Severe upper airway obstruction during sleep

Few disorders may manifest with predominantly sleep-related obstructive breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity and is associated with significant cardiovascular and neurocognitive morbidity. It is estimated that between 8 and 18 million people in the United States have at least mild OSA. Although the exact mechanism of OSA is not well-delineated, multiple factors contribute to the development of upper airway obstruction and include anatomic, mechanical, neurologic, and inflammatory changes in the pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics experience nocturnal symptoms of airflow obstruction secondary to reactive airways disease. Similar cytokine, chemokine, and histologic changes are seen in both disorders. Sleep deprivation, chronic upper airway edema, and inflammation associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic rhinitis may contribute to both OSA and asthma. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP therapy has also been shown to improve both daytime and nighttime peak expiratory flow rates in patients with concomitant OSA and asthma. It is important for allergists to be aware of how OSA may complicate diagnosis and treatment of asthma and allergic rhinitis. A thorough sleep history and high clinical suspicion for OSA is indicated, particularly in asthma patients who are refractory to standard medication treatments.     

The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease and sympathetic activation. However, it is unclear whether this association is independent of obesity and to what extent treatment with nasal continuous positive airway pressure (CPAP) alleviates the vascular inflammation that underpins cardiovascular disease. We therefore evaluated whether short-term withdrawal from CPAP therapy in subjects with moderate-severe OSA would result in increased levels of sympathetic activity and circulating inflammatory cytokines independent of weight. Vascular inflammatory markers (hsCRP, hsIL-6 and hsTNF-alpha) were assessed in 20 subjects after one and seven nights of withdrawal from CPAP together with the hypoxia-responsive angiogenic marker VEGF and urinary catecholamines. Compared with baseline on CPAP, withdrawal from therapy resulted in an immediate return of OSA with an increase in RDI to 26.7 +/- 5.2 and 39.0 +/- 5.9 events per hour after one and seven nights without CPAP, respectively (both P < 0.0001). This was accompanied by a concomitant rise in daytime urinary noradrenaline (P < 0.0001) after seven nights CPAP withdrawal that was positively associated with the severity of hypoxaemia. In contrast, withdrawal from CPAP therapy was not accompanied by any change in measured cytokines or VEGF (all P > 0.1). In conclusion, 1 week of CPAP withdrawal was associated with a return of OSA and a marked increase in sympathetic activity without a concomitant elevation of vascular inflammatory markers.     

Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation

BACKGROUND: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out. OBJECTIVES: We compared changes in AHR to inhaled methacholine and adenosine 5'-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment. METHODS: In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV(1) (PC(20)). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC(20) methacholine, PC(20) AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks. RESULTS: Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 +/- 0.3 doubling doses for methacholine and by 2.6 +/- 0.5 doubling doses for AMP. These changes were significantly different from each other (P =.003). Significant variation in PC(20) methacholine (P <.05) value, PC(20) AMP (P <.001) value, percentage of sputum eosinophils (P <.001), and percentage of sputum epithelial cells (P <.001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC(20) AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 +/- 0.3, 2.2 +/- 0.3, and 2.8 +/- 0.3 doubling doses of PC(20) AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment. CONCLUSIONS: The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.     

Differential gene expression in the T-helper lymphocytes of obstructive sleep apnea patients treated with nasal continuous positive airway pressure (nCPAP)

Obstructive sleep apnea (OSA) is a disease with significant morbidity, increased risk of accidents attributed to daytime somnolence, and has been associated with cardiovascular complications. The treatment of choice for OSA is nasal continuous positive airway pressure (nCPAP). Some OSA patients, however, are unable to benefit from this therapy as they find nCPAP intolerable due to the related nasal inflammation. It is hypothesized that nCPAP may cause nasal inflammation in these patients by inducing changes in the expression of genes that encode interleukins (IL-3, IL-4, IL-6, IL-8, IL-13) or adhesion molecules (i.e., ICAM-1) in T-helper lymphocytes. An understanding of the underlying inflammatory mechanism could lead to specific interventions that render nCPAP therapy tolerable for these individuals.     

Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea

STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study. SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy for at least 6 months. INTERVENTION: Three sleep studies were performed over three consecutive weeks. On night one the pressure level required to prevent apnea, hypopnea, and snoring was determined. On the second and third study nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and subjects slept on the CPAP level determined on the first night. MEASUREMENTS: Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS: The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P < 0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights. The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour), oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29 desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%). CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea.     

