A common clinical dilemma faced by sleep physicians is in deciding the level of severity at which patients with obstructive sleep apnea (OSA) should be treated. There is particular uncertainty about the need for, and the effectiveness of, treatment in mild cases. To help define the role of nasal continuous positive airway pressure (CPAP) treatment in mild OSA we undertook a randomized controlled cross-over trial of CPAP in patients with an apnea- hypopnea index (AHI) of 5 - 30 (mean, 12.9 +/- 6.3 SD). Twenty-four-hour blood pressure and neurobehavioral function were measured at baseline, after 8 wk of treatment with CPAP, and after 8 wk of treatment with an oral placebo tablet. Twenty-eight of 42 patients enrolled in the study completed both treatment arms. Baseline characteristics were not different between those who completed the study and those who did not complete the study. Patients used CPAP for a mean (SD) of 3.53 (2.13) h per night and the mean AHI on the night of CPAP implementation was 4.24 (2.9). Nasal CPAP improved self-reported symptoms of OSA, including snoring, restless sleep, daytime sleepiness, and irritability (in-house questionnaire), more than did placebo, but did not improve objective (Multiple Sleep Latency Test) or subjective (Epworth Sleepiness Scale) measures of daytime sleepiness. We found no benefit of CPAP over placebo in any tests of neurobehavioral function, generic SF-36 (36-item Short Form Medical Outcomes Survey) or sleep-specific (Functional Outcomes of Sleep Questionnaire) quality of life questionnaires, mood score (Profile of Moods States and Beck Depression Index), or 24-h blood pressure. However, the placebo tablet resulted in a significant improvement in a wide range of functional variables compared with baseline. This placebo effect may account for some of the treatment responses to CPAP observed previously in patients with mild OSA.

Polyphasic methods were used to examine the taxonomic positions of three newly identified Grahamella species. A comparison of the 16s rRNA gene sequences of these organisms with the sequences available for other bacteria revealed that these three species form a tight monophyletic cluster with members of the genus Bartonella. This cluster is only remotely related to other members of the order Rickettsiales. Determinations of the levels of DNA relatedness between Grahamella species and Bartonella species (by using a modified hydroxyapatite method) revealed that all of the species belonging to these two genera are distinct but closely related. On the basis of these data and the results of guanine-plus-cytosine content and phenotypic characterization studies, we propose that the genera Grahumella and Bartonella should be unified and that the latter name should be retained. Bartonella talpae and Bartonella peromysci, new combinations for former Grahamella species, are created, and the following three new Bartonella species are described: Bartonella grahamii, Bartonella taylorii, and Bartonella doshiae. A taxonomic analysis of Grahamella species complete the study of all members of the family Bartonellaceae, and the results of this study support the proposal that the family should be transferred out of the order Rickeftsides.Members of the family Bartonellaceae are gram-negative bacteria which can be grown in vitro on nonliving, blood-rich media. In vivo, these organisms are hemotrophic, parasitizing the erythrocytes of their hosts. Arthropod transmission of some members of the family has also been established (33). The family Bartonellaceae comprises two genera, Bartonella and Grahamella (28). The genotypic and phylogenetic relationships between these two genera are unknown, and at the present time these taxa are distinguished on the basis of the following three loose criteria: (i) Bartonella species, but not Grahamella species, infect humans; (ii) Grahamella species are thought to exist exclusively within the erythrocytes of their hosts, whereas Bartonella bacilliformis can exist on the erythrocyte cell surface; and (iii) B. bacillifomis has been shown to have flagella in culture, unlike Grahamella species (28).For a long time the genus Bartonella contained only one species, B. bacilliformis. This bacterium is the etiological agent of Carrion's disease, a biphasic syndrome that affects the erythrocytes and skin of humans and is endemic only to the Andean region of South America (28). The number of members of the genus Bartonella recently increased following a study in which Brenner and his colleagues (7) confirmed the widespread belief that species of the genus Rochalimaea are more correctly placed in the genus Bartonella. This proposal was the culmination of several polyphasic studies of the taxonomic relationship between the two genera (3, 23, 27) and resulted in the unification of the two taxa, with the name Bartonella taking precedence (7). Thus, the genus Bartonella now contains four additional species: Bartone...

Fifty patients with chronic obstructive lung disease were questioned about their sleep quality and their responses were compared with those of 40 similarly aged patients without symptomatic lung disease. Patients with chronic obstructive lung disease reported more difficulty in getting to sleep and staying asleep and more daytime sleepiness than the control group. More than twice as many patients (28%) as controls (10%) reported regular use of hypnotics. In a subgroup of 16 patients with chronic obstructive lung disease (mean FEV, 0-88 (SD 0 44) 1) sleep, breathing, and oxygenation were measured to examine the relationship between night time hypoxaemia and sleep quality. Sleep architecture was disturbed in most patients, arousals occurring from three to 46 times an hour (mean 15 (SD 14)/h). Arterial hypoxaemia during sleep was common and frequently severe. The mean (SD) arterial oxygen saturation (Sao2) at the onset of sleep was 91% (7%). Nine patients spent at least 40% of cumulative sleeping time at an Sao2 of less than 90% and six of these patients spent 90% of sleeping time below this level. Only four of 15 patients did not develop arterial desaturation during sleep. The mean minimum Sao2 during episodes of desaturation was less in rapid eye movement (REM) sleep (72% (17%)) than in non-REM sleep (78% (10%); p < 0 05). The predominant breathing abnormality associated with desaturation was hypoventilation; only one patient had obstructive sleep apnoea. Arousals were related to oxygenation during sleep such that the poorer a patient's arterial oxygenation throughout the night the more disturbed his sleep (arousals/h v Sao2 at or below which 40% of the total sleep time was spent: r = 0-71, p < 0X01). Hypoxaemia during sleep was related to waking values of Sao2 and PaCo2 but not to other daytime measures of lung function.It is well recognised that sleep is associated with arterial oxygen desaturation in patients with chronic obstructive lung disease.' -6 Some physiological consequences of this desaturation, such as pulmonary hypertension, have been well investigated2 7 -9; reports of the consequences of arterial hypoxaemia in terms of quality of sleep and sleep related symptoms, however, are few and conflicting.'0'-4

Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index [AHI] 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.

