Control of breathing in children with mild sleep apnoea: a 6-year follow-up study.

We have previously shown that children (average age 9 yrs) with mildly elevated obstructive apnoea/hypopnoea indices (OAHI) retained CO(2) at rest. Here, we report the results of a 6-yr follow-up study on 14 children from that study. Minute ventilation (V'(E)) and end-tidal CO(2) partial pressure (P(ET,CO(2))) were measured during hypercapnic challenge. OAHI decreased from 7.5+/-4.7 events x h(-1) at age 9 yrs to 2.5+/-1.8 events x h(-1) at age 15 yrs (p<0.001), despite an increase in body mass index from 20+/-4.6 kg x m(-2) to 26+/-5.7 kg x m(-2) (p<0.0001). Eupneic V'(E) increased from 4.1+/-0.31 L x min(-1) x m(-2) to 5.9+/-0.4 L x min(-1) x m(-2) (p<0.01), while P(ET,CO(2)) fell from 44.1+/-0.8 to 33+/-1.0 mmHg (p<0.001). The V'(E)-P(ET,CO(2)) obtained during hypercapnia was left shifted, such that V'(E) at a P(ET,CO(2)) of 50 mmHg increased from 24 L x min(-1) at age 9 yrs to 36 L x min(-1) at age 15 yrs. Central respiratory drive did not change. We hypothesise that somatic growth of the pharynx coupled with a regression of tonsillar tissue mass with age leads to enlargement of the upper airway lumen, a reduction in airway resistance and increased respiratory airflow at a given level of ventilatory drive.

Pharyngeal critical pressure in children with mild sleep-disordered breathing.

There is evidence that narrowing or collapse of the pharynx can contribute to obstructive sleep-disordered breathing (SDB) in adults and children. However, studies in children have focused on those with relatively severe SDB who generally were recruited from sleep clinics. It is unclear whether children with mild SDB who primarily have hypopneas, and not frank apnea, also have more collapsible airways. We estimated airway collapsibility in 10 control subjects (9.4 +/- 0.5 yr old; 1.9 +/- 0.2 hypopneas/h) and 7 children with mild SDB (10.6 +/- 0.5 yr old; 11.5 +/- 0.1 hypopneas/h) during stable, non-rapid eye movement sleep. None of the subjects had clinically significant enlargement of the tonsils or adenoids, nor had any undergone previous tonsillectomy or adenoidectomy. Airway collapsibility was measured by brief (2-breath duration) and sudden reductions in pharyngeal pressure by connecting the breathing mask to a negative pressure source. Negative pressure applications ranging from -1 to -20 cmH(2)O were randomly applied in each subject while respiratory airflow and mask pressure were measured. Flow-pressure curves were constructed for each subject, and the x-intercept gave the pressure at zero flow, the so-called critical pressure of the upper airway (Pcrit). Pcrit was significantly higher in children with SDB than in controls (-10.8 +/- 2.8 vs. -15.7 +/- 1.2 cmH(2)O; P < 0.05). There were no significant differences in the slopes of the pressure-flow relations or in baseline airflow resistance. These data support the concept that intrinsic pharyngeal collapsibility contributes to mild SDB in children.

Association of physical activity and human sleep disorders.

BACKGROUND: It is generally believed that exercise exerts a beneficial effect on the quality of sleep. However, most studies regarding exercise and sleep have been concerned with the influence of exercise on sleep architecture and efficiency, and not on its effects in the prevention and treatment of sleep disorders. Moreover, epidemiological evidence of the benefits of exercise on sleep are limited. OBJECTIVE: To investigate the influence of moderate exercise or physical activity on self-reported sleep disorders among a randomly selected population of adults. SUBJECTS AND METHODS: Study subjects were participants in the Tucson Epidemiological Study of Obstructive Airways Disease who in the 12th survey completed health questionnaires that included several questions on physical exercise and sleep disorders. Sleep disorders were classified as disorders in maintaining sleep, excessive daily sleepiness, nightmares, and any sleep disorder. Six questions regarding exercise and physical activity were asked. Analyses were performed using multivariate logistic regression models with selected measures of sleep disorders as dependent variables and measures of exercise and physical activity as the independent or predictor variables. RESULTS: There were 319 men and 403 women included in the analyses. The results showed that more women than men reported participating in a regular exercise program and having sleep symptoms of disorders in maintaining sleep and nightmares and that more men than women did regular vigorous activity and walking at a brisk pace for more than 6 blocks per day. Both men and women had significantly reduced risk of disorders in maintaining sleep associated with regular activity at least once a week, participating regularly in an exercise program, and walking at a normal pace for more than 6 blocks per day. Reduced risk of any sleep disorder was associated with regular activity at least once a week, and for men, walking at a brisk pace for more than 6 blocks. Among women increases in age also reduced the risk of nightmares. CONCLUSIONS: These data provide additional evidence that a program of regular exercise may be a useful therapeutic modality in the treatment of patients with sleep disorders.

