Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline

INTRODUCTION: This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine (AASM) guidelines on the evaluation and treatment of sleep-disordered breathing in adults. METHODS: The AASM commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use. In addition, the task force adopted foundational recommendations from prior guidelines as "good practice statements", that establish the basis for appropriate and effective diagnosis of OSA. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS: The following recommendations are intended as a guide for clinicians diagnosing OSA in adults. Under GRADE, a STRONG recommendation is one that clinicians should follow under most circumstances. A WEAK recommendation reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. Good Practice Statements: Diagnostic testing for OSA should be performed in conjunction with a comprehensive sleep evaluation and adequate follow-up. Polysomnography is the standard diagnostic test for the diagnosis of OSA in adult patients in whom there is a concern for OSA based on a comprehensive sleep evaluation.Recommendations: We recommend that clinical tools, questionnaires and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography or home sleep apnea testing. (STRONG). We recommend that polysomnography, or home sleep apnea testing with a technically adequate device, be used for the diagnosis of OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. (STRONG). We recommend that if a single home sleep apnea test is negative, inconclusive, or technically inadequate, polysomnography be performed for the diagnosis of OSA. (STRONG). We recommend that polysomnography, rather than home sleep apnea testing, be used for the diagnosis of OSA in patients with significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular condition, awake hypoventilation or suspicion of sleep related hypoventilation, chronic opioid medication use, history of stroke or severe insomnia. (STRONG). We suggest that, if clinically appropriate, a split-night diagnostic protocol, rather than a full-night diagnostic protocol for polysomnography be used for the diagnosis of OSA. (WEAK). We suggest that when the initial polysomnogram is negative and clinical suspicion for OSA remains, a second polysomnogram be considered for the diagnosis of OSA. (WEAK).

Reduced DNA-dependent protein kinase activity is associated with lung cancer.

Reduced DNA repair capacity of carcinogen-induced DNA damage is now thought to significantly influence inherent susceptibility to lung cancer. DNA-dependent protein kinase (DNA-PK) is a serine-threonine kinase activated by the presence of double-strand breaks in DNA that appears to play a major role in non-homologous recombination and transcriptional control. The purpose of this study was to determine whether DNA-PK activity varies among individuals and how this affects lung cancer risk. DNA-PK activity in peripheral mononuclear cells from individuals with lung cancer (n = 41) was compared with lung cancer-free controls (n = 41). Interindividual variability was seen within each group, however, significant differences (P = 0.03) in DNA-PK activity between cases and controls were seen when comparing the distribution of enzyme activity among these two groups. The percentages of cases and controls with DNA-PK activity in the ranges 2.5-5.0 and 7.6-10.0 units were 39 versus 20% and 7 versus 29%, respectively. The enzyme activity in peripheral mononuclear cells reflected that seen in bronchial epithelial cells, one progenitor cell for lung cancer, supporting the use of peripheral mononuclear cells for larger population-based studies of DNA-PK activity. Its role as a potential modifier for lung cancer risk was supported by the fact that cell growth in bronchial epithelial cells exposed to bleomycin was directly associated with enzyme activity. The results of this study demonstrate that reduced DNA-PK repair activity is associated with risk for lung cancer.

Reversal of sleep apnea hypopnea syndrome in end-stage renal disease after kidney transplantation.

Sleep apnea hypopnea syndrome (SAHS) is extremely common in patients with end-stage renal disease (ESRD). Although the underlying mechanisms linking these 2 conditions remain to be better defined, it is likely that multiple factors are involved. We report an individual with ESRD with severe SAHS that resolved after kidney transplantation. The improvement in SAHS paralleling the effective treatment of ESRD suggests the pathogenesis involves an unstable breathing pattern, possibly caused by an altered metabolic state, uremia, and changes in volume status. The possibility that elevations in cytokine levels could be involved also is discussed and deserves further attention.

Treatment of obstructive sleep apnea.

Options for the treatment of obstructive sleep apnea are varied and ever-expanding. This article reviews the currently available treatment modalities in an evidence-based format. Focus is placed on the efficacy and limitations of each particular therapy.

