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(Chest. 2000;118:1332-1338.)
© 2000 American College of Chest Physicians

Inspiratory Effort Sensation to Added Resistive Loading in Patients With Obstructive Sleep Apnea*

Ye Tun, MBBS; Wataru Hida, MD, FCCP; Shinichi Okabe, MD; Yoshihiro Kikuchi, MD; Hajime Kurosawa, MD; Masao Tabata, MD and Kunio Shirato, MD

* From the First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

Correspondence to: Kunio Shirato, MD, Professor and Chairman, First Department of Internal Medicine, Tohoku University School of Medicine, 1–1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Repeated episodes of upper-airway occlusion are the main characteristics of patients with obstructive sleep apnea (OSA) during sleep. It has been reported that an impairment in the sensation of detection and a depression of ventilatory compensation to added load could be observed in such patients. In this study, we examined patients with OSA to evaluate the inspiratory effort sensation (IES), ventilation, and mouth occlusion pressures during added resistive loading while awake and to determine whether they can be reversed by nasal continuous positive airway pressure (CPAP) treatment.

Design: A hospital-based case-control study.

Setting: A sleep laboratory of a medical unit in Japan.

Subjects: Seventeen patients with moderate to severe OSA and 10 control subjects were included in this study.

Measurements: All patients with OSA had undergone standard nocturnal polysomnography. Patients with OSA and control subjects were evaluated for IES measured by a modified Borg score, ventilation, and mouth occlusion pressure during control and inspiratory resistive loaded breathing. These tests were repeated in all patients with OSA after 2 weeks of nasal CPAP treatment.

Results: IES to inspiratory resistive loading was lower in patients with OSA than in control subjects. There were no differences in ventilation and mouth occlusion pressure between patients and control subjects during loaded breathing. After 2 weeks of nasal CPAP, the decreased IES was increased in patients with OSA.

Conclusion: In patients with OSA, the decreased IES to inspiratory resistive loaded breathing is reversible with nasal CPAP. This could be one additional benefit of nasal CPAP in the treatment of OSA.

Key Words: inspiratory effort sensation • inspiratory resistive loading • obstructive sleep apnea


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper-airway occlusion during sleep. These recurrent cessations of airflow are associated with transient episodes of hypoxia, hypercapnia, and increasing inspiratory effort against the obstructed upper airway, all of which finally lead to a brief arousal and restoration of airway patency and blood gas levels.1 To reestablish upper-airway patency, there are several mechanisms involved. Among these mechanisms, afferent pathways originating in the upper airway itself are important in activating upper-airway dilators through a reflex mechanism.2 Patients with OSA show impairments in the detection of added resistive loading3 and ventilatory decompensation to loaded breathing during wakefulness.4 The ventilatory compensatory defect to resistive loading was also found even in patients with OSA who had normal chemoresponsiveness.5

Depressed ventilatory compensation to resistive loading during sleep was also found in healthy offspring of patients with OSA. It is possible that a subtle inherited impairment in load compensation may contribute to the development of OSA in these offspring later in life.6 Based on this finding, the impaired ventilatory response to upper-airway occlusion might be related to the pathogenesis of OSA. However, this hypothesis is in conflict with a study showing that the depressed ventilatory response to loaded breathing during exercise was recovered after nasal continuous positive airway pressure (CPAP) in patients with OSA.4 These investigators concluded that an abnormality in ventilatory load compensation is a reversible consequence rather than a cause of OSA.

In general, the respiratory sensation acts as an optimizer in the respiratory controlling system.7 However, in OSA it is still unknown whether ventilatory decompensation to loaded breathing is related to respiratory sensation while awake. Inspiratory effort sensation (IES) to different levels of inspiratory resistive loaded breathing in patients with OSA has not been elucidated yet.

