Quality of Life in Patients with Obstructive Sleep Apnea* Effect of Nasal Continuous Positive Airway Pressure A Prospective Study Carolyn D Ambrosio, MD; Teri Bowman, MD; and Vahid Mohsenin, MD Background: Obstructive sleep apnea (OSA) is a common condition and is associated with excessive daytime sleepiness and neuropsychological dysfunction. There is limited evidence on the effect of OSA on the quality of life and its response to nasal continuous positive airway pressure (ncpap) treatment. Study objective: To determine the effect of ncpap on the quality of life in patients with OSA. Design: Prospective determination of ncpap effect in a case-series analysis. Patients: We studied 29 patients (23 were male and 6 were female) with a mean ( SE) age of 4.4 2.3 years, a body mass index 36.3 2.0 kg/height (m) 2, and a diagnosis of OSA with respiratory disturbance index (RDI; apnea/hypopnea) of 77 9 events/h. Measurements and results: The quality of life was assessed by administering a Medical Outcomes Study Short Form-36 questionnaire before and after 8 weeks of ncpap therapy in polysomnographically documented OSA. All dimensions of the quality of life were significantly impaired when compared with an age- and gender-matched population, expressed as a percentage of normative data: physical functioning, 75%; vitality, 41%; role functioning (physical, 54%; emotional, 61%; social, 66%); general health, 88%; and mental health, 76%. ncpap therapy significantly improved the sleep-disordered breathing and sleep fragmentation. The ncpap level for the group was 9.4 0.7 cm H 2 O. Eight weeks of ncpap therapy improved vitality (75%), social functioning (90%), and mental health (96%). The magnitude of improvement was related to the degree of quality of life impairment prior to treatment, rather than to the severity of disease as measured by the RDI and arousal indices. Conclusions: All aspects of the quality of life, from physical and emotional health to social functioning, are markedly impaired by OSA. ncpap therapy improved those aspects related to vitality, social functioning, and mental health. (CHEST 1999; 115:123 129) Key words: nasal continuous positive airway pressure; quality of life; sleep apnea Abbreviations: OSA obstructive sleep apnea; ncpap nasal continuous positive airway pressure; SF-36 Medical Outcomes Study Short Form-36; RDI respiratory disturbance index; SE standard error *From the Yale Center for Sleep Disorders, Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT. Manuscript received March 27, 1998; revision accepted July 22, 1998. Correspondence to: Dr. Vahid Mohsenin, 333 Cedar St, New Haven, CT 06520; e-mail: vahid.mohsenin@yale.edu Obstructive sleep apnea (OSA) is characterized by recurrent obstruction of the upper airway, which results in episodic asphyxia, oxygen desaturations, and disruption of the normal sleep pattern. The majority of OSA patients have symptoms related to poor quality sleep, such as excessive daytime sleepiness and tiredness, lack of concentration, memory impairment, and at times psychological disturbances. 1 3 OSA is also associated with cardiovascular and cerebrovascular morbidity and mortality. 4 6 As a result of these symptoms and functional impairments, OSA patients often report having a poor quality of life in social, emotional, and physical domains. 7 9 Treatments for OSA include positional training, weight loss, avoidance of alcohol and sedative drugs, mandibular advancement devices, nasal continuous positive airway pressure (ncpap), and upper airway surgery. The most commonly used and most effective treatment modality has been ncpap. 10 12 ncpap has been shown to decrease the frequency of apneic events and oxygen desaturation during sleep, 10 and to reduce the severity of sleep disturbances and daytime sleepiness. 13,14 In a cross-sectional study by Tousignant et al, 9 CHEST / 115 / 1/ JANUARY, 1999 123
ncpap therapy increased quality adjusted life years. We undertook the present prospective longitudinal study to determine the impact of OSA and ncpap therapy on the overall quality of life. In previous studies, both disease-specific and general assessment tools were used for the estimation of the quality of life measures in OSA. In this study, however, we were interested in evaluating the overall quality of life, rather than symptoms directly associated with the disease. Patients Materials and Methods Twenty-nine patients who were referred to the sleep laboratory for evaluation of sleep-disordered breathing were prospectively enrolled in the study. Those patients with conditions diagnosed as OSA (apnea/hypopnea index 15/h) and given ncpap therapy were included in this study. Patients who had other sleep disorders or received treatment other than ncpap for their OSA were not included in this study. Study Protocol Prior to the onset of ncpap therapy and split-night polysomnography, each patient completed a previously validated health questionnaire, the Medical Outcomes Study Short Form-36 (SF-36), 15 and baseline anthropomorphic measurements were recorded. The optimal ncpap level was determined in the laboratory during the study. Eight weeks later, the SF-36 was readministered, and each patient answered additional questions concerning the number of hours per night and the number of times each week that they received ncpap therapy. Compliance with ncpap was based on self-reports. Quality of Life Assessment The SF-36 questionnaire measures how the patient perceives his/her own functional status, well-being, and overall health. 