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Relationship Between Quality of Life and Mood or Depression in Patients With Severe Obstructive Sleep Apnea Syndrome
Relationship Between Quality of Life and Mood or Depression in Patients With Severe Obstructive Sleep Apnea Syndrome* Tsuneto Akashiba, MD; Seiji Kawahara, MD; Toshiki Akahoshi, MD; Chiharu Omori, MD; Osamu Saito, MD; Tohru Majima, MD; and Takashi Horie, MD, FCCP
Study objectives: To assess the quality of life (QOL) in patients with severe obstructive sleep apnea (OSAS), and the relationship between the QOL and severity of OSAS, excessive daytime sleepiness (EDS), and mood. Methods: Sixty patients with OSAS and 34 normal control subjects were assessed for QOL using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36), for EDS using the Epworth sleepiness scale (ESS), and for mood using the Zung self-rated depression scale (SDS). The associations between each domain and the total score on the SF-36 and the baseline characteristics, polysomnographic parameters, ESS score, and SDS score were examined by simple regression analysis and stepwise multiple regression analysis. Results: Six of eight domains and the total score on the SF-36 were significantly lower than those in the control subjects. The ESS and SDS scores were also more impaired in the patients than in the control subjects. There was no relationship between each domain on the SF-36 and the severity of OSAS and ESS score. Five of eight domains and the total score on the SF-36 were significantly correlated with the SDS score. Stepwise multiple regression analysis selected three variables, the SDS score (partial R2 ⴝ 0.505), the lowest arterial oxygen saturation during sleep (partial R2 ⴝ 0.064), and ESS score (partial R2 ⴝ 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on SF-36 (R2 ⴝ 0.622, p < 0.0001) Conclusions: The QOL of patients with severe OSAS was decreased compared with normal control subjects. The QOL of patients was strongly correlated with the depression scale on simple regression analysis. However, EDS score and oxygen desaturation during sleep also affected the QOL, although the magnitude of its effect was small. (CHEST 2002; 122:861– 865) Key words: depression; Epworth sleepiness scale; excessive daytime sleepiness; obstructive sleep apnea syndrome; quality of life; self-rated depression scale Abbreviations: AHI ⫽ apnea/hypopnea index; BMI ⫽ body mass index; CPAP ⫽ continuous positive airway pressure; EDS ⫽ excessive daytime sleepiness; GHP ⫽ general health perception; MH ⫽ mental health; OSAS ⫽ obstructive sleep apnea syndrome; PF ⫽ physical functioning; QOL ⫽ quality of life; RE ⫽ role limitations due to emotional problems; %REM ⫽ percentage of rapid eye movement; RP ⫽ role limitations due to physical problems; Sao2 ⫽ arterial oxygen saturation; SDS ⫽ self-rated depression scale; SF ⫽ social functioning; SF-36 ⫽ Medical Outcomes Study Short-Form 36 Health Survey; SWS ⫽ slow-wave sleep
sleep apnea syndrome (OSAS) is O bstructive characterized by repeated episodes of upper airway obstruction during sleep, with disturbances in arterial blood gases and increasing inspiratory effort until the upper airway obstruction discontinues due *From the First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Manuscript received October 11, 2001; revision accepted March 22, 2002. Correspondence to: Tsuneto Akashiba, MD, 30-1 Oyaguchi, Kamimachi, Itabashi-ku, Tokyo, Japan 173-8610 www.chestjournal.org
to arousal. Recurrent arousal during sleep causes excessive daytime sleepiness (EDS), which is the primary symptom of patients with OSAS,1,2 and it has been reported that EDS leads to traffic,3 work, and domestic accidents4,5 in patients with severe OSAS. EDS may also contribute to the impaired quality of life (QOL) of patients with OSAS.6 Recently, general health outcomes have received growing recognition as relevant end points for the evaluation of health-care services and clinical trials.7,8 General health evaluation questionnaires aim to CHEST / 122 / 3 / SEPTEMBER, 2002
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quantify self-perceptions concerning general health and functional well-being. Several studies have shown that the QOL in patients with OSAS was more impaired than in normal populations,9 –11 and was improved by effective treatments such as nasal continuous positive airway pressure (CPAP).11–13 Bennet et al12 demonstrated that although the QOL evaluated by the Medical Outcomes Study ShortForm 36 Health Survey questionnaire (SF-36)14 had a poor correlation with the severity of OSAS as assessed with the apnea/hypopnea index (AHI) and sleep fragmentation, the energy and vitality scores on the SF-36 were significantly correlated with EDS as evaluated by both the Epworth sleepiness scale (ESS)15 and the modified maintenance of wakefulness test.16 Recently, Briones et al6 also showed that the EDS, as evaluated by the ESS and multiple sleep latency test, was significantly correlated with the energy/fatigue score on the SF-36. More recently, Baldwin et al13 demonstrated that mild-to-moderate sleep-disordered breathing is associated with reduced vitality, while severe sleep-disordered breathing is more broadly associated with a poorer QOL. Furthermore, they found that subjective sleep symptoms were comprehensively associated with a poorer QOL in a large-scale population study. It has been also reported that neuropsychologic deficits, including decreased concentration, memory loss, irritability, moodiness, depression, psychosis, decreased libido, and impotence, are often found in addition to EDS in patients with