The natural history of insomnia and its relationship to respiratory symptoms.

BACKGROUND: Although insomnia is a frequent complaint among patients, epidemiologic study has been limited. Researchers have reported a wide range in the prevalence of this complaint in a variety of selected populations. Other parameters, such as incidence and remission rates, have not been reported. METHODS: Subjects of the Tucson (Ariz) Epidemiologic Study of Obstructive Lung Disease were asked questions about trouble sleeping in the 1984-1985 (survey I) and 1990-1992 (survey II) surveys. Answers were analyzed along with responses to questions about age, sex, respiratory symptoms, and drug and alcohol use for sleep. RESULTS: The prevalence of insomnia was similar in both surveys, 34.4% in survey I and 34.1% in survey II. Women had a higher prevalence of insomnia than men in both surveys, and insomnia was more common among older subjects (50.6% of the women aged 65 years or older had insomnia in survey II). In addition, the incidence of new insomnia in survey II was higher in the same groups. Grouping subjects by respiratory symptoms, we found that the prevalence of insomnia was significantly related to cough, dyspnea, or wheeze. Furthermore, subjects with persistent or new respiratory symptoms at survey II were less likely to have remission of insomnia by that survey (31.6% vs 51.5%; P < .05; odds ratio, 0.43) and more likely to develop new insomnia (28.6% vs 14.5%; P < 05; odds ratio, 2.36) than subjects with either no symptoms or disappearance of their symptoms by survey II. CONCLUSIONS: In our population, insomnia is a common dynamic complaint whose frequency waxes and wanes in association with respiratory symptoms.

Rapid diagnosis of pulmonary coccidioidomycosis. Cytologic v potassium hydroxide preparations.

In 26 patients with culture-proved pulmonary coccidioidomycosis, cytologic preparations of respiratory secretions were significantly more sensitive (38.5%) than potassium hydroxide (KOH) preparations (15.4%) in identifying spherules of Coccidioides immitis. Those patients able to produce sputum or having multiple-lobe pneumonitis on chest roentgenogram appeared to be more likely to have spherules identified in the sputum by either technique. In the absence of sputum production or multiple-lobe pneumonitis, neither cytologic nor KOH preparations were likely to disclose spherules. Because of its greater sensitivity, a cytologic preparation should be examined in addition to a KOH preparation when pulmonary coccidioidomycosis is a clinical consideration.

Risk factors associated with complaints of insomnia in a general adult population. Influence of previous complaints of insomnia.

BACKGROUND: Insomnia is a common complaint both in the general population and also in physician's offices. However, risk factors for the development of insomnia complaints have not been completely identified. METHODS: To identify population characteristics associated with increased prevalence of insomnia complaints, we surveyed a large general adult population in 1984 through 1985. We evaluated the relationship among current complaints of initiating and maintaining sleep and obesity, snoring, concomitant health problems, socioeconomic status, and documented complaints of difficulty with insomnia 10 to 12 years previously. RESULTS: The strongest risk factor for complaints of initiating and maintaining sleep was previous complaints of insomnia (odds ratio, 3.5). In addition, female gender (odds ratio, 1.5), advancing age (odds ratio, 1.3), snoring (odds ratio, 1.3), and multiple types of concomitant health problems (odds ratios, 1.1 to 1.7) were all risk factors associated with an increased rate of complaints of initiating and maintaining sleep. CONCLUSION: Complaints of insomnia tend to be a persistent or recurrent problem over long periods of time. Female gender, advancing age, and concomitant health problems also are important risk factors.

