|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
ARTICLE |
|---|
TOP
ARTICLE
REFERENCES
|
|---|
We have been asked to argue the case for nasal continuous positive airway pressure therapy (nCPAP) in the treatment of obstructive sleep apnea syndrome (OSAS), which is the combination of sleep-related upper airway collapse and secondary excessive daytime sleepiness. In clinical practice, "proven" means that the strands of evidence unite to put it beyond reasonable doubt that a treatment improves the main end points for which it is prescribed, in the patients for whom it is prescribed, and that this therapeutic response is larger than any placebo effect. Is this the case for nCPAP?
Obstructive apneas require arousal for their termination and therefore inevitably fragment sleep. When these cycles of apnea and sleep fragmentation are frequent enough, excessive daytime sleepiness develops and "OSAS" is established. This physiological cycle has been proven in many studies and is beyond dispute. The first test of nCPAP efficacy is therefore to determine whether raising airway pressure corrects this abnormal cycle and whether it recurs when airway pressure is again reduced. This has been proven in countless studies, only a few of which we have space to reference (1). This correction and relapse of airway closure by raising and lowering airway pressure is so utterly reproducible that it is routinely used as a clinical research tool to study the consequences of OSAS (2, 3).
The next test nCPAP must pass concerns whether abolition
of the above-described cycle improves the associated excessive daytime sleepiness and improves quality of life (the main
indications for which nCPAP is given in OSAS). Removal of
the sleep fragmentation associated with sleeping upper airway
collapse results in the normal rebound in slow wave sleep intensity that follows sleep deprivation (4)
confirming such
deprivation to have been present before treatment. After nCPAP therapy, patients with OSAS report less sleepiness (5, 6),
and objective recordings of the speed at which patients fall
asleep (7, 8) and their ability to resist sleep in a dull environment (9, 10) return toward normal. Self-reported health status
("quality of life") improves enormously (11). Ability to perform tasks such as steering a car, which is abnormal before
treatment (12), improves after therapy (13). These improvements are reproducible across research groups, continents,
and different health care systems (6, 14).
The next test concerns whether these effects are attributable to the nCPAP intervention itself or might be a placebo effect that could be reproduced by another medical intervention not affecting the OSAS itself. This question has been addressed by carefully performed cross-over trials comparing outcome of treatment with nCPAP or an oral placebo. These studies have confirmed that the use of nCPAP is clearly more efficacious in patients with OSA than an inactive oral medication (7, 8).
The final level of proof required is that these treatment effects are truly attributable to the process of reopening the collapsed airway with raised airway pressure, and not just to the use of a physical mask treatment (which might have a more potent placebo effect than a simple tablet). In 1997 Wright and colleagues (15) presented this plausible argument (together with other issues relevant only to cardiovascular disease and so irrelevant to the core debate about nCPAP efficacy [16]), to argue that all previous strands of evidence were inadequate in establishing nCPAP efficacy. In response to this, we and others have performed prospective randomized clinical trials of placebo nCPAP set to a subtherapeutic level, versus real nCPAP set to a therapeutic level (14, 17) in patients with moderate to severe OSAS. These studies have shown that the improvements in objective and subjective sleepiness (14), self-reported health status (14), and simulated steering (18) are significantly greater with therapeutic than subtherapeutic placebo treatment, often by a large margin. Sheldon and colleagues have kindly acknowledged the contribution of this work in establishing this argument (19). The treatment effects seen in our studies are among the largest ever reported with these research tools.
