Effect of Treatment by Nasal CPAP onCardiopulmonary Exercise Test in ObstructiveSleep Apnea Syndrome

Effect of Treatment by Nasal CPAP on

Cardiopulmonary Exercise Test in Obstructive

Sleep Apnea Syndrome

Ching-Chi Lin,1,2 Ching-Kai Lin,1 Kun-Ming Wu,1 and Chon-Shin Chou1

1Chest Division, Department of Internal Medicine, Department of Medical Research, Mackay

Memorial Hospital, Taipei, Taiwan; 2Mackay Junior College of Nursing, Taipei, Taiwan

Abstract. This study was done to evaluate whether cardiac dysfunction orabnormal measurements on cardiopulmonary exercise testing (CPET) can beimproved after 2 months of nasal CPAP treatment. Twenty patients withmoderate or severe OSAS received nasal CPAP treatment. All subjects alsounderwent blood pressure, simple spirometric, and arterial blood gas (ABG)measurements; cardiac evaluation by radionuclide scanning and CPET; and anovernight polysomnography sleep study before and after nasal CPAP treat-ment. No difference in left ventricular ejection fraction (LVEF) was found after2 months of nasal CPAP treatment, but higher right ventricular ejectionfraction (RVEF), VO2peak, VO2peak/kg and workpeak were observed. After2 months of nasal CPAP treatment, these patients had a lower breathing re-serve and a greater increase in anaerobic threshold and oxygen pulse. Moderateto severe OSAS patients before nasal CPAP treatment had abnormal CPET asreflected by lower RVEF, VO2peak/kg, workpeak, anaerobic threshold andoxygen pulse. These abnormalities can be improved after 2 months of nasalCPAP treatment.

Key words: Obstructive sleep apnea syndrome—Cardiopulmonary exercisetest—Nasal CPAP—VO2peak—Anaerobic threshold—Oxygen pulse.

Correspondence to: Ching-Chi Lin; email: [email protected]

Lung (2004) 182:199–212

DOI: 10.1007/s00408-004-2502-7

Introduction

Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive upperairway obstruction leading to a high negative intrathoracic pressure and alveolarhypoventilation [13], resulting in abnormal gas exchange, arterial oxygen desat-uration, abnormal autonomic nerve function, acute and possibly chronic cardiacdysfunction, and hemodynamic impairment [11, 15, 19, 20]. Theoretically, OSASpatients may develop pulmonary hypertension and right ventricular failure due tohypoxic pulmonary vasoconstriction [12, 33, 34] and increased right ventricularafterload related to exaggerated negative intrathoracic pressure swings duringobstructive apnea [21, 33, 34].

Several recent studies indicate that intermittent apnea-related hypoxemia isnot enough to explain sustained pulmonary hypertension. In contrast, diurnalhypoxemia or overlapping syndrome (OSAS + mild to moderate diffuse COPD)is essential for the development of pulmonary hypertension [19, 24, 42]. Manystudies have also reported that OSAS can play a role in the pathogenesis of leftventricle (LV) heart failure. The effects of OSAS on cardiovascular function arethrough a combination of OSAS-related generation of large negative intratho-racic pressure swings against the occluded upper airway [36], hypoxemia, arousalfrom sleep that increased LV afterload, systemic and pulmonary vasoconstriction,reduced stroke volume and cardiac output, and chronically elevated sympat-hoadrenal activity and cardiac arrhythmia [15, 17].

When ventilation is resumed, heart rate and cardiac output abruptly increaseand myocardial oxygen demands are maximal. At this time, desaturated bloodperfuses the coronary circulation predisposing the myocardium to atrial andventricular ectopy.

Cardiovascular disease remains the leading cause of death in developedcountries. OSAS is also common, affecting about 2%–5% of adult men [45].Cardiovascular disturbances have been considered to be one of the most seriouscomplications of OSAS [12, 28, 35]. Strong evidence suggests that snoring andsleep apnea significantly increase the relative risk of ischemic heart disease [26].Substantial evidence has also shown that if OSAS is untreated it may lead tomultiple organ-system dysfunction, including personality changes and intellectualimpairment [25]. Untreated patients with OSAS also have increased mortality[14].