The effect of antireflux treatment on the frequency of awakenings from sleep in patients with Gastroesophageal reflux disease.

BACKGROUND: Up to half of gastroesophageal reflux disease (GERD) patients report having heartburn that awakens them from sleep during the night. Recumbent-awake and conscious awakenings from sleep during the night are commonly associated with acid reflux events. The aim of the study was to assess the effect of esomeprazole 40 mg once daily on nighttime acid reflux, frequency of conscious awakenings associated with acid reflux and the recumbent-awake period. METHODS: Patients with heartburn and/or regurgitation at least three times a week were eligible for this study. All patients underwent upper endoscopy and were evaluated by demographic, Epworth Sleepiness scale, Berlin and GERD symptom checklist questionnaires. Subjects then underwent esophageal pH testing concomitantly with an actigraphy. All subjects were given esomeprazole 40 mg once daily for 7 days and completed a daily symptom record diary. On day 7, subjects repeated the pH test with actigraphy. KEY RESULTS: Twenty patients (mean age of 48.95 ± 18.69, age range 20-81 years) were enrolled. Esophageal acid exposure parameters, during recumbent-awake, recumbent-asleep, and conscious awakenings were significantly improved on last day of treatment as compared to baseline (p < 0.05). However, the frequency and duration of conscious awakenings and duration of recumbent-awake period did not improve as compared to baseline (p > 0.05). CONCLUSIONS & INFERENCES: While esomeprazole significantly reduced esophageal acid exposure during conscious awakenings and recumbent-awake and asleep periods, it did not decrease the number and duration of conscious awakening or duration of recumbent-awake period.

Correlates of daytime sleepiness in 4578 elderly persons: the Cardiovascular Health Study.

OBJECTIVES: To describe the prevalence of self-reported daytime sleepiness in older men and women and to describe their relationships with demographic factors, nocturnal complaints, health status, and cardiovascular diseases (CVD). DESIGN: Cross-sectional survey and clinical exam. SETTING: Participants in the Cardiovascular Health Study, 4578 adults aged 65 and older, recruited from a random sample of non-institutionalized Medicare enrollees in four U.S. communities. MEASURES: Daytime sleepiness measured by the Epworth Sleepiness Scale (ESS), magnetic resonance imaging of the brain (MRI), cognitive function tests, and standardized questionnaires for cardiopulmonary symptoms and diseases, depressive symptoms, social support, activities of daily living, physical activity, and current medications. RESULTS: Approximately 20% of the participants reported that they were "usually sleepy in the daytime". Although elderly black men were less likely to report frequent awakenings than those in the other three race and gender groups, they had significantly higher mean ESS scores. The following were independently associated with higher ESS scores in gender-specific models: non-white race, depression, loud snoring, awakening with dyspnea or snorting, frequent nocturnal awakenings, medications used to treat congestive heart failure, non-use of sleeping pills, a sedentary lifestyle, and limitation of activities of daily living in both men and women; additional correlates included hip circumference and current smoking in men, and hayfever in women. The following were not independently associated with ESS in the models: age, education, use of wine or beer to aid sleep, use of tricyclic antidepressants, long- or short-acting benzodiazepines, asthma, angina, myocardial infarction, congestive heart failure itself, forced vital capacity, social support, cognitive function, or MRI evidence of global brain atrophy or white matter abnormality. CONCLUSIONS: Daytime sleepiness is common in the elderly, probably due to nocturnal disturbances such as frequent awakenings and snoring. The occasional use of sleeping pills for insomnia is associated with reduced daytime sleepiness in the elderly, while the use of medications for congestive heart failure is associated with daytime sleepiness. Surprisingly, anatomic abnormalities such as evidence of previous strokes and brain atrophy (as seen on brain MRI scans) were not associated with daytime sleepiness in these non-institutionalized elderly persons.

Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited. DESIGN: A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. SETTING: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home. PARTICIPANTS: Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5-8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants. INTERVENTIONS: N/A. MEASUREMENTS & RESULTS: Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory. CONCLUSIONS: The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5-12 years in an unattended setting under a research protocol.

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.

Pulmonary lymphangioleiomyomatosis: quantitative analysis of lesions producing airflow limitation.

