Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy

STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment. CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.     

Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea

BACKGROUND: A strong association between obstructive sleep apnea (OSA) and the risk for cardiovascular and cerebrovascular diseases has been reported. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, able not only to reduce daytime sleepiness but also to improve cardiovascular and metabolic outcomes. Autoadjusting CPAP (APAP), an alternative treatment to CPAP, can reduce OSA symptoms while increasing long-term CPAP compliance without the high costs of CPAP titration. However, no data are available on the effects of APAP on cardiovascular risk factors METHODS: We performed standard full polysomnography; obtained plasma levels of glucose, insulin, and C-reactive protein (CRP); and measured systolic BP (SBP) and diastolic BP (DBP) in 31 patients with newly diagnosed, severe OSA. After standard CPAP titration, all subjects were randomized to CPAP or APAP treatment. Measurements were obtained at baseline and after 3 months of treatment. RESULTS: The two groups were similar in terms of age, sex, body mass index (BMI), and severity of OSA. SBP, DBP, heart rate (HR), homeostasis model assessment index (HOMA-IR), and CRP were similar in the two groups. After 3 months of treatment, BMI, HR, and compliance to therapy were also comparable. OSA indexes were significantly reduced in both groups. Significant reductions in SBP, DBP, and HOMA-IR were observed in the CPAP group but not in the APAP group, while CRP plasma levels were similarly reduced. CONCLUSIONS: Our results suggest that CPAP and APAP, despite significant effects on OSA indexes and symptoms, do not improve cardiovascular risk factors in the same fashion.     

Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been associated with increased morbidity and mortality, principally from cardiovascular disease, but the impact of nasal continuous positive airway pressure (CPAP) therapy is unclear. METHODS: We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously, most of whom had been prospectively followed up, having been the subject of an earlier report on cardiovascular risk factors in OSAS patients. The average follow-up period was 7.5 years. We compared the cardiovascular outcomes of those patients who were intolerant of CPAP (untreated group, 61 patients) with those continuing CPAP therapy (107 patients). RESULTS: CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group (48.3 [interquartile range (IQR), 33.6 to 66.4] vs 36.7 [IQR, 27.4 to 55], respectively; p = 0.02), but age, body mass index, and time since diagnosis were similar. Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up (14.8% vs 1.9%, respectively; p = 0.009 [log rank test]), but no significant differences were found in the development of new cases of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie, death and new cardiovascular disease combined) were more common in the untreated group than in the CPAP-treated group (31% vs 18%, respectively; p < 0.05). CONCLUSIONS: The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS.     

Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome

BACKGROUND: The impact of obstructive sleep apnea syndrome (OSAS) on the arterial baroreflex, and its significance, is still under debate. We investigated the baroreflex sensitivity (BRS) during sleep in well-selected OSAS patient and control subject cohorts METHODS: We performed a prospective study of 10 non-OSAS subjects, 14 subjects with mild-to-moderate OSAS, and 14 male subjects with severe OSAS subjects. Groups were matched for age, body mass index, and other relevant variables. Subjects had no other disease and were not receiving regular medication. BP was monitored beat-by-beat (Portapres; Finapres Medical Systems; Amsterdam, the Netherlands) at night during polysomnography. Spontaneous BRS was assessed by the sequence technique. Heart-rate correction was also applied to calculate BRS at a heart rate (HR) of 60 beats/min (BRS-60) to account for intersubject variability in baseline HR. Eight suitable patients were treated with continuous positive airway pressure (CPAP), and BRS measurements were repeated 6 weeks later. RESULTS: BRS and BRS-60 were significantly lower in patients with severe OSAS than in patients with mild-to-moderate OSAS and in non-OSAS subjects, and a separate sleep-stage analysis revealed this difference to be evident in stage 2 non-rapid eye movement sleep and during nocturnal wakefulness. There was no difference in BRS and BRS-60 between non-OSAS subjects and patients with mild-to-moderate OSAS. In multivariate analysis, the desaturation index was the only independent predictor of depressed BRS. CPAP therapy significantly improved the BRS measures. CONCLUSION: Patients with severe OSAS demonstrate depressed BRS during sleep, which may contribute to the cardiovascular pathophysiology in OSAS patients.     

Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy

BACKGROUND: Sympathetic nerve activity is increased in awake and regularly breathing patients with obstructive sleep apnea (OSA). Over time, repetitive hypoxic stress could alter sympathetic chemoreflex function in OSA. METHODS: We determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1, for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24 patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47 +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography], BP, and ventilation were monitored. RESULTS: Basal MSNA was higher in OSA patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4 bursts per minute, respectively; p < 0.05). Furthermore, compared to control subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p < 0.001). Whereas the ventilatory responses to hypoxia tended to be increased in OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45). The neurocirculatory reflex responses to handgrip exercise and to the CPT were similar in the two groups (p = not significant). In OSA patients who were retested after 1 to 24 months of continuous positive airway pressure (CPAP) therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p < 0.01) decreased significantly, whereas the ventilatory responses remained unchanged (p = 0.82). CONCLUSION: These data suggest that the sympathetic responses to hypoxic chemoreflex stimulation are enhanced in OSA and may normalize in part following CPAP therapy.     

Continuous positive airway pressure therapy improves cardiovascular autonomic function for persons with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular morbidity. Dysfunction of the cardiovascular autonomic nervous system may be a potential mechanism whereby SDB is linked to cardiovascular disease. Repetitive sympathetic activation during apneic episodes may impair cardiovascular reflex function, and increased sympathetic activity can stimulate renin release. Given that patients with SDB may have reduced cardiovascular autonomic function, the purpose of this study was to determine whether treatment with continuous positive airway pressure (CPAP) for 6 weeks would improve autonomic function. METHODS: Twenty-nine participants with a diagnosis of SDB, who completed 6 weeks of CPAP therapy, were evaluated for cardiovascular autonomic nerve fiber function at baseline and post therapy. Autonomic function tests included the following: R-R interval variation during deep breathing measured by vector analysis (ie, mean circular resultant [MCR]) and expiration/inspiration (E/I) ratio; and the Valsalva maneuver. Participants were also evaluated prior to CPAP therapy for plasma renin activity levels. RESULTS: Participants in this study showed improved cardiovascular autonomic function after 6 weeks of treatment (baseline vs follow-up) as assessed by the mean (+/- SD) MCR (33.2 +/- 22.5 vs 36.9 +/- 24.2, respectively; p < 0.05) and E/I ratio (1.20 +/- 0.12 vs 1.24 +/- 0.14, respectively; p < 0.01). Improved vagal tone was also noted for subjects with elevated renin levels. CONCLUSIONS: Treatment of SDB with CPAP for 6 weeks improved vagal tone and may be beneficial in reducing the risk of developing clinical manifestations of cardiovascular autonomic dysfunction (eg, increased risk of mortality).     

Prognosis of patients with heart failure and obstructive sleep apnea treated with continuous positive airway pressure

BACKGROUND: Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown. Aims: To determine whether CPAP therapy and compliance affects the prognosis of HF patients with OSA. METHODS: We classified 88 patients with HF and moderate-to-severe OSA into a CPAP-treated group (n = 65) and an untreated group (n = 23), and then those treated with CPAP were further subclassified according to CPAP therapy compliance. The frequency of death and hospitalization was analyzed using multivariate analysis. RESULTS: During a mean (+/- SD) period of 25.3 +/- 15.3 months, 44.3% of the patients died or were hospitalized. Multivariate analysis showed that the risk for death and hospitalization was increased in the untreated group (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.07 to 3.68; p = 0.030) and in less compliant CPAP-treated patients (HR, 4.02; 95% CI, 1.33 to 12.2; p = 0.014). CONCLUSION: Therapy with CPAP significantly reduced the risk of death and hospitalization among patients with HF and OSA. However, reduced compliance with CPAP therapy was significantly associated with an increased risk of death and hospitalization.     

