Effect of Treatment by Laser-assisted Uvulopalatoplasty on Cardiopulmonary Exercise Test in Obstructive Sleep Apnea Syndrome

Otolaryngology–Head and Neck Surgery (2005) 133, 55-61

Effect of Treatment by Laser-assisted Uvulopalatoplasty on Cardiopulmonary Exercise Test in Obstructive Sleep Apnea Syndrome Ching-Chi Lin, MD,a,c Ke-Chang Chang, MD,b Kuo-Sheng Lee, MD,b Kun-Ming Wu, MD,a Chon-Shin Chou, MB,a Ching-Kai Lin, MDa a

From the Chest Division, Department of Internal Medicine, Department of Medical Research, and Department of Otolaryngology, Mackay Memorial Hospital, and c Mackay Medicine, Nursing, and Management College, Taipei, Taiwan. b

OBJECTIVES: To evaluate the effects of successful laserassisted uvulopalatoplasty (LAUP) on cardiopulmonary exercise testing (CPET) in patients with obstructive sleep apnea syndrome (OSAS). STUDY DESIGN AND SETTING: Twenty-five subjects with moderately severe or severe OSAS who desired LAUP were enrolled. All patients had an overnight sleep study and CPET before and 3 months after LAUP. Patients were divided into 2 groups based on the success (group I) or failure (group II) of LAUP to improve their sleep apnea. RESULTS: Successful LAUP in group I was followed by improvement in right ventricular ejection fraction, maximal work rate (WRmax), VO2max/kg, anaerobic threshold, oxygen pulse, and a lower breathing reserve. CPET results were unchanged after LAUP in group II subjects. CONCLUSION: Patients with OSAS before LAUP had abnormal CPET as reflected by low VO2peak/kg, WRmax, anaerobic threshold, and oxygen pulse. All of these variables improved after LAUP that successfully ameliorated OSAS. © 2005 American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. All rights reserved.

O

bstructive sleep apnea syndrome (OSAS) is characterized by repetitive upper airway obstruction leading to a high negative intrathoracic pressure and alveolar hypoventilation, resulting in abnormal gas exchange, arterial oxygen

This research was supported by NSC 92-2314-B-195-024. Reprint requests: Dr Ching-Chi Lin, Chest Section, Department of Internal Medicine, Mackay Memorial Hospital, 92, Sec 2, Chung Shan North Road, Taipei, Taiwan.

desaturation, abnormal autonomic nerve function, acute and possibly chronic cardiac dysfunction, and hemodynamic impairment.1,2 It is thought that OSAS patients may develop pulmonary hypertension and right ventricular failure due to hypoxic pulmonary vasoconstriction3 and increased right ventricular afterload related to exaggerated negative intrathoracic pressure swings during obstructive apnea.3 Several recent studies indicate that intermittent apnea-related hypoxemia is not enough to explain sustained pulmonary hypertension, however. Rather, it has been suggested that diurnal hypoxemia or overlap syndrome (OSAS ⫹ mild to moderate diffuse chronic obstructive pulmonary disease) is essential for the development of pulmonary hypertension.3 OSAS has also been reported to play a role in the pathogenesis of left ventricular (LV) failure. The effects of OSAS on cardiovascular function are through a combination of large negative intrathoracic pressure swings against the occluded upper airway,4 hypoxemia, arousal from sleep with increased LV afterload, systemic and pulmonary vasoconstriction, reduced stroke volume and cardiac output, chronically elevated sympathoadrenal activity, and cardiac arrhythmia.1 When ventilation is resumed after an apneic episode, heart rate and cardiac output abruptly increase, leading to maximal myocardial oxygen demands. However, the blood perfusing the coronary circulation at that time still E-mail address: [email protected].