The lungs of three patients dying of lymphangioleiomyomatosis (LAM), which in two of the patients was associated with tuberous sclerosis, were studied to characterize better the sites of airflow limitation in this condition. Quantitative studies showed that small airways were narrowed and collapsed because of the surrounding emphysema, but few airways contained excess smooth muscle. These findings suggest that the airspace lesions are more important than muscular proliferation in small airways in producing airflow limitation. In the two patients who had LAM with tuberous sclerosis, sex steroid assays were negative. Pleurodesis controlled pleural effusions in all three patients but may have contributed to reductions in lung volume.

Prevalence of reported sleep disturbances in a general adult population and their relationship to obstructive airways diseases.

In order to determine the prevalence of reported sleep disturbances in a general adult population and the relationship of these complaints to age, gender and coexistent obstructive airways disease, 2,187 subjects in the Tucson Epidemiologic Study of Obstructive Airways Disease were surveyed in 1985 regarding their sleep symptoms. At least one symptom of disturbed sleep was present in 41.4 percent of all subjects. Women generally reported a significantly higher prevalence of both disorders of initiating and maintaining sleep (DIMS) and nightmares (NM)(p less than .001). Before age 64 years, the prevalence of complaints of excessive daytime sleepiness (EDS) among men and women were similar. However, the frequency of EDS was significantly higher in men than women after age 64 years. Prevalence of at least one sleep symptom and DIMS increased with advancing age. The prevalence of nightmares appeared to be age-related only among women, who displayed a declining prevalence with advancing age. EDS increased only after age 64 years. There was a significant relationship between DIMS and EDS with coexistent chronic bronchitis, concomitant asthma and chronic bronchitis, and emphysema, but not asthma as a solitary diagnosis. Nightmares were reported with much greater frequency among subjects with asthma, asthma and chronic bronchitis, and emphysema but not in subjects with chronic bronchitis alone. The presence of coexistent asthma and chronic bronchitis was associated with particularly high prevalence of complaints of DIMS, EDS and nightmares. We conclude that, in the general adult population, sleep disorder symptoms increase with age and usually are greater in women. Furthermore, there is an increased prevalence of sleep symptoms among adults with chronic airways obstructive disease, especially those with coexistent asthma and chronic bronchitis.

The relation of sleep complaints to respiratory symptoms in a general population.

Based on data obtained from the Tucson Epidemiologic Study of Chronic Lung Disease that included body weight, questionnaire responses, and spirometry, we found that among subjects with no respiratory symptoms, 28.0 percent reported insomnia (difficulty initiating or maintaining sleep) and 9.4 percent reported daytime sleepiness. Among subjects with respiratory symptoms, cough and/or wheeze, the rates of sleep complaints increased. With one symptom, 39.1 percent reported insomnia and 12.4 percent reported daytime sleepiness. With both symptoms, the rates were 52.8 percent and 22.8 percent, respectively. Overall, we found significant relationships between rates of respiratory symptoms and sleep complaints (trend chi 2 = 73.9, p < 0.001 for insomnia; trend chi 2 = 37.9, p < 0.001 for daytime sleepiness). In separate analyses, obesity, snoring, and a diagnosis of lung disease also influenced the rate of sleep complaints but, when we employed logistic regression, we found that obesity, respiratory symptoms, gender, and age were the only variables related to the risk of insomnia or daytime sleepiness.

Pressure support compensation for inspiratory work due to endotracheal tubes and demand continuous positive airway pressure.

We evaluated the use of pressure support to compensate for the added inspiratory work of breathing due to the resistances of endotracheal tubes and a ventilator demand-valve system for continuous positive airway pressure (CPAP). A mechanical model was used to simulate spontaneous breathing at five respiratory rates through 7-mm, 8-mm, and 9-mm endotracheal tubes with and without a ventilator demand CPAP circuit. Added work was measured as the integral of the product of airway pressure and volume during inspiration. Additional work was a function of the tube's size, and each 1-mm decrease in the tube's diameter resulted in a 67 to 100 percent increase in work. Adding the ventilator CPAP circuit further increased work and was responsible for 30 to 50 percent of the total work resulting from a tube and CPAP circuit together. Pressure support was added to a level at which net work on the airway was zero, and a relationship between mean inspiratory flow (VT/TI) and the optimal level of pressure support was established for each endotracheal tube. The inspiratory work of breathing was then measured in normal subjects breathing with and without each endotracheal tube plus the demand CPAP circuit. Work per liter of minute ventilation due to the endotracheal tube and CPAP circuit was increased from 54 to 240 percent over levels measured while breathing through an open airway. For each endotracheal tube and VT/TI, a level of pressure support (range, 2 to 20 cm H2O) was found which eliminated added work in the spontaneously breathing subject. This level correlated well with that predicted from the data derived using the mechanical model. We conclude that when adjusting for an endotracheal tube's diameter and VT/TI, pressure support can be used to compensate for the added inspiratory work due to artificial airway resistances.