We believe that, taken together, this body of evidence establishes that nCPAP improves sleepiness and quality of life in symptomatic patients with moderate or severe sleep apnea, beyond any reasonable doubt. Indeed, it is difficult to think what further evidence could be sought to further establish this point. This does not mean, of course, that the benefits of nCPAP treatment are established for all levels of OSA severity. Sleep-induced upper airway collapse is a continuum that blurs into normality at its lower end (20), and further studies are warranted to assess how far the proven efficacy of nCPAP for patients with moderate/severe OSA extends into "milder" abnormality. Further work is also needed on secondary outcomes of treatment, such as cardiovascular risk, where our unit is generally known for its cynicism about the strength of the current evidence. Despite these caveats, we believe it is proven unassailably that nCPAP works for the reasons it is mainly given, and for the patients to whom it is mainly prescribed.
| |
References |
|---|
|
TOP
ARTICLE
REFERENCES
|
|---|
1. Sullivan, C. E., F. G. Issa, M. Berthon-Jones, and L. Eves. 1981. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 8225: 862-865 .
2.
Ringler, J.,
R. C. Basner,
R. Shannon,
R. Schwartzstein,
H. Manning,
S. E. Weinberger, and
J. W. Weiss.
1990.
Hypoxemia alone does not
explain blood pressure elevations after obstructive apneas.
J. Appl.
Physiol.
69:
2143-2148
3. Pitson, D. J., A. Sandell, R. van den Hout, and J. R. Stradling. 1995. Use of pulse transit time as a measure of inspiratory effort in patients with obstructive sleep apnoea. Eur. Respir. J. 8: 1669-1674 [Abstract].
4. Issa, F. G., and C. E. Sullivan. 1986. The immediate effects of nasal continuous positive airway pressure treatment on sleep pattern in patients with obstructive sleep apnea syndrome. Electroencephalogr. Clin. Neurophysiol. 63: 10-17 [Medline].
5. Hardinge, F. M., D. J. Pitson, and J. R. Stradling. 1995. Use of the Epworth Sleepiness Scale to demonstrate response to treatment with nasal continuous positive airway pressure in patients with obstructive sleep apnoea. Respir. Med. 89: 617-620 [Medline].
6.
Ballester, E.,
J. R. Badia,
L. Hernandez,
E. Carrasco,
J. de Pablo,
C. Fornas,
R. Rodriguez,
Roisin, and
J. M. Montserrat.
1999.
Evidence of the
effectiveness of continuous positive airway pressure in the treatment
of sleep apnea/hypopnea syndrome.
Am. J. Respir. Crit. Care Med.
159:
495-501
7. Engleman, H. M., S. E. Martin, I. J. Deary, and N. J. Douglas. 1994. Effect of continuous positive airway pressure treatment on daytime function in sleep anpoea/hypopnoea syndrome. Lancet 343: 572-575 [Medline].
8.
Engleman, H. M.,
S. E. Martin,
R. N. Kingshott,
T. W. Mackay,
I. J. Deary, and
N. J. Douglas.
1998.
Randomised placebo controlled trial
of daytime function after continuous positive airway pressure (CPAP)
therapy for the sleep apnoea/hypopnoea syndrome.
Thorax
53:
341-345
9.
Poceta, J. S.,
R. M. Timms,
D. U. Jeong,
S. L. Ho,
M. K. Erman, and
M. M. Mitler.
1992.
Maintenance of wakefulness test in obstructive
sleep apnea syndrome.
Chest
101:
893-897
10.
Bennett, L. S.,
B. A. Langford,
J. R. Stradling, and
R. J. O. Davies.
1998.
Sleep fragmentation indices as predictors of daytime sleepiness and
nCPAP response in OSA.
Am. J. Respir. Crit. Care Med.
158:
778-786
11. Jenkinson, C., J. Stradling, and S. Petersen. 1997. Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea. J. Sleep Res. 6: 199-204 . [Medline]
12. Juniper, M., M. A. Hack, C. F. George, R. J. O. Davies, and J. R. Stradling. 1999. Steering simulation performance in patients with obstructive sleep apnoea (OSA) and matched control subjects. Eur. Respir. J. 15 (In press)
13. George, C. F. P., A. C. Boudreau, and A. Smiley. 1997. Effects of nasal CPAP on simulated driving performance in patients with obstructive sleep apnoea. Thorax 52: 648-653 [Abstract].
