James M. Parish

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately 5% to 15% of the population. The pathophysiology of OSA is characterized by repetitive occlusions of the posterior pharynx during sleep that obstruct the airway, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. Obstructive sleep apnea is associated with daytime sleepiness and fatigue, likely due to fragmented sleep from recurrent arousals. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA and that OSA is a risk factor for the development of hypertension. Recent studies show that OSA may be implicated in stroke and transient ischemic attacks. Obstructive sleep apnea appears to be associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with preexisting pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified to be important in the development of atherosclerosis. Obstructive sleep apnea is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, and plasminogen activator inhibitor, and reduced fibrinolytic activity. Obstructive sleep apnea has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.

Clinical, Anatomical, and Physiologic Relationship Between Sleep and Headache

The intimate relationship between sleep and headache has been recognized for centuries, yet the relationship remains clinically and nosologically complex. Headaches associated with nocturnal sleep have often been perceived as either the cause or result of disrupted sleep. An understanding of the anatomy and physiology of both conditions allows for a clearer understanding of this complex relationship and a more rational clinical and therapeutic approach. Recent biochemical and functional imaging studies in patients with primary headache disorders has lead to the identification of potential central generators which are also important for the regulation of normal sleep architecture.

Sleep-Related Problems in Common Medical Conditions

Common medical problems are often associated with abnormalities of sleep. Patients with chronic medical disorders often have fewer hours of sleep and less restorative sleep compared to healthy individuals, and this poor sleep may worsen the subjective symptoms of the disorder. Individuals with lung disease often have disturbed sleep related to oxygen desaturations, coughing, or dyspnea. Both obstructive lung disease and restrictive lung diseases are associated with poor quality sleep. Awakenings from sleep are common in untreated or undertreated asthma, and cause sleep disruption. Gastroesophageal reflux is a major cause of disrupted sleep due to awakenings from heartburn, dyspepsia, acid brash, coughing, or choking. Patients with chronic renal disease commonly have sleep complaints often due to insomnia, insufficient sleep, sleep apnea, or restless legs syndrome. Complaints related to sleep are very common in patients with fibromyalgia and other causes of chronic pain. Sleep disruption increases the sensation of pain and decreases quality of life. Patients with infectious diseases, including acute viral illnesses, HIV-related disease, and Lyme disease, may have significant problems with insomnia and hypersomnolence. Women with menopause have from insomnia, sleep-disordered breathing, restless legs syndrome, or fibromyalgia. Patients with cancer or receiving cancer therapy are often bothered by insomnia or other sleep disturbances that affect quality of life and daytime energy. The objective of this article is to review frequently encountered medical conditions and examine their impact on sleep, and to review frequent sleep-related problems associated with these common medical conditions.

Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome

Objectives: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. Methods: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. Results: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. Conclusions: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.

Transbronchial Biopsy Interpretation in the Patient With Diffuse Parenchymal Lung Disease

CONTEXT The most common lung tissue samples seen by pathologists worldwide are obtained with the flexible bronchoscope. Specimens taken for examination of diffuse or multifocal parenchymal lung abnormalities pose special challenges for the general surgical pathologist, and these challenges are often compounded by high clinical expectations for accurate and specific diagnosis. OBJECTIVE To present and discuss the most common histopathologic patterns and diagnostic entities seen in transbronchial biopsy specimens in the setting of diffuse or multifocal lung disease. Specifically, acute lung injury, eosinophilic pneumonia, diffuse alveolar hemorrhage, chronic cellular infiltrates, organizing pneumonia, alveolar proteinosis, sarcoidosis, Wegener granulomatosis, intravenous drug abuse-related microangiopathy, Langerhans cell histiocytosis, and lymphangioleiomyomatosis are presented. Clinical and radiologic context is provided for the more specific diagnostic entities. DATA SOURCES The published literature and experience from a consultation practice. CONCLUSIONS The transbronchial biopsy specimen can provide valuable information for clinical management in the setting of diffuse or multifocal lung disease. Computed tomographic scans are useful for selecting appropriate patients to undergo biopsy and in limiting the differential diagnosis. Knowledge of the clinical context, radiologic distribution of abnormalities, and histopathologic patterns is essential. With this information, the surgical pathologist can substantially influence the diagnostic workup and help guide the clinician to an accurate clinical/radiologic/pathologic diagnosis.