severe OSAS.17,18 These neuropsychologic deficits may also have a profound impact on QOL because they affect the normal activities of daily living. However, there are no published studies, to our knowledge, that have examined the relationship between the QOL and neuropsychologic functions in patients with OSAS. Therefore, we aimed to examine the relationship between the QOL and the severity of OSAS, daytime sleepiness, and neuropsychologic functions in patients with severe OSAS. Materials and Methods Sixty male patients with a diagnosis of OSAS by polysomnography and considered candidates for nasal CPAP treatment were included in this study. Our entry criteria were an AHI ⬎ 20/h and severe arterial oxygen desaturation (arterial oxygen saturation [Sao2] ⬍ 80%) accompanied by EDS. These criteria were used because Japanese national health insurance permits the use of nasal CPAP under these conditions. No patients had chronic lung disease, and none were receiving bronchodilator treatment. All patients gave informed consent for this study. Their mean ⫾ SD age and body mass index (BMI) were 47.7 ⫾ 11.2 years and 29.1 ⫾ 5.2, respectively. Polysomnography consisted of a continuous recording of EEG, electro-oculogram, submental electromyogram, ECG, airflow at the nose and mouth (thermistor), movements of the chest and abdomen (inductance plethysmog862
raphy), and oxyhemoglobin saturation (Sao2) by pulse oximetry. The analysis and interpretation of the polysomnography data were performed by standard techniques.19 Apnea was defined as cessation of airflow at the nose and mouth lasting at least 10 s. Hypopnea was defined as a decrease in airflow, and rib cage excursions by ⬎ 50% that was associated with an oxygen saturation of at least 4% below the preceding baseline value.20 The AHI was calculated as the number of apnea and hypopnea events per hour of sleep. The mean and minimum Sao2 also were calculated from the polysomnography data. Subjective sleepiness was assessed using the ESS, a wellvalidated eight-item self-completion questionnaire.15 Patients were asked to score the likelihood of falling asleep in eight different situations with different levels of stimulation, resulting in a final score of 0 (least sleepy) to 24 (most sleepy). QOL was assessed by use of the SF-36 questionnaires.14 In a preparatory longitudinal cohort study21 of several health-status measures, the SF-36 had the best reliability, validity, and responsiveness for patients with OSAS. The SF-36 consists of a 36-item questionnaire that measures physical functioning (PF), role limitations due to physical problems (RP), bodily pain, general health perception (GHP), vitality, social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). The raw scores for each subscale were transformed to scores that ranged from 0 to 100%, according to the formula: transformed score ⫽ ([raw scale score ⫺ lowest possible score]/ possible score range) ⫻ 100%, as recommended.14 In all instances, a higher score is consistent with a more positive health status. We used the Zung self-rated depression scale (SDS)22 as an assessment of depressive state. This inventory has 20 items that tap various symptoms of clinically significant depression. Each item has a 4-point range, and the items are balanced for yes/no tendencies. We chose this instrument for several reasons. It is a self-reported measure with an established degree of subject acceptability and thus is practical to use as a repeated measure. Of particular relevance, it is an instrument that has been widely used both in various patient groups and in normal persons, making available considerable validation data as well as a large number of comparison groups to aid in the interpretation of the results. The SDS scores reported here were obtained, as outlined by Zung,23 by multiplying the raw scores by 1.25. The scores are able to vary between 25 and 100 (raw scores, 20 to 80). Thirty-four age-matched and gender-matched control subjects were also assessed using the ESS, the SF-36 for the QOL, and the SDS score in order to compare with the patients. The control subjects were selected from subjects who were undergoing a routine annual check-up in our hospital and had no suggestive symptoms of OSAS such as loud snoring, EDS, or respiratory abnormalities during sleep. Results are presented as the mean ⫾ SD. Group differences were assessed with Student t test. We also determined the Pearson linear correlation between certain variables. The correlation between the total score on the SF-36 and the anthropometric, polysomnographic variables, ESS, and SDS scores were determined by stepwise multiple regression analysis using a statistical program (Statview, version 4; SAS Institute, Cary, NC). Each of the variables was entered into the multiple regression analysis if its F value was ⬎ 4. A p value ⬍ 0.05 was considered statistically significant.
Results The baseline characteristics of the patients and normal control subjects are shown in Table 1. AlClinical Investigations
Table 1—Baseline Characteristics of the Subjects* Characteristics
Patients
Participants, No. Male/female gender, No. Age, yr BMI ESS score SDS score AHI, per h Mean Sao2, % Lowest Sao2, % Arousal index Stage (1 ⫹ 2), %† SWS, % %REM, %
60 58/2 47.7 ⫾ 11.2 29.1 ⫾ 5.2 10.9 ⫾ 4.2 50.5 ⫾ 11.4 51.6 ⫾ 26.6 90.0 ⫾ 5.5 69.2 ⫾ 9.3 40.5 ⫾ 20.4 74.5 ⫾ 13.8 8.6 ⫾ 15.6 16.5 ⫾ 7.9
Control Subjects
p Value
34 32/2 45.2 ⫾ 11.0 23.7 ⫾ 3.2 4.8 ⫾ 2.2 44.7 ⫾ 7.0
NS ⬍ 0.0001 ⬍ 0.001 ⬍ 0.01
*Data are presented as mean ⫾ SD unless otherwise indicated. NS ⫽ not significant. †Stage (1 ⫹ 2) ⫽ non-rapid eye movement sleep stages 1 and 2.