0194-5998/$30.00 © 2005 American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. All rights reserved. doi:10.1016/j.otohns.2005.03.025

56

Otolaryngology–Head and Neck Surgery, Vol 133, No 1, July 2005

has a relatively low oxygen content, predisposing the myocardium to atrial and ventricular ectopy. Cardiovascular disturbances have been considered one of the most serious complications of OSAS.5,6 Substantial evidence has also shown that, untreated, OSAS may lead to multiple organsystem dysfunction, including personality changes and intellectual impairment, and increased mortality.5,6 Cardiopulmonary exercise testing (CPET) is a means of evaluating cardiac, pulmonary, and muscle function and may help to distinguish which of those systems is a cause of exercise intolerance. In otherwise healthy subjects, exercise limitation is due to heart disease. Patients with OSAS are frequently overweight and may exhibit lung dysfunction related to their weight, including a decrease in functional residual capacity (FRC) due mainly to a decrease in expiratory reserve volume (ERV) and a decrease in compliance of the respiratory system.7 These functional abnormalities increase the energy cost of breathing. In addition, increased body mass is associated with greater metabolic energy requirements during muscular exercise, resulting in further ventilatory stress. During exercise, obese subjects have a high O2 cost to perform external work and an upward displacement of the oxygen consumption-work rate (VO2WR) relationship.8 In addition, these patients may have further impairment of muscle function and exercise fitness because of daytime hypersomnolence, decreased daily activity, and tissue hypoxemia. There are a number of ways to treat OSAS patients, including nonsurgical and surgical methods. Nonsurgical methods include weight reduction, positional therapy, and nasal CPAP treatment, etc. Nasal CPAP is quite effective and has been reported to reduce mortality. However, only about 50% to 75% of patients can tolerate nasal CPAP, and there are problems with long-term compliance.9 Surgical uvulopalatopharyngoplasty was developed as an alternative, although it has a success rate of only 50%.10 There have been conflicting conclusions as to whether this procedure improves survival.11 As far as we are aware, no one has studied the effect of surgical treatment on cardiopulmonary function as assessed by CPET in OSAS. The purpose of this study was to evaluate whether OSAS patients who respond well to laser-assisted uvulopalatoplasty (LAUP) have improvement on CPET after surgery.

MATERIALS AND METHODS Selection of Subjects Twenty-five patients with moderately severe to severe OSAS who desired LAUP were selected. They were otherwise healthy. Thyroid and cardiopulmonary dysfunction, diabetes mellitus, and other diseases that might affect energy expenditure were specifically ruled out by history, physical examination, chest x-ray, electrocardiogram, and blood tests (including free T4, T3 resin uptake,

and pre- and postprandial blood glucose). Subjects were excluded if there was any history or clinical evidence of primary central nervous system, systemic or neuromuscular diseases, or if they had evidence of acute infection within 1 month prior to the study. Alcohol or sedatives were avoided for at least 1 week before the overnight sleep study. Drugs or substances that alter metabolism (eg, caffeine, tea, nicotine, and theophylline) were avoided for at least 2 days. This study was approved by our institutional review board.

Study Protocol After baseline pulmonary, cardiovascular, and exercise assessments as described below, all subjects underwent LAUP. The assessments were then repeated 3 months after surgery.