Cardiopulmonary exercise testing (CPET) is used as a stress test to evaluatecardiac, pulmonary, and muscle function. It has also been used to differentiatewhether the etiology of impairment of the CPET is cardiac, pulmonary or muscledysfunction. In otherwise healthy subjects, cardiac limit to exercise was observed.Patients with OSAS are frequently overweight and may exhibit lung functionabnormalities related to their weight. These include a decrease in the functionalresidual capacity (FRC) due mainly to a decrease in the expiratory reserve volume(ERV) and a decrease in compliance of the respiratory system [27, 29]. Thesefunctional abnormalities cause an increase in the energy cost of breathing. Inaddition, increased body mass is associated with greater metabolic energyrequirements during muscular exercise, resulting in further ventilatory stress.

200 C.-C. Lin et al.

There are reports demonstrating that there are discriminating measurementsduring exercise in obesity, including a high O2 cost to perform external work, andupward displacement of the VO2-WR relationship [3, 43]. OSAS patients havedaytime hypersomnolence, decreased daily activity, and tissue hypoxemia whichmay further impair muscle function and decrease exercise fitness.

Nasal CPAP has been reported to be very effective in treating patients withOSAS [31]. It can reduce daytime hypersomnolence by improving sleep efficiency,decreasing arousal index and sleep fragmentation, and improve intellectualimpairment, personality change, psychological dysfunction, and cardiac function,thus improving tissue oxygenation. Nasal CPAP has also been reported to reducemortality [14]. Jenkinson et al. [16] demonstrated the efficacy of nasal CPAP in aseries of 54 patients receiving therapeutic nasal CPAP and 53 receiving subther-apeutic nasal CPAP (at 1 cm H2O) [16]. Ballester et al. [4] also confirmed thesuperiority of nasal CPAP over conservative measures such as changes in sleepbehavior and weight loss.

To our knowledge, the effect of treatment by nasal CPAP on CPET inobstructive sleep apnea syndrome has never been studied. The purpose of thisstudy was to evaluate whether cardiac dysfunction or abnormal measurements oncardiopulmonary exercise testing (CPET) can be improved after 2 months of nasalCPAP treatment.

Materials and Methods

Selection of Subjects

Patients presenting to the Mackay Memorial Hospital Sleep Laboratory for sleep studies were con-

sidered for enrollment. They came either by referral from a physician who determined they had a

clinical problem meriting overnight sleep polysomnographic evaluation or by their own request. All

subjects underwent blood pressure, simple spirometric, and arterial blood gas (ABG) measurements;

cardiac evaluation by radionuclide scanning; and an overnight polysomnography sleep study.

Twenty patients with moderately severe to severe OSAS proven by overnight sleep study who

desired nasal CPAP treatment for at least 2 months were selected. All were otherwise healthy with

normal thyroid functions, no evidence of cardiopulmonary failure, no diabetes mellitus or other

medical diseases that could affect energy expenditure (EE), as evaluated by clinical history, physical

examination, chest radiograph, electrocardiogram, and biochemistry examinations (including free T4,

T3 resin uptake, and pre- and postprandial blood sugar). 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 one month prior to the study. Alcohol or sedatives were

avoided for at least one week prior to the overnight sleep study. Drugs or substances that alter

metabolism (e.g., caffeine, tea, nicotine and theophylline) were avoided for at least 2 days.

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

Effect of Treatment by Nasal CPAP 201

continuously measured by an Omheda pulse oximeter. Bilateral tibial EMG and ECG were also

monitored from surface electrodes [2]. Sleep was staged by the method of Rechtschaffen and Kales [30]

on the basis of 30-second epochs.

The second sleep study was performed with the patients still on CPAP after two months of

treatment.

Sleep Variables

Apnea/hypopnea was defined as a clear absence or 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 [1, 2], The baseline was defined as the mean

amplitude of stable breathing and oxygenation in the two minutes preceding onset of the event (in

individuals who had a stable breathing pattern during sleep) or the mean amplitude of the three largest

breaths in the two 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 hypopnea and

apnea episodes per hour of sleep. Desaturation event frequency (DEF) was defined as the mean

number of oxygen desaturation episodes per hour of sleep [2]. Sleep apnea syndrome (SAS) was

diagnosed as a RDI equal to or greater than 5 during overnight polysomnography. Moderately severe

or severe SAS was defined as an RDI equal to or greater than 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 3-

to 15-second period of return of a or h 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 [8]. Sleep efficiency was the percentage of

total sleep time divided by total bed time.