We conducted a study of the prevalence of sleep-disordered breathing in subjects derived from a random sample of the population. A total of 2,202 subjects 35 to 69 yr of age were approached. Four hundred forty-one answered a questionnaire concerning their sleep symptoms, general health, and habits such as alcohol consumption, and they were monitored for sleep-disordered breathing (SDB). The sample was biased in favor of snorers and those with other subjective sleep complaints. Fifty-six percent of the subjects were men. Of the 441 subjects 79 (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory distress index [RDI] > or = 15), 289 were snorers but had RDI < 15, and 73 were nonsnorers. The prevalence of SDB in this sample was therefore at least 3.6% (79 of 2,204). The minimum prevalence in men was 5.7%, and in women it was 1.2%. Logistic regression identified only male sex as an independent predictor of snoring without SDB (adjusted odds ratio [OR], 3.24; 95% CI, 1.33 to 7.82), body mass index (adjusted OR for an increase of 5 kg/m2, 0.95; 95% CI, 0.85 to 1.05), and alcohol consumption (adjusted OR for an increase of 10 g/day, 1.05; 95% CI, 0.84 to 1.37) were not significant predictors of snoring. The independent predictors of SDB among snorers were age (adjusted OR for an increase of 5 yr, 1.26; 95% CI, 1.08 to 1.47) and neck circumference (adjusted OR for an increase of 2 cm, 1.53; 95% CI, 1.16 to 2.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal studies have shown activation of upper airway muscles prior to inspiratory efforts of the diaphragm. To investigate this sequence of activation in humans, we measured the electromyogram (EMG) of the alae nasi (AN) and compared the time of onset of EMG to the onset of inspiratory airflow, during wakefulness, stage II or III sleep (3 subj), and CO2-induced hyperpnea (6 subj). During wakefulness, the interval between AN EMG and airflow was 92 +/- 34 ms (mean +/- SE). At a CO2 level of greater than or equal to 43 Torr, the AN EMG to airflow was 316 +/- 38 ms (P < 0.001). During CO2-induced hyperpnea, the AN EMG to airflow interval and AN EMG magnitude increased in direct proportion to CO2 levels and minute ventilation. During stages II and III of sleep, the interval between AN EMG and airflow increased when compared to wakefulness (P < 0.005). We conclude that a sequence of inspiratory muscle activation is present in humans and is more apparent during sleep and during CO2-induced hyperpnea than during wakefulness.

We studied the long-term acceptability of nasal continuous positive airway pressure (CPAP) treatment in 168 consecutive patients, 147 with obstructive sleep apnea (OSA) and 21 with snoring. Follow-up was between 1.5 and 78 months. At latest follow-up 107 of 168 (64%) were still using CPAP. Acceptance of CPAP was least for patients with snoring alone (6 of 21 persisted) and best for patients with both excessive daytime somnolence and severe hypoxemia (minimum SaO2 less than 75%), of whom 40 of 45 (89%) persisted with treatment. Patients with excessive daytime somnolence but without severe hypoxemia were less tolerant of CPAP (39 of 71, 55%, persisted) than patients with no symptoms of excessive somnolence but with severe hypoxemia (21 of 30, 70%, persisted). The most common reasons for discontinuing CPAP were intolerance of the mask (26 of 61), the inconvenience of treatment (16 of 61), and the lack of symptomatic benefit from treatment (10 of 61). We concluded that long-term acceptance of CPAP was difficult to predict in advance but that it was most likely in patients with the most severe sleep apnea. Because intolerance of the mask and inconvenience were the most common reasons for ceasing treatment, improvements in the design of CPAP systems and careful patient training may improve the acceptability of CPAP substantially.

We have investigated the ability of a statistical model developed from clinical data and questionnaire responses to predict disturbance of breathing during sleep. Data from 100 consecutive patients referred for sleep study for suspected sleep apnea were used to develop the model using logistic regression analysis. For each subject, the model predicted the probability of having an apnea-hypopnea index (AHI) greater than 15; this probability was compared with the AHI measured from sleep study. A probability cutoff point (= 0.15) was decided on that minimized the number of subjects with false-negative predictions. Four terms--apneas observed by bed partner, hypertension, body mass index, and age--were found to contribute significantly to the model with observed apneas being by far the most predictive term of the four (adjusted odds ratio 19.7). When the model was tested to estimate the probability of an AHI greater than 15 for 105 patients from a second group of consecutive patients referred for sleep study, the model correctly classified 33 of 36 patients with a measured AHI greater than 15 (sensitivity = 92%) and 35 of 69 patients with a measured AHI less than or equal to 15(specificity = 51%). This study shows that analysis of clinical features of patients presenting with suspected sleep apnea may reduce the need for sleep studies by about one-third yet still lead to the identification of the great majority of patients with abnormal breathing during sleep.