Sleep Variables Apnea/hypopnea was defined by a clear decrease (⬎50%) from baseline in the amplitude of ventilation (summation of chest and abdominal excursion) for longer than 10 seconds as measured by calibrated inductive plethysmography during sleep.12 The baseline was defined as the mean amplitude of stable breathing and oxygenation in the 2 minutes preceding onset of the event (in individuals who had a stable breathing pattern during sleep) or the mean amplitude of the 3 largest breaths in the 2 minutes preceding onset of the event (in individuals without a stable breathing pattern). Apnea/hypopnea events also included a clear amplitude of ventilation reduction during sleep that did not reach the above criterion but was associated with either oxygen desaturation of ⬎3% or arousal. The respiratory disturbance index (RDI) was defined as the mean number of episodes of hypopnea and apnea per hour of sleep. Desaturation event frequency (DEF) was defined as the mean number of oxygen desaturation episodes per hour of sleep.12 Sleep apnea syndrome (SAS) was diagnosed as a RDI ⱖ 5 during overnight polysomnography. Moderately severe or severe SAS was defined as an RDI ⱖ 30. Central apnea was defined as the cessation of nasal and oral airflow with the cessation of respiratory effort, which was appreciated by both inductive plethysmography and diaphragm EMG from a surface electrode. Obstructive apnea was defined as the absence of nasal and oral airflow despite continuing respiratory effort. Mixed apnea had both central and obstructive components, the obstructive part usually following the central. OSAS was diagnosed when obstructive and mixed apneas represented more than 80% of all apneic episodes. Arousal was defined as a minimum of 10 continuous seconds in any stage of sleep before a minimum 10 second period of return of ␣ or ␪ waves with or without an increase in submental EMG measurements in non-REM sleep or with an increase in EMG tone in REM sleep. The arousal index was defined as the mean number of arousals per hour of sleep.13 Sleep efficiency was the percentage of total sleep time divided by total bed time.

Lin et al

Effect of Treatment by Laser-assisted . . .

Sleep Studies Overnight sleep studies were performed with complete polysomnography. An electroencephalogram (EEG) (C4/ A1, C3/A2), EOG, and submental EMG for sleep staging were recorded according to standard criteria. Respiratory movement was monitored by inductance plethysmography. Nasal and oral air flow were monitored by a thermocouple. Arterial oxygen saturation and heart rate were continuously measured by an Omheda pulse oximeter. Bilateral tibial EMG and ECG were also monitored from surface electrodes.12 Sleep was staged by the method of Rechtschaffea and Kales14 on the basis of 30-second epochs.

Multiple Sleep Latency Test A multiple sleep latency test (MSLT) was performed to assess daytime sleepiness according to the recommendation of the American Sleep Disorders Association.15 The subjects were placed in a dark room for 20 minutes 4 times a day (10:00 AM, 12:00 PM, 2:00 PM, and 4:00 PM). All subjects maintained a sleep diary beginning 1 week prior to the experiment to confirm that they had not deviated from their usual routines. Polysomnographic recordings were obtained during the MSLT. Sleep latency was measured when the first epoch of any stage of sleep appeared. Each sleep latency time was measured and the mean value of 4 sleep latency times was calculated.

Pulmonary Function Tests Pulmonary function tests (PFT) were performed prior to entry into the study using a Gould 5000 CPI computerized spirometer with the subjects in a sitting position. The loop with the highest sum of FEV1 and FVC was analyzed. The FEV1, FVC and FEV1/FVC ratio were recorded.

Cardiac Function Evaluation Cardiac function was evaluated by a radionuclide method to determine the left and right ventricular ejection fractions (LVEF, RVEF).

Cardiopulmonary Exercise Test On arrival in the exercise laboratory, the procedure and attendant risks were explained, and written informed consent was obtained. Height, weight, and spirometry (FVC, FEV1) were measured. Exercise tests were performed on an electrically braked cycle ergometer (Erich Jaeger GmbH, Germany) with electrocardiographic monitoring under the supervision of a physician, and with defined criteria for stopping including serious cardiac arrhythmias, hypotension, and electrocardiographic changes. Before exercise, while seated comfortably on the cycle ergometer, subjects breathed for 1 minute through a unidirectional valve (Hans Rudollph, Kansas City, MO) with the expired air going to a universal exercise testing system (Vmax series/6200 Autobox DL Metabolic Cart,