Prevalence of persistent sleep apnea in patients treated with continuous positive airway pressure

STUDY OBJECTIVE: There are limited data on the prevalence of persistent obstructive sleep apnea (OSA) in patients who are clinically asymptomatic with continuous positive airway pressure (CPAP). Our objectives were to estimate the prevalence of persistent OSA and to explore the parameters that may be capable of discriminating these patients. DESIGN: Prospective survey. SETTING: A tertiary-care sleep-disorders clinic. PARTICIPANTS: Consecutive patients treated with single-pressure CPAP for at least 3 months were studied. All had undergone CPAP titrations and were compliant with treatment. They denied snoring or persistent excessive daytime somnolence. Of 114 who qualified, 101 were studied. INTERVENTIONS: Subjects underwent 16-channel polysomnography with electroencephalogram and pneumotachometer while using their CPAP. MEASUREMENTS AND RESULTS: Seventeen of 101 subjects (17%) had an apnea-hypopnea index of over 10. Fifty-one had only split-night protocols for CPAP titration. There was no significant difference between participants with persistent OSA and those with an apnea-hypopnea index < 5 with regard to age, sex, time since diagnosis, reported snoring, change in weight, or quality of life (all p > .10). Mean current CPAP level was higher, with a mean +/- SD 10.6 +/- 2.8 versus 8.6 +/- 2.3 cm H2O (p = .002). Unresolved air leak related to CPAP was more frequent in the patients with persistent OSA. Morning headaches, nonrestorative sleep, and frequent central apneas on the CPAP titration were all associated with persistent OSA. CONCLUSIONS: Persistent OSA is frequent in patients treated with CPAP. This is more frequent in patients with high body mass index, higher prescribed pressures, and unresolved mask leak.     

A self-management approach to improving continuous positive airway pressure adherence and outcomes

Obstructive sleep apnea (OSA) is a condition with serious medical and psychosocial consequences. Low patient adherence to nasal continuous positive airway pressure (CPAP) limits the effectiveness of treatment. Intervention studies based on intensive support protocols have shown modest improvement in CPAP adherence; however, this approach would require significant resources and effort for integration into the existing U.S. health care system. The purpose of this article is to describe the self-management approach to chronic illness, justify the self-management approach as applied to sleep apnea patients prescribed CPAP, and to report initial pilot data on feasibility and efficacy of the Sleep Apnea Self-Management Program. CPAP adherence measured at the end of the 4-session program averaged 5.5 ± 2.3 hr per night. The Sleep Apnea Self-Management Program (SASMP) has the potential to be an effective and practical way to improve CPAP adherence and is designed for integration into current OSA clinical processes.     

Impact of continuous positive airway pressure (CPAP) on quality of life in patients with obstructive sleep apnea (OSA)

Obstructive sleep apnea is a chronic illness with increasing prevalence. In addition to associated cardiovascular comorbidities, obstructive sleep apnea syndrome has been linked to poor quality of life, occupational accidents, and motor vehicle crashes secondary to excessive daytime sleepiness. Although continuous positive airway pressure is the gold standard for sleep apnea treatment, its effects on quality of life are not well defined. In the current study we investigated the effects of treatment on quality of life using the data from the Apnea Positive Pressure Long‐term Efficacy Study (APPLES), a randomized controlled trial of continuous positive airway pressure (CPAP) versus sham CPAP. The Calgary Sleep Apnea Quality of Life Index (SAQLI) was used to assess quality of life. Overall we found no significant improvement in quality of life among sleep apnea patients after CPAP treatment. However, after stratifying by OSA severity, it was found that long‐term improvement in quality of life might occur with the use of CPAP in people with severe and possibly moderate sleep apnea, and no demonstrable improvement in quality of life was noted among participants with mild obstructive sleep apnea.     

Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea: systematic review and meta-analysis

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.     