15,16 The patients were also asked if they had stopped or reduced certain activities because of health or emotional problems, such as depression. They were also asked to assess how much their social activities had been curtailed by their health. The normative data for age- and gender-matched population were used for comparison. 17 Sleep Study Polysomnography was performed between 9:00 pm and 7:00 am as previously described. 18 Briefly described, the sleep state was recorded with two channels of electroencephalogram (C3/A2 or C4/A1, O2/A1 or O1/A2), two channels of electro-oculogram, and one channel of submental electromyogram. Breathing was assessed by monitoring chest wall and abdominal movements using strain gauge pneumographs, and nasal and oral flows were monitored using thermisters. Arterial oxygen saturation was measured using an oximeter (Biox 3700c; Ohmeda; Louisville, CO). Leg movements were monitored with two channels of electromyogram, and an ECG was recorded continuously. All variables were recorded simultaneously and continuously on a 16-channel polygraph (model 78D; Grass Instruments; Quincy, MA). Sleep recordings were scored in 30-s epochs and staged according to standard criteria. 19 Calculated variables included the number of arousals, the respiratory disturbance index (RDI; apnea/hypopnea index), and the number and degree of arterial oxygen desaturations. Apneic variations were classified using the following definitions: apnea was present when there was at least an 80% reduction in airflow for 10 s, obstructive apnea was present when respiratory efforts were present, central apnea was present when respiratory efforts were absent, and mixed apneas occurred when there was a central component followed by an obstructive component. Hypopneas were scored when there was a 50 to 80% decrease in the airflow signal with 4% decrease in arterial oxygen saturation. The optimal ncpap level during the sleep study was the lowest pressure associated with the least number of respiratory events and arousals and the highest sleep efficiency. Statistical Analysis Data are presented as mean SE. Each subject served as his/her own control. The baseline SF-36 parameters were compared with normative data for the same age group using an unpaired Student s t test. 17 The impact of comorbidity on baseline SF-36 parameters was analyzed using analysis of variance. The effects of ncpap therapy on each patient were analyzed using a paired Student s t test. The p value was corrected for multiple comparisons using the Bonferroni adjustment. A linear regression analysis was used to examine the correlation between anthropometric characteristics, indicators of sleep apnea severity, and SF-36 measures. Results Twenty-nine patients (23 were male, and 6 were female) were included in this study. The average age of the patients was 44.4 2.3 years old (range, 23 to 68); the average body mass index was 36.3 2.0 kg/height (m) 2 (range, 21.9 to 54.1). Eight patients had no comorbidities; the others had histories of coronary heart disease, hypertension, COPD, diabetes mellitus, and/or arthritis. All of the patients were medically stable at the time of their initial evaluation and on follow-up. On average, the patients had severe OSA with RDI of 77 9 events/h when sleeping (range, 15 to 200). The apneas were associated with arterial oxygen desaturation, which decreased from 94.1 0.3% while awake to 79.0 2.1% during sleep (p 0.001). The severity of sleep apnea and sleep fragmentation for each patient is shown in Figure 1. Sleep was markedly fragmented during the baseline period, with an increased arousal index of 67 7 arousals/h. The patients had significantly decreased health status in all domains of SF-36 role functioning, physical functioning, vitality, mental health, and health perceptions when compared with age-matched control subjects (Fig 2). To determine the effect of the severity of sleep apnea on the quality of life, the indicators of disease severity, the RDI and arousal indices, and the lowest oxygen saturation during sleep were correlated 124 Clinical Investigations
Figure 1. Arousal index and RDI before and after ncpap therapy. The side bars denote mean SE. with each domain of the SF-36. There were no significant correlations among any of these measures. Some patients with mild OSA reported significant impairment in their quality of life, although others with more severe OSA perceived a lesser amount of functional decline. The impact of comorbidity on SF-36 domains was examined using analysis of variance for the absence or presence of comorbidity. The presence of comorbidity significantly curtailed role functioning related to work or other daily activities as a result of physical health: 72.8 11.3 with no comorbidity vs 22.7 9.6 with at least one comorbidity (p 0.003). All patients underwent and responded to ncpap treatment, with a reported use time of 6.0 1.6 h/night. The RDI decreased from 77 9to4 6 events/h (p 0.0001), and the arousal index decreased from 67 7to13 3 arousals/h (p 0.001) (Fig 1). The arterial