57 Sensor Medics, Anaheim, CA). After 1 minute of loadless pedaling, the subjects cycled at 60 revolutions per minute at an initial power output of 100 kpm/min. At the end of each minute the power output was increased by 100 kpm/min. Measurements included heart rate, blood pressure, ventilation, respiratory rate, tidal volume, oxygen consumption (VO2), oxygen consumption per kg of body weight (VO2/kg), carbon dioxide production (VCO2), work rate (WR), minute ventilation (VE) (BTPS; L/min), anaerobic threshold (AT), tension of O2 (end-tidal) in expired alveolar gas (PETO2), tension of CO2 (end-tidal) in expired alveolar gas (PETCO2), ventilatory equivalent for O2 (VE/VO2), ventilatory equivalent for CO2 (VE/VCO2) (BTPS ⫽ gas volume at body temperature (37°C) and pressure (PB), saturated with water vapor at 37°C (47 mmHg)), ratio of dead space to tidal volume (VD/VT), and respiratory quotient (RQ). Patients were encouraged to continue exercise until exhaustion. They were asked to estimate the intensity of discomfort of breathing and the intensity of leg effort every minute by matching their subjective estimate to a number from zero to 10; the numbers were tagged to simple descriptive terms such as slight, moderate, and severe (Borg scale). After completion, they were asked why they stopped exercise, whether because of leg symptoms, chest discomfort, breathlessness, etc. Maximal work rate (WRmax) was defined as the highest power output maintained for at least 30 seconds. The equations of Jones et al16 were used to predict subjects, exercise capacity. The anaerobic threshold was determined with the following criteria: (1) inflection point in the VE and/or VCO2 versus VO2 diagram; (2) point of increase in endtidal PO2 (PETO2), and (3) point of increase in the ventilatory equivalent of O2 (VE/VO2) without a concomitant reduction of end tidal PCO2 (PETCO2).17

LAUP Technique LAUP was performed with the patient under general anesthesia with nasotracheal intubation. A handheld CO2 laser was used to resect a wedge or crescent of soft palate on either side of the uvula and then to ablate the uvula itself. Laser settings were 14 to 18 watts, using the Sharplan Swiftlase system. If the faucial tonsil was enlarged and crossed the plane of the anterior and posterior pillars, the tonsil was also removed. Successful LAUP was defined as more than a 50% decrease in RDI and an RDI ⬍ 20 in a postoperative sleep study. The patients in whom LAUP was successful were designated as group I, and those in whom it failed were designated as group II.

Data Analysis A paired or unpaired Student’s t test was used for statistical analysis where it is appropriate. All values were expressed as the mean ⫾ standard deviation, with significance accepted when P ⬍ 0.05.

58

Otolaryngology–Head and Neck Surgery, Vol 133, No 1, July 2005

Table 1 Patient characteristics and PFT measurements Group I (n ⫽ 6) Before Age, years Sex (male/female) Systolic pressure, mmHg Diastolic pressure, mmHg BMI, kg/m2; male LVEF, % RVEF, % FEV1, % predicted FVC, % predicted FEV1/FVC Hematocrit pH Pa02, mmHg PaC02, mmHg

40 ⫾ 6 6/0 136.2 ⫾ 8.6* 84.3 ⫾ 8.4* 28.2 ⫾ 2.5 59.7 ⫾ 5.6 38.1 ⫾ 4.1* 90.6 ⫾ 4.7 88.2 ⫾ 4.6 83.7 ⫾ 4.3 40.4 ⫾ 1.7 7.41 ⫾ 0.04 96.5 ⫾ 1.9 38.4 ⫾ 1.8

Group II (n ⫽ 19) After

Before

After

126.4 74.6 28.3 62.2 45.3 90.4 88.4 83.1 40.2 7.40 96.9 39.1

42 ⫾ 7 17/2 134.8 ⫾ 9.3 83.4 ⫾ 8.5 28.5 ⫾ 2.4 60.6 ⫾ 5.3 39.4 ⫾ 4.2 91.4 ⫾ 4.8 89.6 ⫾ 4.9 84.2 ⫾ 4.9 40.8 ⫾ 1.9 7.41 ⫾ 0.03 96.4 ⫾ 1.8 39.3 ⫾ 1.5

133.5 82.7 28.3 60.3 40.4 90.5 88.8 84.1 40.6 7.39 96.8 39.6

⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

6.4 5.1 2.4 5.7 3.3 4.9 4.4 4.5 1.5 0.03 2.1 1.6

⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

8.8 8.2 2.7 5.1 4.5 5.2 5.1 4.7 1.5 0.04 2.2 1.9

BMI, body mass index; LVEF, left ventricular ejection fraction; RVEF, right ventricular ejection fraction; FVC, forced vital capacity. The student’s t test was used. *P ⬍ 0.05 comparison between before and after LAUP.