Therefore, this study was aimed (1) to examine IES and the ventilatory response to added inspiratory resistive loading, and (2) to study the effect of nasal CPAP on these parameters in patients with OSA.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects
This study included 17 patients (one female patient) with moderate to severe OSA and 10 age-matched control subjects (two female subjects). All patients had a history of habitual snoring and excessive daytime sleepiness, they had recently received a diagnosis of OSA, and they had never been treated with nasal CPAP or any other treatment for sleep apnea. Patients with major medical illness, such as severe heart failure, neurologic disorders, uncontrolled diabetes mellitus, etc., were excluded from this study. Daytime sleepiness was scored by the Epworth sleepiness scale (ESS).8 We also recruited 10 control subjects who were free from snoring and daytime sleepiness. Each subject gave informed consent to the protocol, which was approved by the Human Research Committee of our institute.

Overnight Sleep Study and Nasal CPAP Titration
An overnight sleep study was carried out for all patients in a darkened quiet room using standard polysomnographic equipment. Briefly, EEG (C4/A1, C3/A2), electro-oculography, submental electromyography, and ECG with surface electrodes, air flow at the nose and mouth with thermistors, respiratory movements of the rib cage and abdomen with inductive plethysmography (Respitrace; Ambulatory Monitoring; Ardsley, NY), and percutaneous arterial oxygen saturation (SaO2) with a finger pulse oximeter (Biox 3700; Ohmeda, Boulder, CO) were simultaneously measured. All variables were recorded on an eight-channel thermal chart recorder (Model 360; NEC San-ei; Tokyo, Japan) and a personal computer using MacLab with a chart 3.5 system (ADInstruments; Castle Hill, Australia).

Apnea is defined as a cessation of airflow lasting >= 10 s, and hypopnea is defined as a > 50% decrease in thoracoabdominal amplitude (Respitrace signal) associated with a decline in SaO2 of > 4% from the preceding value. The apnea-hypopnea index (AHI) was calculated according to the definition of Guilleminault and associates.1 Sleep stages were determined according to international standard criteria.9 Since all control subjects were apparently healthy and free from symptoms of OSA, we did not perform standard nocturnal polysomnography on these subjects. However, nocturnal desaturation was ruled out in these subjects by screening with a portable monitor (Apnomonitor; Chest Corporation; Tokyo, Japan).

Nasal CPAP titration was performed under standard polysomnography on the following day after the diagnostic polysomnography. The pressure with which the patients continued to use nasal CPAP was determined on the titration night. All patients in this study were hospitalized for 2 weeks and were managed with a supervised program including dietary therapy.

Spirometry and Arterial Blood Gas Analysis
Vital capacity and FEV1 were measured with a rolling-seal spirometer (Fudac-70s; Fukuda; Tokyo, Japan) in all patients and control subjects. Blood gas tension analysis, including PaO2 and PaCO2, was done with a blood gas analyzer (Model 213; Instrumentation Laboratories; Lexington, MA) in all patients.

Responses to Added Inspiratory Resistive Loads
This test was done in patients and control subjects when seated and awake. Before the tests, they had been resting for 20 to 30 min to establish physical and mental relaxation. Subjects wearing nose clips were allowed to breathe through an apparatus containing a low dead space respiratory valve (model 1900; Hans Rudolph; Kansas City, MO) with inspiratory and expiratory limbs. The resistance of the apparatus was 0.9 cm H2O/L/s and linear to 3 L/s. At the inspiratory limb, resistive loads (RLs) of 10, 20, and 30 cm H2O/L/s were added during the trials. At first, the subjects breathed through the apparatus for 1 min without resistive loading (control); later, three kinds of inspiratory RLs were added for 1 min at each level in random order so that the subject could not guess the magnitude of resistive loading. After breathing for 1 min at each level of inspiratory RL, the patients rated the IES to inspiratory resistive loaded breathing using a modified Borg score.10 This is a linear scale of verbal descriptions that depict the magnitude of difficulty in inspiration from zero (none) to 10 (maximum). Intermediate values between verbal descriptions were also accepted. The phrase "difficulty in inspiration" was not defined, but the patients were instructed to avoid rating nonrespiratory sensations, such as dryness of mouth and throat, headache, etc.