oxygen saturation during sleep increased from 79.0 2.1% to 91.6 0.8%, and the mean optimal ncpap level was 9.4 0.7 cm H 2 O. After 8 weeks of ncpap treatment, the patients reported a significant improvement in vitality (p 0.0004), social functioning (p 0.009), and mental health (p 0.01) when compared to baseline values for each individual. There was no correlation between the severity of sleep apnea, the RDI, the lowest arterial oxygen saturation or frequency of oxygen desaturations, and the degree of improvement in quality of life measures after ncpap treatment. We used multiple regression analysis to identify the factors of age, body mass index, RDI and arousal indices, and the use of ncpap as independent variables that could have predicted the improvement in SF-36 measures. None of these variables had any significant bearing on the changes in SF-36 parameters with ncpap treatment. However, significant correlations were found between quality of life scores on the SF-36 at baseline and prior to ncpap administration and the subsequent change in scores after treatment, except for role physical. In other words, patients with lower scores and more impairments on the SF-36 before treatment demonstrated larger improvements in SF-36 domains after treatment (Fig 3). Discussion Our study demonstrates that the quality of life in patients with OSA is severely impaired and can be improved with ncpap therapy. All domains of the quality of life, from emotional and mental health functioning to vitality and physical health, were impaired by OSA when compared with the agematched normal population. OSA impacted on the quality of life in various ways. Some patients with rather mild OSA reported the same degree of impairment in SF-36 domains, as did those with more severe cases of the disease. The diminished quality of life measures did not correlate with disease severity. Similar to the present study, other investigators have shown no correlation between the severity of sleep apnea, as defined by the number of apnea/hypopnea events per hour, and the health profile indices. 7,8 OSA is commonly associated with neuropsychiatric disturbances that could interfere with the capacity of the patient to fully appreciate the quality of his/her state of health. 1 This could explain the lack of correlation between OSA severity and the self-perceived health status. Our data and the data mentioned above differ from the study of Tousignant et al, 9 which demonstrated a correlation between RDI and pretreatment health state indicating the higher the severity of disease the lower the health status. The reason for this discrepancy may be because this study was conducted retrospectively and, therefore, CHEST / 115 / 1/ JANUARY, 1999 125
Figure 2. SF-36 domains before and after 8 weeks of ncpap treatment. The third column denotes age-matched normative values. The p values are corrected for multiple comparisons using the Bonferroni adjustment. may have been biased because of errors in recall about the pretreatment health state. Furthermore, there were some inconsistencies in the response to treatment in the aforementioned study. The respiratory indices and daytime sleepiness improved with treatment, although there was either worsening or no changes in some of psychological symptoms such as depression. 126 Clinical Investigations
Figure 3. The relationship between quality of life domains prior to ncpap treatment and the degree of improvement in these domains after ncpap treatment. An optimal ncpap level was achieved for all patients during the study. The use of ncpap ranged from 3 to 8 h/night for the duration of study. After 8 weeks of ncpap therapy, the SF-36 scores on mental health, social functioning, and vitality improved significantly and were no longer statistically CHEST / 115 / 1/ JANUARY, 1999 127
different from normal age- and gender-matched subject scores. The improvement in these domains was independent of the baseline apnea/hypopnea index or other indicators of OSA severity. The degree of impairment in quality of life domains but not the severity of disease determined the degree of improvement with ncpap. In a study by Engleman et al 20 of 204 ncpap users, there was a significant improvement in daytime sleepiness and a reduction in road traffic incident rate. The use of ncpap correlated positively with symptoms prior to treatment and not with OSA severity. The reported average ( SD) use of ncpap in this study was 5.8 2.0 h/night, which is comparable to our average of 6.0 1.6 h/night. One explanation is that patients with more severe OSA but with less perceived impairment in life domains did not use ncpap regularly and did not report a significant change in their functions. Another reason for the lack of a relationship between OSA severity and the perceived improvement in quality of life could be that patients with severe OSA having cognitive deficit could underestimate the impairment in their own quality of life domains. The patient s symptoms and especially the degree of sleepiness have been shown to be good predictors of acceptance 21,22 or compliance with ncpap therapy. 11,23 Some patients with mild OSA but with more severe impairment in quality of life measures demonstrated significant increases in SF-36 scores after ncpap. This type of response has also been observed by other investigators. 