Faculty Bibliography

STUDY OBJECTIVES: We examined agreement among multiple sleep clinicians when presented with clinical data plus the full tracings and data obtained from unattended limited monitoring (ULM) or a full polysomnography (PSG). METHODS: Subjects included 66 patients with complaints of sleep disordered breathing (SDB) and 19 volunteers willing to undergo 2 nights of ULM followed by PSG. Two assessment packages were created for each subject with identical clinical history (Hx) and ARES Symptom Questionnaire, plus the electronic record of signals collected on the ARES Unicorder (Hx+ULM) or on the PSG (Hx+PSG). Data were presented to 4 sleep-trained clinicians for diagnosis and treatment recommendation. For agreement on diagnosis and treatment, comparisons were made between clinicians using ULM or PSG, and within clinicians comparing both techniques. RESULTS: For diagnosis, agreement between pairs of clinicians using Hx+PSG ranged from 74% to 86% and 66% to 85% when using Hx+ULM. For treatment, agreement using Hx+PSG ranged from 74% to 86% and 58% to 77% when using Hx+ULM. Agreement between clinicians was highest in the subjects with the highest RDI and fell off markedly at the lowest RDI, irrespective of whether the clinicians used the Hx+PSG or Hx+ULM. This pattern was also seen for the decisions made by an individual clinician using Hx+ULM vs. Hx+PSG. CONCLUSION: Our data show that sleep clinicians have significant disagreements for diagnosis even when presented with the 'gold standard' of a PSG and clinical data. Agreement was high when the SDB index was elevated and lower when the SDB index was in the mild-to-moderate range, regardless of the technique used to obtain it

OBJECTIVE: The purpose of this study is to systematically characterize sleep disordered breathing (SDB) during acute heart failure (HF) decompensation. BACKGROUND: SDB, both Cheyne-Stokes breathing (CSB) and obstructive sleep apnea, is common in stable congestive HF patients, but its presence and characteristics in decompensated HF is unknown. METHODS: Eighteen men and 11 women (mean age 57+/-17 years, plasma brain-natriuretic peptide 1660+/-1179pg/ml, left ventricular ejection fraction 20+/-6%) admitted with decompensated systolic HF without other active cardiorespiratory morbidity underwent echocardiography and overnight bedside polysomnography within 48h of admission. Ten patients underwent follow-up polysomnography just before or immediately after hospital discharge. RESULTS: Twenty-eight of 29 patients demonstrated an apnea+hypopnea index (AHI)>5 events/h (mean AHI 41+/-29/h); 22 patients had an AHI>15/h. SDB was predominantly CSB (central events 39+/-29/h; obstructive events 2+/-2/h, p<0.001). Time in CSB was 51+/-33% of total sleep time (TST); nadir oxygen saturation (SaO2) was 81+/-10%. SDB was similar on admission vs. follow-up polysomnography (mean AHI 44+/-39/h vs. 38+/-31/h; CSB 53+/-38% vs. 46+/-37% TST). Follow-up polysomnography showed a higher nadir SaO2 than admission (84+/-11% vs. 79+/-12%, p=0.05), but TST with SaO2<90% was not reduced. CONCLUSIONS: CSB is common and severe in patients hospitalized with decompensated HF. Acute treatment of HF does not consistently improve CSB. The effect of CSB on ventricular function and prognosis in decompensated HF remains to be demonstrated

The extent to which a single breath measurement represents available gas dilutional as well as compressible thoracic volume in emphysema patients has not been quantified. We therefore measured single breath (TLCSB) and rebreathe helium dilution (TLCRB), and plethysmographic lung volume (TLCpleth), in fifty-five outpatients with clinical and radiographic emphysema, and in twenty-one normal controls. Among emphysema patients, TLCSB increasingly underestimated both TLCpleth and TLCRB as FEV1% predicted decreased (p for interaction=0.001 for both) by a mean of 1.7 l for TLCRB (p<0.001) and 2.2l for TLCpleth (p<0.001). In contrast, TLCRB underestimated TLCpleth by a mean of 0.5l (p<0.001) regardless of FEV1% (p for interaction=0.25). TLCSB, TLCRB, and TLCpleth showed strong agreement among normal subjects. We conclude that TLCSB underestimates available gas dilutional and compressible lung volume as physiologic emphysema severity increases. In contrast, TLCRB and TLCpleth show closer agreement which is unaffected by physiologic emphysema severity

The distinction between malignant mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike other tumor suppressor genes, is restricted mostly to mesenchymally derived tissues, we hypothesized that the WT1 gene products could serve as a potential marker for mesothelioma. The expression of WT1 mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens. WT1 mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WT1 mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a 52- to 54-kd protein was present in 4 mesothelioma cell lines. Immunostaining with this antibody localized the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WT1 mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, in particular, adenocarcinoma