Continuous Positive Airway Pressure Reduces Risk of Motor Vehicle Crash among Drivers with Obstructive Sleep Apnea: Systematic Review and Meta-analysis

Abstract

Context:

Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle crash.

Objective:

We performed a systematic review of the literature concerning the impact of continuous positive airway pressure (CPAP) treatment on motor vehicle crash risk among drivers with OSA. The primary objective was to determine whether CPAP use could reduce the risk of motor vehicle crash among drivers with OSA. A secondary objective involved determining the time on treatment required for CPAP to improve driver safety.

Data Sources:

We searched seven electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) and the reference lists of all obtained articles.

Study Selection:

We included studies (before-after, case-control, or cohort) that addressed the stated objectives. We evaluated the quality of each study and the interplay between the quality, quantity, robustness, and consistency of the evidence. We also tested for publication bias.

Data Extraction:

Data were extracted by two independent analysts. When appropriate, data were combined in a fixed or random effects meta-analysis.

Results:

A meta-analysis of 9 observational studies examining crash risk of drivers with OSA pre- vs. post-CPAP found a significant risk reduction following treatment (risk ratio = 0.278, 95% CI: 0.22 to 0.35; P < 0.001). Although crash data are not available to assess the time course of change, daytime sleepiness improves significantly following a single night of treatment, and simulated driving performance improves significantly within 2 to 7 days of CPAP treatment.

Conclusions:

Observational studies indicate that CPAP reduces motor vehicle crash risk among drivers with OSA.

Citation:

Tregear S; Reston J; Schoelles K; Phillips B. Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea. SLEEP 2010;33(10):1373-1380.

OF ALL OCCUPATIONS IN THE UNITED STATES, WORKERS IN THE TRUCKING INDUSTRY EXPERIENCE THE THIRD HIGHEST FATALITY RATE, ACCOUNTING FOR 12% of all worker deaths. In 2006, there were 368,000 police-reported large truck crashes, resulting in 4,321 fatalities and 77,000 injuries.¹ The Federal Motor Carrier Safety Administration (FMCSA) was established as a separate administration within the U.S. Department of Transportation (DOT) pursuant to the Motor Carrier Safety Improvement Act of 1999. The primary mission of the FMCSA is to reduce crashes, injuries, and fatalities involving large trucks and buses. Among the strategies employed by the FMCSA to accomplish this goal are the development and maintenance of medical fitness standards for drivers of commercial vehicles; these standards are applied by medical examiners to commercial drivers, who are required by Federal statute to undergo medical qualification examinations at least every two years.

Obstructive sleep apnea (OSA) is a prevalent and potentially dangerous condition among commercial motor vehicle (CMV) drivers. While OSA is conservatively estimated to affect approximately 5% of the general population,² the condition appears to be much more prevalent in commercial drivers. Howard et al. estimated that 50% of more than 3000 commercial drivers were at risk for sleep apnea.³ Pack et al. found that 28.2% of 406 commercial drivers had at least mild sleep apnea, and 4.7% had severe sleep apnea by conventional criteria.⁴ The majority of research indicates that OSA is a significant cause of motor vehicle crashes.^3,5–9 Thus, assessment of the risk of OSA and development of effective methods to identify and treat commercial drivers with OSA is an important part of the FMCSA's mission. Since the most recent standards for medical examiners regarding OSA are from a Federal Highway Administration (FHWA) sponsored conference in 1991,¹⁰ these standards required an evidence-based update.

The current study was originally designed to provide evidence for updating the standards by conducting a systematic review of the relevant literature concerning OSA and CMV drivers. The literature consists predominantly of cohort and case-control studies. Given that few studies specifically enroll CMV drivers, studies that included non-CMV drivers were also evaluated.

Continuous positive airway pressure (CPAP) is a treatment generally recommended for patients with OSA who have not responded to more conservative therapies (e.g., behavior modification, oral appliances). It is the most commonly prescribed treatment for OSA and has been shown to lower the number of apnea-hypopnea (blocked or reduced airflow) events per hour of sleep in patients with OSA. Since these events lead to interrupted sleep cycles and consequent daytime sleepiness, a reduction in such events may increase driver alertness.