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.     

Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome

BACKGROUND: Obesity, hypertension, dyslipidemia, and hyperglycemia are prevalent in obstructive sleep apnea syndrome (OSAS). Metabolic syndrome, however, is defined by visceral fat obesity plus at least two of these factors. However, whether OSAS contributes to the development of metabolic syndrome has not been defined. We investigated whether the components of metabolic syndrome were associated with OSAS in nonobese patients. METHODS: We investigated the occurrence of hypertension, dyslipidemia, and hyperglycemia in 42 men with OSAS and 52 men without OSAS matched for age, body mass index (BMI), and visceral fat accumulation. RESULTS: Although serum levels of triglycerides, high-density lipoprotein cholesterol, and diastolic BP did not differ significantly between the two groups, fasting blood glucose (111 +/- 6 mg/dL vs 93 +/- 3 mg/dL) [mean +/- SE] and the percentage of hypertensive patients (45% vs 15%) were significantly higher in the group with OSAS. In addition, a significantly higher percentage of patients with OSAS (19% vs 4%) had at least two of the following: hypertension, hyperglycemia, and dyslipidemia. Logistic regression analysis showed that the apnea-hypopnea index value was the predictor of number of metabolic syndrome parameters such as hypertension, hyperglycemia, and dyslipidemia, while BMI and lowest arterial oxygen saturation during sleep did not. CONCLUSION: Independent of visceral fat obesity, OSAS was associated with hypertension, dyslipidemia, and hyperglycemia. It is possible that OSAS may predispose even nonobese patients to the development of metabolic syndrome.     

Relationship between serum substance P levels and daytime sleepiness in obstructive sleep apnea syndrome

OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum substance P levels, and that this effect might in turn contribute in excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and 15 age-matched nonapneic control subjects were enrolled in this study. Full polysomnography was performed in all patients. Single blood samples were drawn between 8:00 am and 9:00 am after the sleep study. Substance P levels were analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age, gender, body mass index, smoking habit, and snoring between the two groups. Serum substance P levels in the OSAS group were significantly lower than that in the control group (p < 0.0001). Serum substance P levels were positively correlated with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r = 0.324, p = 0.049) phases. Serum substance P levels were negatively correlated with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total apneas during the night (r = - 0.247, p = 0.036), number of respiratory events during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p = 0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We concluded that EDS seen in some of the OSAS patients might be associated with various pathophysiologic mechanisms including substance P levels.     

Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure

BACKGROUND: Polysomnography findings between matched groups with obstructive sleep apnea (OSA) and OSA plus obesity-hypoventilation syndrome (OHS) before and after continuous positive airway pressure (CPAP), particularly in the extremely severe obese (body mass index [BMI] >or= 50 kg/m2), are unclear. DESIGN: Prospective study of subjects (BMI >or= 50 kg/m2) undergoing diagnostic polysomnography. Subjects with an apnea-hypopnea index (AHI) >or= 15/h underwent a second polysomnography with CPAP. The effect of 1 night of CPAP on sleep architecture, AHI, arousal indexes, and nocturnal oxygenation was assessed. OHS was defined as those subjects with obesity, PaCo2 > 45 mm Hg, and PaO2 < 70 mm Hg in the absence of lung disease. RESULTS: Twenty-three subjects with moderate-to-severe OSA and 23 subjects with moderate-to-severe OSA plus OHS underwent a 1-night trial of CPAP. Both groups were matched for spirometry, BMI, and AHI, but oxygen desaturation was worse in the OSA-plus-OHS group. CPAP significantly improved rapid eye movement (REM) duration (p < 0.005), AHI (p < 0.005), arousal indexes (p < 0.005), and percentage of total sleep time (TST) with oxygen saturation (SpO2) < 90% (p < 0.005) in both groups. In subjects with OSA plus OHS, 43% continued to spend > 20% of TST with SpO2 < 90%, compared to 9% of the OSA group, despite the adequate relief of upper airway obstruction. CONCLUSIONS: Extremely severe obese subjects (BMI >or= 50 kg/m2) with moderate-to-severe OSA plus OHS exhibit severe oxygen desaturation but similar severities of AHI, arousal indexes, and sleep architecture abnormalities when compared to matched subjects without OHS. CPAP significantly improves AHI, REM duration, arousal indexes, and nocturnal oxygen desaturation. Some subjects with OHS continued to have nocturnal desaturation despite the control of upper airway obstruction; other mechanisms may contribute. Further long-term studies assessing the comparative role of CPAP and bilevel ventilatory support in such subjects with OHS is warranted.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.     