Airflow was measured with the use of a Fleisch pneumotachograph inserted in the common inspiratory line, and the integrated volume signal was recorded. Tidal volume, respiratory frequency, and their product, minute ventilation, were determined. The mouth occlusion pressure that developed during the first 100 ms of airway occlusion (P0.1) was measured through a transducer (Validyne Engineering; Northridge, CA) according to the previously described method.11 During control and resistive loaded breathing, ventilation and P0.1 were recorded on a multichannel thermal polygraph (Recti-Horiz-8K; NEC San-ei; Tokyo, Japan). From the unidirectional respiratory valve, the end-tidal oxygen tension and end-tidal carbon dioxide tension (PETCO2) were measured continuously with a mass spectrometer (WSMR-1400; Westron; Chiba, Japan). SaO2 was monitored continuously with a finger pulse oximeter as mentioned previously. The data were analyzed at the final 20 s of each minute when breathing became stable. These tests were repeated two times, and average values were used for data analysis.

After 2 weeks of nasal CPAP, we repeated these tests in all patients with OSA to determine whether these parameters were altered by the treatment. To determine the learning effect, tests were repeated in four control subjects 2 weeks after the initial test.

Statistical Analysis
All data were expressed as means ± SD. Data of patients and control subjects were compared by unpaired t test. The parameters before and after nasal CPAP were compared by paired t test. Two-way analysis of variance was applied to determine significance among sensation, ventilation, and P0.1 during loaded breathing before and after nasal CPAP; if significant, a paired t test was used as a post hoc test. A two-tailed p value < 0.05 was considered significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Characteristics of Subjects and Patients With OSA
The characteristics of the control subjects and patients are shown in Table 1 . There were no significant differences in age and body mass index between control subjects and patients with OSA.


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  		Table 1. Characteristics of Control Subjects and Patients With OSA*

 
Patients had excessive daytime sleepiness with an ESS score of 16.3. None of the patients had apparent obstructive airway disease. They had moderate to severe OSA with a mean AHI of 55.1 episodes. The patients had lost significant weight 2 weeks after nasal CPAP as a result of supervised dietary management. The daytime sleepiness of patients was decreased after nasal CPAP treatment as the ESS score decreased. After nasal CPAP, PaO2 was increased significantly and PaCO2 was decreased but not significantly. The effectiveness of the nasal CPAP was indicated by the decreased AHI and improved lowest SaO2 during sleep.

IES During Inspiratory Resistive Loaded Breathing
IES values measured by the modified Borg score in control subjects and patients with OSA were compared (Table 2 ). There was no difference in sensation at control breathing between the two groups. Patients with OSA had lower sensation to added inspiratory resistive loading of three different magnitudes compared to control subjects. In both control subjects and patients, IES was increased as the magnitude of added resistive loading was increased.


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  		Table 2. IES of Control Subjects and Patients With OSA Before and After Nasal CPAP at Different Levels of Added Resistive Loadings*

 
Patients with OSA showed a reversible increase in IES to loaded breathing at three levels of added inspiratory resistive loading after 2 weeks of nasal CPAP (Fig 1 ).



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  		Figure 1. Comparison of IES at three different levels of added inspiratory resistive loading before and after nasal CPAP in 17 patients with OSA. There is a significant improvement in the decreased IES after treatment. RL 10 = RL 10 cm H2O/L/s; RL 20 = RL 20 cm H2O/L/s; RL 30 = RL 30 cm H2O/L/s. Data are expressed as mean ± SD.

 
Ventilation and P0.1 During Inspiratory Resistive Loaded Breathing
Patients with OSA had no significant differences in ventilation and P0.1 during added inspiratory resistive loading when compared to control subjects. After nasal CPAP, patients with OSA showed decreases in respiratory frequency but did not reveal significant changes in ventilation and P0.1 at control breathing and the three different levels of added inspiratory resistive loads after nasal CPAP (Table 3 ).


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  		Table 3. Ventilation and P0.1 During Inspiratory Resistive Loaded Breathing of Control Subjects and Patients With OSA*

 
PETCO2 and SaO2 During Inspiratory Resistive Loaded Breathing
During control and inspiratory resistive loaded breathing, PETCO2 was not different between control subjects and patients before nasal CPAP. Moreover, PETCO2 was not changed significantly after nasal CPAP treatment (Table 4 ). SaO2 was also not different between control subjects and patients before nasal CPAP and was not changed significantly after nasal CPAP treatment at control and loaded breathing (Table 4) .


