A randomized, controlled trial of 1 week of continuous positive airway pressure treatment on quality of life☆☆☆★

Methods 

Patients were located by public advertisements and word-of-mouth referral. All patients signed written informed consent, and the protocol was approved by the University of California, San Diego (UCSD) Institutional Review Board. Patients were eligible if they were between the ages of 30 and 65 years and were 100% to 170% of ideal body weight as determined by Metropolitan norms.16 Patients with any ongoing medical problems other than sleep apnea and hypertension were excluded. Only patients naïve to CPAP treatment were enrolled in this protocol.

Participants were admitted to the UCSD Clinical Research Center for a confirmatory overnight polysomnograph (Nihon Koden model 4412p). The following parameters were recorded: central and occipital electroencephalogram; bilateral electro-oculogram, submental and anterior tibialis electromyogram; electrocardiogram; nasal or oral airflow with a thermistor; and respiratory effort with chest and abdominal inductance belts. Oxyhemoglobin saturation was recorded with a pulse oximeter (Biox 3740). Patients whose respiratory disturbance index (RDI; number of apneas plus number of hypopneas per hour of sleep) was >15 were considered to have OSA and were eligible to continue participation. On the following night, patients were randomized to receive either CPAP or placebo-CPAP. Patients receiving CPAP underwent a standard CPAP titration with a Devilbis CPAP machine and a comfortable fitting mask. Pressure in the mask started at 2 cm H20 and was increased during the night by 2 cm H2O increments until no additional apneic episodes were observed or until a pressure of 8 to 10 cm was reached. Additional pressure titration then increased in increments of 1 cm H2O on the basis of the presence of apnea, hypopnea, or snoring associated with arousals. The titration was considered successful when respiratory events were controlled with CPAP while the patient was in the supine position and in the second or third rapid eye movement sleep period, or until a pressure of 20 cm had been reached. All patients in this protocol had their sleep apnea successfully treated by this definition within this pressure range.

Patients randomized to receive placebo-CPAP underwent a mock titration night. These patients wore a mask that had 5, one-quarter inch drill holes to create a large leak through the mask. Their CPAP pressure was set at 2 cm H2O and was not advanced. All CPAP units had a hidden compliance clock that allowed measurement of the amount of time the machine was operating.

As this investigation of QOL effects took place as part of a larger study examining CPAP effects on sympathetic nervous system activity, patients remained hospitalized overnight a second night to complete other aspects of the protocol. They were then discharged from the hospital for 1 week of continuing CPAP or placebo-CPAP treatment at home. The research staff was in frequent contact with patients to answer questions about mask placement and to encourage compliance with the treatment. Following the 1-week treatment period, participants were readmitted to the UCSD Clinical Research Center for testing, including overnight polysomnography as well as other aspects of the larger protocol.

QOL was measured on 2 occasions, before randomization and after the 1-week treatment period. QOL was measured with the instrument from the Medical Outcomes Study (MOS).15 The MOS instrument has been employed across several disease populations and measures a number of aspects of QOL.

Data were analyzed with repeated measures analysis of variance techniques with SPSS software.

Results 

Table II summarizes the sample characteristics. Thirty-nine patients were studied. Those randomized to the 2 treatments were comparable in age, pretreatment RDI, and screened blood pressure; however, patients randomized to receive CPAP were heavier (P <.05). The mean mask pressure required in the CPAP group was 10.1 cm H2O; placebo-CPAP patients all received CPAP at a pressure of 2 cm H2O, as indicated above. Both patient groups complied equivalently with the CPAP treatment during the 1-week interval of home treatment (>5 hours per night for each group). As expected, patients receiving CPAP demonstrated a significantly greater drop in RDI than was observed in patients assigned to the placebo-CPAP group (P = .001) (Table II). Specifically, mean RDI after treatment in the active group was 3.2 (± 3.9) versus 28.1 (± 22.9) in the placebo arm.

Table II. Patient sample characteristics (Values expressed as mean ± SD)

		CPAP	Placebo-CPAP
	n	21	18
	Age (years)	47.7 ± 8.1	48.9 ± 9.9
	BMI	32.7 ± 4.9*	28.5 ± 5.0
	RDI (baseline)	53.6 ± 23.2	41.7 ± 25.6
	RDI (after 7 days of treatment)	3.2 ± 3.9*	28.1 ± 22.9
	*Significantly different from Placebo-CPAP (P < 0.05).

BMI = body mass index; RDI = respiratory disturbance index.