Individuals at high risk for lung cancer have airway epithelial cells with chromosome aberrations frequently found in lung tumor cells.

Identification of individuals at greatest risk of developing lung cancer could enhance the efficacy of intervention modalities, thereby greatly reducing mortality from this disease. One strategy for identifying these people is to establish molecular markers which reflect the severity of their cancerization field. Thus, investigations were initiated to determine of cells with chromosome aberrations frequently exhibited by lung tumor cells, i.e., trisomy 7, trisomy 20, and deletion of 9p23, are prevalent within the uninvolved airways of cancer patients. As a result, cells containing these aberrations were consistently found at significantly elevated levels by using fluorescence in situ hybridization (FISH). In contrast, cells collected from non-smokers who had never smoked were normal by this assay. The next objective was to determine of cells exhibiting these alterations are also present in upper airways of exposed, but cancer-free smokers and ex-uranium miners. The results showed that, although only a subset of these people will develop lung cancer in their lifetimes, they universally harbor increased numbers of abnormal cells within their airway epithelium. However, the number of sites with multiple verities of abnormal cells tended to be fewer compared with the cancer patients. Thus, quantifying cells with molecular alterations within the cancerization field of a smoker may delineate those with a lesser grade of damage, and these individuals may be at a lesser risk of developing disease. However, differences in the extent of genetic damage afforded by these assays may not clearly define individuals with pending disease, and additional molecular assays must be devised.

Detection of trisomy 7 in nonmalignant bronchial epithelium from lung cancer patients and individuals at risk for lung cancer.

Early identification and subsequent intervention are needed to decrease the high mortality rate associated with lung cancer. The examination of bronchial epithelium for genetic changes could be a valuable approach to identify individuals at greatest risk. The purpose of this investigation was to assay cells recovered from nonmalignant bronchial epithelium by fluorescence in situ hybridization for trisomy of chromosome 7, an alteration common in non-small cell lung cancer. Bronchial epithelium was collected during bronchoscopy from 16 cigarette smokers undergoing clinical evaluation for possible lung cancer and from seven individuals with a prior history of underground uranium mining. Normal bronchial epithelium was obtained from individuals without a prior history of smoking (never smokers). Bronchial cells were collected from a segmental bronchus in up to four different lung lobes for cytology and tissue culture. Twelve of 16 smokers were diagnosed with lung cancer. Cytological changes found in bronchial epithelium included squamous metaplasia, hyperplasia, and atypical glandular cells. These changes were present in 33, 12, and 47% of sites from lung cancer patients, smokers, and former uranium miners, respectively. Less than 10% of cells recovered from the diagnostic brush had cytological changes, and in several cases, these changes were present within different lobes from the same patient. Background frequencies for trisomy 7 were 1.4 +/- 0.3% in bronchial epithelial cells from never smokers. Eighteen of 42 bronchial sites from lung cancer patients showed significantly elevated frequencies of trisomy 7 compared to never smoker controls. Six of the sites positive for trisomy 7 also contained cytological abnormalities. Trisomy 7 was found in six of seven patients diagnosed with squamous cell carcinoma, one of one patient with adenosquamous cell carcinoma, but in only one of four patients with adenocarcinoma. A significant increase in trisomy 7 frequency was detected in cytologically normal bronchial epithelium collected from four sites in one cancer-free smoker, whereas epithelium from the other smokers did not contain this chromosome abnormality. Finally, trisomy 7 was observed in almost half of the former uranium miners; three of seven sites positive for trisomy 7 also exhibited hyperplasia. Two of the former uranium miners who were positive for trisomy 7 developed squamous cell carcinoma 2 years after collection of bronchial cells. To determine whether the increased frequency of trisomy 7 reflects generalized aneuploidy or specific chromosomal duplication, a subgroup of samples was evaluated for trisomy of chromosome 2; the frequency was not elevated in any of the cases as compared with controls. The studies described in this report are the first to detect and quantify the presence of trisomy 7 in subjects at risk for lung cancer. These results also demonstrate the ability to detect genetic changes in cytologically normal cells, suggesting that molecular analyses may enhance the power for detecting premalignant changes in bronchial epithelium in high-risk individuals.