Portable monitoring and autotitration versus polysomnography for the diagnosis and treatment of sleep apnea

STUDY OBJECTIVES: To compare a clinical pathway using portable monitoring (PM) for diagnosis and unattended autotitrating positive airway pressure (APAP) for selecting an effective continuous positive airway pressure (CPAP) with another pathway using polysomnography (PSG) for diagnosis and treatment of obstructive sleep apnea (OSA). DESIGN: Randomized parallel group SETTING: Veterans Administration Medical Center PATIENTS: 106 patients with daytime sleepiness and a high likelihood of having OSA MEASUREMENTS AND RESULTS: The AHI in the PM-APAP group was 29.2 +/- 2.3/h and in the PSG group was 36.8 +/- 4.8/h (P= NS). Patients with an AHI > or = 5 were offered CPAP treatment. Those accepting treatment (PM-APAP 45, PSG 43) were begun on CPAP using identical devices at similar mean pressures (11.2 +/- 0.4 versus 10.9 +/- 0.5 cm H2O). At a clinic visit 6 weeks after starting CPAP, 40 patients in the PM-APAP group (78.4% of those with OSA and 88.8% started on CPAP) and 39 in the PSG arm (81.2% of those with OSA and 90.6% of those started on CPAP) were using CPAP treatment (P = NS). The mean nightly adherence (PM-APAP: 5.20 +/- 0.28 versus PSG: 5.25 +/- 0.38 h/night), decrease in Epworth Sleepiness Scale score (-6.50 +/- 0.71 versus -6.97 +/- 0.73), improvement in the global Functional Outcome of Sleep Questionnaire score (3.10 +/- 0.05 versus 3.31 +/- 0.52), and CPAP satisfaction did not differ between the groups. CONCLUSIONS: A clinical pathway utilizing PM and APAP titration resulted in CPAP adherence and clinical outcomes similar to one using PSG.     

Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study

STUDY OBJECTIVE: We investigated the short-term effectiveness of continuous positive airway pressure (CPAP) and oxygen in improving sleep quality in patients with obstructive sleep apnea (OSA). DESIGN: Randomized, double-blind, placebo-controlled, parallel study. SETTING: General Clinical Research Center at a university hospital. PATIENTS: Seventy-six patients with untreated OSA. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatments (CPAP, placebo-CPAP, or nocturnal oxygen at 3 L per minute) for 2 weeks. Sleep quality was assessed at baseline and after 1 and 14 days of therapy. Repeated-measures analysis of variance was used to evaluate treatment and time effects, and their interaction. MEASUREMENTS AND RESULTS: Sixty-three patients completed the protocol. When compared with placebo-CPAP and nocturnal oxygen, CPAP increased rapid eye movement (REM) sleep and significantly reduced stage 1 sleep and the number of stage shifts (p < or = .003). CPAP improved, to within normal limits, the apnea-hypopnea index, total arousal index, and mean oxyhemoglobin saturation (p < or = .001). The effects of CPAP were apparent during the first night of therapy. Oxygen improved only mean nocturnal saturation (p = .009). CPAP had no significant effect on stage 2 sleep or slow-wave sleep. CONCLUSIONS: CPAP was associated with an improvement in sleep quality in patients with OSA by consolidating sleep, reducing stage 1 sleep, and improving REM sleep. CPAP was effective in correcting the respiratory and arousal abnormalities of OSA. The effectiveness of supplemental oxygen was limited to oxyhemoglobin desaturation.     

Effects of continuous positive airway pressure on cognitition and neuroimaging data in sleep apnea

Obstructive sleep apnea (OSA) has been associated with a broad range of neurocognitive difficulties. The current view is that the neurocognitive impairment in OSA is due to the adverse effects of sleep fragmentation and/or intermittent hypoxia. The overall picture of cognitive deficits in OSA is complex. On balance, there appears to be negative effects of OSA on cognition, most likely in the domains of attention/vigilance, verbal and visual delayed long-term memory, visuospatial/constructional abilities, and executive dysfunction. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment of OSA. In the majority of studies of OSA patients treated with CPAP, attention/vigilance improved, but changes in global functioning, executive functioning, and memory improved in about half of the studies. This may be due, in part, to variability in study design and sampling methodology across studies.     

A long-term randomized, cross-over comparison of auto-titrating and standard nasal continuous airway pressure