Multiple Sleep Latency Test

A multiple sleep latency test (MSLT) was performed to assess sleepiness according to the recom-

mendation of the American Sleep Disorders Association [5]. The subjects were placed in a dark room

for 20 minutes four times a day (10:00 a.m., 12:00 p.m., 2:00 p.m., and 4:00 p.m.). All subjects

maintained a sleep diary from one week prior to the experiment to confirm that they had not deviated

from their usual routine. Polysomnographic recordings were obtained during the measurement. Sleep

latency was measured when the first epoch of any stage of sleep appeared. Each sleep latency time was

measured and then the mean value of four 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.

The maximal minute ventilation (MVV, L/min, BTPS) was measured directly. When MVV was

measured, patients were asked to sit up very straight and make sure nothing was restricting chest

movement or airflow (such as tie, coat, belt, chewing gum, etc). Obese adults stood rather than sat for


the test and began by breathing normally through the mouthpiece, followed by breathing as deeply

(recommended depth: 1/2 to 3/4 of the patient’s vital capacity) and rapidly (recommended rate: 70 to

150 breaths per minute) as possible. At the end of the measurement interval, they were told to resume

normal breathing and remove the mouthpiece. At least two trials were done showing consistent effort

with reproducible results.

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 with electrocardiographic monitoring

under the supervision of a physician, and with defined criteria for stopping such as serious cardiac

arrhythmias, hypotension, and electrocardiographic changes. Termination of exercise by the super-

vising physician according to those criteria was not required in any subject. Before exercise, while

seated comfortably on the cycle ergometer (Erich Jaeger GmbH, Germany), subjects breathed for

1 min through a unidirectional valve (Hans Rudollph, Kansas City, MO, USA) with the expired air

going to a universal exercise testing system (Vmax series/6200 autobox DL metabolic cart, Sensor

Medics, Anaheim, California, USA). After 1 min of loadless pedaling, subjects cycled at 60 revolutions

per min at an initial power output of 100 kpm/min. At the end of each minute the power output was

increased by 100 kpm/min. Heart rate, blood pressure, ventilation, respiratory rate and tidal volume

were measured.

Patients were encouraged to continue exercise until exhaustion. They were asked to estimate the

intensity of breathing discomfort and the intensity of leg effort every minute by matching their sub-

jective estimate to a number from 0 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 the

exercise. Symptoms attributed to the leg muscles (leg effort or fatigue) were limiting in all subjects.

Maximal power output (MPO) was defined as the highest power output maintained for at least 30 s.

The breathing reserve = 1)[VEmax/MVV], where VEmax is the maximal minute ventilation (L/min,

BTPS) at maximal exercise.

The anaerobic threshold was determined by using the following criteria: (1) inflection point in the

minute ventilation (VE) and/or VCO2 vs VO2 diagram; (2) point of increase in end-tidal PO2

(PETO2); and (3) point of increase in the ventilatory equivalent of O2 (VE/VO2) without a con-

comitant reduction of end tidal PCO2 (PETCO2) [10, 23, 40].

Study Protocol

After baseline measurements, subjects receiving nasal CPAP treatment for 2 months were followed by

a second sleep study, CPET, and cardiac function evaluation by a radionuclide method to determine

the left and right ventricular ejection fractions 2 months later.

Nasal CPAP Treatment

On the night following the sleep study, patients received nasal CPAP. Those receiving CPAP under-

went standard CPAP titration with the use of a Sullivan machine and a comfortably fitting mask.


Pressure in the mask started at 2 cm H2O and increased over the night by 2 cm H2O increments until

apneic episodes had been obliterated or until a pressure of 8–10 cm was reached. Further pressure

titration was then done in increments of 1 cm H2O on the basis of the presence of apnea, hypopnea, or

snoring associated with arousals. The titration was considered ended when most respiratory events had

been controlled with CPAP while the patient was in the supine position and in the second or third rapid

eye movement sleep period or until a pressure of 20 cm had been reached. All patients had their apnea

treated within this pressure.

