Improving the performance of peripheral arterial tonometry-based testing for the diagnosis of obstructive sleep apnea.

Outside sleep laboratory settings, peripheral arterial tonometry (PAT, eg, WatchPat) represents a validated modality for diagnosing obstructive sleep apnea (OSA). We have shown before that the accuracy of home sleep apnea testing by WatchPat 200 devices in diagnosing OSA is suboptimal (50%-70%). In order to improve its diagnostic performance, we built several models that predict the main functional parameter of polysomnography (PSG), Apnea Hypopnea Index (AHI). Participants were recruited in our Sleep Center and underwent concurrent in-laboratory PSG and PAT recordings. Statistical models were then developed to predict AHI by using robust functional parameters from PAT-based testing, in concert with available demographic and anthropometric data, and their performance was confirmed in a random validation subgroup of the cohort. Five hundred synchronous PSG and WatchPat sets were analyzed. Mean diagnostic accuracy of PAT was improved to 67%, 81% and 85% in mild, moderate-severe or no OSA, respectively, by several models that included participants' age, gender, neck circumference, body mass index and the number of 4% desaturations/hour. WatchPat had an overall accuracy of 85.7% and a positive predictive value of 87.3% in diagnosing OSA (by predicted AHI above 5). In this large cohort of patients with high pretest probability of OSA, we built several models based on 4% oxygen desaturations, neck circumference, body mass index and several other variables. These simple models can be used at the point-of-care, in order to improve the diagnostic accuracy of the PAT-based testing, thus ameliorating the high rates of misclassification for OSA presence or disease severity.

Performance of peripheral arterial tonometry-based testing for the diagnosis of obstructive sleep apnea in a large sleep clinic cohort.

STUDY OBJECTIVES: Peripheral arterial tonometry (PAT)-based technology represents a validated portable monitoring modality for the diagnosis of OSA. We assessed the diagnostic accuracy of PAT-based technology in a large point-of-care cohort of patients studied with concurrent polysomnography (PSG). METHODS: During study enrollment, all participants suspected to have OSA and tested by in-laboratory PSG underwent concurrent PAT device recordings. RESULTS: Five hundred concomitant PSG and WatchPat tests were analyzed. Median (interquartile range) PSG AHI was 18 (8-37) events/h and PAT AHI3% was 25 (12-46) events/h. Average bias was + 4 events/h. Diagnostic concordance was found in 42%, 41%, and 83% of mild, moderate, and severe OSA, respectively (accuracy = 53%). Among patients with PAT diagnoses of moderate or severe OSA, 5% did not have OSA and 19% had mild OSA; in those with mild OSA, PSG showed moderate or severe disease in 20% and no OSA in 30% of patients (accuracy = 69%). On average, using a 3% desaturation threshold, WatchPat overestimated disease prevalence and severity (mean + 4 events/h) and the 4% threshold underestimated disease prevalence and severity by -6 events/h. CONCLUSIONS: Although there was an overall tendency to overestimate the severity of OSA, a significant percentage of patients had clinically relevant misclassifications. As such, we recommend that patients without OSA or with mild disease assessed by PAT undergo repeat in-laboratory PSG. Optimized clinical pathways are urgently needed to minimize therapeutic decisions instituted in the presence of diagnostic uncertainty.

Legal Aspects of Sleep Medicine in the 21st Century.

Multiple manifestations of sleep disorders may interact with the law, making it important to increase awareness of such interactions among clinicians. Patients with excessive sleepiness may have civil (and in some states criminal) liability if they fall asleep while driving and cause a motor vehicle accident. Employers may be held vicariously liable because of the actions of sleepy employees. Hence, awareness of causes of excessive sleepiness, such as sleep deprivation and OSA, is increasing among trucking, railroad, and other safety-sensitive occupations. Interestingly, litigation related to perioperative complications because of OSA is more frequent than nonoperative issues such as a failure to diagnose OSA. Parasomnia-associated sleep-related violence represents a challenge to clinicians because they may be asked to consider parasomnia as a possible contributing, mitigating, or exculpatory factor in criminal proceedings. Clinicians should also familiarize themselves with the legal and regulatory aspects of running an independent sleep laboratory. Sleep telemedicine practice using 21st century technology has opened novel and unique challenges to existing laws. In this review, we cover the most common interactions between sleep disorders and the law, including the challenges of excessive sleepiness and driving, other legal issues involving patients with OSA, and the liabilities associated with parasomnia disorder. We will also cover some practical legal aspects involving independent sleep laboratories and the field of sleep telemedicine.

Legal and Regulatory Aspects of Sleep Disorders.