though there were no significant differences in age and gender between patients and control subjects, the BMI, ESS, and SDS indexes were significantly higher in patients than in control subjects. Thirtytwo of the 60 patients (53%) were hypersomnolent (ESS score ⬎ 11),24 and 29 patients (48%) were depressive (SDS score ⬎ 50).23 The polysomnography data showed that the patients had severe OSAS and disturbances of sleep architecture. Six (RP, GHP, vitality, SF, RE, and MH) of eight domains and the total score on the SF-36 were significantly lower in the patients than in the normal control subjects (Fig 1). We examined the relationships between the ESS and SDS scores and the polysomnography parameters (Table 2). The ESS score was significantly correlated with the mean Sao2 and percentage of rapid eye movement (%REM). No significant correlation was observed between the SDS score and the
Figure 1. Comparison between patients with OSAS and control subjects on the SF-36. VT ⫽ vitality; BP ⫽ bodily pain. www.chestjournal.org
polysomnography parameters. The SDS score was not correlated with the ESS score. We also examined the relationship between each domain and the total score on the SF-36 and age, BMI, polysomnography parameters, ESS score, and SDS score (Table 3). The slow-wave sleep (SWS) was correlated with the RE (p ⬍ 0.05). The SDS score was significantly correlated with five (RF, GHP, vitality, RE, and MH) of eight domains and the total score on the SF-36 (p ⬍ 0.005 and p ⬍ 0.0001, respectively). Stepwise multiple regression analysis identified three variables, the SDS score (partial R2 ⫽ 0.505), the lowest Sao2 (partial R2 ⫽ 0.064), and ESS score (partial R2 ⫽ 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on the SF-36 (R2 ⫽ 0.622, p ⬍ 0.0001).
Discussion The subjects in this study had severe OSAS and a reduced QOL compared with gender-matched and age-matched control subjects. Six of eight domains and the total score on the SF-36 were significantly lower in the patients than in the control subjects, showing that the patients with severe OSAS had a poorer general health status. These results are consistent with previous reports.9 –13 Recently, Baldwin et al13 demonstrated that patients with severe OSAS (respiratory disturbance index ⬎ 30) have lower scores in six of eight domains on the SF-36 than healthy subjects, and that EDS was associated with a reduced QOL in a large population study. We found that one half of the patients were depressive, and that the SDS score was significantly correlated with five of eight domains and the total score on the SF-36. Although neuropsychologic deficits including mood disturbance and depression were demonstrated in patients with OSAS in previous studies,17,18 no published reports have examined the relationship between the QOL and mood. The findings that the mood or depressive state may play an important role in QOL is reasonable because mood disturbances may also affect activities of daily living as well as EDS. Previous reports showed that patients with OSAS often complained of mood disturbances; an early report by Guilleminault and Dement25 showed that 24% of their patients with sleep apnea had seen psychiatrists for symptoms of depression and anxiety. Furthermore, 28% of their patients had elevated depression scale scores on the Minnesota Multiphasic Personality Inventory. Kales et al26 found that 28 of 50 patients with OSAS severe enough to warrant tracheostomy had high scores on CHEST / 122 / 3 / SEPTEMBER, 2002
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Table 2—Correlation Coefficients Between the ESS Score and the SDS Score and the Polysomnography Parameters* Variables
Age
BMI
AHI
Mean Sao2
Lowest Sao2
Arousal Index
Stage (1 ⫹ 2)
SWS
%REM
ESS SDS score
⫺ 0.023 ⫺ 0.033
0.211 ⫺ 0.104
0.104 ⫺ 0.010
⫺ 0.271† 0.235
⫺ 0.206 0.023
0.085 0.052
⫺ 0.085 0.255
0.205 ⫺ 0.233
⫺ 0.307† ⫺ 0.037
*See Table 1 for expansion of abbreviation. †p ⬍ 0.05.
the Minnesota Multiphasic Personality Inventory for depression. Millman et al27 also showed that 45% of patients had depressive symptoms (SDS score ⬎ 50), and nasal CPAP decreased their SDS score to the normal range. Twenty-nine of 60 patients (48%) were depressive in the present study, consistent with the studies by Kales et al26 and Millman et al.27 This depressive state was significantly correlated with the PF, GHP, vitality, RE, MH, and the total score on the SF-36. The GHP, vitality, RE, MH, and total score had a relatively strong correlation with the SDS score (r ⬎ 0.57, p ⬍ 0.0001). This is the first report showing a significant relationship between the QOL and depression in patients with OSAS. Since EDS is a primary symptom in patients with OSAS and an important symptom for activities of daily living, it appears to be related to the decrease of the QOL. Therefore, a number of studies6,12,13 have examined the relationship between the EDS and QOL and found that the EDS, whether evaluated subjectively or objectively, was correlated with the decrease in the QOL. However, there were no significant correlations between the EDS as evaluated by the ESS and each domain on the SF- 36 in the present study. The reason for this difference between our results and previous studies is unclear. Although there was no significant relationship between the ESS and each domain on SF-36 by simple
