined by incremental CPAP trials.

Rates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing.

OBJECTIVES: To evaluate study failure and sensor loss in unattended home polysomnography and their relationship to age, gender, obesity, and severity of sleep-disordered breathing (SDB). DESIGN: A cross-sectional analysis of data gathered prospectively for the Sleep Heart Health Study (SHHS). SETTING: Unattended polysomnography was performed in participants' homes by the staff of the sites that are involved in SHHS. PARTICIPANTS: 6,802 individuals who met the inclusion criteria (age >40 years, no history of treatment of sleep apnea, no tracheostomy, no current home oxygen therapy) for SHHS. RESULTS: A total of 6802 participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%) were acceptable. Obesity was associated with a decreased likelihood of a successful initial study. After one or more attempts, 6440 participants (94.7%) had studies that were judged as acceptable. The mean duration of scorable signals for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects of age, gender, BMI, and RDI on specific signal durations were not clinically significant. CONCLUSION: Unattended home PSG as performed for SHHS was usually successful. Participant characteristics had very weak associations with duration of scorable signal. This study suggests that unattended home PSG, when performed with proper protocols and quality controls, has reasonable success rates and signal quality for the evaluation of SDB in clinical and research settings.

Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice.

The objective assessment of patients with a presumptive diagnosis of obstructive sleep apnea (OSA) has primarily used attended polysomnographic study. Recent technologic advances and issues of availability, convenience and cost have led to a rapid increase in the use of portable recording devices. However, limited scientific information has been published regarding the evaluation of the efficacy, accuracy, validity, utility, cost effectiveness and limitations of this portable equipment. Attaining a clear assessment of the role of portable devices is complicated by the multiplicity of recording systems and the variability of clinical settings in which they have been analyzed. This paper reviews the current knowledge base regarding portable recording in the assessment of OSA, including technical considerations, validation studies, potential advantages and disadvantages, issues of safety, current clinical usage and areas most in need of further study.

The Sleep Heart Health Study: design, rationale, and methods.

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group.

This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.

Tidal volume reduction in ARDS. Effect on cardiac output and arterial oxygenation.

During continuous positive pressure ventilation (CPPV), mean airway pressure and lung volume will be influenced both by the tidal volume (VT) employed and the amount of positive end-expiratory pressure (PEEP). The effect of varying levels of CPPV on PaO2 and cardiac output (Q) has been previously assessed by adjusting the level of PEEP at constant VT. This study examined the influence of a 200-ml reduction in VT, at a constant PEEP of 15 cm H2O, on the PaO2 and Q of 21 patients with adult respiratory distress syndrome (ARDS). The relationship between change in Q and change in total respiratory system compliance (Cst) after VT reduction was also examined. VT reduction from 14.1 +/- 0.8 ml/kg to 11.2 +/- 0.9 ml/kg yielded an increase in Q (+ 15 +/- 12 percent, p less than 0.01) without a significant change in PaO2 (-6.3 +/- 15.0 mm Hg, p = 0.08). Cst increased with VT reduction (+ 3.1 +/- 1.8 ml/cm H2O). There was only a modest correlation (r = +0.42, p = 0.06) between delta Q percent and delta Cst following VT reduction. VT reduction at high level PEEP may yield a significant improvement in Q and net O2 delivery, but the degree of hemodynamic improvement is variable and is not reliably predicted noninvasively by measurement of Cst.

Paragonimiasis in the United States. A report of nine cases in Hmong immigrants.

Nine cases of paragonimiasis have been encountered in Laotian Hmong immigrants from Camp Ban Vinai in Thailand. Symptoms included cough, hemoptysis, and fever. Chest x-ray films showed segmental infiltrates and pleural effusions, often bilateral. The clinical presentation mimics tuberculosis. All Hmong patients with chronic infiltrates and pleural disease in whom tuberculosis has not been proven should have parasitologic and serologic evaluation to exclude paragonimiasis.

A possible mechanism for mixed apnea in obstructive sleep apnea.