RESULTS Patient Characteristics, Pulmonary Function Testing, and Sleep Studies Before and After LAUP LAUP succeeded in improving OSAS in 6 of the 25 subjects (group 1), whereas it failed in 19 (group II). The patient characteristics and PFT results before and after LAUP are summarized in Table 1. In terms of these variables, the groups had statistically similar results both before and after surgery, with the exception of systolic

and diastolic pressures and RVEF, all of which improved significantly in group I but remained unchanged in group II. Of note is that the BMI did not change in the 3-month interval between testing. The results of the sleep studies that defined LAUP success or failure are shown in Table 2. The 2 groups did not differ significantly before surgery, but after LAUP group I had significant improvement in all parameters, and group II did not. The only variable unchanged in group I was the baseline (that is, before sleep) SaO2 (97.9 ⫾ 0.6 before and 98.1 ⫾ 0.5 after LAUP).

Table 2 Results of sleep study before and after LAUP Group I (n ⫽ 6) Before RDI, times/hour DEF, times/hour Mean Sa02, % Baseline Sa02, % Lowest Sa02, % Sleep architecture Stage 1, % Stage 2, % Stage 3⫹4, % REM, % AI, times/hour MSLT, minutes

Group II (n ⫽ 19) After

Before

After

38.3 33.2 92.7 97.9 68.6

⫾ ⫾ ⫾ ⫾ ⫾

6.8* 5.3* 0.5* 0.4 5.5*

9.4 6.2 95.8 98.1 90.5

⫾ ⫾ ⫾ ⫾ ⫾

3.8 3.4 0.4 0.5 2.4

40.2 34.3 92.6 97.6 69.1

⫾ ⫾ ⫾ ⫾ ⫾

8.7 6.1 0.6 0.5 5.4

38.3 32.2 92.7 97.9 69.3

⫾ ⫾ ⫾ ⫾ ⫾

8.3 6.9 0.5 0.6 5.7

29.8 49.7 3.8 16.7 31.6 4.4

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

5.2* 5.3* 1.8* 3.2* 6.5* 2.7*

10.9 56.3 11.5 21.3 8.8 9.2

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

3.7 3.1 3.8 2.1 3.2 2.8

29.3 49.4 5.1 16.2 33.6 4.6

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

5.6 5.8 1.7 3.6 6.2 2.2

29.5 50.1 3.9 16.5 31.3 4.2

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

5.4 5.6 1.6 3.4 5.8 2.6

RDI, respiratory disturbance index; DEF, desaturation event frequency; REM, rapid eye movement; AI, arousal index. Student’s t test was used. *P ⬍ 0.05 comparison between before and after LAUP.

Lin et al

Effect of Treatment by Laser-assisted . . .

59

Table 3 Cardiopulmonary exercise test results Group I (n ⫽ 6) Before Intensity of dyspnea Intensity of leg effort WRmax, watts VO2max, L/min VO2max/kg, mL/kg/min AT, L/min Heart rate, bpm Heart rate reserve, bpm VEmax, (L/min) BTPS Breathing reserve, % O2 Pulse, ml/beat PetO2 PetCO2 VE/VO2 VE/VCO2 Respiratory quotient VD/VT, % SaO2, %

6.9 7.1 115.4 1.557 20.51 0.87 147.4 18.2 63.0 49.6 10.4 115.6 38.6 32.9 35.0 1.23 17.8 95.2

⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

Group II (n ⫽ 14) After

1.1 1.3 10.7* 0.343* 3.12* 0.15* 6.3 5.8 7.4* 5.7* 1.8* 4.0 3.6 4.7 2.9 0.10 3.5 2.3