Data Analysis

Student’s t-test was used for statistical analysis where appropriate. All values were expressed as the

mean ± standard deviation, with significance accepted when p < 0.05. Simple linear regression was

used to look for a correlation between changes in RDI and DEF and changes in the VO2 maximum

and oxygen pulse.

Results

Patient Data and Baseline Measurements

These are summarized in Table 1. There were no significant differences in age, sex,BMI, hematocrit, FEV1, FVC, FEV1/FVC, pH, PaO2 or PaCO2 after nasalCPAP treatment. There was also no significant change in LVEF after nasal CPAPtreatment, whereas RVEF increased. Systolic and diastolic blood pressure de-creased after nasal CPAP treatment.

Table 1. Patient characteristics and baseline measurements

Before CPAP After CPAP

(n = 20) (n = 20)

Age, years 43 ± 8 43 ± 8

Sex (male/female) 18/2 18/2

Systolic pressure (mmHg) 135.7 ± 10.3* 125.8 ± 9.3

Diastolic pressure (mmHg) 85.4 ± 10.4* 77.7 ± 9.7

BMI, kg/m2; male 29.7 ± 3.6 29.6 ± 3.4

LVEF, % 58.4 ± 5.8 62.3 ± 6.5

RVEF, % 37.6 ± 4.2* 45.3 ± 3.5

FEV1, % predicted 88.8 ± 5.1 89.3 ± 5.4

FVC, % predicted 88.7 ± 5.5 88.5 ± 5.8

FEV1/FVC 82.2 ± 5.8 82.4 ± 5.9

Hematocrit 40.4 ± 1.2 40.2 ± 1.6

pH 7.41 ± 0.03 7.40 ± 0.03

Baseline PaO2, mmHg 95.5 ± 2.3 96.8 ± 1.8

Baseline PaCO2, mmHg 39.8 ± 2.4 39.2 ± 2.1

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 nasal CPAP treatment.


Sleep Measurements

RDI and DEF were higher before nasal CPAP treatment than after nasal CPAPtreatment. The lowest SpO2 increased after nasal CPAP treatment. There was amore abnormal sleep architecture characterized by a higher percentage of stage 1sleep but a lower percentage of stage 2 and REM stage sleep and a higher arousalindex before nasal CPAP treatment (Table 2). The MSLT was lower in beforenasal CPAP treatment than after nasal CPAP treatment.

Response to the Cardiopulmonary Exercise Test

Results of the CPET study are shown in Table 3. The intensity of dyspnea(median rating 7, very severe) and leg effort (median rating 7, very severe) werethe same before and after nasal CPAP treatment. However, there was a lowerVO2peak, VO2peak/kg, workpeak, anaerobic threshold and oxygen pulse be-fore nasal CPAP treatment (Table 3). A higher breathing reserve but a lowerVEmax were observed before nasal CPAP treatment. There was no differencein PetO2, PetCO2, VE/VO2, VE/VCO2, respiratory quotient, VD/VT, SpO2,heart rate, and heart rate reserve before and after nasal CPAP treatment(Table 3).

Figure 1 is an example of a CEPT before nasal CPAP treatment and Figure 2an example of a CPET for the same OSA subject after nasal CPAP treatment(age: 45, sex: male, height: 167 cm, body weight: 80 kg). The anaerobic threshold(AT) is shown. The VCO2 increased linearly up to the AT, at which point itbecame nonlinear, rising more steeply (Fig. 1 and 2).