Prior systematic reviews by our group and others have found convincing evidence that individuals with OSA are at an increased risk for a motor vehicle crash when compared to individuals without OSA.^11,12 The primary objective of the current study was to determine whether treatment with CPAP could reduce the risk of crash among drivers with OSA. If so, then a secondary objective was to determine the minimum length of time required for CPAP to improve driver safety.

METHODS

Identification of Evidence Bases

Separate evidence bases for each of the objectives of this evidence report were identified using a process consisting of a comprehensive search of the literature; examination of abstracts of identified studies to determine which articles would be retrieved; and the selection of the actual articles that would be included in each evidence base.

A total of 7 electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) were searched (through May 27, 2009). All database searches were conducted by masters-level medical information specialists. To supplement the electronic searches, we also examined the bibliographies/reference lists of included studies, recent narrative reviews, and scanned the content of new issues of selected journals and selected relevant gray literature sources. A complete list of the electronic databases searched and the search strategy used to identify relevant studies are available upon request.

In order to be included in the evidence base, an article must have been full-length, published in the English language, representing a unique (not multiply published) data set, limited to the study of individuals with OSA, or including a separate analysis of those with OSA. In addition, studies must have included ≥ 10 subjects aged ≥ 18 years. With regard to the primary objective of this review, included articles must have used actual crash data to measure the risk for crash among individuals receiving CPAP, and the data must have been presented in a manner that allowed calculation of effect-size estimates and confidence intervals. With regard to the secondary objective, the study must have attempted to determine the duration following initiation of CPAP treatment for individuals with OSA to reach a degree of improvement that would permit safe driving (as determined through indirect measures of crash risk; i.e., driving simulators or cognitive/psychomotor functioning). In addition, the study must have reported results within 2 weeks following initiation of CPAP.

Analytic Methods

Data were extracted by 2 independent analysts. Individual study quality was assessed using 2 quality scales developed by ECRI Institute, one specific for controlled trials and another specific for single-arm pre-post studies. These quality instruments are available upon request.

Random- and fixed-effects meta-analyses were used to pool data from different studies.^13–17 Differences in the findings of studies (heterogeneity) were identified using the Q-statistic and I².^18–20 Sensitivity analyses aimed at testing the robustness of findings included the use of cumulative fixed- and random-effects meta-analysis.^21–23 The presence of publication bias was tested for using the “trim and fill” method.^24–26

RESULTS

CPAP and Crash Risk

Nine articles describing 9 unique studies met the inclusion criteria for the primary objective.^27–35 Study characteristics are presented in Table 1. To date, no prospective trial, either randomized or nonrandomized, has attempted to examine the treatment impact on crash rates among individuals with OSA. Given the long follow-up times that are required to obtain an adequate quantity of crash-rate data for meaningful analysis (as crash is a rare event), it seems unlikely that such a study will be performed in the future for ethical reasons. It is difficult to justify withholding treatment to an individual with moderate-to-severe OSA for a period of ≥ 2 years.

Table 1.

Characteristics of studies that evaluated CPAP and crash risk

	Year	No. of Individuals in study (n = )	Study design	Age Distribution	AHI (SD)	Mean BMI (SD)	Mean ESS (SD)	% Male	Factors controlled for (if compared to controls)	Driving Exposure	Definition of Crash	Crash data objective?
Barbe et al.27	2006	80	Before-After + case-control*	49 years (SEM: 1)	>20 per hour	33 kg/m2(SEM: 0.7)	12 (SEM: 1.0)	97.5	Age, sex, alcohol consumption	25,000 km/year (SEM: 2,000)	Accident resulting in property damage > $500 and/or personal injury	No
George et al.28	2001	210	Before-After + case-control*	51 years (11)	54 per hour (29)	35.5 kg/m2(10)	NR	NR	Age, sex, driver class	22,700 km/year (16,500)	NR	Yes (MTO data)
Findley et al.29	2000	36	Before-After + case-control*	54 years (SEM: 2)	37.9 per hour (SEM: 5.0)	NR	NR	83.3	Age, sex	NR	Accident resulting in property damage > $500 or personal injury for which the driver was convicted of a traffic violation	Yes (State DMV records)
Horstmann et al.30	2000	71	Before-After	NR	NR	NR	NR	NR	NA	17,784 km/year	Accident causing material damage or personal injury	No
Yamamoto et al.32	2000	39	Before-After	49.5 years (10.8)		29.2 kg/m2 (5.4)	12.6 (4.9)	100.0	NA	NR	NR	No
Scharf et al.31	1999	316	Before-After	48.8 years (SEM: 0.7)	42.9 per hour (SEM: 1.7)	NR	NR	74.1	NA	NR	NR	No
Krieger et al.33	1997	893	Before-After	56.6 years (10.7)	34.9 per hour (21.1)	33.7 kg/m2(6.8)	NR	86.5	NA	NR	NR	No
Cassel et al.34	1996	78	Before-After	48.0 years (SEM:1.0)	34.2 per hour (SEM: 3.1)	31 kg/m2(SEM: 0.6)	NR	100.0	NA	29,606 km/year (SEM: 2,367)	NR	No
Engelman et al.35	1996	253	Before-After	46 years (9)	47 (38)	NR	15.6 (6.0)	NR	NA	NR	Minor (not injurious) and major (causing injury)	No

