Association of overlap syndrome with incident atrial fibrillation.

Increasingly compelling data link chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) to cardiovascular complications independent of known comorbidities. It remains unclear whether the association is amplified in the presence of both conditions. The aims of this study are to assess the prevalence of atrial fibrillation (AF) in overlap syndrome (OS) and to identify risk factors predisposing to this atrial arrhythmia. We conducted a retrospective cohort study of 268 adults without past or current AF who were referred for an initial diagnostic polysomnogram from 2012 to 2019. A logistic regression analysis was performed to identify risk factors for incident AF. Incident AF occurred in 64 subjects [cumulative probability 24%, 95% confidence interval (CI) 19-29]. Independent predictors of incident AF were age-adjusted Charlson index [Odds ratio (OR) 1.62; 95% confidence interval (CI) 1.3-2.0], percentage of time spent with O2 saturation below 90% (CT90) (OR 3.72, 95% CI 1.18-11.71), and CPAP adherence (OR 0.32, 95% CI 0.13-0.71). OS patients with AF experienced higher hospitalization rates (OR 1.25, 95% CI 1.03-2.37) and worse mortality rates (OR 1.92, 95% CI 1.04-3.54). In multivariate Cox proportional regression, age-adjusted Charlson Index, severity of airflow obstruction, and CPAP adherence were independent predictors of mortality. The burden of hypoxemia and severity of comorbidities are independent factors for incident AF in individuals with OS. CPAP adherence may mitigate the risk of AF and reduce the rate of mortality in this population.

Predictors of cognitive behavioral therapy outcomes for insomnia in veterans with post-traumatic stress disorder.

BACKGROUND: Insomnia is a well-recognized co-morbid condition in veterans with post-traumatic stress disorder (PTSD) with negative personal and social consequences. Cognitive behavioral therapy (CBT) is considered an efficacious treatment, yet little attention has been devoted to treatment response in this population. The aim of this study was to identify factors that may predict clinical response to CBT for insomnia (CBT-I) in veterans with PTSD. METHODS: A retrospective chart review of 136 veterans with PTSD-related insomnia was conducted. Epworth Sleepiness Score (ESS), PTSD Checklist (PCL), and Insomnia Severity Index (ISI) were assessed at baseline. We converted prescribed antidepressant and hypnotic dosages before and after CBT-I to dose equivalent of fluoxetine diazepam, respectively. A 6-point reduction or greater in ISI scores at 6-month follow-up visit was defined as CBT-I responsiveness. RESULTS: CBT-I responsiveness was observed in 47% of veterans with PTSD. Seventy-seven percent completed treatment. Lack of perceived benefit was the most given reason for failure to return for follow-up. In contrast to hypnotics, antidepressants usage decreased in those who had experienced benefit from CBT-I (p = 0.001). Younger age, non-white race, and use of hypnotics prior to behavioral therapy were independently associated with lack of response to CBT-I. CONCLUSIONS: While CBT-I ameliorates insomnia in veterans with PTSD, the use of hypnotics prior to instituting behavioral therapy may negatively affect the response rate to CBT-I. Future studies should examine whether racial and cultural influences on the generation of insomnia in veterans with PTSD affects the response to CBT-I.

Drug treatment strategies for insomnia in patients with post-traumatic stress disorder.

INTRODUCTION: Insomnia is among the most reported sleep disturbances in patients with post-traumatic stress disorder (PTSD). The pervasiveness of this disorder among trauma-inflicted civilians and military personnel has been associated with reduced quality of life, impaired psychosocial functioning including cognitive impairments, negative mood swings, cardiovascular complications, and increased utilization of medical services. AREAS COVERED: This review describes the current state of science with respect to the impact of the most dispensed pharmacological interventions for posttraumatic insomnia. At the present, there are no established treatment algorithms for PTSD-related insomnia. Pharmacotherapy offers an alternative treatment modality for patients with PTSD who fail or decline cognitive behavioral therapy (CBT). Selection of a hypnotic/sedative agent should be based on the patient's history, precipitating and perpetuating factors of insomnia, side effect profile, and potential medication-related interactions. Antipsychotics and benzodiazepines appear ineffective or are associated with significant harm in treating PTSD-related insomnia. EXPERT OPINION: In the absence of randomized controlled trials, prescription patterns have been guided by anecdotal reports and expert opinion. Due to the complexity and multifactorial etiology of insomnia in PTSD, clinical investigations should examine available pharmacologic agents in comparative trials or in combination with CBT or complementary therapies to assess both short-term and long-term sleep outcomes in this population.

Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the long-term cardiovascular mortality in patients with severe obstructive sleep apnoea (OSA) treated with either continuous positive airway pressure (CPAP) or mandibular advancing device (MAD). METHODS: A non-concurrent cohort study of 570 subjects with severe OSA (apnoea/hypopnoea index (AHI) ≥ 30/h) and a control group of 269 subjects (AHI < 5/h) were followed up for a median of 79 months (interquartile range 76-88 months). All patients received CPAP initially. MAD was offered for those who were non-adherent to CPAP. The endpoint was cardiovascular death. RESULTS: Two hundred and eight control subjects, 177 patients treated with CPAP, 72 with MAD and 212 who declined treatment were analysed. Forty-two patients had a fatal cardiovascular event during the course of the study. The non-apnoeic group had the lowest cardiovascular death rate (0.28 per 100 person-years (95% confidence interval (CI): 0.08-0.71)) followed by the CPAP-treated (0.56 per 100 person-years (95% CI: 0.20-1.23)) and the MAD-treated OSA group (0.61 per 100 person-years (95% CI: 0.13-1.78)), with the highest cardiovascular mortality rate observed in the untreated OSA group (2.1 per 100 person-years (95% CI: 1.37-2.92)). Although residual AHI for MAD-treated patients was significantly higher than CPAP-treated patients (16.3 ± 5.1/h vs. 4.5 ± 2.3/h; P < 0.001), there was no difference in cardiovascular death rate between the two groups (hazard ratio 1.08 (95% CI: 0.55-1.74); P = 0.71). CONCLUSIONS: Both CPAP and MAD may be equally effective therapy in reducing the risk of fatal cardiovascular events in patients with severe OSA.

Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis.

PURPOSE: Clinical and epidemiologic investigations suggest a strong association between obesity and obstructive sleep apnea (OSA). The purpose of this study is to evaluate the currently available literature reporting on the effectiveness of dietary weight loss in treating OSA among obese patients. METHODS: Relevant studies were identified by computerized searches of PubMed, EMBASE, CINAHL, Web of Science, and The Cochrane Central Register of Controlled Trials through September 2011 as well as the reference lists of all obtained articles. Information on study design, patient characteristics, pre- and post-dietary weight loss measures of OSA and body mass index (BMI), and study quality was obtained. Data were extracted by two independent analysts. Weighted averages using a random-effects model are reported with 95 % confidence intervals. RESULTS: Nine articles representing 577 patients were selected. Dietary weight loss program resulted in a pooled mean BMI reduction of 4.8 kg/m(2) (95 % confidence interval [CI] 3.8-5.9). The random-effects pooled apnea hypopnea (AHI) indices at pre- and post-dietary intervention were 52.5 (range 10.0-91.0) and 28.3 events/h (range 5.4-64.5), respectively (p < 0.001). Compared to control, the weighted mean difference of AHI was decreased by -14.3 events/h (95 % CI -23.5 to -5.1; p = 0.002) in favor of the dietary weight loss programs. CONCLUSIONS: Dietary weight loss programs are effective in reducing the severity of OSA but not adequate in relieving all respiratory events. Weight reduction programs should be considered as adjunct rather than curative therapy.

Toll-like receptor activity in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to chronic inflammation and cardiovascular diseases. Considerable evidence suggests that innate immune defense mechanisms might interact with proinflammatory pathways and contribute to atherogenesis. We hypothesized that the classical pathogen recognition receptors of the innate immune response, Toll-like receptors, are involved in modulating the inflammatory response in OSA. METHODS: Expression of TLR2 and TLR4 on circulating monocytes from 29 subjects with documented OSA and 18 controls were compared with the use of flow cytometry and reverse transcription-polymerase chain reaction at baseline and after 8 weeks of continuous positive airway pressure (CPAP). RESULTS: There was a significant increase in both TLR2 and TLR4 surface expression and mRNA levels on monocytes after adjustment for age, body mass index, and waist-to-hip ratio. This was paralleled by enhanced nuclear factor-κB nuclear binding and an increased release of IL-6, INF-γ, and TNF-α in OSA versus control subjects. Following 8 weeks of treatment, continuous positive airway pressure downregulated TLR2 and TLR4 expression and abrogated the release of inflammatory cytokines. CONCLUSION: OSA is associated with enhanced expression and signaling events downstream of TLR2 and TLR4 in circulating monocytes. These observations are mitigated by CPAP therapy, which suggest that TLR2 and TLR4 activation may be involved as a signaling mechanism in immune-mediated progression of atherosclerosis in OSA.