Usual interstitial pneumonia-pattern fibrosis in surgical lung biopsies. Clinical, radiological and histopathological clues to aetiology

Pulmonary fibrosis in surgical lung biopsies is said to have a ‘usual interstitial pneumonia-pattern’ (UIP-pattern) of disease when scarring of the parenchyma is present in a patchy, ‘temporally heterogeneous’ distribution. These biopsies are one of the more common non-neoplastic specimens surgical pathologists encounter and often pose a number of challenges. UIP is the expected histopathological pattern in patients with clinical idiopathic pulmonary fibrosis (IPF), but the UIP-pattern can be seen in other conditions on occasion. Most important among these are the rheumatic interstitial lung diseases (RILD) and chronic hypersensitivity pneumonitis (CHrHP). Because theses entities have different mechanisms of injury, approach to therapy, and expected clinical progression, it is imperative for the surgical pathologist to correctly classify them. Taken in isolation, the UIP-pattern seen in patients with IPF may appear to overlap with that of RILD and CHrHP, at least when using the broadest definition of this term (patchy fibrosis). However, important distinguishing features are nearly always present in our experience, and the addition of a multidisciplinary approach will often resolve the critical differences between these diseases. In this manuscript, we review the distinguishing clinical, radiologic and histopathological features of UIP of IPF, RILD and CHrHP, based, in part, on the existing literature, but also lessons learned from a busy lung biopsy consultation practice.

High Prevalence of Abnormal Nocturnal Oximetry in Patients With Hypertrophic Cardiomyopathy

OBJECTIVES We sought to determine the prevalence of nocturnal oxygen desaturation and obstructive sleep apnea (OSA) in a population of patients with hypertrophic cardiomyopathy (HCM). BACKGROUND The coexistence of sleep apnea and HCM, 2 common cardiovascular conditions, has been largely unrecognized in the treatment of patients with HCM. The nocturnal hypoxia-induced hyperadrenergic state in OSA is expected to worsen hemodynamics and outcomes in HCM. METHODS One hundred subjects with HCM between June 1, 2006, and July 14, 2008, were screened with nocturnal oximetry. Clinical variables were collected for statistical analysis. Oximetry was classified abnormal (suspicion of sleep-disordered breathing) in the presence of repetitive desaturation (> or =5 events/h) followed by a rapid return to baseline oxygen saturation (SaO(2)) level with a decrease of > or =4% and threshold of 90%. RESULTS Seventy-one (71%) patients with HCM had abnormal nocturnal oximetry (71 +/- 9%, 95% confidence interval: 62% to 80%). Subjects with abnormal oximetry were older (age 59.5 +/- 15.3 years) and more were hypertensive (n = 39 [55%]) than those with normal oximetry (age 45.8 +/- 18.5 years, n = 9 [31%], p < 0.001, p = 0.03). Patients with HCM were more symptomatic in the presence of abnormal oximetry (New York Heart Association functional class II to III) (62% vs. 83%, p = 0.023). HCM patients had a higher prevalence of abnormal nocturnal oximetry (n = 71, 71%) compared with a control group of similar age and sex distribution (n = 49, 49%) (p = 0.001). CONCLUSIONS Abnormal nocturnal oximetry is common in patients with HCM, suggesting that OSA is prevalent. OSA may impact hemodynamics and symptoms in HCM. Further studies are needed to determine the long-term benefit of OSA treatment on hemodynamics and disease progression in HCM.