AHI, Apnea-hypopnea index; BMI body mass index; CPAP, continuous positive airway pressure; DMV, department of motor vehicles; ESS, Epworth Sleepiness Scale; MTO, Ministry of Transportation of Ontario; NA, not applicable; NR, not reported; SD, standard deviation; SEM, standard error of the mean. Study included a control group; however, for the purposes of this analysis the study is a before-after study (see text).

All 9 included studies used a retrospective before-after study design in which individuals with moderate-to-severe OSA (as determined by PSG in a sleep lab), all of whom were candidates for treatment with CPAP, were queried about their motor vehicle crash history during some time period (from 1 to 5 years) preceding enrollment in the study. Following a corresponding period of time on treatment, patients were again asked about their crash history. The difference between the pretreatment crash rate and the post-treatment crash rate was calculated, and this outcome was assumed to be the consequence of treatment.

While for the purposes of addressing this objective all nine included studies must be considered as before-after studies, 3 studies did use a separate control group.^27–29 In all 3 cases, this control group comprised individuals who did not have OSA. Data from these individuals were used to determine whether the post-treatment crash risk was reduced to a rate that was similar to that expected among comparable individuals without OSA. In all 3 cases, individuals in the control group were matched to those in the OSA group by age and sex. Only one of the studies attempted to match cases and controls for driving exposure.²⁸

Different studies collected different types of crash data. Some studies included any motor vehicle crashes in their estimates; others considered only crashes which resulted in property damage. Still others defined a crash as being any collision in which the individual of interest was deemed responsible. Between-studies differences in the type of crash data considered may manifest themselves as between-studies heterogeneity. This may impede our ability to provide an accurate estimate of the true effects of treatment on crash risk.

Overall, our analysis found the quality of the studies in the evidence base to be low. Before-after studies are susceptible to several sources of bias. A major potential source of bias arises from the fact that the time periods over which on- and off-treatment crash data are collected are not concurrent. Pretreatment crash data were collected retrospectively, and post-treatment crash data were, in general, collected prospectively following entry into the study. A problem with this data collection approach is that individuals who enter a study and are aware of its purpose will not behave in the same manner as they did prior to entering the study; a phenomenon known as the Hawthorne effect. In this case, individuals enrolled in the included studies may become more aware of their driving behavior and begin to drive more carefully, thus reducing the likelihood of a crash.

Another design problem common to many risk assessment studies is the failure to control adequately for exposure. In this instance, the exposure variable of critical importance is the number of miles driven per unit time. Since exposure cannot be controlled for in a before-after study, articles describing such studies should report on exposure to risk prior to treatment and also during the follow-up period following treatment. Such information was not presented by any included study. This limits the confidence that one can have in the strength of the relationship between treatment and any change in crash rate observed prior to and following the onset of that treatment.

The sample size of individuals enrolled in the included studies ranged from 36 to 893, and the observation periods over which pre-and post-treatment crash rates were determined ranged from 6 months to 5 years. Small studies with short observation periods may underestimate crash rates, because there is a high probability that a crash will not be observed. Neither of the two smallest studies in the evidence base observed any crashes among enrollees following treatment initiation,^29,32 which is not a realistic estimate of the crash rate among any group of individuals.

