An overview of nasal CPAP therapy in the management of obstructive sleep apnea.

Abstract

Obstructive sleep apnea is readily reversible with nasally administered continuous positive airway pressure, although its effectiveness can be limited by poor patient compliance with therapy. With recent developments in technology, the ability to both diagnose and manage this disorder is dramatically improving. Assessment and therapeutic intervention can now be carried out not only in attended settings, such as sophisticated sleep laboratories, but in semiattended and unattended situations, including the home. What impact these advances will have on improving patient tolerance to therapy and reducing long-term clinical consequences of obstructive sleep apnea remains to be seen. However, there is no doubt that sleep-trained professionals now have many more tools at their disposal to diagnose and treat this disorder.

Introduction

Obstructive sleep apnea (OSA) is characterized by repetitive collapse of the upper airway during sleep. The resulting reduction (hypopnea) or cessation (apnea) of airflow (inspiratory flow limitation) produces dips in oxygen saturation, increases in inspiratory efforts against the obstructed airway, and sleep fragmentation. [1] These nocturnal physiologic events lead to a variety of neurophysiologic and cardiovascular complications, including daytime hypersomnolence, cognitive impairments, systemic and pulmonary hypertension, and cardiac arrhythmias (figure 1). Several investigators have reported an increased risk of myocardial infarction and stroke associated with OSA. [2-4] Left untreated, moderate OSA increases the risk of death. [5]

Despite the serious consequences of this disorder, the actual prevalence of OSA in the general population remains unclear. [6] Evidence does suggest that in the middle-aged population, 4% of men and 2% of women have OSA. [7] There are three primary reasons why the extent of this common disorder has gone largely unrecognized until recently. First, there is no tight relationship between the number of abnormal respiratory events that occur during sleep and the subjective reporting of daytime symptoms by patients. [8] For example, in a population study, Young et al found that 24% of men and 9% of women had an apneahypopnea index (AHI) of 5 or more events per hour. [7] However, only 4 and 2%, respectively, had this degree of sleep disordered breathing (SDB) in conjunction with daytime sleepiness and therefore met the criteria for the obstructive sleep apnea syndrome (OSAS). The difference between the two groups could reflect individual differences in the way sleep fragmentation affects daytime function, or it might be that many individuals simply do not recognize their degree of sleepiness and therefore do not report it.

Second, there has been no general agreement as to what degree of SDB is abnormal. The minimum number of events per hour of sleep that is considered to be significant by different sleep centers ranges from 5 to 15. Nor is it clear what degree of SDB is required to produce a specific clinical effect. [9] This can make it difficult for the physician to determine when intervention should be offered. There is little question that the physician should treat a patient who has an AHI of 10 with accompanying significant daytime symptoms. But it is not clear if treatment is best for a patient with the same AHI but no symptoms.

Finally, as our understanding of this disorder evolves, so do our definitions. Twenty-five years ago, OSA was considered to be a rare disorder that was confined to the grossly obese. Therapy, in the form of tracheostomy, was offered only to those who were in a life-threatening situation. With the advent of more widespread and sophisticated testing, it became apparent that the full clinical picture of OSAS does occur in patients who do not have frank apnea but who experience decreased airflow (hypopnea) and arousals from sleep, a set of symptoms called the obstructive apnea-hypopnea syndrome. [10]

By the early 1990s, Guilleminault et al described patients who experienced sleep fragmentation and daytime sleepiness, but who did not experience the obvious apneic or hypopneic events that caused the brief arousals that were observed. [11,12] These arousals were attributed to an abnormal amount of inspiratory effort, a cause that was confirmed by the presence of high esophageal pressure swings. Known as the upper airway resistance syndrome, this disorder can occur in the absence of snoring (figure 2). [12] Therefore, OSAS should be considered as a continuum of upper airway instability, ranging from simple snoring to severe, repetitive, complete airway closure. Aging and obesity push the predisposed patient toward the severe end of the sleep apnea spectrum.