14. Jenkinson, C., R. J. Davies, R. Mullins, and J. R. Stradling. 1999. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 353: 2100-2105 [Medline].
15.
Wright, J.,
R. Johns,
I. Watt,
A. Melville, and
T. Sheldon.
1997.
Health
effects of obstructive sleep apnoea and the effectiveness of continuous
positive airways pressure: a systematic review of the research evidence.
Br. Med. J.
314:
851-860
16.
Davies, R. J..
1998.
Cardiovascular aspects of obstructive sleep apnoea
and their relevance to the assessment of the efficacy of nasal continuous positive airway pressure therapy.
Thorax
53:
416-418
17. Montserrat, J. M., L. Hernandez, R. Farre, E. Ballester, and D. Navajas. 1999. Compliance of sham-CPAP compared with optimal CPAP in sleep apnea syndrome (abstract). Eur. Respir. J. 14(Suppl. 30):409.
18.
Hack, M. A.,
R. J. O. Davies,
R. Mullins,
S. J. Choi,
S. Ramdassingh-Dow,
C. Jenkinson, and
J. R. Stradling.
2000.
Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea.
Thorax
55:
224-231
19. Wright, J., T. A. Sheldon, and I. Watt. 1999. Sleep apnoea [Letter]. Lancet 354: 600 [Medline].
20. Davies, R. J. O., and J. R. Stradling. 1996. The epidemiology of sleep apnoea. Thorax 51(Suppl. 2):S65-S70.
This article has been cited by other articles:
 |
|
 |
|
  S. R. Patel, D. P. White, A. Malhotra, M. L. Stanchina, and N. T. Ayas Continuous Positive Airway Pressure Therapy for Treating gess in a Diverse Population With Obstructive Sleep Apnea: Results of a Meta-analysis Arch Intern Med, March 10, 2003; 163(5): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ohga, T. Tomita, H. Wada, H. Yamamoto, T. Nagase, and Y. Ouchi Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1 J Appl Physiol, January 1, 2003; 94(1): 179 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Thys, J. Roeseler, M. Reynaert, G. Liistro, and D.O. Rodenstein Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial Eur. Respir. J., September 1, 2002; 20(3): 545 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Douglas, H. M. Engleman, J. F. Faccenda, and N. McArdle THE SCIENCE OF DESIGNING ETHICAL CPAP TRIALS Am. J. Respir. Crit. Care Med., January 1, 2002; 165(1): 132a - 134. [Full Text] [PDF]
|
|
|
|
|
|
M. J. TOBIN Sleep-disordered Breathing, Control of Breathing, Respiratory Muscles, Pulmonary Function Testing, Nitric Oxide, and Bronchoscopy in AJRCCM 2000 Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1362 - 1375. [Full Text] [PDF]
|
|
|
|
|
|
O. Parra Sleep-disordered breathing and stroke: is there a rationale for treatment? Eur. Respir. J., October 1, 2001; 18(4): 619 - 622. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Barbe, L. R. Mayoralas, J. Duran, J. F. Masa, A. Maimo, J. M. Montserrat, C. Monasterio, M. Bosch, A. Ladaria, M. Rubio, et al. Treatment with Continuous Positive Airway Pressure Is Not Effective in Patients with Sleep Apnea but No Daytime Sleepiness: A Randomized, Controlled Trial Ann Intern Med, June 5, 2001; 134(11): 1015 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ferguson Oral Appliance Therapy for Obstructive Sleep Apnea . Finally Evidence You Can Sink Your Teeth Into Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1294 - 1295. [Full Text]
|
|
|
|
|
|
J. H. T. Karlawish and A. I. Pack Addressing the Ethical Problems of Randomized and Placebo-Controlled Trials of CPAP Am. J. Respir. Crit. Care Med., March 15, 2001; 163(4): 809 - 810. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Proc. Am. Thorac. Soc. | Am. J. Respir. Cell Mol. Biol. |