Crash rate data reported by 7 of the included studies was based on self-report.^27,30–35 The degree of confidence that one can have in such data is unclear, primarily because questionnaires depend on the memory and honesty of the individual being questioned. The remaining 2 studies obtained crash data from a State or Provincial government agency.^28,29 Since we have no way of determining the accuracy of the information contained within these databases, the degree of confidence that one may have in data extracted from them is also not clear.

In this evidence base, enrolled individuals tended to be middle aged, obese males with moderate-to-severe sleep apnea. The generalizability of these individuals to CMV drivers is unclear, as none of the studies focused on the impact of CPAP on crash risk among CMV drivers with OSA. Four of the 9 studies reported on the amount of driving to which their enrollees were exposed.^27,28,30,34 All 4 studies reported annual mileage figures that are far lower than those associated with professional drivers. None of these 4 studies reported on the type of driving (highway, local driving only, night driving, etc.) engaged in by enrollees. The remaining 5 included studies did not provide any driving exposure information.

The included studies reported substantial reductions in crash risk from baseline levels following CPAP therapy. The exception to this finding was for the subgroup of individuals in the study of Engleman et al.³⁵ who experienced noninjurious crashes and appeared to gain no benefit from CPAP. Because this subgroup of individuals is an outlier, we have not included it in the remainder of our analyses.

Tests of the remaining data from the nine included studies for homogeneity found that these data were heterogeneous (Q = 62.56, P < 0.001; I² = 87.22). Consequently, we did not pool these data using a fixed-effects meta-analysis. Since there were fewer than 10 studies, we did not attempt to explore this heterogeneity using meta-regression.

Pooling of the data using a random-effects model meta-analysis (Figure 1) found that CPAP significantly reduces the risk for a motor vehicle crash among individuals with severe OSA (Pre-Post Treatment Crash Risk Ratio [RR] = 0.278, 95% CI: 0.22 to 0.35; P < 0.001). This equates to large reduction in observed crash risk (65% to 78%) following the onset of treatment. A series of sensitivity analyses found our findings to be robust. We performed an additional sensitivity analysis to determine whether excluding data from the subgroup of individuals included in Engleman et al.³⁵ who experienced noninjurious crashes had an impact on our findings. We examined the impact of replacing the findings from the injurious treatment group in this study with crash data from the group of individuals who experienced noninjurious crashes. This analysis confirmed the robustness of our original findings.

Figure 1.

Random-effects meta-analysis of pre-post CPAP crash risk ratio data.

Despite the relatively low quality of the studies that provide the data for our analysis, the consistently large magnitude of risk reduction observed across all studies and the robustness of our analyses (as assessed through sensitivity analysis), it is reasonable to conclude that the risk for a crash among individuals with moderate-to-severe OSA is markedly reduced among those treated with CPAP.

Although the findings of the above studies demonstrate that CPAP treatment reduces the risk of experiencing a motor vehicle crash among drivers with severe OSA, it remains unclear whether the observed reductions in crash risk are large enough to reduce crash risk among this population to the extent expected among comparable individuals without the disorder. In order to determine this, we examined data from the three included studies that directly compared post-treatment crash rates from OSA patients with a control group comprised of comparable individuals without the disorder.^27–29

The findings of the 3 studies are inconsistent. One included study found that, despite large reductions in crash risk, individuals treated with CPAP remain at an increased risk for a motor vehicle crash.²⁷ The remaining 2 studies, however, found no evidence that CPAP-treated individuals remain at an increased risk for a motor vehicle crash.^28,29 Formal heterogeneity testing confirmed that the findings of the 3 studies were inconsistent (Q = 16.41, P < 0.001; I² = 87.81). Because the size of the evidence precludes exploration of this heterogeneity, one is precluded from using meta-regression to determine the reason that the findings of Barbe et al.²⁷ differ so markedly from those of George et al.²⁸ and Findley et al.²⁹

Pooling of these data using a random-effects meta-analysis (Figure 2) found that CPAP-treated individuals with OSA did not show a significantly greater crash risk than their counterparts who do not have the disorder (RR = 1.29, 95% CI: 0.55 to 3.06).

Figure 2.

Random-effects meta-analysis of post CPAP crash risk versus no OSA controls.

How Soon after CPAP Initiation Does Driver Safety Improve?