Even though the minimum level of SDB that must be present to pose a significant health problem has not been defined, recent epidemiologic evidence suggests that even low indices of SDB--for example, an AHI as low as 5 events per hour--are statistically associated with an increased incidence of hypertension and other cardiovascular events. [13] The question of when to intervene still has not been clearly answered, but patients with increasingly milder levels of SDB are now being screened and treated.

Nasal CPAP therapy

The fundamental principle underlying the treatment of sleep apnea is that therapy will be successful if one eliminates the cause of the sleep disruption. In order to achieve this, the airway must be stabilized, blood gas levels must be normalized, and inspiratory effort must be reduced (figure 3).

Since its introduction in 1981, nasal continuous positive airway pressure (CPAP) has become widely accepted as the treatment of choice for obstructive sleep apnea. [14] CPAP equipment acts as a pneumatic splint, creating positive pressure inside the airway throughout the respiratory cycle. [14] One reason that CPAP is so effective in abolishing sleep apnea is that the pressure acts along the entire upper airway so that all potentially occluding segments are stabilized. [15]

When nasal CPAP was introduced, its effectiveness in eliminating abnormal respiratory events and normalizing both oxygen saturation and sleep quality was obvious. As a result, there were few properly controlled studies performed to evaluate its benefits on daytime function. Evidence of CPAP efficacy had been based primarily on clinical experience in tens of thousands of patients. This led some health administrators to question the impact of CPAP therapy on daytime functioning. [16] In response to these doubts, several studies that look at this issue are now emerging. One recent study that compared CPAP with an oral placebo demonstrated that CPAP improved measures of sleepiness and cognitive function in patients with moderate OSA. [17] This was despite the fact that the mean duration of CPAP use was less than 4 hours per night. In another study, Ballester et al confirmed the effectiveness of CPAP in reducing the incidence of sleepiness and other sleep apnea-related symptoms, over and above conservative measures alone. [18] In this study, the odds ratio of experiencing a treatment response with CPAP plus conservative measures compared with conservative measures alone was 6.52.

Historically, CPAP therapy has been recommended primarily for patients who have moderate to severe OSA. However, with increased awareness and diagnosis of this disorder, therapy has been extended to patients with mild disease, although, as mentioned, the minimum level of disease severity at which patients will derive benefit from therapy is still unclear. Engleman et al performed a randomized, placebo-controlled study of 34 patients who experienced mild sleep apnea (AHI: 5-15 events/hr) and daytime sleepiness. [19] They found that CPAP resulted in clinically significant improvements in subjective sleepiness and in health and functional status, even though effective CPAP use averaged only 2.8 hours per night. In a much larger study by Redline et al, patients with mild disease who were randomized to CPAP experienced a twofold improvement in well-being over those who were managed with conservative measures. [20] Furthermore, this study identified two subgroups of patients in this setting who are most likely to benefit from CPAP intervention: those with an underlying comorbidity such as hypertension or diabetes and those with no history of sinus problems. One of the major advantages that nasal CPAP has over other therapies for OSA is that CPAP can be given to a patient on a trial basis and easily modified or withdrawn if it is not tolerated or if the expected clinical response is not achieved.

Determining CPAP pressures

In order to determine what level of CPAP is appropriate for an individual, a so-called pressure titration is performed. The patient is fitted with an appropriately sized nasal mask and sleeps overnight with the mask in place. While the patient sleeps, the pressure is increased incrementally until apneas, hypopneas, snoring, and desaturation are stopped. In the past, such a procedure required manual alterations in pressure by an attendant, who frequently had to tend to an array of sensors that monitored both sleep and breathing parameters. However, recent improvements in CPAP technology have seen the development of "autotitrating" devices that use proprietary algorithms to automatically alter the pressure in the presence of upper airway instability. One such device, the AutoSet (ResMed Corp., San Diego), increases pressure in response to snore or flow limitation rather than waiting for hypopneas and apneas to occur. [21] The AutoSet does not require a technician to intervene when pressure alterations are needed. The CPAP pressure levels determined by this device have been shown to be comparable with manual titration in patients with uncomplicated OSA. [22,23] This technological development provides the opportunity for the procedure to be performed in semiattended or unattended environments.