Sleep disorders may interact with the law, making awareness important. Insufficient sleep and obstructive sleep apnea (OSA) are prevalent and associated with excessive sleepiness. Patients with excessive sleepiness may have civil or criminal liability if they fall asleep and cause a motor vehicle accident. Awareness of screening and treatment of OSA is increasing in certain industries. Parasomnia associated sleep-related violence represents a challenge to clinicians, who may be called on to consider parasomnia as a contributing, mitigating, or exculpatory factor in criminal proceedings. Improving access to sleep medicine care is an important aspect in reducing the consequences of sleep disorders.

Restless legs syndrome.

Restless legs syndrome is a common sensorimotor disorder characterized by an urge to move, and associated with uncomfortable sensations in the legs (limbs). Restless legs syndrome can lead to sleep-onset or sleep-maintenance insomnia, and occasionally excessive daytime sleepiness, all leading to significant morbidity. Brain iron deficiency and dopaminergic neurotransmission abnormalities play a central role in the pathogenesis of this disorder, along with other nondopaminergic systems, although the exact mechanisms are still. Intensive care unit patients are especially vulnerable to have unmasking or exacerbation of restless legs syndrome because of sleep deprivation, circadian rhythm disturbance, immobilization, iron deficiency, and use of multiple medications that can antagonize dopamine.

Sleep and sleep disorders in the hospital.

Sleep abnormalities are common and underrecognized in hospitalized patients. Sleep restriction is common and can have undesirable behavioral and physiologic effects. The general pattern of polysomnographic abnormalities observed in hospitalized patients is reduction in total sleep time, stages R (rapid eye movement), and N3 (slow wave) and increase in stage N1 percentage. Sleep is also fragmented with more arousals and awakenings. Multiple factors are responsible for sleep disruption in hospitalized patients and include environmental noise. Abnormalities in melatonin secretion leading to circadian rhythm abnormalities have also been noted. Hospitalized patients may also present with symptoms of obstructive sleep apnea. Protocols for sleep enhancement and management of obstructive sleep apnea are being implemented at various hospitals. Outcome data are awaited from these measures.

Sleep-disordered breathing during pregnancy.

Pregnancy is associated with many physiologic and hormonal changes along with changes in sleep architecture, placing pregnant women at risk for the development of sleep-disordered breathing or worsening of preexisting sleep apnea. Snoring, the most common symptom of sleep-disordered breathing, is markedly increased during pregnancy. The exact prevalence of obstructive sleep apnea in pregnant women is unknown. Because the apneic episodes are commonly associated with oxyhemoglobin desaturations, the combination of obstructive sleep apnea and pregnancy can be potentially harmful to the fetus given the low oxygen reserves during pregnancy. Obstructive sleep apnea has been associated with an increased risk of hypertension among the general population, and this raises the possibility of its association with gestational hypertension and preeclampsia. In this clinical review, we discuss the physiologic changes of pregnancy that predispose pregnant women to the development of obstructive sleep apnea and the effects of sleep-disordered breathing on pregnancy outcomes. We also review the recommendations regarding evaluation for sleep apnea and treatment options during pregnancy and postpartum.

The utility of spirometry in diagnosing pulmonary restriction.

The aim of this retrospective study was to determine the utility of the spirometric measurements FVC, FEV1, and FEV1/FVC in diagnosing pulmonary restriction. Spirometry and lung volume measurements performed on the same patient visit were analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of (1) FVCor=LLN were compared to diagnose restriction based on lung volume measurements. In all, 18,282 pulmonary function tests from 8,315 patients were analyzed. Twenty-six percent of the patients (n=2,213) had restriction based on lung volume measurements. The sensitivity, specificity, PPV, and NPV of FVCor=normal to diagnose restriction based on lung volume criteria were 72.4%, 87.1%, 64.4%, and 90.7%, respectively. Analysis of ROC curves showed that spirometric criteria based on FVC alone performed better (area under the curve=0.817) than those based on the combined criteria of FVC and FEV1/FVC (area under the curve=0.584). Consistent with earlier findings, the negative predictive value for a normal FVC (>or=LLN) to exclude pulmonary restriction was high in this series (up to 95.7%). Also, a spirometric diagnosis of "restriction" (FVCor=LLN) had a positive predictive value of 26.3-73.9%. On this basis, normal FVC can be regarded as excluding restriction with high reliability.