7.0 7.2 139.5 2.152 28.68 1.24 151.8 13.8 77.9 37.7 13.2 116.6 38.7 33.3 32.6 1.21 15.9 94.8

Before ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

1.2 1.4 7.5 0.457 5.13 0.17 7.1 5.2 8.3 6.5 1.7 4.4 4.2 4.2 3.5 0.11 3.1 2.6

6.8 7.1 117.1 1.589 21.16 0.90 147.6 18 62.7 49.8 11.1 114.4 39.2 33.1 35.2 1.24 16.8 95.0

⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

After 1.3 1.1 10.2 0.303 3.57 0.18 7.9 5.9 7.1 7.0 2.0 4.8 3.9 4.6 2.6 0.12 3.4 2.7

6.9 7.2 119.5 1.622 21.58 0.99 150.8 14.8 63.4 49.3 11.5 115.3 39.5 32.5 34.5 1.20 16.2 94.6

⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾

1.2 1.2 9.3 0.356 4.61 0.17 7.7 5.1 7.7 6.0 2.2 5.1 4.8 3.9 3.8 0.09 3.7 1.9

Wrmax, maximal work rate; VO2, oxygen consumption (ml/min); VE, minute ventilation (BTPS; L/min); AT, anaerobic threshold; PETO2, tension of O2 (end-tidal) in expired alveolar gas; PETCO2, tension of CO2 (end-tidal) in expired alveolar gas; VE/VO2, ventilatory equivalent for O2; VE/VCO2, ventilatory equivalent for CO2; BTPS, gas volume at body temperature (37°C) and pressure (PB), saturated with water vapor at 37°C (47 mmHg); VD/VT, ratio of dead space to tidal volume (VD/VT); RQ, respiratory quotient. *P ⬍ 0.05 comparison between before and after LAUP.

Response to Cardiopulmonary Exercise Testing During the testing, no subjects required termination of the exercise by the supervising physician according to the defined criteria. Results of CPET are shown in Table 3. There were no significant differences in any of the variables studied between the 2 groups before surgery. After LAUP, group II had no significant improvement in their CPET performance. By contrast, after successful LAUP, group I had significant improvement in WRmax, VO2max, VO2max/kg, anaerobic threshold, and oxygen pulse. They also had a higher VEmax and a lower breathing reserve after surgery (Table 3, Figs 1 and 2). An example of CPET results in 1 subject is shown before LAUP (Fig 3) and after LAUP (Fig 4). The subject was a 48-year-old man, 165 cm in height and weighing 72 kg. The anaerobic threshold (AT) is shown. The VCO2 increased linearly up to the AT, at which point it became nonlinear, rising more steeply (Figs 3 and 4).

DISCUSSION In this study, we found that OSAS patients in whom LAUP successfully improved sleep apnea also had improved CEPT performance after surgery, with improved WRmax, VO2max, and VO2max/kg. The reasons for exercise limitation in patients with OSAS are not well understood. Poten-

Figure 1 Maximal oxygen consumption (VO2max, L/min), anaerobic threshold (AT, L/min), and O2 pulse (mL/beat) in response to CPET before and after LAUP for group I patients. There was a significantly higher VO2max, anaerobic threshold and O2 pulse (mL/beat) for group I patients after LAUP. (*, P ⬍ 0.05 comparison between before and after LAUP for group I patients. Statistical analysis was performed using paired Student’s t test.)

60

Otolaryngology–Head and Neck Surgery, Vol 133, No 1, July 2005

Figure 2 VO2max (L/min), AT (L/min), and O2 pulse (mL/ beat) in response to CPET before and after LAUP for group II patients. There was no significant improvement in VO2max, anaerobic threshold and O2 pulse (mL/beat) for group II patients after LAUP. (Statistical analysis was performed using paired Student’s t test.)

tial contributing factors include dyspnea, leg weakness, cardiac dysfunction, respiratory mechanics/respiratory muscle dysfunction, arterial hypoxemia, lack of fitness, hypoventilation, diastolic LV dysfunction, pulmonary hypertension, RV dysfunction, and possibly others, such as motivation or peripheral vascular disease.