It is important to realize that the first night of CPAP therapy will be strange and possibly anxiety-provoking for the patient. Education regarding the need for CPAP therapy, as well as an explanation of the purpose of the titration study, can help alleviate some of a patient's uncertainties. A period of time with the mask in place at a low level of pressure (5-7 cm [H.sub.2]O) can be useful in preparing patients for the sensations they will experience while wearing a mask during sleep. Sleep quality itself might be altered during the first few nights of therapy; longer-than-normal durations of both slow-wave and rapid eye movement (REM) sleep are frequently observed during this initial treatment period. [24,25]

Despite CPAP, daytime somnolence persists in some patients. This might be the result of poor compliance with therapy (as discussed later). [26,27] Alternatively, the level of CPAP prescribed, although appropriate to eliminate apneas and hypopneas, might be subtherapeutic if it does not also prevent an elevation in upper airway resistance. [21] The resulting flow limitation increases the patient's work of breathing. If this problem is not identified, it can lead to an incomplete resolution of symptoms and poor compliance. One possible difficulty is that CPAP titration is often performed using qualitative signals from sensors, such as thermistors. Although apneas and hypopneas can be identified from such signals, flow limitation cannot; this can result in the CPAP level being set inadvertently low. On the other hand, a pressure can also be set inappropriately high, which can cause problems related to comfort and side effects from airway dryness; this can, in turn, have an impact on the patient's willingness and ability to use CPAP. Even so, high pressures, when used appropriately, do not predispose to lower compliance. [28] There appears to be no relationship between the CPAP pressure required and difficulties encountered. [27,29] Getting the correct pressure level is important, both in terms of the impact that therapy will have on the patient's clinical response and in minimizing side effects.

In this context, a question might then arise regarding the accuracy of a CPAP level based on a single night of titration. Various factors--for example, weight change, [30] nasal patency, [31] and sleep state and body position [32]--can all affect pressure requirements, not only within a single night, but from night to night. Several investigators have suggested that pressure requirements would decrease from the initial titration levels in time, with the resolution of traumatic upper airway edema and normalization of REM duration. [33,34] However, a study by Teschler et al recently demonstrated little change in pressure requirements from the initial titration level at 3 and 8 months' followup. [25] These findings are in contrast with those of Series et al, who reported a decrease in titration pressure of approximately 20% over time. [34] One possible explanation for these different results could lie in the way the two groups determined pressure levels. Series et al used manual titration, while Teschler et al used an autotitrating system, which acted to eliminate flow limitation as well as snoring and apneas.

Side effects

Minor side effects with nasal CPAP are common, with up to 40 to 50% of patients who commence therapy complaining of at least one side effect. [35,36] Although these problems are generally minor in nature, they nevertheless can be distressing enough for the patient to limit the use of therapy, particularly if the patient has experienced few daytime symptoms associated with sleep apnea. Engleman et al found that CPAP use by patients who reported problems was about only 60% of that reported by patients who did not complain of problems with CPAP. [35] These findings emphasize the importance of the early recognition of any problems that could arise from using CPAP and the necessity of dealing with these issues promptly (table).

In early studies, pain and skin breakdown over the bridge of the nose was common, occurring in up to 30% of patients. [36] There is now a wide range of mask sizes and styles available so that an appropriate fit and seal should be achieved in most patients. Features such as silicon flaps and bubbles over the mask cushion are useful in reducing leakage into the eyes and minimizing the amount of pressure required to achieve a seal between the cushion and the patient's skin. Attention to finding a mask that the patient finds comfortable and that has minimal leakage is key to establishing long-term acceptance of therapy. Few individuals will continue to wear a mask if they have painful open sores over the nasal bridge or if air is rushing into their eyes.