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  		Table 4. PETCO2 and SaO2 During Inspiratory Resistive Loaded Breathing of Control Subjects and Patients With OSA*

 
Repeated Tests in Control Subjects
Test for IES was repeated in four control subjects 2 weeks after the initial test. These four control subjects were comparable to the original 10 control subjects in age (40.3 ± 9.1 years vs 46.6 ± 8.4 years) and in body mass index (27.0 ± 1.7 kg/m2 vs 27.2 ± 4.6 kg/m2), respectively. In control subjects, there were no significant changes in IES at control breathing (0.3 ± 0.3 vs 0.3 ± 0.5) and at different inspiratory resistive loading levels (RL 10, 2.2 ± 1.3 vs 2.3 ± 1.3; RL 20, 4.3 ± 2.3 vs 3.5 ± 11.0; and RL 30, 5.5 ± 1.5 vs 5.0 ± 1.7), respectively. No significant changes were found in ventilation and P0.1 at control breathing and at different inspiratory resistive loading levels after 2 weeks.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study has found that IES to added inspiratory RLs was impaired in patients with OSA, and that the impaired sensation to loaded breathing was reversed after 2 weeks of nasal CPAP in these patients.

The method used to evaluate IES should be considered. We have used the modified Borg scale to measure IES to loaded breathing. This scale was also validated in studies of measuring the sensation to carbon dioxide in normal subjects12 and the perception of dyspnea sensation in asthmatic patients.13 14 In this study, the patients were allowed to breathe with an added resistive loading for 1 min. This duration is approximately comparable to that of actual apnea during sleep.

There are three possible mechanisms explaining why patients with OSA have impaired IES to added resistive loading while awake. First, daytime sleepiness in our patients (Table 1) may have been responsible for the impaired sensation to added resistive loading. Sleep fragmentation in normal subjects can cause daytime sleepiness and impair their mood.15 It was confirmed that the sensation is reversible after nasal CPAP in such patients when daytime sleepiness was apparently decreased in this study and in the previous study.16 Before nasal CPAP, we had observed that more than half of the patients became sleepy during the test. These patients seemed more alert after nasal CPAP.

The second possible mechanism is that abnormalities in afferent pathways of the upper airway may be responsible for the decreased IES in patients with OSA. In OSA, upper-airway injury caused by snoring vibration and repeated forceful suction collapse of the pharynx results in mucosal edema, inflammation, and nerve damage.17 18 These changes disappear after nasal CPAP treatment18 in patients with OSA. An increase in the inspiratory effort against an obstructed upper airway follows upper-airway occlusion during sleep in OSA. The reopening of the upper airway requires an arousal response that is caused by a variety of stimuli.19 Kimoff and coworkers20 showed that afferent mechanoreceptor stimuli were produced during increasing inspiratory effort against the obstructed upper airway, and that they play an important role in mediating arousal and apnea termination. This finding is supported by other studies in which topical oropharyngeal anesthesia delayed arousal21 and caused a lengthening of the apnea duration during sleep in patients with OSA.22 Although these nocturnal processes could not be applied directly to awake condition, it may be speculated that the afferent sensory pathways of the upper airway are responsible for IES to loaded breathing in OSA.

The third possibility is that increased opioid activity in OSA may depress the sensation effort to resistive loading. After nasal CPAP treatment, opioid activity is decreased23 and the sensation of effort to loaded breathing is recovered. This fact is supported by one study14 in which naloxone injection in asthmatic patients with bronchoconstriction induced by methacholine showed an increase in dyspnea sensation.

In our study, the decreased IES to inspiratory resistive loaded breathing was recovered, but ventilation and respiratory drive during added resistive loading did not change after nasal CPAP. Our method applied resistive loading for 1 min, which might have caused little change in arterial blood gas tension (Table 4) . If there is an arterial blood gas tension derangement, it will stimulate ventilation and respiratory drive.24 The changes in arterial blood gas tension and ventilation may influence the respiratory effort sensation.25 But the present study found a marginal increase in respiratory frequency and a nonsignificant decrease in tidal volume during loaded breathing. The change in the breathing pattern may be related to the increase in IES to loaded breathing. However, this study design could not determine whether the increase in IES causes a change in the breathing pattern or vice versa.