Sleep disorders in morbid obesity.

The increasing prevalence of obesity has lead to an increase in the prevalence of sleep disordered breathing in the general population. The disproportionate structural characteristics of the pharyngeal airway and the diminished neural regulation of the pharyngeal dilating muscles during sleep predispose the obese patients to pharyngeal airway collapsibility. A subgroup of obese apneic patients is unable to compensate for the added load of obesity on the respiratory system, with resultant daytime hypercapnia. Weight loss using dietary modification and life style changes is the safest approach to reducing the severity of sleep apnea, but its efficacy is limited on the long run. Although it has inherent risks, bariatric surgery provides the most immediate result in alleviating sleep apnea. Obesity has been linked also to narcolepsy. The loss of neuropeptides co-localized in hypocretin neurons is suggested as the potential mechanism. Poor sleep quality, which leads to overall sleep loss and excessive daytime sleepiness has also become a frequent complaint in this population. Identifying abnormal nocturnal eating is critically important for patient care. Both sleep related eating disorder and night eating syndrome are treatable and represent potentially reversible forms of obesity.

Emerging therapies for obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent disorder often associated with daytime sleepiness, cognitive dysfunction, and adverse cardiovascular consequences. Available therapies are limited by either lack of long-term adherence or low response rates. Two emerging therapies hold promise in providing alternatives to patients with OSA. The first stems from the importance of the upper-airway dilator muscles in maintaining pharyngeal stability. Electrical stimulation of the genioglossus muscle improves both upper-airway diameter and ameliorates pharyngeal obstruction. The results of phase I and II clinical trials hold promise, but the reported improvements in the apnea-hypopnea index vary between subjects and concerns about long-term safety await long-term studies. The second technology relies on creating an increased expiratory nasal resistance via a bidirectional valve designed to be worn just inside the nostrils. Initial findings of clinical trials suggest reduction in severity of sleep apnea and subjective daytime sleepiness. Considerable heterogeneity in response to the nasal device was noted despite the high adherence rates. It remains unclear which patients will likely benefit a priori from these devices.

Lectin-like oxidized low-density lipoprotein receptor-1 modulates endothelial apoptosis in obstructive sleep apnea.

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is the major receptor for oxidized low-density lipoprotein in endothelial cells, and its expression is enhanced in proatherogenic settings. The objective of this study was to investigate the association between LOX-1 in freshly harvested human venous endothelial cells and apoptotic circulating endothelial cells in patients with obstructive sleep apnea (OSA). METHODS: We conducted a prospective, interventional study of 38 patients with newly diagnosed OSA free of disease and 12 healthy control subjects. Plasma LOX-1 (pLOX-1) levels were measured using a commercially available enzyme-linked immunosorbent assay. Protein expression of LOX-1 was quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 8 weeks of continuous positive airway pressure (CPAP) therapy. Circulating apoptotic endothelial cells (CD146(+), CD45(-), and CD31(1)) were assessed concomitantly by flow cytometry. RESULTS: pLOX-1 levels were higher in subjects with OSA than in control subjects (326.9 ± 267.1 pg/mL and 141.1 ± 138.6 g/mL, respectively; P = .004). Patients with OSA showed a threefold increase in baseline endothelial expression of LOX-1 relative to control subjects. CPAP therapy resulted in a significant decrease in endothelial LOX-1 expression only in CPAP-adherent patients. Circulating apoptotic endothelial cells correlated directly with baseline expression of LOX-1 (R(2) = 0.32, P = .01) after adjustment for age, BMI, and waist to hip ratio. CONCLUSIONS: Increased expression of LOX-1 in vivo is associated with endothelial apoptosis. Adherence to CPAP therapy may reverse these derangements.

Does linezolid modulate lung innate immunity in a murine model of methicillin-resistant Staphylococcus aureus pneumonia?