Several studies have shown that there is no correlation between the frequency of reported side effects and the level of pressure. [28,36] Not surprisingly, the one factor that does appear to affect CPAP use is claustrophobia. [26] In such individuals, changing the mask style might be effective. Lightweight, transparent masks are now available; patients with claustrophobia could find these easier to tolerate than the older, more solid masks. Nasal pillows, where interface contact with the patient is only around the nostrils, might also be of benefit in this patient group.

Mouth leaks are common and are responsible for a large number of uncomfortable side effects. The main problem is related to airway drying, which might be problematic enough to affect nasal CPAP use. [35] Complaints include rhinitis, nasal congestion, mouth dryness, and sore throat. Where leaks are small, a chinstrap can maintain a more effective lip seal and might minimize symptoms. However, when a leak is large and persistent, heated humidification is the most effective means of reducing patient discomfort. [37]

Occasionally, patients complain of chest discomfort during or following therapy. This discomfort is musculoskeletal in nature and is suggested to be secondary to the elevation of lung volume during positive pressure. [38] It might be relieved by lowering the pressure for a period while the patient acclimatizes.

Significant complications from CPAP therapy are rare, but there are case reports of massive epistaxis, [39] atrial arrhythmia, [40] and pneuomocephalus. [41]

Compliance with therapy

Although CPAP is highly effective in eliminating obstructive events during sleep, its effectiveness can be limited by incomplete patient acceptance of and compliance with therapy. Among unselected OSA patients, acceptance of CPAP therapy has ranged between 50 and 90%. [28,42,43] Studies of self-reported data suggest that 75% of patients who use CPAP do so on a daily basis [44] for at least 6 hours a night. [38] However, such subjective data are known to be notoriously inaccurate, as patients consistently overestimate their CPAP use. Using covert, objective measurements of CPAP use and duration, Kribbs et al found that while 60% of the patients they studied claimed to have used CPAP nightly, only 46% met their criteria for regular use, which they defined as at least 4 hours per night during 70% of monitored nights. [26] The mean duration of CPAP use in the Kribbs study was 4.88 hours per night. This figure is consistent with those reported by investigators who used built-in machine timers; they found the mean duration of CPAP use to be around 4.7 to 5.6 hours per night. [28,35,42] Although not a universal finding, it seems that patients who are objectively sleepier at baseline are more likely to be better users of CPAP. [26,29,44] This trend supports the notion that relieving daytime symptoms is a positive motivator for the continued use of CPAP. A number of factors have been identified as having a negative impact on CPAP use, including the absence of hypoxemia [44] and previous palatal surgery. [29,45]

Although patients are usually instructed to use CPAP during any major sleep period on a daily basis, it appears that many use it only intermittently. Some investigators have suggested that it might not be necessary to use CPAP on such a regular basis to attain clinical benefit. [24] However, regular use does appear to improve breathing during sleep; one study reported that SDB was an average of 35% less severe during 1 night of CPAP withdrawal than it was at baseline. [46] It is thought that long-term CPAP therapy might improve airway stability through a number of mechanisms, including a reduction in upper airway edema, resolution of chronic sleepiness, and improved nocturnal oxygen saturation. Other investigators have found that when CPAP was discontinued after 4 hours of sleep, its benefit in terms of oxygen level and sleep quality remained throughout the night. [47] These findings support those of Engleman et al, who demonstrated that even after an average of only 4 hours of CPAP use, there were improvements in subjective reports of daytime symptoms, as well as objective measurements of daytime sleepiness. [17] It appears then that even though many patients use CPAP at a level less than that prescribed, its use is probably titrated to achieve a satisfactory degree of symptomatic relief. Indeed, there are some patients who use CPAP for less than 3 hours per night and yet are still satisfied with therapy. [28] Further studies are warranted to determine if there is a level of CPAP use below which longer-term benefits are not achieved.