Hypopneas or pauses in respiratory effort frequently precede episodes of obstructive sleep apnea resulting in mixed apneas. We studied five subjects after chronic tracheostomy for obstructive sleep apnea. During stable non-REM (NREM) sleep, subjects breathed entirely through the tracheostomy. Tracheostomy occlusion caused experimental obstructive apnea which lasted 13.9 +/- 4.7 sec and ended with transient arousal and pharyngeal opening. At the end of the apnea there was marked hyperventilation (inspired minute ventilation rose 21.6 +/- 3.5 L on the first breath) followed by hypocapnia, hypopnea, and pauses in inspiratory effort as the subjects resumed NREM sleep. Hypocapnia was greater before inspiratory pauses lasting at least 5 sec than before shorter pauses (PETco2, 4.2 +/- 1.8 mm Hg below baseline vs 1.2 +/- 2.5 mm Hg below baseline). In three patients, pauses in inspiratory effort following experimental obstructive apnea were prevented by administration of 4 percent CO2 and 40 percent O2 inspired gas. This study suggests that: hyperventilation with hypocapnia occurs at the termination of obstructive apneas, and hypocapnia may be responsible for the attenuation or cessation of respiratory effort initiating the subsequent cycle of obstruction.

Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans.

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10-15 min and maintained for 2-3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.

Respiratory sinus arrhythmia in humans: an obligatory role for vagal feedback from the lungs.

Respiratory sinus arrhythmia (RSA) is used as a noninvasive measure of vagal cardiac input, but its causative mechanisms in humans remain undetermined. We compared the RSA of five lung-denervated double-lung transplant patients with intact hearts to six normal (N) control subjects, five heart-denervated patients, and two liver transplant patients at matched tidal volumes (VT's) and breathing frequencies. In N and liver transplant subjects, RSA was significant during eupnea and increased two- to threefold with increasing VT and inspiratory effort. In heart- and lung-denervated subjects, RSA at eupnea was significant but was only 53% of that in N subjects and was not respondent to changing VT, inspiratory effort, or breathing frequency. We also compared the RSA of N subjects during voluntary (active) and passive positive pressure ventilation at normocapnia. RSA was reduced from 11 +/- 2.2 beats/min during active ventilation to 5.4 +/- 0.8 beats/min during PPV. We conclude that vagal feedback from pulmonary stretch receptors is obligatory for the generation of a neurally mediated RSA in awake humans at normal and raised levels of VT and respiratory motor output. In intact humans, we also hypothesize an important effect for nonpulmonary central and/or peripheral modulation of RSA. It is likely that the key mechanisms for neurally mediated RSA in unanesthetized humans are mutually dependent.

Effect of respiratory alkalosis during exercise on blood lactate.

A biofeedback model of hyperventilation during exercise was used to assess the independent effects of pH, arterial CO2 partial pressure (PaCO2), and minute ventilation on blood lactate during exercise. Eight normal subjects were studied with progressive upright bicycle exercise (2-min intervals, 25-W increments) under three experimental conditions in random order. Arterialized venous blood was drawn at each work load for measurement of blood lactate, pH, and PaCO2. Results were compared with those from reproducible control tests. Experimental conditions were 1) biofeedback hyperventilation (to increase pH by 0.08-0.10 at each work load); 2) hyperventilation following acetazolamide (which returned pH to control values despite ventilation and PaCO2 identical to condition 1); and 3) metabolic acidosis induced by acetazolamide (with spontaneous ventilation). The results showed an increase in blood lactate during hyperventilation. Blood lactate was similar to control with hyperventilation after acetazolamide, suggesting that the change was due to pH and not to PaCO2 or total ventilation. Exercise during metabolic acidosis (acetazolamide alone) was associated with blood lactate lower than control values. Respiratory alkalosis during exercise increases blood lactate. This is due to the increase in pH and not to the increase in ventilation or the decrease in PaCO2.

Uvulopalatopharyngoplasty for obstructive sleep apnea: a community's experience.

Uvulopalatopharyngoplasty (UPPP) has become an accepted method for treating obstructive sleep apnea (OSA), with a reported success rate as high as 77%, depending upon inclusionary and outcome criteria. The authors reviewed the records of 90 patients with moderately severe OSA (apnea plus hypopnea index [AHI] greater than 20) who underwent UPPP at either a private community or an academic hospital. Forty percent of patients experienced more than a 50% reduction in their AHI with UPPP. Only 22 (24%) of the patients had a postoperative AHI less than 50% of the preoperative AHI and less than 20, i.e., met the authors' criteria for surgical success. The success rate for community otolaryngologists was no different than that achieved in the academic institution. When data from previously published reports were analyzed using these criteria for success, similar results were observed. This study suggests that the effectiveness of UPPP performed by the general otolaryngologic community is equivalent to that reported in the literature. However, more rigorous criteria must be applied to UPPP when evaluating its results and in counseling potential candidates for this procedure.