An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare idiopathic autoimmune lung disease in adults characterized by the accumulation of lipoproteinaceous material within the alveoli of the lung. The natural history of this disease is poorly defined. Current therapy of bilateral whole-lung lavage (WLL) under general anesthesia is invasive and has its limitations. Data suggest that relative granulocyte macrophage colony stimulating factor (GM-CSF) deficiency may be involved in the pathogenesis of this disease. There have been several case series that have described clinical improvement with exogenous GM-CSF therapy in a subset of patients with PAP. We describe the results of a prospective, open-label clinical trial of daily subcutaneous GM-CSF therapy in a group of adult patients with idiopathic PAP. In this series of 25 patients, the largest reported to date, administration of GM-CSF improved oxygenation as assessed by a 10 mm Hg decrease in alveolar-arterial oxygen gradient, as well as improvement in other clinical and quality of life parameters in 12 of 25 patients (48%) with moderate symptomatic disease who completed the trial. In addition, the serum anti-GM-CSF antibody titer correlated with lung disease activity and was a predictor for responsiveness to therapy. These data indicate that subcutaneous GM-CSF therapy is a promising alternative to WLL for symptomatic patients with PAP.

Surgical intervention in patients with moderate to severe pulmonary arterial hypertension.

BACKGROUND: Patients with pulmonary arterial hypertension are believed to experience severe postoperative complications after major surgery. METHODS: We retrospectively analyzed the data of 21 patients with pulmonary arterial hypertension who underwent 28 surgical procedures at our institution between 1996 and 2002. RESULTS: The average mean pulmonary arterial pressure was 53 +/- 14.4 mm Hg. Twenty-two procedures were performed under general anesthesia. Extubation occurred within 24 hours of surgery in 72% and an intensive care unit stay was not required after 43% of the procedures. Perioperative morbidity and mortality were typically related to the surgical procedure or underlying disease. CONCLUSIONS: In our study, patients with moderate to severe pulmonary arterial hypertension had an 18% per procedure mortality and a 19% rate of right heart failure after surgical intervention.

Estimating FVC from FEV2 and FEV3: assessment of a surrogate spirometric parameter.

BACKGROUND: In the context that accurate measurement of FVC is important in diagnosing airflow obstruction and in assessing restriction, strategies to achieve reliable and accurate FVC measurement have drawn much attention. OBJECTIVES: Because the rate of achieving end-of-test criteria during spirometry has been shown to be low, with resultant under-recording of the FVC, the current study proposes a regression equation for estimating FVC from measured values of the forced expiratory volume in 2 s (FEV2) and forced expiratory volume in 3 s (FEV3). METHODS: The predictive equation for the estimated FVC from volume measurements within the first 3 s of exhalation (estimated FVC3) was generated based on 330 consecutive acceptable spirograms performed in the Cleveland Clinic Foundation Pulmonary Function Laboratory. The equation was applied to an independent validation set comprised of spirometry measurements on 370 different consecutive patients. RESULTS: In the validation spirometry sample, in which the prevalence of obstruction was 34% (based on values of the measured FEV1/FVC compared to National Health and Nutrition Examination Survey III values), the sensitivity, specificity, and positive and negative predictive values of FEV1/estimated FVC3 for obstruction were 93.8%, 89.1%, 81.2%, and 96.9%, respectively. The misclassification rate was 9.2%. In the same cohort, the mean difference (+/- SD) between estimated FVC3 and measured FVC was 24.7 +/- 237 mL. CONCLUSIONS: Given that FVC is frequently under-recorded, with resultant overestimation of FEV1/FVC and underdiagnosis of airflow obstruction, we believe that estimating FVC from FEV2 and FEV3 can offer practical diagnostic advantages.

Pulmonary alveolar proteinosis. Clinical manifestations and optimal treatment strategies.

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant phospholipids and proteins within the lung alveoli. Important advances have been made over the past 8 years in our understanding of this disease, offering new directions for research and patient care. First, genetically altered mice that are homozygous for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene developed a lung lesion with histologic resemblance to PAP. The surfactant is thought to be catabolized or cleared mostly by alveolar macrophages, this process being dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found in serum and bronchoalveolar lavage fluid of patients with idiopathic PAP but not in healthy controls, thereby raising the suspicion that human PAP may be an autoimmune disease. The relationship between the antibody and disease pathogenesis remains unclear but data suggest that the GM-CSF antibody may have a potential role as a diagnostic test. No specific therapy exists for PAP. Sequential whole lung lavage is the standard of care. Exogenous therapy with GM-CSF may improve the lung disease in some patients with PAP but this therapy is still experimental. Interventions directed at treating a relative GM-CSF deficiency by administration of GM-CSF or lowering the antibody level (i.e. by plasmapheresis or immunosuppression) may hold promise as future therapy for this rare disease.