What can be done to improve compliance by patients who require long-term therapy? Chervin et al found that simple interventions, such as frequent phone followup and brief written instructions regarding CPAP use, could be effective in improving compliance. [48] They reported that patients who received these interventions used CPAP an average 1.3 and 2.7 hours longer, respectively, than did control subjects who were not provided with such interventions. Furthermore, they found that these interventions were more effective in those individuals who were about to start CPAP than in those who were already on therapy. How patients are introduced to therapy, and the followup and support they receive during the first few weeks, are crucial to maximizing the likelihood of patient acceptance of therapy and is a major determinant of CPAP use in the longer term. [17] In a recent study by Hoy et al, it was shown that intensive support--including a supervised 3-night trial of CPAP followed by home visits--in addition to the standard support significantly improved CPAP use and outcomes compared with those seen in patients who underwent standard support-group care (initial education, phone calls, and clinic visits).[49] These results clearly point to the need for early followup and ongoing support to monitor clinical response to therapy and to promptly identify and manage any problems.

Technological strategies for improving compliance and comfort

One crucial factor must be taken into account when one assesses the patient compliance data reported in the literature: CPAP technology has improved dramatically during the past few years. Great strides have been taken in the development of better patient interfaces, a key aspect of compliance. In addition, the availability and importance of heated humidification to reduce nasal resistance is now better appreciated.[37] Finally, nasal CPAP devices now have better pressure-flow characteristics.

Although these significant changes in technology are expected to improve compliance, prospective studies to determine whether they actually have done so have not yet been published. Many studies have focused attention on the physical side effects that could arise with CPAP use; psychosocial factors such as inconvenience, expense, and claustrophobia can also pose problems for patients. Certainly, device manufacturers have recognized patients' early complaints about machine noise, and most devices are now remarkably quiet. In fact, the loudest noise now is made by air being vented from the exhalation ports on the mask. Moreover, the devices are now much smaller and more compact than earlier models, making them less intrusive on the patient's lifestyle, particularly for those individuals who travel regularly. Today's CPAP devices also incorporate a number of new design features, such as delay timers and ramps, that might play a role in improving compliance.

Ramping. Ramping, a feature that is now routinely included in most CPAP devices, is a method of slowly increasing the airway pressure level to its setpoint over a period of 5 to 30 minutes. This feature can assist the patient who might perceive higher CPAP pressures as uncomfortable while awake, but who both tolerates and requires the higher pressure levels during sleep. By progressively ramping the pressure up, a patient can become accustomed to the gradual sensation of increased pressure rather than being hit with high initial pressure.

Humidification. Nasal congestion and drying of the airways affect between 30 and 50% of patients who use CPAP, and for some the discomfort is severe enough to reduce compliance. [26] These symptoms are related to mouth leaks. The degree of mouth leak that occurs with CPAP use depends on several factors, including the pressure in the mask, nasal resistance, and the degree to which the mouth opens during sleep. [37] At CPAP pressures above 10 cm [H.sub.2]O, leaks greater than 40 to 60 L/min are not uncommon, although they can be difficult to assess clinically. [37] Some of the newer autotitrating devices are able to continuously measure leaks during CPAP application, providing the clinician with an objective indicator of the frequency and severity of such leaks. Richards et al demonstrated that mouth leaks during the application of nasal CPAP resulted in symptoms of nasal drying, followed by nasal congestion and increased nasal secretions. [37] As a consequence, nasal resistance increased substantially. However, these authors demonstrated that with heated humidification, nasal symptoms and alterations in nasal resistance could be largely prevented. There are now commercially available heated humidification systems for CPAP devices. Although no study has looked at differences in CPAP use when patients with symptoms are placed on humidification, clinical reporting indicates substantially greater patient comfort with humidification. Theoretically, the use of humidification, which prevents increases in nasal resistance, should improve the amount of positive pressure delivered to the oropharynx, rendering CPAP therapy more effective.