regression analysis, we found that the ESS had additive effects on the QOL from stepwise multiple regression analysis. Although the SDS score was strongly correlated with the total score on the SF-36 (r ⫽ 0.710) on simple regression analysis, this variable itself accounted for only 50.5% of the total variance in the total score on the SF-36. Stepwise multiple regression analysis showed that an additional 11.7% or 62.2% of the total variance was accounted for by the incorporation of the lowest Sao2 and the ESS into the regression, respectively. Therefore, the EDS as evaluated by ESS might affect, at least somewhat, the QOL of our subjects. A number of previous studies6,9 –13 have emphasized the relationship between the EDS and QOL. However, correlations between the EDS and several domains on the SF-36 were relatively weak in these studies. As mood disturbances or a depressive state had a relatively strong correlation with most of the domains on the SF-36 in this study, mood or depression may play a more important role than the EDS in QOL. It has been reported that patients with severe OSAS have a poor prognosis,28,29 and that cardiovascular complications are the main cause of death.29 Recently, a significant relationship between OSAS and cardiovascular complications has been demonstrated in large-scale population studies.30,31 Al-
Table 3—Correlation Coefficients Between the Domains on the SF-36 and the Polysomnography Parameters*
Age, yr BMI AHI Mean Sao2 Lowest Sao2 Arousal index Stage (1 ⫹ 2), % SWS, % %REM, % ESS score SDS score
PF
RP
Bodily Pain
GH
Vitality
SF
RE
MH
Total
⫺ 0.229 ⫺ 0.202 ⫺ 0.018 0.213 ⫺ 0.109 ⫺ 0.025 0.064 0.012 0.152 ⫺ 0.222 ⫺ 0.424‡
⫺ 0.228 ⫺ 0.012 0.202 0.116 ⫺ 0.071 0.165 0.219 ⫺ 0.035 0.025 ⫺ 0.130 ⫺ 0.202
⫺ 0.127 0.117 0.039 ⫺ 0.158 ⫺ 0.206 ⫺ 0.041 0.058 0.012 ⫺ 0.168 ⫺ 0.081 ⫺ 0.260
⫺ 0.092 ⫺ 0.015 ⫺ 0.079 0.056 ⫺ 0.086 ⫺ 0.154 ⫺ 0.011 ⫺ 0.035 0.099 ⫺ 0.059 ⫺ 0.571§
0.139 0.121 0.055 ⫺ 0.158 ⫺ 0.211 0.002 0.004 0.006 ⫺ 0.020 ⫺ 0.074 ⫺ 0.570§
⫺ 0.137 0.136 0.234 ⫺ 0.238 ⫺ 0.315 0.204 0.084 ⫺ 0.071 ⫺ 0.027 ⫺ 0.156 ⫺ 0.117
⫺ 0.072 ⫺ 0.046 0.206 ⫺ 0.004 ⫺ 0.116 0.193 0.269 ⫺ 0.294† 0.028 ⫺ 0.153 ⫺ 0.572§
⫺ 0.026 0.127 0.185 ⫺ 0.209 ⫺ 0.220 0.061 ⫺ 0.031 0.055 ⫺ 0.0710 0.021 ⫺ 0.726§
⫺ 0.128 0.006 0.117 ⫺ 0.120 0.226 0.026 0.059 ⫺ 0.065 ⫺ 0.006 ⫺ 0.120 ⫺ 0.710§
*See Table 1 for expansion of abbreviation. †p ⬍ 0.05. ‡p ⬍ 0.005. §p ⬍ 0.0001. 864
Clinical Investigations
though improving a patient’s prognosis may be the main goal of clinicians, improving the QOL is also important for patients. Since the severity of OSAS was not always associated with reductions in the QOL, as shown in present study, a careful evaluation of the mood or depressive state of a patient will be needed to improve the QOL of patients with severe OSAS. Stepwise regression analysis also showed a significant effect of the lowest Sao2 during sleep on the total score on the SF-36, although the magnitude of its effect was small. Although the relationship between oxygen desaturation and QOL is still uncertain, it is possible that severe oxygen desaturation during sleep plays a substantial role in development of neuropsychologic disturbances and a reduced QOL. References 1 Bradley TD, Phillipson EA. Pathogenesis and pathophysiology of obstructive sleep apnea. Med Clin North Am 1985; 69:1169 –1185 2 McNamara SG, Grunstein RR, Sullivan CE. Obstructive sleep apnoea. Thorax 1993; 48:754 –764 3 Findley L, Unverzagt M, Suratt P. Automobile accidents involving patients with obstructive sleep apnea. Am Rev Respir Dis 1988; 138:337–340 4 Mitler MM, Carskadon MA, Czeisler CA, et al. Catastrophes, sleep, and public policy: consensus report. Sleep 1988: 11: 100 –109 5 Leger D. The cost of sleep-related accidents: a report for the National Commission on Sleep Disorders Research. Sleep 1994; 17:84 –93 6 Briones B, Adams N, Strauss M, et al. Relationship between sleepiness and general health status. Sleep 1996: 19:583–588 7 Anderson RT, Aaronson NK, Wilkin D. Critical review of the international assessment of health-related quality of life. Qual Life Res 1993; 2:369 –395 8 Tarlov AR, Ware JE Jr, Greenfield S, et al. The Medical Outcomes Study: an application of methods for monitoring the results of medical care. JAMA 1989; 262:925–930 9 Gall R, Isaac L, Kryger M. Quality of life in mild obstructive sleep apnea. Sleep 1993; 16:S59 –S61 10 Fornas C, Ballester E, Arteta E, et al. Measurement of general health status in obstructive sleep apnea hypopnea patients. Sleep 1995; 18:876 – 879 11 D’Ambrosio C, Bowman T, Mohsenin V. Quality of life in patients with obstructive sleep apnea: effects of nasal continuous positive airway pressure; a prospective study. Chest 1999; 115:123–129 12 Bennet LS, Barbour C, Langford B, et al. Health status in obstructive sleep apnea: relationship with sleep fragmentation and daytime sleepiness, and effects of continuous positive airway pressure. Am J Respir Crit Care Med 1999; 159:1884 – 1890
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13 Baldwin CM, Griffith MPH, Neito J, et al. The association of sleep symptoms with quality of life in the sleep heart health study. Sleep 2001; 24:96 –105 14 Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992; 30:473– 483 15 Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14:540 –545 16 Mitler MM, Gujavarty S, Browman CP. Maintenance of wakefulness test: a polysomnographic technique for evaluating treatment efficacy in patients with excessive somnolence. Electroencephalogr Clin Neurophysiol 1982; 53:658 – 661 17 Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndrome. In: Guilleminult C, Dement WC, eds. Sleep apnea syndromes. New York, NY: Alan R. Liss, 1978 18 Sullivan CE, Issa FG. Obstructive sleep apnea. Clin Chest Med 1985; 6:633– 651 19 Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring systems for sleep stages of human subjects. Washington, DC: National Institute of Health, 1968; publication No. 204 20 Gould GA, Whyte KF, Rhind GB, et al. The sleep hypopnea syndrome. Am Rev Respir Dis 1988; 137:895– 898 21 Jenkinson C, Stradling J, Petersen S. Comparison of three measures of quality of life outcome in the evaluation of continuous positive airway