Figure 3 Example of 1 OSAS subject before LAUP. The AT is shown. The VCO2 increases linearly up to the AT, at which point it becomes nonlinear, rising more steeply.

Certain factors have been reported to influence the outcome of CPET in general, including age and BMI. However, these variables in both groups of our patients were similar, and there was no significant weight loss after surgery in either group. The most common symptoms limiting exercise in our patients were shortness of breath (SOB) and leg muscle weakness. These are different sensations, and either one or both can limit CPET. There were no significant differences in the grading of these symptoms in any of our patients. Even though those in group I had a higher WRmax after LAUP, their subjective scoring of dyspnea and leg effort before and after LAUP remained unchanged. Their breathing reserve at the end of exercise was significantly lower after LAUP than before. Most subjects stopped exercising at submaximal ventilation and submaximal symptom intensity, making it difficult to isolate the true limiting factors. The degree of discomfort the subjects could tolerate ranged from “somewhat severe” to “very severe.” However, the majority stopped when the symptom intensity of leg discomfort and/or dyspnea reached 7 (“very severe”), and few were willing to exercise to maximal symptom intensity. There are a number of factors that may have contributed to exercise limitation, including degree of motivation, over- or underscoring based on individual understanding of the scoring system, physical activity and exercise habits, and lack of fitness. Daytime hypersomnolence that decreases daily activity may be a reason for lack of fitness.18 Sleep deprivation may also factor in, as it impairs ventilatory response to hypoxia and carbon dioxide. Sleep restores cellular aerobic enzyme activity and cellular function, especially the brain and muscles of exercise, such that VO2max increases.18 The

Figure 4 CPET results for the same subject as in Fig 3 after successful LAUP. The AT is shown. The VCO2 increases linearly up to the AT, at which point it becomes nonlinear, rising more steeply.

Lin et al

Effect of Treatment by Laser-assisted . . .

improvement in sleep architecture after successful LAUP may thus have contributed to improved exercise capacity in group I. The results of PFT did not change significantly for either group after surgery. On the exercise testing, gas exchange data also remained unchanged, although group I patients did have an increased VEmax and a decreased breathing reserve after surgery, suggesting they were able to exercise to a greater degree than previously. These results imply that the improvement in CPET performance in group I was not due to pulmonary factors. Improved exercise tolerance in group I may thus have been more related to cardiovascular responses brought about by improvement in their OSAS. Malone et al19 studied the effects of 1 month of nasal CPAP in 8 patients with coexisting dilated cardiomyopathy and OSAS. There was complete abolition of obstructive apnea events and a significant improvement in LVEF from 37% to 49%, a better result than that seen in OSAS patients without CHF. Takasaki et al20 studied 5 patients with congestive heart failure, symptoms of sleep apnea, and Cheyne-Stokes respiration during sleep. The mean resting LVEF increased from 31% to 38% after nasal CPAP treatment, as measured by radionuclide ventriculography. Their symptoms of heart failure also improved.20 Ross et al21 reported a child who had severe sleep apnea and severe concentric LVH and an enlarged right ventricle on echocardiogram. The LVH resolved after a tracheostomy. Tal et al22 evaluated 27 children with clinical features of OSAS who had improvement in RVEF and right ventricular wall after adenotonsillectomy. In OSAS patients whose apnea improved after UPPP, Dickson et al23 documented significant decreases in systolic and diastolic pressures, from a mean of 142/90 to 132/86. Zohar et al24 found that both RVEF and LVEF improved after UPPP. These studies are all consistent with our results, where successful LAUP resulted in lower blood pressure and higher RVEF, as well as improved anaerobic threshold and oxygen pulse. Improvement in OSAS may decrease sympathetic nerve activity, reduce myocardial ischemia and arrhythmias, and improve cardiac function. Both anaerobic threshold and oxygen pulse have been considered related to cardiac function.17,25 Therefore, improvement of cardiac function may contribute to improved CPET in patients with OSAS who are successfully treated with LAUP. We thank Ms Shwu-Fang Liaw for her help in the laboratory work.