Table 2. Results of sleep study


RDI, times / hour 47.3 ± 15.7* 5.1 ± 2.2

DEF, times / hour 32.7 ± 10.2* 2.3 ± 1.2

Baseline SpO2, % 96.9 ± 0.6 97.3 ± 0.7

Lowest SpO2, % 62.7 ± 7.3* 91.6 ± 1.5

Percent of total sleep time at each sleep stage

Stage 1, % 32.3 ± 8.7* 15.4 ± 2.6

Stage 2, % 47.9 ± 6.8* 56.4 ± 1.5

Stage 3+4, % 3.2 ± 2.2* 6.5 ± 1.1

REM, % 16.6 ± 3.8* 21.7 ± 1.9

Sleep efficiency, % 75.2 ± 6.4* 86.8 ± 3.2

AI, times / hour 42.3 ± 7.9* 4.3 ± 1.1

MSLT, minutes 4.2 ± 2.9* 8.6 ± 2.6

RDI: respiratory disturbance index; DEF: desaturation event frequency; REM: rapid eye movement;

AI: arousal index.

Data are presented as mean ± SD.The student’s t-test was used.



Correlation Between Changes in RDI and DEF and Changes in VO2 Maximum andOxygen Pulse

Table 4 shows a negative correlation between changes in RDI and changes in theVO2 maximum and oxygen pulse before and after nasal CPAP treatment. Asimilar relationship was seen for DEF. Figure 3 shows the correlation between thechange of RDI and the change of VO2 maximum before and after nasal CPAPtreatment (r = )0.66, p < 0.05).

Discussion

In this study we found that OSAS patients before nasal CPAP treatment had alower VO2 peak, VO2 peak/kg, and workpeak. The reasons for exercise limitationin patients with OSAS are not well understood. Potential contributing factorsinclude dyspnea, leg weakness, cardiac dysfunction, respiratory mechanics/respiratory muscle dysfunction, arterial hypoxemia, lack of fitness, hypoventila-tion, diastolic LV dysfunction, pulmonary hypertension, RV dysfunction andpossibly others, such as motivation or peripheral vascular disease.

Many factors have been reported which may influence the outcome of CPET,including age, BMI, and exercise habits. There were no significant differences inage or BMI in our study before or after nasal CPAP treatment. The patients alsodid not change their exercise habits during the course of the study, nor were they

Table 3. Cardio-pulmonary exercise test results


Intensity of dyspnea 6.9 ± 1.2 6.8 ± 1.1

Intensity of leg effort 7.0 ± 1.3 7.1 ± 1.4

VO2peak, L/min, 1.678 ± 0.237* 2.168 ± 0.331

VO2peak/kg, mL/kg/min 20.41 ±3.31* 26.3 ± 4.29

Workpeak, watts 129.6 ± 14.9* 151.5 ± 13.6

Anaerobic threshold, L/min 0.91 ± 0.14* 1.28 ± 0.12

Heart rate, bpm 150.9 ± 10.9 155.2 ± 10.7

Heart rate reserve, bpm 14.9 ± 7.9 10.3 ± 6.6

VEmax, (L/min) BTPS 71.3 ± 10.2* 87.2 ± 9.7

Breathing reserve, % 47.4 ± 7.3* 35.7 ± 6.6

O2 Pulse, ml/beat 9.4 ± 1.8* 12.3 ± 1.7

PetO2 114.2 ± 6.4 113.4 ± 6.2

PetCO2 39.3 ± 4.2 39.9 ± 4.6

VE/VO2 32.5 ± 4.8 32.1 ± 4.2

VE/VCO2 34.2 ± 3.2 32.3 ± 3.4

Respiratory quotient 1.17 ± 0.07 1.21 ± 0.07

VD/VT, % 17.4 ± 3.2 15.3 ± 3.8

SpO2, % 95.2 ± 4.4 95.1 ± 3.3

Data are presented as mean ± SD. The student’s t-test was used.



given specific exercise training. Therefore, it is likely the improvements we foundwere related to nasal CPAP treatment rather than to other confounding factors.