Risk factors in a general population for snoring. Importance of cigarette smoking and obesity.

In order to study risk factors associated with snoring in a general adult population, 2,187 subjects in the Tucson Epidemiologic Study of Obstructive Airways Disease were surveyed to determine the prevalence of snoring. Major independent risk factors for snoring were male gender, age between 40 and 64 years, obesity, and current cigarette smoking. Furthermore, greater intensity of cigarette smoking also was associated with higher snoring prevalence rates. Snoring prevalence remained elevated in subjects who recently quit smoking, but declined in ex-smokers to the level of never smokers within four years of smoking cessation. The presence of cough or sputum production was associated with an increase in snoring prevalence especially in ex-smokers. Snoring prevalence was slightly increased in subjects who regularly used alcohol or medications as aids to sleep. We conclude that cigarette smoking, obesity, male gender, age over 40, and use of alcohol or sleep medications are important risk factors for snoring. We propose that the effect of smoking may be related to the production of upper airway inflammation and edema by cigarette smoke, and that smoking cessation may eventually reduce snoring risk.

Diffuse epithelial pleural mesothelioma presenting as a solitary lung mass.

We report the occurrence of a malignant pleural epithelial mesothelioma which presented radiographically and at surgery as a localized solitary mass, but was found microscopically to involve grossly normal pleura. Clinically diffuse mesothelioma recurred 19 months later. Localized malignant mesothelioma has been associated with the same poor prognosis as the diffuse form and, as suggested by this case, may represent an early phase of diffuse disease.

Bilateral paramediastinal post-traumatic lung cysts.

Unilateral post-traumatic and paramediastinal lung cysts are uncommon. Conservative therapeutic measures are usually sufficient. This report describes a patient whose bilateral post-traumatic paramediastinal lung cysts, a previously undescribed entity, were presumed to be bilateral hemidiaphragmatic hernias and, consequently, led to unnecessary surgery.

Incidence and remission of habitual snoring over a 5- to 6-year period.

Habitual snoring is associated with an increased prevalence of hypertension, stroke, and ischemic heart disease. To determine factors that influence the incidence and remission of habitual snoring, we analyzed responses to successive self-administered questionnaires with questions pertaining to snoring in a group of subjects participating in the Tucson Epidemiologic Study of Obstructive Airways Disease. In this study, 1,476 subjects were surveyed 5.8 +/- 0.6 (SD) years apart. Among subjects who habitually snored on the initial survey, 58.2% snored persistently and 35.5% remitted on the ensuing survey. Among subjects who did not habitually snore in the initial survey, 10.5% developed it on the subsequent survey. In further analyses, we found that male sex, obesity, and respiratory symptoms were significant independent risk factors for development of habitual snoring. Age over 65 years, the absence of obesity, and the absence of respiratory symptoms were associated with remission of habitual snoring.

Obstructive sleep apnea in heart transplant patients. A report of five cases.

Clinically significant obstructive sleep apnea syndrome (OSAS) was diagnosed in five patients who had undergone heart transplantation and they represent 2.5 percent of our transplantation series. To determine if these individuals had unique clinical features that would have suggested the presence of OSAS, we reviewed their case histories. Although four of five patients had symptoms of OSAS prior to transplant, none was suspected of having the diagnosis before their surgery. Excessive daytime sleepiness and loud snoring were noted in all patients, and there were no unusual clinical features that characterized these individuals. Our data indicate that the occurrence of OSAS in heart transplant recipients approximates the prevalence in the general population. Because OSAS may adversely affect cardiac function, we recommend that heart transplantation candidates be screened for a history suggestive of OSAS, and that polysomnography be performed if it is present.