REFERENCES 1. Hedner J, Darpo B, Ejnell H, et al. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J 1995;8:222–9. 2. Fletcher EC, Schaaf JW, Miller J, et al. Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease. Am Rev Respir Dis 1987;135:525–33.

61 3. Sajkov D, Cowie RJ, Thornton AT, et al. Pulmonary hypertension and hypoxia in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 1994;149:416 –22. 4. Shiomi T, Guilleminault C, Stoohs R, et al. Leftward shift of the interventricular septum and pulsus paradoxus in obstructive sleep apnea syndrome. Chest 1991;100:894 –902. 5. 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. 6. Mooe T, Franklin KA, Holmstrom K, et al. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med 2001;164:1910 –3. 7. Ray CS, Sue DY, Bray G, et al. Effect of obesity on respiratory function. Am Rev Respir Dis 1983;128:501– 6. 8. Whipp BJ, Davis JA. The ventilatory stress of exercise in obesity. Am Rev Respir Dis 1984;129(suppl):S90 –2. 9. Zozula R, Rosen R. Compliance with continuous positive airway pressure therapy: assessing and improving treatment outcomes. Curr Op Pulm Med 2001;7:391– 8. 10. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156 –77. 11. Keenan SP, Burt H, Ryan CF, et al. Long-term survival of patients with obstructive sleep apnea treated by uvulopalatopharyngoplasty or nasal CPAP. Chest 1994;105:155–9. 12. American Thoracic Society. Indications and standards for cardiopulmonary sleep studies. Am Rev Respir Dis 1989;139:559 – 68. 13. EEG Arousals. Scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 1992;15:174 – 84. 14. Rechtschaffea A, Kales A, eds. A manual of standardized terminology techniques and scoring systems for sleep stages of human subjects. Bethesda, MD: National Institutes of Health, 1968. 15. Carskadon MA, Dement WC, Mitler MM, et al. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 1986;9:519 –24. 16. Jones NL, Makrides L, Hitchcock C, et al. Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985;131:700 – 8. 17. ERS Task Force on Standardization of Clinical Exercise Testing. Clinical exercise testing with reference to lung diseases: indications, standardization, and interpretation strategies. Eur Respir J 1997;10: 2662– 89. 18. Vondra K, Brodan V, Bass A, et al. Effects of sleep deprivation on the activity of selected metabolic enzymes in skeletal muscle. Eur J Appl Physiol Occup Physiol 1981;47:41– 6. 19. Malone S, Liu PP, Holloway R, et al. Obstructive sleep apnea in patients with dilated cardiomyopathy: effect of continuous positive airway pressure. Lancet 1991;338:1480 – 4. 20. Takasaki Y, Orr D, Popkin J, et al. Effect of nasal continuous positive airway pressure on sleep apnea in congestive heart failure. Am Rev Respir Dis 1989;140:1578 – 84. 21. Ross RD, Daniels SR, Loggie JM, et al. Sleep apnea-associated hypertension and reversible left ventricular hypertrophy. J Pediatr 1987; 111:253–5. 22. Tal A, Leiberman A, Margulis G, et al. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide assessment. Pediatr Pulmonol 1988;4:139 – 43. 23. Dickson RI, Blokmanis A. Treatment of obstructive sleep apnea by uvulopalatopharyngoplasty. Laryngoscope 1987;97:1054 –9. 24. Zohar Y, Talmi YP, Frenkel H, et al. Cardiac function in obstructive sleep apnea patients following uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1992;107:390 – 4. 25. Weisman IM, Zeballos RJ. An integrated approach to the interpretation of cardiopulmonary exercise testing. Clin Chest Med 1994;15:421– 45.