Our secondary objective was to identify the length of time required following initiation of CPAP for individuals with OSA to reach a degree of improvement that would permit safe driving as determined through indirect measures of crash risk (simulated driving outcomes or reported daytime sleepiness). Six articles reported at least one of these outcomes and addressed this objective.^36–41 Key characteristics of these studies are summarized in Table 2. One study was a placebo-controlled randomized controlled trial (RCT),³⁶ three were randomized crossover trials,^39–41 one was a non-randomized controlled study,³⁸ and one was a prospective case series.³⁷

Table 2.

Characteristics of studies that evaluated timing of driving improvement following CPAP

	Year	No. of Individuals in study (n = )	Study design	Age Distribution	AHI (SD)	Mean BMI (SD)	Mean ESS (SD)	% Male	Factors controlled for (if compared to controls)	Relevant outcomes reported
Loredo et al.36	2006	CPAP: 22	Randomized, double-blind, placebo-controlled, parallel trial	CPAP: 48.2 ± 10.9	65.9 ± 28.6	31.8 ± 5.5	11.6 ± 4.9	82	Daily average treatment duration	Sleepiness
		Placebo:19		Placebo: 48.3 ± 11.2	57.5 ± 32.1	31.8 ± 6.8	12.3 ± 6.7	84
		Oxygen:22		Oxygen: 43.4 ± 8.6	64.9 ± 33.7	32.0 ± 6.4	12.8 ± 4.5	73
Orth et al.37	2005	31	Prospective case series	55.3 ± 10.2	NR	NR	NR	100	NA	Simulated driving, sleepiness
Turkington et al.38	2004	CPAP:18	Controlled trial	CPAP: 49.9 ± 10	NR	39 ± 7.7	Median: 15.5	94	Age, gender, RDI, BMI, ESS	Simulated driving, sleepiness
		Control:18		Control: 51.7 ± 12.2		36.6 ± 5.3	Median: 16	94
Wiest et al.39	2002	44	Randomized, cross-over trial	54.1 ± 9.7	53.6 ± 20.4	32.9 ± 5.3	14.9 ± 4.8	80	NA	Sleepiness
Ficker et al.40	2000	18	Randomized, cross-over trial	50.6 ± 10.5	48.0 ± 28.1	NR	13.3 ± 3.0	100	NA	Sleepiness
Saletu et al.41	1999	13	Randomized, cross-over trial	58.1 ± 8.7	29.1 ± 13.0	NR	NR	100	NA	Sleepiness

Two included studies reported data on driving simulator performance following CPAP treatment in individuals with OSA.^37,38 Both studies had findings that indicated significant improvements in driving performance following 2 days of CPAP use. Orth et al.³⁷ (Quality Rating: Low) reported significant reduction of crashes and concentration faults after 2 days of CPAP therapy, with the improvements continuing throughout the therapeutic course. Turkington et al.³⁸ (Quality Rating: High) reported that driving simulator performance was significantly better in the CPAP-treated group than in the controls after 7 days of CPAP therapy.

All 6 included studies (Median Quality Rating: High) provided data assessing the relationship between daytime sleepiness and treatment with CPAP. The results of these 6 studies indicate that with CPAP treatment, individuals with OSA show significant improvement in daytime sleepiness after as little as one night of treatment. In Loredo et al.,³⁶ all groups tested demonstrated improvements in daytime sleepiness with CPAP treatment; however, the CPAP group demonstrated the greatest reduction in daytime sleepiness. Orth et al.,³⁷ Turkington et al.,³⁸ Wiest et al.,³⁹ and Ficker et al.⁴⁰ reported that average ESS scores improved significantly during CPAP therapy, with the mean ESS scores for each study falling below 9 (highest SD 4.8). Saletu et al.⁴¹ reported that sleep latency improved among individuals who underwent CPAP therapy.

DISCUSSION

The primary findings of this study are that treatment with CPAP reduces crash risk among drivers with moderate-to-severe OSA. In addition, CPAP can relieve excessive daytime sleepiness symptoms associated with OSA within one day of treatment. These findings have implications for the clinical management of OSA in drivers, both commercial and private.