pressure therapy for sleep apnoea. J Sleep Res 1997; 6:199 –204 22 Zung WWK. A self-rating depression scale. Arch Gen Psychiatry 1965; 12:63–70 23 Zung WWK. From art to science: the diagnosis and treatment of depression. Arch Gen Psychiatry 1973; 29:328 –337 24 Chervin RD, Aldrich MS. The Epworth sleepiness scale may not reflect objective measures of sleepiness or sleep apnea. Neurology 1999; 52:125–131 25 Guilleminault C, Dement WC. Sleep apnea syndrome due to upper airway obstruction. Arch Intern Med 1977; 137:296 – 300 26 Kales A, Caldwell AB, Cadieux CD, et al. Severe obstructive sleep apnea: II. Associated psychopathological and psychological consequences. J Chronic Dis 1985; 38:427– 434 27 Millman RP, Fogel BS, McNamara ME, et al. Depression as a manifestation of obstructive sleep apnea: reversal with nasal continuous positive airway pressure. J Clin Psychiatry 1989; 50:348 –351 28 He J, Kryger MH, Zorick, FG, et al. Mortality and apnea index in obstructive sleep apnea. Chest 1988; 94:9 –14 29 Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients: mortality. Chest 1988; 94:1200 –1204 30 Nieto FJ, Young TB, Lind BK, et al. Association of sleepdisordered breathing, sleep apnea, and hypertension in large community-based study: Sleep Heart Health Study. JAMA 2000; 283:1829 –1836 31 Shahar E, Whitney CW, Redline S, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001; 163:19 –25
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Study objectives: To assess the quality of life (QOL) in patients with severe obstructive sleep apnea (OSAS), and the relationship between the QOL and severity of OSAS, excessive daytime sleepiness (EDS), and mood. Methods: Sixty patients with OSAS and 34 normal control subjects were assessed for QOL using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36), for EDS using the Epworth sleepiness scale (ESS), and for mood using the Zung self-rated depression scale (SDS). The associations between each domain and the total score on the SF-36 and the baseline characteristics, polysomnographic parameters, ESS score, and SDS score were examined by simple regression analysis and stepwise multiple regression analysis. Results: Six of eight domains and the total score on the SF-36 were significantly lower than those in the control subjects. The ESS and SDS scores were also more impaired in the patients than in the control subjects. There was no relationship between each domain on the SF-36 and the severity of OSAS and ESS score. Five of eight domains and the total score on the SF-36 were significantly correlated with the SDS score. Stepwise multiple regression analysis selected three variables, the SDS score (partial R2 ⴝ 0.505), the lowest arterial oxygen saturation during sleep (partial R2 ⴝ 0.064), and ESS score (partial R2 ⴝ 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on SF-36 (R2 ⴝ 0.622, p < 0.0001) Conclusions: The QOL of patients with severe OSAS was decreased compared with normal control subjects. The QOL of patients was strongly correlated with the depression scale on simple regression analysis. However, EDS score and oxygen desaturation during sleep also affected the QOL, although the magnitude of its effect was small. (CHEST 2002; 122:861– 865) Key words: depression; Epworth sleepiness scale; excessive daytime sleepiness; obstructive sleep apnea syndrome; quality of life; self-rated depression scale Abbreviations: AHI ⫽ apnea/hypopnea index; BMI ⫽ body mass index; CPAP ⫽ continuous positive airway pressure; EDS ⫽ excessive daytime sleepiness; GHP ⫽ general health perception; MH ⫽ mental health; OSAS ⫽ obstructive sleep apnea syndrome; PF ⫽ physical functioning; QOL ⫽ quality of life; RE ⫽ role limitations due to emotional problems; %REM ⫽ percentage of rapid eye movement; RP ⫽ role limitations due to physical problems; Sao2 ⫽ arterial oxygen saturation; SDS ⫽ self-rated depression scale; SF ⫽ social functioning; SF-36 ⫽ Medical Outcomes Study Short-Form 36 Health Survey; SWS ⫽ slow-wave sleep
sleep apnea syndrome (OSAS) is O bstructive characterized by repeated episodes of upper airway obstruction during sleep, with disturbances in arterial blood gases and increasing inspiratory effort until the upper airway obstruction discontinues due *From the First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Manuscript received October 11, 2001; revision accepted March 22, 2002. Correspondence to: Tsuneto Akashiba, MD, 30-1 Oyaguchi, Kamimachi, Itabashi-ku, Tokyo, Japan 173-8610 www.chestjournal.org
to arousal. Recurrent arousal during sleep causes excessive daytime sleepiness (EDS), which is the primary symptom of patients with OSAS,1,2 and it has been reported that EDS leads to traffic,3 work, and domestic accidents4,5 in patients with severe OSAS. EDS may also contribute to the impaired quality of life (QOL) of patients with OSAS.6 Recently, general health outcomes have received growing recognition as relevant end points for the evaluation of health-care services and clinical trials.7,8 General health evaluation questionnaires aim to CHEST / 122 / 3 / SEPTEMBER, 2002