Surgery for Pulmonary Coccidioidomycosis: A 10-Year Experience

BACKGROUND Coccidioidomycosis results from infection with Coccidioides species endemic to the southwestern United States. The mobile US population has resulted in incremental cases being found throughout the world. The fungal infection can result in pulmonary sequelae, including nodules, cavities, and complications requiring treatment by the thoracic surgeon. METHODS A retrospective chart review was conducted of 1,496 patients with coccidioidomycosis treated at our institution (January 1998 to December 2008) to identify those requiring surgery. RESULTS Of the 1,496 patients, 86 (6%; mean age, 58 years [range, 18 to 81], 48 women) underwent operations. Radiographs revealed 59 nodules, 18 cavities, 2 infiltrates, and 7 complications of disease (e.g., effusion, pneumothorax, and empyema). Of the 86 patients, 40% underwent resection for persistent symptoms or disease progression despite adequate antifungal therapy. One third of the operations were performed by video-assisted thoracoscopic surgery. Morbidity, 21% (18 patients), and in-hospital mortality, 2% (2 patients), were greater after resection for cavitary lesions with resultant complications versus for nodular disease: 41% versus 12% (p < or = 0.002) and 8% versus 0% (p < 0.005). Prolonged air leaks or bronchopleural fistulas were the most common complications (13 patients). Postoperative antifungal therapy was administered to 42% of patients (89% of cavitary and complicated). There were no cases of recurrence at follow-up (mean, 24 months). CONCLUSIONS Surgical intervention was indicated for only a few patients, most commonly for diagnostic dilemmas involving nodular disease, symptomatic nonresponsive cavitary disease, or complications. Prolonged air leaks were the main cause of morbidity. Resection should result in symptom resolution and long-term freedom from recurrence.

Idiopathic rapid-eye-movement (REM) sleep behavior disorder is associated with future development of neurodegenerative diseases.

Objective:To determine whether a diagnosis of idiopathic rapid-eye-movement sleep behavior disorder (RBD) is associated with a future risk of development of neurodegenerative diseases. Methods:We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, summary of best evidence, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. Results:A retrospective study of 44 consecutive patients diagnosed with idiopathic RBD demonstrated that 20 patients (45%) developed a neurologic disorder, most commonly Parkinson disease or Lewy body dementia, after a mean of 11.5 years from reported symptom onset and 5.1 years after RBD diagnosis. Conclusion:Currently available evidence is limited to cross-sectional and retrospective analyses of patients with RBD. Although ascertainment biases and the retrospective nature of the available evidence limits quantitative analyses, the diagnosis of idiopathic RBD portends a risk of greater than 45% for future development of a clinically defined neurodegenerative disease. This finding has significant implications for clinical neurologic and sleep disorder practice and neurodegenerative disease research.

Is obstructive sleep apnea an independent risk factor for stroke? A critically appraised topic.

Background:Obstructive sleep apnea (OSA) is associated with hypertension, atrial fibrillation, coronary artery disease, congestive heart failure, and diabetes. These disorders are also risk factors for stroke. Objective:To determine whether OSA increases the risk of stroke independently of other cerebrovascular risk factors. Methods:The objective was addressed through the development of a structured critically appraised topic. This evidence-based methodology included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of sleep medicine and vascular neurology. Results:A large observational cohort study was selected and appraised to address this prognostic question. The unadjusted analysis revealed that OSA (apnea-hypopnea index >5) was associated with stroke or death from any cause (hazard ratio, 2.24; 95% confidence interval [CI], 1.30–3.86; P = 0.004). The adjusted OSA analysis retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95% CI, 1.12–3.48; P = 0.01). In separate unadjusted analyses, OSA was associated with death and stroke with relative risks of 1.68 (95% CI, 1.10–2.25) and 5.16 (95% CI, 3.72–6.60), respectively. Conclusions:OSA independently contributes to stroke risk.