The most common symptoms limiting the CPET were dyspnea and leg muscleweakness. Dyspnea and leg effort are different sensations, and either one or bothcan limit CPET [9]. In this study, there was no difference in scoring of dyspneaand leg effort before and after nasal CPAP treatment at the level of peak exercise,but the peak of work was lower before nasal CPAP treatment. Most subjectsstopped exercising at submaximal ventilation and submaximal symptom intensi-ties, making it difficult to isolate the true limiting factors. Some subjects toleratedonly a little discomfort (somewhat severe) while most could tolerate a greaterdegree of discomfort (very severe). However, the majority stopped when thesymptom intensity of leg discomfort and/or dyspnea reached 7 (very severe), withfew willing to exercise to maximal symptom intensity. Individual motivation andsymptom tolerance are related factors. The symptom score, of course, is verysubjective. Overrating or underrating by individual subjects is another factor thatmight influence the outcome of the scoring. Physical activity and exercise habits ofthe participants may also be limiting factors. Lack of fitness is another possiblereason for exercise limitation in OSA patients before nasal CPAP treatment whostopped at submaximal levels but had a higher breathing reserve than after nasalCPAP treatment. The reasons for lack of fitness are poorly understood. Daytimehypersomnolence which decreases daily activity may be a reason [6, 39].

We found that the sleep efficiency and sleep architecture improved after nasalCPAP and that the RDI and DEF decreased after nasal CPAP treatment. Thechanges of RDI and DEF correlated negatively with the changes of VO2 maxi-

Fig. 1. Example of a cardiopulmonary exercise test for one OSAS subject before nasal CPAP treat-

ment. The anaerobic threshold (AT) is shown. The VCO2 increases linearly up to the AT, at which

point it becomes nonlinear, rising more steeply.


mum and the oxygen pulse. It is unclear why our patients had so little stage 3 and4 sleep after nasal CPAP treatment. It did not appear to be due to disruptions ofsleep, since the arousal index was only 4.3 events per hour. There were no changesin medications which may affect sleep architecture. It may be that the subjects didnot sleep very deeply because they were in an unfamiliar bed for the sleep study.Sleep deprivation can impair ventilatory response to hypoxia and carbon dioxide.Conversely, sleep restores cellular aerobic enzyme activity and cellular function,especially in the brain and in the muscles that increase the VO2max duringexercise. Better daytime alertness after nasal CPAP may also contribute to im-proved motivation and performance of the CPET, with an accompanying increasein VO2max [39, 44].

Fig. 2. Cardiopulmonary exercise test results for the same subject after nasal CPAP treatment. The

anaerobic threshold (AT) is shown. The VCO2 increases linearly up to the AT, at which point it

becomes nonlinear, rising more steeply.

Table 4. Relationship between changes in RDI and changes in VO2 maximum and oxygen pulse

@RDI @DEF

@VO2 maximum r = )0.66* r = )0.59*@Oxygen pulse r = )0.64* r = )0.56*

Simple linear regression was used. *p < 0.05

@RDI = RDI before nasal CPAP treatment) RDI after nasal CPAP treatment;

@DEF = DEF before nasal CPAP treatment) DEF after nasal CPAP treatment;

@VO2 maximum = VO2 maximum before nasal CPAP treatment) VO2 maximum after nasal CPAP

treatment;

@Oxygen pulse = Oxygen pulse before nasal CPAP treatment) Oxygen pulse after nasal CPAP

treatment.


In this study, there was no significant difference in baseline FVC, FEV1,FEV1/FVC and baseline PaO2, PaCO2 after nasal CPAP treatment. However, wedemonstrated that there was a lower VEmax but higher breathing reserve inpatients before nasal CPAP treatment. There was no difference in VD/VT, PetO2,PetCO2, VE/VO2, VE/VCO2 or SpO2 during exercise after nasal CPAP treat-ment, implying that improvement in CPET after nasal CPAP treatment was notdue to pulmonary factors.

Nasal CPAP treatment may affect a number of measures of cardiovascularresponse. Kaneko et al [18] have shown that in medically treated patients withheart failure, treatment of coexisting OSAS by CPAP reduces systolic bloodpressure and improves left ventricular systolic function. Malone et al. [22] studiedthe effects of 1 month of nasal CPAP in 8 patients with idiopathic dilated car-diomyopathy coexisting with OSAS and found that the treatment completelyabolished obstructive apneic events and significantly improved LVEF (from 37%to 49%). Takasaki et al. [37] studied 5 patients with congestive heart failure,symptoms of sleep apnea, and Cheyne-Stokes respiration during sleep. NasalCPAP treatment improved the mean resting LVEF from 31% to 38% as measuredby radionuclide ventriculography. The symptoms of heart failure also improved.Ross et al. [32] reported one child with severe sleep apnea who had severe con-centric LV hypertrophy and an enlarged right ventricle on echocardiography.After a tracheostomy, the LV hypertrophy resolved. Zohar et al. [47] found thatboth RVEF and LVEF in 19 OSAS patients improved after uvulopalatoplasty(UPPP). In this study, we found that nasal CPAP is very effective in treatingpatients with either moderate or severe OSAS. It can abolish obstructive apneas(decreased RDI and DEF), decrease arousal index and sleep fragmentation,