It could be considered that the increase in IES in the patient with OSA after 2 weeks of nasal CPAP may be related to the learning effect of sensation. But we still believe that this effect must be related to the treatment of nasal CPAP, since there were no changes in IES in control subjects after 2 weeks without nasal CPAP treatment. Indeed, the sensation evaluated by the Borg scale was reproducible at short-term and long-term intervals even in an exercise test.26 Thus, the increase in the decreased IES in OSA after nasal CPAP results substantially from the treatment.

It must be acknowledged that the basal ventilation at control breathing in control subjects and patients with OSA may be slightly higher than the normal range. Both control subjects and patients with OSA were obese and had higher body surface areas. Such obese persons have higher basal ventilation,27 and these values were comparable to other studies.4 12 Moreover, we did these tests in all subjects during physically and mentally stable conditions. Therefore, a relatively high basal ventilation might not affect the basal IES, which was also not different in the control subjects and patients with OSA (Table 2) . We believe that this level of ventilation was not due to the circuit used in this study, since the apparatus has low resistance and low dead space (see "Materials and Methods" section).

Moreover, the sensation to loaded breathing is affected by age.28 This was proved in one study in which the perception of ventilatory loads was lower in older than in younger subjects. Thus, we compared the effort sensation of patients with OSA to that of age-matched normal subjects. In this study, a body-weight reduction was found that might be related to the change in IES to added resistive loading. But we do not believe that a decrease in body weight of only 2 kg in mean value could affect the sensation in our patients. In the present study, patients with OSA had a nonsignificantly higher body mass index than the control subjects. However, this fact would not affect our results concerning differences in IES to added resistive loading of the patients with OSA and the control subjects, since we did not find a significant relation between the body mass index and IES to added resistive loadings in the two groups.

In humans, the respiratory sensation plays an important role in the respiratory control system.7 Our findings suggest that patients with OSA have an impaired sensation of effort to loaded breathing. With nasal CPAP therapy, they regain the normal sensation to loaded breathing, which could be one beneficial effect on the respiratory control system in patients with OSA.


   Acknowledgements
 
The authors thank Mr. B. Bell for reading the manuscript.


   Footnotes
 
Abbreviations: AHI = apnea-hypopnea index; CPAP = continuous positive airway pressure; ESS = Epworth sleepiness scale; IES = inspiratory effort sensation; OSA = obstructive sleep apnea; P0.1 = mouth occlusion pressure that developed during the first 100 ms of airway occlusion; PETCO2 = end-tidal carbon dioxide tension; RL = resistive load; SaO2 = arterial oxygen saturation