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quantify self-perceptions concerning general health and functional well-being. Several studies have shown that the QOL in patients with OSAS was more impaired than in normal populations,9 –11 and was improved by effective treatments such as nasal continuous positive airway pressure (CPAP).11–13 Bennet et al12 demonstrated that although the QOL evaluated by the Medical Outcomes Study ShortForm 36 Health Survey questionnaire (SF-36)14 had a poor correlation with the severity of OSAS as assessed with the apnea/hypopnea index (AHI) and sleep fragmentation, the energy and vitality scores on the SF-36 were significantly correlated with EDS as evaluated by both the Epworth sleepiness scale (ESS)15 and the modified maintenance of wakefulness test.16 Recently, Briones et al6 also showed that the EDS, as evaluated by the ESS and multiple sleep latency test, was significantly correlated with the energy/fatigue score on the SF-36. More recently, Baldwin et al13 demonstrated that mild-to-moderate sleep-disordered breathing is associated with reduced vitality, while severe sleep-disordered breathing is more broadly associated with a poorer QOL. Furthermore, they found that subjective sleep symptoms were comprehensively associated with a poorer QOL in a large-scale population study. It has been also reported that neuropsychologic deficits, including decreased concentration, memory loss, irritability, moodiness, depression, psychosis, decreased libido, and impotence, are often found in addition to EDS in patients with severe OSAS.17,18 These neuropsychologic deficits may also have a profound impact on QOL because they affect the normal activities of daily living. However, there are no published studies, to our knowledge, that have examined the relationship between the QOL and neuropsychologic functions in patients with OSAS. Therefore, we aimed to examine the relationship between the QOL and the severity of OSAS, daytime sleepiness, and neuropsychologic functions in patients with severe OSAS. Materials and Methods Sixty male patients with a diagnosis of OSAS by polysomnography and considered candidates for nasal CPAP treatment were included in this study. Our entry criteria were an AHI ⬎ 20/h and severe arterial oxygen desaturation (arterial oxygen saturation [Sao2] ⬍ 80%) accompanied by EDS. These criteria were used because Japanese national health insurance permits the use of nasal CPAP under these conditions. No patients had chronic lung disease, and none were receiving bronchodilator treatment. All patients gave informed consent for this study. Their mean ⫾ SD age and body mass index (BMI) were 47.7 ⫾ 11.2 years and 29.1 ⫾ 5.2, respectively. Polysomnography consisted of a continuous recording of EEG, electro-oculogram, submental electromyogram, ECG, airflow at the nose and mouth (thermistor), movements of the chest and abdomen (inductance plethysmog862
raphy), and oxyhemoglobin saturation (Sao2) by pulse oximetry. The analysis and interpretation of the polysomnography data were performed by standard techniques.19 Apnea was defined as cessation of airflow at the nose and mouth lasting at least 10 s. Hypopnea was defined as a decrease in airflow, and rib cage excursions by ⬎ 50% that was associated with an oxygen saturation of at least 4% below the preceding baseline value.20 The AHI was calculated as the number of apnea and hypopnea events per hour of sleep. The mean and minimum Sao2 also were calculated from the polysomnography data. Subjective sleepiness was assessed using the ESS, a wellvalidated eight-item self-completion questionnaire.15 Patients were asked to score the likelihood of falling asleep in eight different situations with different levels of stimulation, resulting in a final score of 0 (least sleepy) to 24 (most sleepy). QOL was assessed by use of the SF-36 questionnaires.14 In a preparatory longitudinal cohort study21 of several health-status measures, the SF-36 had the best reliability, validity, and responsiveness for patients with OSAS. The SF-36 consists of a 36-item questionnaire that measures physical functioning (PF), role limitations due to physical problems (RP), bodily pain, general health perception (GHP), vitality, social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). The raw scores for each subscale were transformed to scores that ranged from 0 to 100%, according to the formula: transformed score ⫽ ([raw scale score ⫺ lowest possible score]/ possible score range) ⫻ 100%, as recommended.14 In all instances, a higher score is consistent with a more positive health status. We used the Zung self-rated depression scale (SDS)22 as an assessment of depressive state. This inventory has 20 items that tap various symptoms of clinically significant depression. Each item has a 4-point range, and the items are balanced for yes/no tendencies. We chose this instrument for several reasons. It is a self-reported measure with an established degree of subject acceptability and thus is practical to use as a repeated measure. Of particular relevance, it is an instrument that has been widely used both in various patient groups and in normal persons, making available considerable validation data as well as a large number of comparison groups to aid in the interpretation of the results. The SDS scores reported here were obtained, as outlined by Zung,23 by multiplying the raw scores by 1.25. The scores are able to vary between 25 and 100 (raw scores, 20 to 80). Thirty-four age-matched and gender-matched control subjects were also assessed using the ESS, the SF-36 for the QOL, and the SDS score in order to compare with the patients. The control subjects were selected from subjects who were undergoing a routine annual check-up in our hospital and had no suggestive symptoms of OSAS such as loud snoring, EDS, or respiratory abnormalities during sleep. Results are presented as the mean ⫾ SD. Group differences were assessed with Student t test. We also determined the Pearson linear correlation between certain variables. The correlation between the total score on the SF-36 and the anthropometric, polysomnographic variables, ESS, and SDS scores were determined by stepwise multiple regression analysis using a statistical program (Statview, version 4; SAS Institute, Cary, NC). Each of the variables was entered into the multiple regression analysis if its F value was ⬎ 4. A p value ⬍ 0.05 was considered statistically significant.