Variability of the prevalence of undiagnosed airflow obstruction in smokers using different diagnostic criteria

PURPOSES: To estimate the prevalence of undiagnosed airflow obstruction (AFO) in Hong Kong smokers with no previous diagnosis of respiratory disease, and to assess its variability when applying different prediction equations and diagnostic criteria. METHODS: A multicenter, population-based, cross-sectional prevalence study was performed in smokers aged 20 to 80 years. Three different criteria (fixed 70% [Global Initiative for Chronic Obstructive Lung Disease and British Thoracic Society], fixed 75%, and European Respiratory Society [ERS]) were applied to define a lower limit of normal (LLN) of the FEV(1)/FVC ratio to compare with the Hong Kong Chinese reference equation (criterion 1), which had used a distribution-free method to obtain the lower fifth percentile of FEV(1)/FVC ratio as the LLN. RESULTS: In 525 male patients, using criterion 1 (local internal prediction equation) and defining AFO as FEV(1)/FVC less than LLN, the overall prevalence of AFO was 13.7%: 8.3% in age > or = 20 to 40 years, 14.0% in age > or = 40 to 60 years, and 17.8% in age > or = 60 to 80 years. When the local internal prediction equation was used as the comparison reference, the fixed-ratio methods tended to miss AFO in younger age groups and overdiagnose AFO in old age, while the ERS criteria, which uses an almost lower fifth percentile-equivalent method, showed less of such a trend but still only showed moderate agreement with criterion 1. CONCLUSIONS: Undiagnosed AFO was prevalent in Hong Kong smokers. Estimated prevalence rates were highly affected by the criteria used to define AFO. The predicted lower fifth percentile values calculated from a local reference equation as the LLN of FEV(1)/FVC ratio should be used for the diagnosis of AFO.     

Spirometric criteria for airway obstruction: Use percentage of FEV1/FVC ratio below the fifth percentile, not < 70%

BACKGROUND: Current authoritative spirometry guidelines use conflicting percentage of FEV1/FVC ratios (FEV1/FVC%) to define airway obstruction. The American Thoracic Society/European Respiratory Society Task Force characterizes obstruction as a FEV1/FVC% below the statistically defined fifth percentile of normal. However, many recent publications continue to use the Global Initiative for Chronic Obstructive Lung Disease (GOLD) primary criterion that defines obstruction as a FEV1/FVC% < 70%. Data from the Third National Health and Nutrition Examination Survey (NHANES-III) should identify and quantify differences, help resolve this conflict, and reduce inappropriate medical and public health decisions resulting from misidentification. METHODS: Using these two guidelines, individual values of FEV1/FVC% were compared by decades in 5,906 healthy never-smoking adults and 3,497 current-smokers of black (African American), Hispanic (Latin), or white ethnicities aged 20.0 to 79.9 years. RESULTS: In the never-smoking population, the lower limits of normal used in other reference equations fit reasonably well the NHANES-III statistically defined fifth percentile guidelines. But nearly one half of young adults with FEV1/FVC% below the NHANES-III fifth percentile of normal were misidentified as normal because their FEV1/FVC% was > 70% (abnormals misidentified as normal). Approximately one fifth of older adults with observed FEV1/FVC% above the NHANES-III fifth percentile had FEV1/FVC% ratios < 70% (normals misidentified as abnormal). CONCLUSIONS: The GOLD guidelines misidentify nearly one half of abnormal younger adults as normal and misidentify approximately one fifth of normal older adults as abnormal.     