14 However, in the latter study, those with a higher apnea/hypopnea index and increased frequency of microarousal had better compliance and greater improvement in quality of life. Although factors other than sleep apnea, such as obesity and comorbidities, can adversely affect the quality of life, the rapid improvement in functions after ncpap therapy suggests that sleep apnea is the main cause of functional impairment. We used a general instrument rather than a disease-specific instrument to examine the effect of ncpap therapy. Previous studies have already shown improvement in daytime sleepiness and neuropsychiatric manifestations in OSA patients. 3,24 The sleepiness correlated with vitality and general health perception domains of SF-36 in a group of patients with mild to moderate OSA. 25 The fact that some of the SF-36 domains showed significant improvement in the expected direction indicates that this instrument has reasonable sensitivity to show a change after intervention. These types of instruments have the potential for being used in the initial evaluation of OSA patients and perhaps as a predictor of ncpap response. A ncpap study with a longer follow-up period is needed to assess the long-term effect of ncpap treatment on other domains of the quality of life that may have a physical basis. 26 In conclusion, this study demonstrated a marked impairment of the quality of life in patients with even mild OSA, and that 8 weeks of ncpap treatment improves the quality of life domains related to vitality, social functioning, and mental health. References 1 Kales A, Caldwell A, Cadieux R, et al. Severe obstructive sleep apnea-ii: Associated psychological and psychosocial consequences. J Chronic Dis 1985; 38:426 437 2 Greenberg G, Watson R, Deptula D. Neuropsychological dysfunction in sleep apnea. Sleep 1987; 10:254 262 3 Derderian S, Bridenbaugh R, Rajagopal K. Neuropsychologic symptoms in obstructive sleep apnea improve after treatment with nasal continuous positive airway pressure. Chest 1988; 94:1023 1027 4 Parish M, Shepard J. Cardiovascular effects of sleep disorders. Chest 1990; 97:1220 1226 5 Stoohs R, Guilleminault C. Cardiovascular changes associated with the obstructive sleep apnea syndrome. J Appl Physiol 1992; 75:583 589 6 Thomas R. The cardiomyopathy of obstructive sleep apnea [letter]. Ann Intern Med 1996; 125:425 7 Gall R, Isaac L, Kryger M. Quality of life in mild obstructive sleep apnea. Sleep 1993; 16:S59 S61 8 Fornas C, Ballester E, Arteta E, et al. Measurement of general health status in obstructive sleep apnea hypopnea patients. Sleep 1995; 18:876 879 9 Tousignant P, Cosio M, Levy R, et al. Quality adjusted life years added by treatment of obstructive sleep apnea. Sleep 1994; 17:52 60 10 Sullivan C, Issa F, Brethon-Jones M, et al. Reversal of obstructive sleep apnea by continuous positive airway pressure applied through the nares. Lancet 1981; 1:862 865 11 Waldhorn R, Herrick T, Nguyen M, et al. Long-term compliance with nasal continuous positive airway pressure therapy of obstructive sleep apnea. Chest 1990; 97:33 38 12 Hudgel D. Treatment of obstructive sleep apnea: a review. Chest 1996; 109:1346 1358 13 Partlett J, Pitson D, Davies R, et al. Daytime vigilance in patients with obstructive sleep apnoea and after CPAP treatment. Thorax 1994; 49:412 14 Engleman H, Martin S, Deary I, et al. Effect of CPAP therapy on daytime function in patients with mild sleep apnoea/hypopnoea syndrome. Thorax 1997; 52:114 119 15 Ware J, Sherbourne C. The MOS 36-item Short-Form Health Survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30:473 483 16 Ziebland S. The Short Form 36 Health Status Questionnaire: clues from the Oxford region s normative data about its usefulness in measuring health gain in population surveys. J Epidemiol Community Health 1995; 49:102 105 17 Ware J, Snow K, Kosonski K, et al. SF-36 Health survey: manual and interpretation guide. Boston, MA: The Health Institute, New England Medical Center; 1993. 18 Mohsenin V, Valor R. Sleep apnea in patients with hemispheric stroke. Arch Phys Med Rehabil 1995; 76:71 76 19 Rechtschaffen A, Kales A. A manual of standardized techniques and scoring system for sleep stages of human sleep. Los Angeles: Brain Information Service/Brain Research Institute, University of California Los Angeles; 1968. 128 Clinical Investigations
20 Engleman H, Asgari-Jirhandeh N, McLeod A, et al. Selfreported use of CPAP and benefits of CPAP therapy: a patient survey. Chest 1996; 109:1470 1476 21 Rolfe I, Olson L, Saunders N. Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea. Am Rev Respir Dis 1991; 144:1130 1133 22 Rauscher H, Popp W, Wanke T, et al. Acceptance of CPAP therapy for sleep apnea. Chest 1991; 100:1019 1023 23 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:S136 S143 24 Rajagopal K, Bennett L, Dillard T, et al. Overnight nasal CPAP improves hypersomnolence in sleep apnea. Chest 1986; 90:172 176 25 Briones B, Adams N, Strauss M, et al. Relationship between sleepiness and general health status. Sleep 1996; 19:583 588 26 Wright J, Johns R, Watt I, et al. Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airway pressure: a systematic review of the research evidence. BMJ 1997; 314:851 860 CHEST / 115 / 1/ JANUARY, 1999 129