Fig. 3. Correlation between the change of RDI and the change of VO2 maximum. There was a negative

correlation between these two measurements. (@RDI = RDI before nasal CPAP treatment-RDI after

nasal CPAP treatment; @ VO2 maximum = VO2 maximum before nasal CPAP treatment-VO2

maximum after nasal CPAP treatment).


improve blood oxygenation (increased mean SaO2 and lowest SaO2) which maythus reduce sympathetic nerve activity, reduce myocardial ischemia, cardiacarrhythmia and improve cardiac function. However, in our series, the LVEF didnot change significantly after nasal CPAP treatment (58.4 ± 5.8 before and62.3 ± 6.5 after CPAP). This discrepancy between our findings and those ofother investigators may be because our patients did not have overt CHF. PerhapsOSAS in patients with CHF have a greater improvement in their cardiac functionas a result of nasal CPAP [37]. In this study, heart rate and heart rate reserve didnot change, but the systolic and diastolic pressures both fell significantly afternasal CPAP, a result consistent with the findings of Dickson and Blokmanis [7].They studied 40 OSAS patients who underwent UPPP and found that 77.5% hada documented reduction of 50% or more in the apnea index 3 months after UPPP.Over that interval, the systolic and diastolic pressures both fell significantly froman average of 142/90 to 132/86 [7]. The RVEF at rest improved significantly afternasal CPAP treatment in our study, which is consistent with other studies [18, 22,32, 37, 47].

It is therefore surprising that we did not find a significant improvement inLVEF despite definite improvement in the RVEF. We did not insert pulmonaryartery catheters in our patients, nor did we perform echocardiography. Therefore,we could not document changes in pulmonary artery pressures that might haveled to selective improvement in RVEF. However, there were some indirect indi-cations that this might have been the case. There was a small drop in VE/VCO2after nasal CPAP, as well as a decrement in DVD/VT (DVD/VT = VD/VT at rest-VD/VT at peak exercise). The DVD/VT after CPAP therapy was 14.7 ± 3.5compared with 12.6 ± 2.9 before nasal CPAP. If the treatment improved thesevariables, it is reasonable to speculate that it may also have induced a decrease inpulmonary artery pressure as well. Tal et al. [38] evaluated 27 children withclinical features of OSAS and found improved right ventriular wall motion andRVEF measured by radionuclide angiography after adenotonsillectomy(35.7 ± 2.4 before and 46.7 ± 3.4 after surgery). However, the LVEF was notsignificantly improved (67.5 ± 2.5 before and 68.4 ± 2.8 after surgery), a resultconsistent with our findings, although we must be cautious in comparing childrenand adults.

In this study, the patients had significant lower anaerobic threshold andoxygen pulse before nasal CPAP treatment. Both anaerobic threshold and oxygenpulse have been considered to be related to cardiac function [10, 23, 40, 41, 46].Therefore, improvement in cardiac impairment may contribute to improvedCPET in patients with OSAS.

In conclusion, OSAS patients before nasal CPAP treatment had abnormalCPET as reflected by lower VO2peak/kg, workpeak, anaerobic threshold, andoxygen pulse, all of which improved after nasal CPAP. Furthermore, our findingsmay suggest that these changes are results of improvements in the patients’ car-diac function, daytime somnolence, and fitness.

Acknowledgments. This research was supported by NSC 89-2314-B-195-005.


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Accepted for publication: 27 April 2004


Documents

Effect of Treatment by Nasal CPAP onCardiopulmonary Exercise Test in ObstructiveSleep Apnea Syndrome