As with any medical treatment, the effectiveness of CPAP ultimately depends both on the extent of identification of OSA and the degree of adherence to treatment among diagnosed individuals. CPAP adherence remains one of the most difficult problems in the management of sleep apnea. A classic study reported that about 60% of patients diagnosed with sleep apnea were “compliant” (defined as ≥ 4 h of use for at least 70% of nights,⁴² though more recent data suggest that adherence may have improved in recent years.⁴³ A recent study found that only one out of 20 CMV drivers diagnosed with OSA could document adequate adherence to CPAP treatment.⁴⁴

Although this is based on a small sample, it illustrates that CPAP is difficult to tolerate for some patients, and suggests that CPAP compliance in commercial drivers might be lower than in the general population. However, it is likely that CPAP adherence in general is no worse that adherence to other medical treatments.⁴⁵ Interventions such as education, autotitrating CPAP, and humidification may improve it.^43,46 Of note, the studies on the time course of improvement after initiation of CPAP treatment are based on simulated driving, and may not accurately represent real life.

Although the original goal of this review was to assess the effectiveness of CPAP treatment on OSA in CMV drivers, the majority of data available pertains to private drivers, and thus is more applicable to the general driving population. Because data from studies of CMV drivers with OSA is scarce, relevant data from studies that investigated crash risk associated with OSA among the general driver populations is currently the primary source of evidence about OSA and crash risk. While the generalizability of the findings of these studies to CMV drivers may not be clear, such findings do at the very least allow one the opportunity to draw evidence-based conclusions about the effect of CPAP on motor vehicle crash risk in the overall group of drivers with OSA. And while specific data about the crash rate for commercial drivers with OSA is rare, it is clear that such crashes carry an increased burden of cost and injury than do those for private drivers, because of the increased size and passenger loads of commercial vehicles. Indeed, when rates of fatality are calculated standardized for exposure (distance travelled), the fatality rates for large trucks is substantially higher than for all vehicles.⁴⁷

Based on the available data, it is not possible to determine whether other treatment methods (surgery, oral appliances, drugs, behavior modification) are effective in reducing crash risk for drivers with OSA.⁴⁸ It is also not possible from this analysis to determine whether OSA-associated crash was associated with increased risk of death or injury. However, in a study of patients with OSA compared with age and gender-matched controls, Mulgrew and colleagues reported that patients with OSA had more than a threefold increase in the odds of crashes associated with injury.⁴⁹ Studies looking specifically at severe motor vehicle crashes have suggested that sleepiness at the wheel is associated with a more severe spectrum of crashes; it is possible that such crashes may result from a failure of reaction, resulting in driving off the road or crashing at higher speeds.^50,51

The current FMCSA medical standard applicable to OSA is 49 CFR 391.41 (b)(5) which indicates that the driver; “Has no established medical history or clinical diagnosis of a respiratory dysfunction likely to interfere with his ability to control and drive a motor vehicle safely.” Two previous conference reports have addressed the issue of OSA and commercial drivers.^10,52 The 1991 Respiratory/Pulmonary report for the Federal Highway Administration of the U.S. Department of Transportation recommended screening drivers by asking if they snore and frequently fall asleep during the day.¹⁰ The report recommended that those with suspected or diagnosed but untreated OSA sleep apnea should not return to work for one month, and should not be medically qualified to drive until the diagnosis was eliminated or the condition was successfully treated. The report also stated that prior to returning to safety-sensitive work, the driver should have either a repeat sleep study, showing resolution of the apneas or a normal Multiple Sleep Latency Test (MSLT). Yearly sleep studies or MSLTs were recommended for follow-up. The 1988 Neurologic Disorders report, also prepared for the Federal Highway Administration, recommended that CMV operators with sleep apnea and excessive daytime sleepiness not be permitted to operate in interstate commerce.⁵² The latter report only addressed surgical treatment, and a three-month wait and laboratory studies (MSLT or polysomnogram) were recommended prior to resuming commercial driving. The current analysis provides new evidence which will inform an update of the medical standards relevant to OSA.

DISCLAIMER

This study was funded by U.S. Department of Transportation, Federal Motor Carrier Safety Administration (contract GS-10F-0177N/DTMC75-06-F-00039).

The opinions of the authors expressed herein do not necessarily state or reflect those of the United States Government.

DISCLOSURE STATEMENT

This was not an industry supported study. Dr. Phillips has received honoraria from, The American College of Chest Physicians, Boehringer Ingelheim, the Federal Motor Carrier Safety Administration, GlaxoSmithKline, Resmed, and Philips Respironics. The other authors have indicated no financial conflicts of interest.