This study is a 12-week randomized, cross-over, single-blind comparison of the tolerance, compliance, and symptomatic improvement obtained with standard nasal continuous positive airway pressure (CPAP) vs. an auto-titrating, self-adjusting device (APAP). Sixty newly diagnosed patients, 53 with obstructive sleep apnea (OSA) and seven with upper airway resistance syndrome were studied. Thirty-nine patients (65%) completed the 24-week protocol. Data were complete in 33. In these 33 patients CPAP and APAP reduced the Epworth Sleepiness score from 15+/-1 (+/-SEM) to 8+/-1 and 9+/-1 respectively (both <0.0001 from baseline but NS between modes). The APAP average pressure was lower than the CPAP pressure, 6.4+/-0.4 and 10.6+/-0.4 cm H20, respectively. The average daily machine use was greater with APAP, 6.0+/-0.3 hrs. versus 5.5+/-0.3 hrs. with CPAP (P < 0.04). The number of days of machine use, and the pattern of use were not different between CPAP and APAP. A higher proportion of patients who did not complete the study was randomized to CPAP for their initial treatment period. This study showed that: 1) CPAP and APAP produced an equivalent improvement in daytime sleepiness, 2) APAP pressure was lower than CPAP pressure, 3) patients wore the APAP device longer during nights they used the pressure support system, and 4) patients who began the study with APAP were more prone to continue treatment. We conclude that APAP was better tolerated and used a greater number of hours than CPAP, but the extent of improvement in excessive daytime sleepiness was similar between the two modes of therapy.     

Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children

Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.     

Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness

Human bronchial asthma is characterized by airway hyperresponsiveness (AHR), eosinophilic airway inflammation, mucus hypersecretion and high serum level of IgE. IL-18 was originally regarded to induce T(h)1-related cytokines from Th1 cells in the presence of IL-12. However, our previous reports clearly demonstrated that IL-18 with IL-2 promotes Th2 cytokines production from T cells and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to produce Th2 cytokines. Thus, we examined the capacity of IL-2 and IL-18 to induce AHR, airway eosinophilic inflammation and goblet cell metaplasia. Intranasal administration of IL-2 and IL-18 induces AHR, mucus hypersecretion and eosinophilic inflammation in the lungs of naive mice. CD4+ T cells are prerequisite for this IL-2 plus IL-18-induced bronchial asthma, because CD4+ T cells-depleted or Rag-2-deficient (Rag-2-/-) mice did not develop bronchial asthma after IL-2 plus IL-18 treatment. Both STAT6-/- mice and IL-13-neutralized wild-type mice failed to develop AHR, goblet cell metaplasia and airway eosinophilic inflammation, while IL-4-/- mice almost normally developed, suggesting that IL-13 is a major causative factor and IL-4 mainly enhances the degree of AHR and eosinophilic inflammation. Both IL-4 and IL-13 equally induce eotaxin in mouse embryonic fibroblasts. However, only IL-13 blockade inhibited asthma symptoms, suggesting that IL-13 but not IL-4 is produced abundantly and plays a critical role in the pathogenesis of bronchial asthma in this model. As airway epithelial cells store robust IL-18, IL-18 might be critically involved in pathogen-induced bronchial asthma, in which pathogens stimulate epithelial cells to produce IL-18 without IL-12 induction.     

Change in periodic limb movement index during treatment of obstructive sleep apnea with continuous positive airway pressure

STUDY OBJECTIVES: The following hypotheses were investigated: 1) severe obstructive sleep apnea (OSA) can mask concurrent periodic limb movement (PLM) disorder (PLMD), which becomes evident or worsens after treatment with continuous positive airway pressure (CPAP); 2) in patients with mild OSA, PLMs are not masked but may be triggered by subclinical hypopneas or respiratory effort-related arousals and improve after CPAP. DESIGN: Retrospective analysis was performed on 2 polysomnographic studies per patient--1 baseline, the second with CPAP titration. The apnea-hypopnea index (AHI) and PLM index (PLMI) under the 2 conditions were statistically analyzed. SETTING: University hospital sleep disorders center. PATIENTS: Patients were selected if they had a baseline AHI of 5 or greater and CPAP titration resulted in reduced AHI. Also, each needed to have either a PLMI of 5 or greater on baseline PSG or during CPAP titration. Patients who started or discontinued a medication that could affect PLMs after the baseline PSG were excluded. INTERVENTIONS: As clinically indicated, CPAP for OSA. MEASUREMENTS AND RESULTS: Eighty-six patients qualified and were divided into 3 groups based on OSA severity. Significant correlations (P < 0.05) were found between AHI and PLMI on the baseline PSG (-0.50), between AHI on baseline PSG and PLMI on CPAP titration (0.49), and between PLMI on baseline PSG and on CPAP titration (-0.21). The increase in PLMI during CPAP titration in patients with severe OSA was statistically significant (P < 0.001). The PLMI decreased with CPAP in 20 of 86 patients, mostly in the mild OSA subgroup. Regression of post-CPAP reduction of AHI and change in PLMI yielded a significant logarithmic relationship (R2 = 0.3042). CONCLUSIONS: Severity of OSA may determine the effect of CPAP on PLMs. The PLMs may increase in moderate to severe OSA due mainly to "unmasking" of underlying PLMD. The PLMs may decrease in mild OSA post-CPAP due to resolution of PLMs associated with respiratory effort-related arousals. This suggests that PLMs may have more than 1 etiology and may be categorized as spontaneous (as in PLMD) and induced (when secondary to respiratory effort-related arousals).     

Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a meta-analysis

STUDY OBJECTIVE: To compare the effectiveness of auto-titrating continuous positive airway pressure (APAP) versus conventional continuous positive airway pressure (CPAP) in reducing the apnea-hypopnea index (AHI), reducing the mean airway pressure, improving subjective sleepiness, and improving treatment adherence in patients with obstructive sleep apnea (OSA). DESIGN: Meta-analysis and metaregression of published randomized trials comparing APAP to CPAP. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: We identified 9 randomized trials studying a total of 282 patients. Compared to CPAP, there was no significant advantage of APAP in reducing AHI or sleepiness (pooled APAP-CPAP posttreatment AHI and Epworth Sleepiness Scale score = -0.20 events per hour, 95% confidence interval:[-0.74,0.35], and -0.56 [-1.4,0.3] respectively). The use of APAP reduced the mean applied pressure across the night by 2.2 cm water [1.9,2.5] compared to CPAP. Adherence with therapy was not substantially improved with APAP; pooled estimate of improvement was 0.20 hours per night ([-0.16,0.57], P = .28) using a random-effects model. CONCLUSIONS: Compared to standard CPAP, APAP is associated with a reduction in mean pressure. However, APAP and standard CPAP were similar in adherence and their ability to eliminate respiratory events and to improve subjective sleepiness. Given that APAP is more costly than standard CPAP, APAP should not be considered first-line chronic therapy in all patients with OSA. However, APAP may be useful in other situations (eg, home titrations, detection of mouth leak) or in certain subgroups of patients with OSA. Identifying circumstances in which APAP is a definite improvement over CPAP in terms of costs or effects should be the focus of future studies.     

Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. OBJECTIVE: To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. METHODS: We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. RESULTS: Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30-1340 vs 280 cells/mm2; range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. CONCLUSION: We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.     

Comparative study of autotitrating and fixed-pressure CPAP in the home: a randomized, single-blind crossover trial

STUDY OBJECTIVES: To compare compliance and treatment response between continuous positive airway pressure (CPAP) and auto-titrating positive airway pressure (APAP) and to develop selection criteria for the use of APAP. DESIGN: Randomized, single-blinded, parallel crossover study. SETTING: Tertiary referral sleep disorders center. PATIENTS: Consecutive patients with obstructive sleep apnea syndrome requiring treatment with CPAP. INTERVENTIONS: 2-month treatment each of conventional CPAP and APAP in random order comparing objective compliance, Epworth Sleepiness Score, SF-36 Health Survey, visual-analog measures of ease of and attitude to treatment, side effects, and treatment pressures or system leaks obtained from the Autoset T device. MEASUREMENTS AND RESULTS: There were no differences between treatment modes in overall compliance (CPAP 4.86 +/- 2.65, APAP 5.05 +/- 2.38 hours per night, P = .14), Epworth Sleepiness Scale scores (baseline 12.4 +/- 5.1, CPAP 8.4 +/- 5.2, APAP 7.9 +/- 4.8, P < .001 relative to baseline, NS between modes), SF-36 scores (significant improvements in Role Physical and Vitality domains relative to baseline, P < .001 but NS between modes). There were fewer reported side effects in APAP mode (CPAP 28, APAP 15 reports, P = .02) and compliance was greater with APAP in those reporting any side effect (95% confidence interval CPAP 0-6.8, APAP 2.9-7.8 hours per night, P < .001). APAP delivered significantly lower median and 95th centile airway pressures and fewer system leaks. CONCLUSIONS: Compliance, subjective sleepiness, and quality of life are similar between patients who used CPAP and APAP. APAP delivers lower pressures and results in lower-pressure leaks and fewer reported side effects. Compliance is higher with APAP in subjects reporting any side effect. APAP may be indicated in patients reporting side effects with conventional CPAP.     

The cholinergic system may play a role in the pathophysiology of residual excessive sleepiness in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12–14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.