Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea.

BACKGROUND: Obstructive sleep apnoea/hypopnoea (OSAH) appears to be associated with an increased risk of motor vehicle crashes (MVCs). However, its impact on crash patterns, particularly the severity of crashes, has not been well described. A study was undertaken to determine whether OSAH severity influenced crash severity in patients referred for investigation of suspected sleep-disordered breathing. METHODS: Objective crash data (including the nature of crashes) for 783 patients with suspected OSAH for the 3 years prior to polysomnography were obtained from provincial insurance records and compared with data for 783 age- and sex-matched controls. The patient group was 71% male with a mean age of 50 years, a mean apnoea-hypopnoea index (AHI) of 22 events/h and a mean Epworth Sleepiness Scale score of 10. RESULTS: There were 375 crashes in the 3-year period, 252 in patients and 123 in controls. Compared with controls, patients with mild, moderate and severe OSAH had an increased rate of MVCs with relative risks of 2.6 (95% CI 1.7 to 3.9), 1.9 (95% CI 1.2 to 2.8) and 2.0 (95% CI 1.4 to 3.0), respectively. Patients with suspected OSAH and normal polysomnography (AHI 0-5) did not have an increased rate of MVC (relative risk 1.5 (95% CI 0.9 to 2.5), p = 0.21). When the impact of OSAH on MVC associated with personal injury was examined, patients with mild, moderate and severe OSAH had a substantially higher rate of MVCs than controls with relative risks of 4.8 (95% CI 1.8 to 12.4), 3.0 (95% CI 1.3 to 7.0) and 4.3 (95% CI 1.8 to 8.9), respectively, whereas patients without OSAH had similar crash rates to controls with a relative risk of 0.6 (95% CI 0.2 to 2.5). Very severe MVCs (head-on collisions or those involving pedestrians or cyclists) were rare, but 80% of these occurred in patients with OSAH (p = 0.06). CONCLUSION: Patients with OSAH have increased rates of MVCs, and disproportionately increased rates of MVCs are associated with personal injury.

The impact of obstructive sleep apnea and daytime sleepiness on work limitation.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) participate in the work force. However, the impact of OSA and sleepiness on work performance is unclear. METHODS: To address this issue, we administered the Epworth Sleepiness Scale (ESS), the Work Limitations Questionnaire (WLQ), and an occupational survey to patients undergoing full-night polysomnography for the investigation of sleep-disordered breathing. Of 498 patients enrolled in the study, 428 (86.0%) completed the questionnaires. Their mean age+/-standard deviation (SD) was 49+/-12 years, mean body mass index (BMI) was 31+/-7 kg/m(2) mean apnea hypopnea index (AHI) was 21+/-22 events/h, and mean ESS score was 10+/-5. Subjects worked a mean of 39+/-18 h per week. The first 100 patients to complete the survey were followed up at two years. RESULTS: In the group as a whole, there was no significant relationship between severity of OSA and the four dimensions of work limitation. However, in blue-collar workers, significant differences were detected between patients with mild OSA (AHI 5-15/h) and those with severe OSA (AHI>30/h) with respect to time management (limited 23.1% of the time vs. 43.8%, p=0.05) and mental/personnel interactions (17.9% vs. 33.0%, p=0.05). In contrast, there were strong associations between subjective sleepiness (as assessed by the ESS) and three of the four scales of work limitation. That is, patients with an ESS of 5 had much less work limitation compared to those with an ESS 18 in terms of time management (19.7% vs. 38.6 %, p<0.001), mental-interpersonal relationships (15.5% vs. 36.0%, p<0.001) and work output (16.8% vs. 36.0%; p<0.001). Of the group followed up, 49 returned surveys and 33 who were using continuous positive airway pressure (CPAP) showed significant improvements between the initial and second follow-up in time management (26% vs. 9%, p=0.0005), mental-interpersonal relationships (16% vs. 11.0%, p=0.014) and work output (18% vs. 10%; p<0.009). CONCLUSION: We have demonstrated a clear relationship between excessive sleepiness and decreased work productivity in a population referred for suspected sleep-disordered breathing. Screening for sleepiness and sleep-disordered breathing in the workplace has the potential to identify a reversible cause of low work productivity.

Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials.