Bilevel pressure. Bilevel devices permit the patient to independently adjust the inspiratory and expiratory pressure levels. These devices have not been shown to alter compliance in patients with uncomplicated OSA. [50] However, for patients with hypercapnia during wakefulness and for those who have coexisting lung disease, these devices not only improve breathing comfort, but by offering a boost to inspiration they also assist ventilation and lower carbon dioxide levels. When setting bilevel therapy, it is important to set the expiratory positive airway pressure at a level that is sufficient to ensure that airway patency is maintained. Failure to do so will cause a partial or complete airway closure, and result in either the reappearance of symptoms or an inadequate blood gas improvement.

Autotitrating CPAP. The concept behind autotitrating CPAP devices is that the amount of pressure required to eliminate events can vary from night to night. Autotitrating devices vary the pressure levels within a night, as well as from night to night, in response to changes in nasal obstruction, sleep stage, and body position. There are a number of potential uses and advantages of these devices in titration and in the followup of patients who require nasal CPAP therapy. In those individuals who have variable pressure requirements during a night, overall mean airway pressures can be reduced because pressure would be increased only when required. [51] By reducing pressure-related side effects, comfort and compliance should be improved.

Likewise, individuals who have seasonal rhinitis might benefit from an autotitrating device because pressure is automatically increased when nasal resistance is high, then reduced again when nasal patency improves. In those patients who are already established on therapy, an autotitrating device can be used over a period of time in a patient's home to determine if the prescribed pressure level remains appropriate. Because this technology is still evolving, it must be borne in mind that not all autotitrating devices work in the same manner; some use more sophisticated algorithms to both measure upper airway events and respond to them. [52] Variations in the design of these systems might influence patient outcomes, so clinicians need to be aware of how an individual device operates in order to evaluate the information that is derived from them.

From the Centre for Respiratory Failure and Sleep Disorders, Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, Australia (Dr. Piper) and the ResMed Corp., San Diego (Dr. Stewart).

Reprint requests: Amanda Piper, PhD, Department of Cardiology, VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161. Phone: [phone], ext. 254; fax: [phone]; e-mail: [e-mail]

References

(1.) Cistulli PA, Sullivan CE. Pathophysiology of sleep apnea. In: Saunders NA, Sullivan CE, eds. Sleep and Breathing. 2nd ed. New York: Marcel Dekker, 1994:405-48.

(2.) Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261-4.

(3.) Koskenvuo M, Kaprio J, Telakivi T, et al. Snoring as a risk factor for ischaemic heart disease and stroke in men. Br Med J (Clin Res Ed) 1987;294:16-9.

(4.) Palomaki H, Partinem M, Erkinjuntti T, Kaste M. Snoring, sleep apnea syndrome, and stroke. Neurology 1992;42(7 Suppl 6):75-81.

(5.) He J, Kryger MH, Zorick FJ, et al. Mortality and apnea index in obstructive sleep apnea: Experience in 385 male patients. Chest 1988;94:9-14.

(6.) Stradling JR. Sleep-related breathing disorders. 1. Obstructive sleep apnoea: Definitions, epidemiology, and natural history. Thorax 1995;50:683-9.

(7.) Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230-5.

(8.) Jennum P, Soul A. Epidemiology of snoring and obstructive sleep apnoea in a Danish population age 30-60. J Sleep Res 1992;1:240-4.

(9.) McNamara SG, Grunstein RR, Sullivan CE. Obstructive sleep apnoea. Thorax 1993;48:754-64.

(10.) Gould GA, Whyte KF, Rhind GB, et al. The sleep hypopnea syndrome. Am Rev Respir Med 1988;137:895-8.