Results The baseline characteristics of the patients and normal control subjects are shown in Table 1. AlClinical Investigations
Table 1—Baseline Characteristics of the Subjects* Characteristics
Patients
Participants, No. Male/female gender, No. Age, yr BMI ESS score SDS score AHI, per h Mean Sao2, % Lowest Sao2, % Arousal index Stage (1 ⫹ 2), %† SWS, % %REM, %
60 58/2 47.7 ⫾ 11.2 29.1 ⫾ 5.2 10.9 ⫾ 4.2 50.5 ⫾ 11.4 51.6 ⫾ 26.6 90.0 ⫾ 5.5 69.2 ⫾ 9.3 40.5 ⫾ 20.4 74.5 ⫾ 13.8 8.6 ⫾ 15.6 16.5 ⫾ 7.9
Control Subjects
p Value
34 32/2 45.2 ⫾ 11.0 23.7 ⫾ 3.2 4.8 ⫾ 2.2 44.7 ⫾ 7.0
NS ⬍ 0.0001 ⬍ 0.001 ⬍ 0.01
*Data are presented as mean ⫾ SD unless otherwise indicated. NS ⫽ not significant. †Stage (1 ⫹ 2) ⫽ non-rapid eye movement sleep stages 1 and 2.
though there were no significant differences in age and gender between patients and control subjects, the BMI, ESS, and SDS indexes were significantly higher in patients than in control subjects. Thirtytwo of the 60 patients (53%) were hypersomnolent (ESS score ⬎ 11),24 and 29 patients (48%) were depressive (SDS score ⬎ 50).23 The polysomnography data showed that the patients had severe OSAS and disturbances of sleep architecture. Six (RP, GHP, vitality, SF, RE, and MH) of eight domains and the total score on the SF-36 were significantly lower in the patients than in the normal control subjects (Fig 1). We examined the relationships between the ESS and SDS scores and the polysomnography parameters (Table 2). The ESS score was significantly correlated with the mean Sao2 and percentage of rapid eye movement (%REM). No significant correlation was observed between the SDS score and the
Figure 1. Comparison between patients with OSAS and control subjects on the SF-36. VT ⫽ vitality; BP ⫽ bodily pain. www.chestjournal.org
polysomnography parameters. The SDS score was not correlated with the ESS score. We also examined the relationship between each domain and the total score on the SF-36 and age, BMI, polysomnography parameters, ESS score, and SDS score (Table 3). The slow-wave sleep (SWS) was correlated with the RE (p ⬍ 0.05). The SDS score was significantly correlated with five (RF, GHP, vitality, RE, and MH) of eight domains and the total score on the SF-36 (p ⬍ 0.005 and p ⬍ 0.0001, respectively). Stepwise multiple regression analysis identified three variables, the SDS score (partial R2 ⫽ 0.505), the lowest Sao2 (partial R2 ⫽ 0.064), and ESS score (partial R2 ⫽ 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on the SF-36 (R2 ⫽ 0.622, p ⬍ 0.0001).
Discussion The subjects in this study had severe OSAS and a reduced QOL compared with gender-matched and age-matched control subjects. Six of eight domains and the total score on the SF-36 were significantly lower in the patients than in the control subjects, showing that the patients with severe OSAS had a poorer general health status. These results are consistent with previous reports.9 –13 Recently, Baldwin et al13 demonstrated that patients with severe OSAS (respiratory disturbance index ⬎ 30) have lower scores in six of eight domains on the SF-36 than healthy subjects, and that EDS was associated with a reduced QOL in a large population study. We found that one half of the patients were depressive, and that the SDS score was significantly correlated with five of eight domains and the total score on the SF-36. Although neuropsychologic deficits including mood disturbance and depression were demonstrated in patients with OSAS in previous studies,17,18 no published reports have examined the relationship between the QOL and mood. The findings that the mood or depressive state may play an important role in QOL is reasonable because mood disturbances may also affect activities of daily living as well as EDS. Previous reports showed that patients with OSAS often complained of mood disturbances; an early report by Guilleminault and Dement25 showed that 24% of their patients with sleep apnea had seen psychiatrists for symptoms of depression and anxiety. Furthermore, 28% of their patients had elevated depression scale scores on the Minnesota Multiphasic Personality Inventory. Kales et al26 found that 28 of 50 patients with OSAS severe enough to warrant tracheostomy had high scores on CHEST / 122 / 3 / SEPTEMBER, 2002
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Table 2—Correlation Coefficients Between the ESS Score and the SDS Score and the Polysomnography Parameters* Variables
Age
BMI
AHI
Mean Sao2
Lowest Sao2
Arousal Index
Stage (1 ⫹ 2)
SWS
%REM
ESS SDS score
⫺ 0.023 ⫺ 0.033
0.211 ⫺ 0.104
0.104 ⫺ 0.010
⫺ 0.271† 0.235
⫺ 0.206 0.023
0.085 0.052
⫺ 0.085 0.255
0.205 ⫺ 0.233
⫺ 0.307† ⫺ 0.037
*See Table 1 for expansion of abbreviation. †p ⬍ 0.05.