Patients with untreated obstructive sleep apnea hypopnea (OSAH) are predisposed to developing hypertension, and therapy with continuous positive airway pressure (CPAP) may reduce blood pressure (BP). The purpose of this study was to assess the impact of CPAP therapy on BP in patients with OSAH. We performed a comprehensive literature search up to July 2006 [Medline, PubMed, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane controlled trials register (CCTR), and Database of Abstract and Reviews of Effect (DARE)] to identify clinical studies and systemic reviews that examined the impact of CPAP on BP. Studies were included if they (1) were randomized controlled trials with an appropriate control group, (2) included systolic and diastolic BP measurements before and after CPAP/control in patients with OSAH, and (3) contained adequate data to perform a meta-analysis. To calculate pooled results, studies were weighted by inverse variances, with either a fixed or a random effects model used depending on the presence of heterogeneity (assessed with Q test). Ten studies met our inclusion criteria (587 patients): three studies were crossover (149 patients) and seven were parallel in design. Seven studies (421 patients) used 24-h ambulatory BP and three used one-time measurements. Two studies were of patients with heart failure (41 patients). Overall, the effects of CPAP were modest and not statistically significant; CPAP (compared to control) reduced systolic BP (SBP) by 1.38 mmHg (95% CI: 3.6 to -0.88, p = 0.23) and diastolic BP (DBP) by 1.52 mmHg (CI: 3.1 to -0.07; p = 0.06). Six of the trials studied more severe OSAH (mean AHI > 30/h, 313 patients); in these six trials, CPAP reduced SBP by 3.03 mmHg (CI 6.7 to -0.61; p = 0.10) and DBP by 2.03 mmHg (CI: 4.1 to -0.002; p = 0.05). There was a trend for SBP reduction to be associated with CPAP compliance. In unselected patients with sleep apnea, CPAP has very modest effects on BP. However, we cannot exclude the possibility that certain subgroups of patients may have more robust responses-this may include patients with more severe OSAH or difficult-to-control hypertension. Future randomized controlled trials in this area should potentially concentrate on these subgroups of patients.

Efficacy and patient satisfaction with autoadjusting CPAP with variable expiratory pressure vs standard CPAP: a two-night randomized crossover trial.

Expiratory pressure relief (C-Flex) technology monitors the patient's airflow during expiration and reduces the pressure in response to the patient. Increased comfort levels associated with C-Flex therapy have potential to improve patient adherence to therapy. The purpose of this study was to assess the combination of autoadjusting CPAP (APAP) and C-Flex in terms of (1) treatment efficacy, and (2) patient preference when compared to standard CPAP. Fifteen patients who had previously undergone formal CPAP titration polysomnography were treated with either one night of the APAP with C-Flex or one night of conventional CPAP, in a crossover trial. Patient satisfaction levels were recorded using visual analog scales (VAS) on the morning after the study. Mean patient age was 50 +/- 12 years, body mass index (BMI) was 36 +/- 6 kg/m(2), baseline AHI was 53 +/- 31 events/h, and CPAP Pressure was 11 +/- 2 cm/H(2)O. APAP with C-Flex was as effective as CPAP, with no differences detected in sleep latency (17 +/- 5 vs 12.3 +/- 3 min, p = 0.4), or respiratory indices (AHI of 4.2 +/- 2 vs 2.4 +/- 0.7 events/h, p = 0.1). VAS scores (scale 0-10) indicated a trend towards increased patient satisfaction while using APAP with C-Flex (7.9 vs 7.2, p = 0.07). 10 patients expressed a preference for APAP with C-Flex (VAS, 0 to 10) over standard CPAP (total positive score of 68, mean score of 4.8 +/- 4.3). One patient expressed no preference. Four patients expressed a preference for CPAP (total positive score of 13, mean score of 0.9 +/- 1.9) (APAP with C-Flex vs standard CPAP, p < 0.01 paired t test). APAP with C-Flex eliminates sleep disordered breathing as effectively as standard CPAP. Patients indicated a preference for APAP with C-Flex suggesting a possible advantage in terms of patient adherence for this mode of treatment.

Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor.

A number of serine proteases, matrix metalloproteases, and cysteine proteases were evaluated for their ability to cleave and inactivate the antiprotease, secretory leucoprotease inhibitor (SLPI). None of the serine proteases or the matrix metalloproteases examined cleaved the SLPI protein. However, incubation with cathepsins B, L, and S resulted in the cleavage and inactivation of SLPI. All three cathepsins initially cleaved SLPI between residues Thr(67) and Tyr(68). The proteolytic cleavage of SLPI by all three cathepsins resulted in the loss of the active site of SLPI and the inactivation of SLPI anti-neutrophil elastase capacity. Cleavage and inactivation were catalytic with respect to the cathepsins, so that the majority of a 400-fold excess of SLPI was inactivated within 15 min by cathepsins L and S. Analysis of epithelial lining fluid samples from individuals with emphysema indicated the presence of cleaved SLPI in these samples whereas only intact SLPI was observed in control epithelial lining fluid samples. Active cathepsin L was shown to be present in emphysema epithelial lining fluid and inhibition of this protease prevented the cleavage of recombinant SLPI added to emphysema epithelial lining fluid. Taken together with previous data that demonstrates that cathepsin L inactivates alpha(1)-antitrypsin, these findings indicate the involvement of cathepsins in the diminution of the lung antiprotease screen possibly leading to lung destruction in emphysema.