Regarding QOL, significant time effects were observed for the following subscales of the MOS: satisfaction with physical functioning, effects of pain, pain severity, cognitive functioning, mental health index I, psychological well-being I, depression/behavioral-emotional control, anxiety I, psychological distress I, positive affect II, mental health index II, psychological distress II, anxiety II, psychological well-being II, mental health index III, role limitations due to emotional problems, and physical/physiologic functioning. Fig 1 portrays these findings.

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Fig. 1. MOS subscales in which significant time effects were observed. Bars represent both groups because no time by treatment interaction effects were observed.

Discussion 

CPAP is widely considered the treatment of choice for sleep apnea. If patients are compliant, CPAP is effective in controlling the respiratory symptoms of sleep apnea in most patients. Our results suggest that the effects of CPAP on QOL, however, may be less straightforward.

As mentioned in the introduction, randomized placebo-controlled trials in this area are rare. Had we not administered placebo-CPAP to a comparison group, we would have concluded that 1 week of treatment with CPAP leads to significant improvements in QOL. However, our findings with placebo-CPAP make that conclusion less certain. We interpret the uniform improvements in several aspects of QOL in our study to a nonspecific effect of treatment—a placebo effect. Patients were observed closely by our research staff, and all patients used elaborate CPAP machinery that was similar in appearance regardless of its effectiveness. Adherence to CPAP use was measured in this study through the use of timers measuring the number of hours per night of use for each apparatus. Level of adherence did not differ between groups. Nonetheless, the combination of professional attention and patient expectations, given the machinery, may well have influenced our findings regarding QOL. In addition, many patients with OSA have been suffering for years without treatment. The effect of access to a diagnosis and treatment provided in this study may explain the improvements observed in the placebo-CPAP group. Our findings suggest that short-term CPAP treatment may well have beneficial, although nonspecific, effects on QOL. It remains to be seen whether longer-term treatment is associated with improvements in QOL specific to active CPAP treatment.

The study has a number of limitations. Because respiratory symptoms are successfully treated almost immediately with CPAP and because we were uneasy about imposing a lengthy placebo treatment on patients who had a definitive diagnosis of sleep apnea, we examined CPAP effects for only a 1-week interval. It is possible that the effect of CPAP on QOL may become more pronounced over a longer treatment period. However, our study is not alone in questioning whether CPAP confers broad-based benefits in addition to its correction of the respiratory distress itself. A recently published article by Munoz et al17 examined responses to CPAP during 1 year of treatment in 80 patients with sleep apnea and 80 healthy controls. This controlled study also reported no beneficial change in depression or anxiety after 1 year of treatment. In any event, future studies should examine the effects of CPAP on QOL during longer treatment periods.

Our sample size is admittedly small. All of our patients had substantial levels of apnea (the average RDI before treatment was 48.1), but they were otherwise relatively healthy. We excluded patients with other major illnesses requiring treatment, such as those with congestive heart failure, a history of myocardial infarction, or morbid obesity. Perhaps the QOL benefits of CPAP treatment would be greater in such patients. This possibility should be examined in future research.

We employed the MOS instrument to measure QOL in this study. This instrument has been shown to be applicable to both healthy and chronically ill adults and is widely used across a variety of general, medical, and psychiatric populations. The MOS instrument has also been previously employed in studies of sleep apnea patients. Although the MOS does measure symptoms relevant to sleep apnea patients (eg, fatigue), our findings may be limited by the use of an instrument that is not disease-specific. Future studies may choose to employ a general instrument such as the MOS as well as an instrument designed to measure QOL as related to sleep apnea specifically.

In addition, patients randomized to receive active CPAP treatment had significantly higher body mass index than those randomized to receive placebo-CPAP. It is possible that this difference in body mass index may have influenced our results.

Finally, the placebo arm of this study employed CPAP pressure of 2 cm H2O. It is possible that this pressure may have had some effect on QOL, diminishing the between-group differences observed. Indeed, RDI improved slightly in the placebo group after treatment. However, at 28.1, mean RDI in the placebo group remained clinically significant, even by the strictest diagnostic standards. RDI in the active treatment group improved significantly and, at 3.2, was no longer clinically significant, even by the strictest diagnostic standards. Nonetheless, future studies in this area should employ placebo-CPAP at even lower pressures.

Our study provides yet another demonstration of the value and importance of a placebo arm in medical research. Although CPAP is clearly effective in controlling the respiratory symptoms of sleep apnea, it is less clear whether observed improvements in QOL are a result of active treatment or to nonspecific placebo effects.