OBJECTIVES: Methicillin-resistant Staphylococcus aureus is an important cause of mortality among nosocomial infections. Recent investigations suggest that linezolid is superior to vancomycin in achieving clinical cure in patients with nosocomial pneumonia. We hypothesized that linezolid may exhibit anti-inflammatory properties in vivo model of pneumonia. DESIGN: Prospective interventional study. SETTING: University affiliated laboratory. SUBJECTS: BALB/c mice. INTERVENTIONS: Three groups of BALB/c mice were inoculated with methicillin-resistant S. aureus American Type Culture Collection 33,591 to induce pneumonia. Each group (n = 6) underwent bronchoalveolar lavage at 24 hrs, 48 hrs, and 72 hrs after inoculation after treatment with vancomycin, linezolid, or no antibiotic. Bronchoalveolar lavage fluid levels of monocyte chemotactic protein-5 and interleukin-6 were quantified using cytometric bead array. Metalloproteinase-9 was detected by enzyme-linked immunosorbent assay and gelatin zymography. Neutrophil apoptosis in bronchoalveolar lavage was assessed by annexin V and 7-aminoactinomycin D staining. Neutrophil activity was determined by myeloperoxidase enzyme activity. Phagocytosis of apoptotic neutrophils by linezolid- vs. vancomycin treated-alveolar macrophages was examined in vitro. MEASUREMENTS AND MAIN RESULTS: Infected mice had a significant reduction in lung bacterial titers compared with controls (p < .05) after treatment with linezolid or vancomycin. There was no difference in bronchoalveolar lavage levels of monocyte chemotactic protein-5 or interleukin-6 between vancomycin- and linezolid-treated groups. Both antimicrobials were comparable in modulating the expression of matrix metalloproteinase-9 in bronchoalveolar lavage. Neutrophil apoptosis was comparable in both vancomycin- and linezolid-treated groups at all three time points. Vancomycin showed lower myeloperoxidase activity compared with linezolid in the first 24 hrs after inoculation (p = .03), but the difference was undetectable at 48 hrs and 72 hrs. Neither compound had an impact on the process of removal of apoptotic neutrophils by alveolar macrophages. CONCLUSIONS: Linezolid did not display an advantage over vancomycin in modulating pulmonary innate immune response in a murine model of methicillin-resistant S. aureus pneumonia.

Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study.

BACKGROUND: The high efficacy of continuous positive airway pressure (CPAP) in treating obstructive sleep apnea (OSA) is limited by poor compliance often related to pressure intolerance. Mandibular advancement devices (MADs) are proven alternative therapy although not universally effective. A combination of nasal CPAP and MAD may provide another option for CPAP-intolerant patients with incomplete response to MAD. METHODS: Ten patients with residual apnea/hypopnea events on MAD who were intolerant to CPAP were recruited prospectively from the sleep clinic. After a washout period of 1 week off MAD, subjects were asked to use an auto-CPAP unit along with their prescribed MAD for three consecutive nights. Oxygen desaturations were obtained from overnight oximetry. Efficacy of the combination therapy was evaluated by the Epworth Sleepiness Scale and Smartcard data recordings. RESULTS: The combination of MAD and nasal CPAP was well tolerated by all participants. Compared to CPAP alone, the optimal CPAP pressure required to eliminate all obstructive events on the combination therapy was reduced from 9.4 ± 2.3 to 7.3 ± 1.4 cm H2O (p = 0.001). The residual apnea hypopnea index on the MAD decreased from 11.2 ± 3.9 to 3.4 ± 1.5 on the combination therapy (p < 0.001). The number of oxygen desaturations was also less with the combination therapy than with MAD (p < 0.001). Both the MAD and the combination therapy were effective in reducing daytime sleepiness from 12.7 ± 2.1 at baseline to 9.7 ± 3.1 (p = 0.04) and 7.5 ± 4.1 (p = 0.007), respectively. CONCLUSIONS: Combination therapy of MAD and nasal CPAP is effective in normalizing respiratory disturbances of sleep apnea in selected OSA patients who are intolerant to CPAP.

Endothelial function in patients with post-CPAP residual sleepiness.

STUDY OBJECTIVES: The significance of residual excessive daytime sleepiness (EDS) on cardiovascular markers in patients with adequately treated obstructive sleep apnea (OSA) remains unclear. The objective of this study was to investigate flow-mediated dilatation (FMD) and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in continuous positive airway pressure (CPAP)-compliant patients with residual EDS compared with CPAP-compliant patients without residual EDS. METHODS: FMD of the brachial artery was measured by ultrasound in 12 CPAP-compliant patients with OSA who had residual EDS and 12 age-, sex-, and body mass index-matched CPAP-compliant patients with OSA who did not have residual EDS on week 8 after initiation of CPAP. Twelve otherwise-healthy subjects without sleep disordered breathing were used as control subjects. Serum concentrations of CRP, TNF-alpha, and IL-6 were quantified by enzyme-linked immunosorbent assays. RESULTS: Baseline FMD was comparable among CPAP-compliant patients with residual EDS (7.2 +/- 2.3), CPAP-compliant patients without residual EDS (8.6 +/- 2.1), and control subjects (7.7 +/- 1.4) (p = 0.37). The concentrations of CRP, TNF-alpha, and IL-6 were also not significantly different between subjects with CPAP-compliant residual EDS and those without residual EDS (p = 0.44, p = 0.37, and p = 0.42; respectively). CONCLUSIONS: Residual EDS in patients with adequately treated OSA may not represent a risk factor for cardiovascular diseases.