Lung function accurately predicts hypercapnia in patients with Duchenne muscular dystrophy

BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), implementation of mechanical ventilation depends on sleep investigation and measurement of CO2 tension. The objective of this cross-sectional study was to determine which noninvasive lung function parameter best predicts nocturnal hypercapnia and diurnal hypercapnia in these patients. METHODS: According to transcutaneous CO2 (TcCO2) measurement, 114 DMD patients were classified into three groups: nocturnal hypercapnia (n = 38) [group N], diurnal hypercapnia (n = 39), despite nocturnal ventilation (group D), and 24-h normocapnia and spontaneous breathing (n = 37) [group S] as control. TcCO2 tension and lung function variables included vital capacity (VC) and maximal inspiratory pressure (MIP), and breathing pattern variables included tidal volume (Vt) and respiratory rate (RR), measured at the time of group inclusion. The rapid and shallow breathing index (RSBI [RR/Vt]) and Vt/VC ratio were calculated. Areas under the curve from the receiver operating characteristic (ROC) were calculated for those parameters. RESULTS: Compared to group S, lung function was significantly worse in group N and group D. VC, RR, and RSBI distinguished group S from group N by ROC comparison. Cut-off values of VC < or = 680 mL (ROC, 0.968), MIP < or = 22 cm H2O (ROC, 0.928), and Vt/VC > 0.33 (ROC, 0.923) accurately discriminated group D from group N, but RSBI, RR, and Vt did not. CONCLUSIONS: Lung function is useful to predict nocturnal hypercapnia in patients with DMD. Moreover, VC < 680 mL is very sensitive to predict daytime hypercapnia.     

Depressed myocardial contractile reserve in patients with obstructive sleep apnea assessed by tissue Doppler imaging with dobutamine stress echocardiography

BACKGROUND: Hypoxia has been suggested to affect myocardial contractile function in patients with obstructive sleep apnea (OSA). We sought to determine whether myocardial contractile reserve (MCR), as evaluated by echocardiographic tissue Doppler imaging with dobutamine stress (TDDS), might be depressed in OSA patients. METHODS: Thirty patients with suspected OSA (25 men and 5 women; mean age, 51 +/- 11 years [+/- SD]) underwent overnight polysomnography and TDDS. Peak myocardial systolic velocity (Sm) and peak myocardial early diastolic velocity (Em) in the 12 myocardial segments of the left ventricular (LV) walls were averaged, and the mean Sm and Em during TDDS were compared between patients with apnea-hypopnea index (AHI) <15/h (group 1, n = 13) and those with AHI >/= 15/h (group 2, n = 17). MCR was calculated as the difference between the resting and peak Sm during TDDS. RESULTS: In both groups, Sm increased dose dependently during TDDS. However, the relative increase in Sm was significantly lower in group 2, resulting in a lower value of MCR (5.5 +/- 1.2 cm/s vs 7.4 +/- 1.3 cm/s, p < 0.001). The Em was lower in group 2 compared with group 1 throughout TDDS. MCR was correlated significantly with AHI (r = - 0.67, p < 0.0001), resting Em (r = 0.53, p < 0.005), and body mass index (r = - 0.46, p < 0.05) independent of the LV mass index. CONCLUSIONS: OSA can affect MCR, implying an etiologic contribution from repetitive hypoxic events. TDDS could identify subtle abnormalities of OSA-related cardiac involvement.     