Received for publication December 8, 1999. Accepted for publication June 26, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Guilleminault, C, Tilkian, A, Dement, WC (1976) The sleep apnea syndromes. Ann Rev Med 27,465-484[CrossRef][ISI][Medline]
  2. Cistulli, PA, Sullivan, CE (1994) Pathophysiology of sleep apnea. Saunders, NA Sullivan, CE eds. Sleep and breathing ,405-448 Marcel Dekker New York, NY.
  3. McNicholas, WT, Bowes, G, Zamel, N, et al (1984) Impaired detection of added inspiratory resistance in patients with obstructive sleep apnea. Am Rev Respir Dis 129,45-48[ISI][Medline]
  4. Greenberg, HE, Scharf, SM (1993) Depressed ventilatory load compensation in sleep apnea: reversal by nasal CPAP. Am Rev Respir Dis 148,1610-1615[ISI][Medline]
  5. Rajagopal, KR, Abbrecht, PH, Tellis, CJ (1984) Control of breathing in obstructive sleep apnea. Chest 85,174-180[Abstract/Free Full Text]
  6. Pillar, G, Schnall, RP, Peled, N, et al (1997) Impaired respiratory response to resistive loading during sleep in healthy offspring of patients with obstructive sleep apnea. Am J Respir Crit Care Med 155,1602-1608[Abstract]
  7. Cherniack, NS (1996) Respiratory sensation as a respiratory controller. Adams, L Guz, A eds. Respiratory sensation ,213-230 Marcel Dekker New York, NY.
  8. Johns, MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14,540-545[ISI][Medline]
  9. Rechtschaffen, A, Kales, A (1968) A manual of standardized terminology: techniques and scoring system for sleep stages of human subjects. UCLA Brain Information Service/Brain Research Institute Los Angeles, CA.
  10. Borg, GA (1982) Psychological bases of perceived exertion. Med Sci Sports Exerc 14,377-381[ISI][Medline]
  11. Hida, W, Suzuki, R, Kikuchi, Y, et al (1987) Effect of local vibration on ventilatory response to hypercapnia in normal subjects. Bull Eur Physiopathol Respir 23,227-232[ISI][Medline]
  12. De Vito, EL, Roncoroni, AJ, Berizzo, EEA, et al (1998) Effects of spontaneous and hypercapnic hyperventilation on inspiratory effort sensation in normal subjects. Am J Respir Crit Care Med 158,107-110[Abstract/Free Full Text]
  13. Kikuchi, Y, Okabe, S, Tamura, G, et al (1994) Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 330,1329-1334[Abstract/Free Full Text]
  14. Bellofiore, S, Di Maria, GU, Privitera, S, et al (1990) Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction. Am Rev Respir Dis 142,812-816[ISI][Medline]
  15. Martin, SE, Wraith, PK, Deary, IJ, et al (1997) The effect of nonvisible sleep fragmentation on daytime function. Am J Respir Crit Care Med 155,1596-1601[Abstract]
  16. Taguchi, O, Hida, W, Okabe, S, et al (1997) Improvement of exercise performance with short-term nasal continuous positive airway pressure in patients with obstructive sleep apnea. Tohoku J Exp Med 183,45-53[CrossRef][ISI][Medline]
  17. Petrof BJ, Hendricks JC, Pack AI. Does upper airway muscle injury trigger a vicious cycle in obstructive sleep apnea?: a hypothesis. Sleep 1996; 19:465–471
  18. Ryan, CF, Lowe, AA, Li, D, et al (1991) Magnetic resonance imaging of the upper airway in obstructive sleep apnea before and after chronic nasal continuous positive airway pressure therapy. Am Rev Respir Dis 144,939-944[ISI][Medline]
  19. Phillipson, EA, Sullivan, CE (1978) Arousal: the forgotten response to respiratory stimuli. Am Rev Respir Dis 118,807-809[ISI][Medline]
  20. Kimoff, RJ, Cheong, TH, Olha, AE, et al (1994) Mechanisms of apnea termination in obstructive sleep apnea: role of chemoreceptor and mechanoreceptor stimuli. Am J Respir Crit Care Med 149,707-714[Abstract]
  21. Basner, RC, Ringler, J, Garpestad, E, et al (1992) Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep. J Appl Physiol 73,642-648[Abstract/Free Full Text]
  22. Cala, SJ, Sliwinski, P, Cosio, MG, et al (1996) Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea. J Appl Physiol 81,2618-2626[Abstract/Free Full Text]
  23. Gislason, T, Almqvist, M, Boman, G, et al (1989) Increased CSF opioid activity in sleep apnea syndrome: regression after successful treatment. Chest 96,250-254[Abstract/Free Full Text]
  24. Oliven, A, Kelsen, SG, Deal, EC, et al (1983) Mechanisms underlying CO2 retention during flow-resistive loading in patients with chronic obstructive pulmonary disease. J Clin Invest 71,1442-1449
  25. Chonan, T, Mulholland, MB, Leitner, J, et al (1990) Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation. J Appl Physiol 68,2100-2106[Abstract/Free Full Text]
  26. Wilson, RC, Jones, PW (1989) A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise. Clin Sci 76,277-282[Medline]
  27. Gilbert, R, Sipple, JH, Auchincloss, JH, Jr (1961) Respiratory control and work of breathing in obese subjects. J Appl Physiol 16,21-26[Abstract/Free Full Text]
  28. Tack, M, Altose, MD, Cherniack, NS (1982) Effect of aging on the perception of resistive ventilatory loads. Am Rev Respir Dis 126,463-467[ISI][Medline]




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