Antibiotic prescription patterns in hospitalized patients with nursing home-acquired pneumonia.

BACKGROUND: Considerable research has increased our understanding of antibiotic prescribing practices in hospital settings when it comes to nosocomial pneumonia. Much less is known about the antibiotic prescribing patterns for hospitalized non-critically ill patients with nursing home-acquired pneumonia (NHAP). OBJECTIVE: As part of a multisite quality improvement project, we sought to examine patterns of antibiotic prescription among healthcare providers as a function of underlying comorbid, functional, and clinical factors. SETTING: Three tertiary care centers. INTERVENTION: Chart reviews of 397 individual admissions were performed on patients admitted from nursing homes with the diagnosis of pneumonia between January 2005 and September 2007. RESULTS: Compliance with national guidelines for the treatment of NHAP was poor. Overall, the 3 most commonly used compounds for inpatient treatment were fluoroquinolones (51.4%), ceftriaxone (45.0%), and azithromycin (42.1%). Monotherapy was prescribed in 57.1%. Fluoroquinolones represented 79.5% of these cases. Patients with higher acuity of illness were more likely to receive a combination of vancomycin plus piperacillin/tazobactam (P < 0.001). Median duration of treatment was 8.0 (range, 3-21) days. Stratified analyses showed that combination therapy was used more often on University-affiliated services than on private service (54% vs. 35%; P < 0.001). CONCLUSIONS: There was poor adherence with antibiotic guidelines for the treatment of NHAP. In the absence of outcome data on guidelines compliance, antibiotic use was influenced by patients' age, severity of illness, and providers' academic affiliation. Future research should focus on outcome measures and physicians factors that influence nonadherence.

Effect of antibiotic guidelines on outcomes of hospitalized patients with nursing home-acquired pneumonia.

OBJECTIVES: To compare the 2003 community-acquired pneumonia (CAP) guideline and the 2005 healthcare-associated pneumonia (HCAP) guideline on time to clinical stability, length of hospital stay, and mortality in nursing home patients hospitalized for pneumonia. DESIGN: Retrospective study. SETTING: Three tertiary-care hospitals. PARTICIPANTS: Three hundred thirty-four nursing home patients. MEASUREMENTS: Patients were classified according to the antibiotic regimens they received based on the 2003 CAP guideline or the 2005 HCAP guideline. Time to clinical stability, time to switch therapy, and mortality were evaluated in an intention-to-treat analysis. A multivariate survival model using propensity analysis was used to adjust for heterogeneity between the two groups. RESULTS: Of the 334 patients, 258 (77%) were treated according to the 2003 HCAP guideline. Time to clinical stability did not differ between those treated according to the 2003 CAP or the 2005 HCAP guidelines. Only the Pneumonia Severity Index (P=.006) and multilobar involvement (P=.005) were significantly associated with delay in achieving clinical stability. Adjusted in-hospital and 30-day mortality were comparable in both cohorts (odds ratio (OR)=0.87, 95% confidence interval (CI)=0.49-1.34, and OR=0.79, 95% CI=0.42-1.31, respectively), although time to switch therapy and length of stay were longer for those treated according to the 2005 HCAP guideline. CONCLUSION: In hospitalized nursing home patients with pneumonia, treatment with an antibiotic regimen according to the 2003 CAP guideline achieved comparable time to clinical stability and in-hospital and 30-day mortality with a regimen based on the 2005 HCAP guideline.

Predicting optimal CPAP by neural network reduces titration failure: a randomized study.