the Minnesota Multiphasic Personality Inventory for depression. Millman et al27 also showed that 45% of patients had depressive symptoms (SDS score ⬎ 50), and nasal CPAP decreased their SDS score to the normal range. Twenty-nine of 60 patients (48%) were depressive in the present study, consistent with the studies by Kales et al26 and Millman et al.27 This depressive state was significantly correlated with the PF, GHP, vitality, RE, MH, and the total score on the SF-36. The GHP, vitality, RE, MH, and total score had a relatively strong correlation with the SDS score (r ⬎ 0.57, p ⬍ 0.0001). This is the first report showing a significant relationship between the QOL and depression in patients with OSAS. Since EDS is a primary symptom in patients with OSAS and an important symptom for activities of daily living, it appears to be related to the decrease of the QOL. Therefore, a number of studies6,12,13 have examined the relationship between the EDS and QOL and found that the EDS, whether evaluated subjectively or objectively, was correlated with the decrease in the QOL. However, there were no significant correlations between the EDS as evaluated by the ESS and each domain on the SF- 36 in the present study. The reason for this difference between our results and previous studies is unclear. Although there was no significant relationship between the ESS and each domain on SF-36 by simple
regression analysis, we found that the ESS had additive effects on the QOL from stepwise multiple regression analysis. Although the SDS score was strongly correlated with the total score on the SF-36 (r ⫽ 0.710) on simple regression analysis, this variable itself accounted for only 50.5% of the total variance in the total score on the SF-36. Stepwise multiple regression analysis showed that an additional 11.7% or 62.2% of the total variance was accounted for by the incorporation of the lowest Sao2 and the ESS into the regression, respectively. Therefore, the EDS as evaluated by ESS might affect, at least somewhat, the QOL of our subjects. A number of previous studies6,9 –13 have emphasized the relationship between the EDS and QOL. However, correlations between the EDS and several domains on the SF-36 were relatively weak in these studies. As mood disturbances or a depressive state had a relatively strong correlation with most of the domains on the SF-36 in this study, mood or depression may play a more important role than the EDS in QOL. It has been reported that patients with severe OSAS have a poor prognosis,28,29 and that cardiovascular complications are the main cause of death.29 Recently, a significant relationship between OSAS and cardiovascular complications has been demonstrated in large-scale population studies.30,31 Al-
Table 3—Correlation Coefficients Between the Domains on the SF-36 and the Polysomnography Parameters*
Age, yr BMI AHI Mean Sao2 Lowest Sao2 Arousal index Stage (1 ⫹ 2), % SWS, % %REM, % ESS score SDS score
PF
RP
Bodily Pain
GH
Vitality
SF
RE
MH
Total
⫺ 0.229 ⫺ 0.202 ⫺ 0.018 0.213 ⫺ 0.109 ⫺ 0.025 0.064 0.012 0.152 ⫺ 0.222 ⫺ 0.424‡
⫺ 0.228 ⫺ 0.012 0.202 0.116 ⫺ 0.071 0.165 0.219 ⫺ 0.035 0.025 ⫺ 0.130 ⫺ 0.202
⫺ 0.127 0.117 0.039 ⫺ 0.158 ⫺ 0.206 ⫺ 0.041 0.058 0.012 ⫺ 0.168 ⫺ 0.081 ⫺ 0.260
⫺ 0.092 ⫺ 0.015 ⫺ 0.079 0.056 ⫺ 0.086 ⫺ 0.154 ⫺ 0.011 ⫺ 0.035 0.099 ⫺ 0.059 ⫺ 0.571§
0.139 0.121 0.055 ⫺ 0.158 ⫺ 0.211 0.002 0.004 0.006 ⫺ 0.020 ⫺ 0.074 ⫺ 0.570§
⫺ 0.137 0.136 0.234 ⫺ 0.238 ⫺ 0.315 0.204 0.084 ⫺ 0.071 ⫺ 0.027 ⫺ 0.156 ⫺ 0.117
⫺ 0.072 ⫺ 0.046 0.206 ⫺ 0.004 ⫺ 0.116 0.193 0.269 ⫺ 0.294† 0.028 ⫺ 0.153 ⫺ 0.572§
⫺ 0.026 0.127 0.185 ⫺ 0.209 ⫺ 0.220 0.061 ⫺ 0.031 0.055 ⫺ 0.0710 0.021 ⫺ 0.726§
⫺ 0.128 0.006 0.117 ⫺ 0.120 0.226 0.026 0.059 ⫺ 0.065 ⫺ 0.006 ⫺ 0.120 ⫺ 0.710§
*See Table 1 for expansion of abbreviation. †p ⬍ 0.05. ‡p ⬍ 0.005. §p ⬍ 0.0001. 864
Clinical Investigations
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