Impalpable pulmonary nodules with ground-glass opacity: Success for making pathologic sections with preoperative marking by lipiodol

BACKGROUND: The developments in high-resolution CT scanning have increased the chance of detecting small bronchioloalveolar carcinoma (BAC) or atypical adenomatous hyperplasia (AAH) that appears as a ground-glass opacity (GGO). However, these lesions are not only difficult to localize during surgery, but they are also hard to make pathologic sections of because they are usually impalpable. Here, we report a method of making pathologic sections for impalpable GGO lesions. METHODS: Twenty-nine impalpable GGO lesions < 1 cm in size were marked by 0.4 to 0.5 mL of lipiodol under CT scan before surgery. The lesions were resected under C-arm fluoroscopy. The radiopaque areas marked by lipiodol within the formalin-fixed specimens were cut serially under conventional fluoroscopy for pathologic examinations. RESULTS: The mean (+/- SD) size of the lesions was 0.5 +/- 0.2 cm (range, 0.2 to 1 cm), and the mean depth from the pleural surface was 1.6 +/- 1.4 cm (range, 0.2 to 6 cm). The mean number of sections submitted for pathologic examinations was 2.3 +/- 1.7 per lesion (range, 1 to 7 per lesion). While 11 of the 29 lesions (38%) were invisible even on the cut surface of the specimens, all were demonstrated in hematoxylin-eosin sections. The pathologic diagnosis was BAC in 17 lesions, AAH in 10 lesions, and organized pneumonia in 2 lesions. The use of lipiodol did not affect the pathologic findings. CONCLUSIONS: The use of fluoroscopy to cut sections from resected specimens after preoperative marking with lipiodol was useful for making pathologic sections of impalpable GGOs < 1 cm in size.     

Nocturnal noninvasive ventilation

Nocturnal noninvasive ventilation (NNV), the provision of ventilatory assistance via a noninvasive interface mainly during sleep, has assumed an important role in the management of chronic hypoventilatory syndromes. This review focuses on recent developments related to the use of NNV to treat various forms of chronic respiratory failure or insufficiency. In the past, NNV has been used mainly to treat respiratory insufficiency in patients with neuromuscular disease (NMD) or chest wall deformity; it should be instituted when these patients have orthopnea or daytime symptoms associated with nocturnal hypoventilation. An emerging application is to treat obesity-hypoventilation syndrome, particularly in continuous positive airway pressure (CPAP) failures. Additionally, it has a role in managing some patients with obstructive sleep apnea who are hypoventilating or find the lower expiratory pressure with bilevel positive pressure ventilators more tolerable than with CPAP alone. NNV to treat severe, stable COPD remains controversial, although a subgroup of patients with hypercapnea and sleep-disordered breathing (SDB) seems most likely to respond favorably. NNV to treat central SDB in patients with congestive heart failure continues to be investigated. Recent findings from a Canadian CPAP trial were disappointing, but preliminary results on a novel adaptive NNV mode are promising.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea is common in obese people. Leptin is an adipocyte-derived signaling factor that has an important role in metabolic control. There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the relation between polymorphisms of the leptin and leptin receptor (LEPR) genes and OSAS. METHODS: The study population consisted of 130 patients with OSAS and 50 healthy control subjects. All the subjects were Japanese. Diagnostic polysomnography was performed in all patients and control subjects. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and three single nucleotide polymorphisms (SNPs) [Lys109Arg (A/G) in exon 4, Gln223Arg (A/G) in exon 6, and Lys656Asn (G/C) in exon 14] in the LEPR gene were examined. RESULTS: There were no significant differences in allelic frequencies and genotype distributions of the examined polymorphisms of the leptin and LEPR genes between OSAS patients and control subjects. For the LEPR gene, the wild-type alleles of the Gln223Arg and Lys656Asn SNPs had a marginally significant effect on mild OSAS, which was defined as an apnea-hypopnea index from 10 and 20 events/h in the dominant model. CONCLUSIONS: The tetranucleotide repeat polymorphism of the leptin gene and the Lys109Arg, Gln223Arg, and Lys656Asn SNPs in the LEPR gene were not associated with OSAS in the Japanese population. Further studies are required to confirm the association of the wild types of Gln223Arg and Lys656Asn SNPs with the severity of OSAS.