PURPOSE: Continuous positive airway pressure (CPAP) is considered the standard therapy for obstructive sleep apnea syndrome. In the absence of standard protocol, CPAP titration may be unsuccessful. The purpose of this study was to test the hypothesis that application of an artificial neural network (ANN) to CPAP titration would achieve an optimal CPAP pressure within a shorter time interval and would lead to a decrease in CPAP titration failure. METHODS: One hundred fifteen patients were randomized 1:1 to either conventional CPAP titration (n = 58) or to an ANN-guided CPAP titration (n = 57). Both groups were assessed for time to optimal CPAP pressure, for titration failure, and for CPAP compliance therapy. RESULTS: Patients in the ANN-guided CPAP titration arm were able to achieve optimal CPAP at a shorter time interval compared to the conventional group (198.7 +/- 143.8 min versus 284.0 +/- 126.5 min) (p < 0.001). There was also a lower titration failure in patients randomized to the ANN-guided CPAP titration arm (16%) compared to the conventional arm (36%) (p = 0.02). Compliance with treatment did not differ across the two arms. CONCLUSIONS: The use of ANN for guiding CPAP titration may be superior to the conventional method in maximizing the time to achieve optimal CPAP and in reducing CPAP titration failure.

Impact of nasal continuous positive airway pressure therapy on markers of platelet activation in patients with obstructive sleep apnea.

BACKGROUND: Considerable evidence implicates CD40 signaling in the pathogenesis of atheromas. Exposure to CD40 ligand induces platelet-leukocyte conjugation, a heightened expression of inflammatory cytokines, matrix-degrading enzymes, and procoagulant factors. OBJECTIVES: To investigate the association between plasma soluble CD40 ligand (sCD40L) and platelet-monocyte aggregates in patients with obstructive sleep apnea (OSA) and to determine whether treatment of OSA with nasal continuous positive airway pressure (nCPAP) alters this relationship. METHODS: Twelve patients with OSA who were free of other diseases and 12 healthy controls matched for age, gender, and body mass index had blood drawn for sCD40L and platelet-monocyte aggregate measurements. A repeat assessment was obtained following 8 weeks of nCPAP therapy. RESULTS: Subjects with OSA had significantly higher plasma sCD40L levels and exhibited elevated platelet-monocyte aggregates compared to nonapneic subjects (7.6 +/- 4.3 versus 1.7 +/- 1.1, p = 0.004; and 41.3 +/- 23.7 versus 6.7 +/- 4.9, p = 0.001, respectively). Both parameters correlated positively with the percentage of time spent with SpO(2) <90% (r = 0.69, p = 0.01 and r = 0.6, p = 0.03, respectively). After 8 weeks of nCPAP treatment, sCD40 levels declined by 47% (p = 0.003) and platelet-monocyte aggregates by 42% (p = 0.002). None of the controls showed any changes in either sCD40L or platelet- monocyte aggregates after nCPAP therapy. CONCLUSIONS: OSA is associated with upregulation of circulating sCD40L levels and platelet-monocyte aggregation that may account for the increased incidence of cardiovascular events in this population. Treatment with nCPAP may alleviate this risk.

Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.

RATIONALE: Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates. OBJECTIVES: To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response. METHODS: Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay. MEASUREMENTS AND MAIN RESULTS: Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins. CONCLUSIONS: The increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.

Triggering receptors expressed on myeloid cells in pulmonary aspiration syndromes.

OBJECTIVE: To investigate the potential role of serum and alveolar soluble triggering receptor expressed on myeloid cells (sTREM-1) as a biological marker of pulmonary aspiration syndromes. DESIGN: Prospective cohort study. SETTING: University-affiliated intensive care unit. PATIENTS: Seventy-five patients with pulmonary aspiration and 13 controls receiving mechanical ventilation. INTERVENTIONS: Blood and bronchoalveolar lavage (BAL) fluid samples were collected on enrollment. Soluble TREM-1 levels were measured by an enzyme-linked immunosorbent assay. MEASUREMENTS AND RESULTS: Thirty-eight of 75 participants had documented BAL culture-positive pulmonary aspiration. While circulating levels of sTREM-1 were comparable between those with aspiration syndromes (19.81 +/- 12.09 pg/ml) and controls (15.96 +/- 11.16 pg/ml) (p=0.27), the alveolar levels of sTREM-1 were higher in patients with culture-positive pulmonary aspiration (344.41 +/- 152.82 pg/ml) compared with those culture-negative pulmonary aspiration (142.76 +/- 89.88 pg/ml; p < 0.001). A cut-off value of 250 pg/ml for alveolar sTREM-1 achieved a sensitivity of 65.8% (95% CI 48.6-80.4) and a specificity of 91.9% (95% CI 78.1-98.2) with an area under the curve of 0.87 (95% CI 0.78-0.94). CONCLUSIONS: Alveolar sTREM-1 levels can be a potential biomarker for distinguishing BAL culture-positive from BAL culture-negative pulmonary aspiration.