Foamy alveolar casts: diagnostic specificity for Pneumocystis carinii pneumonia in bronchoalveolar lavage fluid cytology.

Pneumocystis carinii pneumonia (PCP) is a major infectious complication of immunodeficiency states, including the acquired immunodeficiency syndrome (AIDS). Bronchoalveolar lavage (BAL) is a safe and effective procedure for making this diagnosis. In addition to the characteristic organisms, both histologic and cytologic material often reveals exudate in the form of foamy alveolar casts (FACs). To test the diagnostic utility of FACs in BAL fluids, we compared 20 PCP-positive and 28 PCP-negative fluids as assessed by silver stains. All PCP-positive fluids contained FACs on Papanicolaou-stained material. Only one PCP-negative lavage contained FACs, and transbronchial biopsy in this case revealed PCP. We suggest that FACs in BAL fluids are highly sensitive and specific for the diagnosis of PCP.

Pulmonary mycetomas in immunocompetent patients: diagnosis by fine-needle aspiration.

Mycetomas usually grow within preexisting cavities and frequently lead to pulmonary hemorrhage. We describe four males, aged 38 to 72 years, in whom myceotomas were diagnosed by FNA. Preexisting cavitary lesions resulted from tuberculosis, anaerobic abscess, and bullous lung disease (two cases). Fine needle aspiration yielded tangled mats of fungal hyphae (large and grossly visible in three cases) and acute inflammatory cells. The atypical cells often seen in the walls of such lesions were not identified. Cultures showed Aspergillus (3 cases) Pseudoallescheria boydii (1 case). The diagnosis was surgically confirmed in two cases. Two patients were too ill for surgery and the fourth refused. At 7 and 10 months, the two remaining individuals have pulmonary hemorrhage but no evidence of progression or malignancy. In poor surgical candidates, conservative management of mycetomas diagnosed by fine needle aspiration is appropriate. Excluding mycetoma secondary to cavitary lung carcinoma requires careful correlation of historical, clinical, radiographic, cytologic, and follow-up data.

Awake inspiratory airway occlusion in normal humans is followed by hyperpnea and hypocapnia.

The ventilatory response following 15 seconds of inspiratory airway occlusion at functional residual capacity (FRC) was studied in nine normal supine awake subjects. Expired minute ventilation (VE), CO2 output (VCO2), tidal volume (VT), and end-tidal PCO2 (PETCO2) were measured on a breath-by-breath basis. Alveolar PCO2 rose 5.6 mm Hg during the apnea (P less than 0.001). Ventilation rose 10.8 L/min on the first breath following apnea and remained elevated above control measurements for five breaths (P less than 0.05). The persistent hyperpnea was due to an increase in tidal volume and was associated with alveolar hypocapnia for 6 breaths or 30 sec (P less than 0.05) and an increase in CO2 output for 4 breaths (P less than 0.05). Changes in end-tidal PCO2 correlated with excess CO2 output relative to control measurements immediately prior to airway occlusion (P less than 0.03). After 15 sec airway occlusion at FRC, there is alveolar hypercapnia with a 2.6-fold first breath rise in ventilation. Persistent alveolar hyperventilation lasting 30 sec following airway occlusion may be due to delays in central chemoreceptor response or an afterdischarge phenomenon. This overshoot hypercapnia following airway occlusion may have some relevance to the development of central apneas following obstructive apnea episodes.

Diagnosis of pulmonary embolism.

Pulmonary embolism (PE) is often unrecognized or misdiagnosed because of the lack of specificity of clinical signs and symptoms. PE shares many of the clinical features of pneumonia and is therefore often unrecognized in elderly patients who present with low-grade fever, modest leukocytosis, and pulmonary infiltrates. Assessment of clinical risk factors increases the usefulness of diagnostic tests. The accuracy of diagnosis is improved if specific tests are performed. Ventilation-perfusion lung scans, noninvasive or contrast venography, and pulmonary angiography increase the likelihood of correct diagnosis. Since pulmonary angiography is a relatively low-risk procedure, it should be performed in most patients suspected of having PE who have nondiagnostic lung scans and negative lower extremity venous studies.