(11.) Guilleminault C, Stoohs R, Duncan S. Snoring (I): Daytime sleepiness in regular heavy snorers. Chest 1991;99:40-8.

(12.) Guilleminault C, Stoohs R, Clerk A, et al. A cause of excessive daytime sleepiness: The upper airway resistance syndrome. Chest 1993;104:781-7.

(13.) Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746-52.

(14.) Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981;1:862-5.

(15.) Rapoport DM. Methods to stabilize the upper airway using positive pressure. Sleep 1996;19(9 Suppl):S123-30.

(16.) Wright J, Johns R, Watt I, et al. Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: A systematic review of the research evidence. BMJ 1997;314:851-60.

(17.) Engleman HM, Martin SE, Deary IJ, Douglas NJ. Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome. Lancet 1994;343:572-5.

(18.) Ballester E, Badia JR, Hernandez L, et al. Evidence of the effectiveness of continuous positive airway pressure in the treatment of sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999;159:495-501.

(19.) Engleman HM, Kingshott RN, Wraith PK, et al. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome. Am J Respir Crit Care Med 1999;159:461-7.

(20.) Redline S, Adams N, Strauss ME, et al. Improvement of mild sleep-disordered breathing with CPAP compared with conservative therapy. Am J Respir Crit Care Med 1998;157:858-65.

(21.) Montserrat JM, Ballester B, Olivi H, et al. Time-course of stepwise CPAP titration: Behavior of respiratory and neurological variables. Am J Respir Crit Care Med 1995;152:1854-9.

(22.) Teschler H, Berthon-Jones M, Thompson AB, et al. Automated continuous positive airway pressure titration for obstructive sleep apnea syndrome. Am J Respir Crit Care Med 1996;154:734-40.

(23.) Lloberes P, Ballester E, Montserrat JM, et al. Comparison of manual and automatic CPAP titration in patients with sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1996;154:1755-8.

(24.) Issa FG, Sullivan CE. The immediate effects of nasal continuous positive airway pressure treatment on sleep pattern in patients with obstructive sleep apnea syndrome. Electroencephalogr Clin Neurophysiol 1986;63:10-7.

(25.) Teschler H, Farhat AA, Exner V, et al. AutoSet nasal CPAP titration: Constancy of pressure, compliance and effectiveness at 8 month follow-up. Eur Respir J 1997;10:2073-8.

(26.) Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887-95.

(27.) Hoffstein V, Viner S, Mateika S, Conway J. Treatment of obstructive sleep apnea with nasal continuous positive airway pressure: Patient compliance, perception of benefits, and side effects. Am Rev Respir Dis 1992;145:841-5.

(28.) Krieger J, Kurtz D, Petiau C, et al. Long-term compliance with CPAP therapy in obstructive sleep apnea patients and in snorers. Sleep 1996;19(9 Suppl):S136-43.

(29.) Waldhorn RE, Herrick TW, Nguyen MC, et al. Long-term compliance with nasal continuous positive airway pressure of obstructive sleep apnea. Chest 1990;97:33-8.

(30.) Miljeteig H, Hoffstein V. Determinants of continuous positive airway pressure level for treatment of obstructive sleep apnea. Am Rev Respir Dis 1993;147:1526-30.

(31.) McNicholas WT, Tarlo S, Cole P, et al. Obstructive apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 1982;126:625-8.

(32.) Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep 1984;7:110-4.

(33.) Sullivan CE, Grunstein RR. Continuous positive airway pressure in sleep-disordered breathing. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: W.B. Saunders, 1989:559-70.

(34.) Series F, Marc I, Cormier Y, La Forge J. Required levels of nasal Continuous positive airway pressure during treatment of obstructive sleep apnoea. Eur Respir J 1994;7:1776-81.

(35.) Engleman HM, Martin SE, Douglas NJ. Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. Thorax 1994;49:263-6.

(36.) Pepin JL, Leger P, Veale D, et al. Side effects of nasal continuous positive airway pressure in sleep apnea syndrome: Study of 193 patients in two French sleep centers. Chest 1995;107:375-81.

(37.) Richards GN, Cistulli PA, Ungar RG, et al. Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance. Am J Respir Crit Care Med 1996;154:182-6.

(38.) Sanders MH, Gruendl CA, Rogers RM. Patient compliance with nasal CPAP therapy for sleep apnea. Chest 1986;90:330-3.

(39.) Strumpf DA, Harrop P, Dobbin J, Millman RP. Massive epistaxis from nasal CPAP therapy. Chest l989;95:1141.

(40.) Meurice JC, Mergy J, Rostykus C, et al. Atrial arrhythmia as a complication of nasal CPAP. Chest 1992;102:640-2.

(41.) Jarjour NN, Wilson P. Pneumocephalus associated with nasal continuous positive airway pressure in a patient with sleep apnea syndrome. Chest 1989;96:1425-6.

(42.) Rauscher H, Formanek D, Popp W, Zwick H. Self-reported vs measured compliance with nasal CPAP for obstructive sleep apnea. Chest 1993;103:1675-80.

(43.) Grunstein RR, Dodd MJ, Costas L, Sullivan CE. Home nasal CPAP for sleep apnea--acceptance of home therapy and its usefulness. Aust N Z J Med 1986;16:635.

(44.) Rolfe I, Olson LG, Saunders NA. Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea. Am Rev Respir Dis 1991;144:1130-3.

(45.) Mortimore IL, Bradley PA, Murray JA, Douglas NJ. Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea syndrome. Am J Respir Crit Care Med 1996;154:1759-62.

(46.) Kribbs NB, Pack Al, Kline LR, et al. Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:1162-8.

(47.) Hers V, Liistro G, Dury M, et al. Residual effect of nCPAP applied for part of the night in patients with obstructive sleep apnoea. Eur Respir J 1997;l0:973-6.

(48.) Chervin RD, Theut S, Bassetti C, Aldrich MS. Compliance with nasal CPAP can be improved by simple interventions. Sleep 1997;20:284-9.

(49.) Hoy CJ, Vennelle M, Kingshott RN, et al. Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome? Am J Respir Crit Care Med 1999;159:1096-l00.

(50.) Reeves-Hoche MK, Meek R, Zwillich CW. Nasal CPAP: An objective evaluation of patient compliance. Am J Respir Crit Care Med 1994;149:l49-54.

(51.) Berthon-Jones M, Lawrence 5, Sullivan CE, Grunstein R. Nasal continuous positive airway pressure treatment: Current realities and future. Sleep 1996; 19(9 Suppl):S131-5.

(52.) Schwartz AR, Veit CA, Schwartz JR. A comparative study of commercially available autotitrating devices for obstructive sleep apnea. Sleep 1998;21:S94.

         Common problems related to theuse of nocturnal nasal CPAP
               and some of the possible management strategies
Problem                 Management strategy
Skin reddening or pain  Refit the mask
  over the nasal bridge Refit with a bubble- or flap-
                         style cushion
                        Apply skin protection, such
                         as Duoderm
                        Ensure that the headstrap is
                         not too tight
Leaks into the eyes,    Ensure that the mask fit is
  conjunctivitis         appropriate
                        Use a bubble- or flap-style
                         cushion
                        Cushion the mask with nasal
                         pillows
Mouth leaks             Ensure nasal patency
                        Apply a chinstrap
                        Use heated humidification
                        Use a full face mask
Claustrophobia          Let the patient acclimate
                         gradually
                        Try a lightweight, transparent
                         nasal mask
                        Use nasal pillows
Intolerance to pressure Use the ramping feature
                        Try bilevel pressure
                        Try autotitrating CPAP
Treatment inconvenient  Educate the patient and
                         partner
                        Recommend patient support
                         groups
                        Encourage participation in
                         Internet chat box