Effectiveness of high-flow nasal cannula on pulmonary rehabilitation in subjects with chronic respiratory failure.

BACKGROUND: The effects of exercise training using both high fraction of inspired oxygen (FIO2) and high flow oxygen delivered through a high-flow nasal cannula (HFNC) on exercise capacity in patients with chronic respiratory failure (CRF) receiving long-term oxygen therapy (LTOT) are unknown. METHODS: In this randomized study, 32 patients with CRF receiving LTOT were assigned to undergo 4 weeks of exercise training on a cycle ergometer using an HFNC (flow: 50 L/min) with a FIO2 of 1.0 (HFNC group; n = 16) or ordinary supplemental oxygen via a nasal cannula (flow: 6 L/min) (oxygen group; n = 16). A 6-min walking test and a constant-load test were performed before and after 4 weeks of exercise training. RESULTS: Following 4 weeks of exercise training, change in the 6-min walking distance was significantly greater in the HFNC than in the oxygen group (55.2 ± 69.6 m vs. -0.5 ± 87.3 m; p = 0.04). However, there was no significant difference between the two groups in the degree of improvement in the duration of the constant-load exercise test after exercise training. CONCLUSIONS: Considering the effect on daily activities (e.g., walking), exercise training using both high FIO2 and high flow through an HFNC is a potentially superior exercise training modality for patients with CRF receiving LTOT. Clinical Trial Registration - http://www. CLINICALTRIALS: gov. Unique identifier: NCT02804243.

Low Levels of PaO2 after Long-term Noninvasive Ventilation are a Poor Prognostic Factor in Patients with Restrictive Thoracic Disease.

Objective The effects of partial pressure of arterial oxygen (PaO2) after introducing long-term noninvasive ventilation (NIV) on the prognosis of patients with restrictive thoracic disease and chronic respiratory failure are not exactly known. Methods Data from 141 patients with restrictive thoracic disease under long-term nocturnal NIV were retrospectively examined. We divided the patients into 2 groups according to the daytime PaO2 value while breathing spontaneously with prescribed oxygen at 12 months after introducing NIV: PaO2≥80 Torr group (n=76) and PaO2<80 Torr group (n=65). Results During the 4-year follow-up, the mortality was significantly higher in the PaO2<80 Torr group than in the PaO2≥80 Torr group (50.8% vs. 32.9%, p=0.03). Independent factors associated with the 4-year mortality after introducing NIV determined by a multivariate logistic regression analysis were a low body mass index [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.77 to 0.97; p=0.01], assisted mode with NIV (OR 4.11; 95% CI, 1.79 to 9.45; p=0.0009), hospitalization during the first year of introducing NIV (OR 1.72; 95% CI, 1.06 to 2.79; p=0.03), and daytime PaO2<80 Torr at 12 months after introducing NIV (OR 2.30; 95% CI, 1.03 to 5.10; p=0.04). Conclusion A low daytime PaO2 at 12 months after introducing NIV was an independent risk factor for mortality. Keeping the daytime PaO2≥80 Torr through the adjustment of the nocturnal NIV settings or increased diurnal supplemental oxygen may help improve the prognosis in patients with restrictive thoracic disease who are under NIV.

Successful desensitization therapy for a patient with isoniazid-induced hypersensitivity pneumonia.

A 57-year-old male was diagnosed with mycobacterium tuberculoma and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Three weeks after initiation of treatment, he presented with fever and appetite loss. Chest radiograph showed diffuse micronodular shadows on both lung fields. High-resolution chest computed tomography findings were diffuse parenchymal micronodules in both lungs, which was consistent with hypersensitivity pneumonia. Because drug-induced pneumonia was suspected, the antituberculous regimen was discontinued. The symptoms and diffuse micronodular shadows improved. A drug lymphocyte stimulation test was only positive for isoniazid, so we suspected that the pneumonia was induced by isoniazid. Rifampicin and ethambutol were reintroduced without any recurrence of the abnormal shadows. Next, we tried desensitization to isoniazid over a period of two weeks, which was successful without any adverse events. Although isoniazid-induced pneumonia is extremely rare, it is important to recognize that isoniazid can cause such an adverse reaction. In addition, drug desensitization may be useful in drug-induced pneumonia.

Plasma Incretin Levels and Dipeptidyl Peptidase-4 Activity in Patients with Obstructive Sleep Apnea.

RATIONALE: Incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) activity are important factors in glucose metabolism and have not been investigated in patients with obstructive sleep apnea (OSA). OBJECTIVES: The objective of this study was to investigate the association between OSA and incretin and DPP-4 activity. METHODS: This study included 96 consecutive patients without diabetes who were suspected of having OSA. We investigated the fasting and post-prandial incremental area under the curve (IAUC) of GLP-1, GIP serum levels, and serum DPP-4 activity levels, as well as their association with OSA. Changes in clinical variables were evaluated in the 43 patients who continued continuous positive airway pressure therapy for 3 months. MEASUREMENTS AND MAIN RESULTS: Apnea-hypopnea index was an independent determining factor for fasting GLP-1 (ß = 0.31; P = 0.0019) and IAUC GIP (ß = -0.21; P = 0.037) after adjusting for known confounding factors. In those with very severe OSA (apnea-hypopnea index ≥50), the IAUCs for GLP-1 and GIP were significantly decreased, while fasting GLP-1 and fasting GIP were significantly increased. DPP-4 activity had no relation to OSA parameters or severity, while body mass index was significantly higher in those with severe OSA. Although significant changes in incretin secretion were not seen for 3 months after onset of continuous positive airway pressure therapy, the fasting GLP-1 level in the treated patients with severe OSA decreased to the same level as in untreated patients with normal to moderately severe OSA. CONCLUSIONS: OSA is associated with elevated serum levels of the incretin hormones GLP-1 (fasting) and GIP (post-prandial) in patients without diabetes. A significant association between body mass index and DPP-4, which is said to exist in healthy persons, was not found in the patients with OSA. Fasting GLP-1 in patients without diabetes with OSA may influence fasting glucose levels.

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity.

RATIONALE: Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. OBJECTIVES: To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. METHODS: Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. RESULTS: Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. CONCLUSIONS: Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation.

Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment.

STUDY OBJECTIVES: There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. METHODS: Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index ≥ 15, n = 39) participants in a single institute. There were no differences in age, sex, BMI, or visceral fat accumulation between the two groups. Twenty-one patients with moderate-to-severe OSA who received CPAP treatment also prospectively underwent the same testing following 3 months of CPAP treatment. RESULTS: Although fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p < 0.01). After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA participants, AG/DAG did not change significantly, but other ghrelin-related parameters including AG/insulin significantly decreased compared with values before treatment but remained higher than in no or mild OSA. CONCLUSION: Among several important metabolic factors, ghrelin-related factors had the strongest associations with moderate-to-severe OSA. These results indicate that continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of CPAP treatment. Methods to prevent OSA as well as treatment in its early stage may be recommended.

Association between endothelial function (assessed on reactive hyperemia peripheral arterial tonometry) and obstructive sleep apnea, visceral fat accumulation, and serum adiponectin.

BACKGROUND: Visceral obesity, low adiponectin, and severe obstructive sleep apnea (OSA) are associated with cardiovascular diseases, but the interactions among these factors on endothelial dysfunction are not well known. METHODS AND RESULTS: Endothelial function in 133 patients after polysomnography was evaluated as reactive hyperemia index (RHI) on reactive hyperemia peripheral arterial tonometry. Visceral obesity was defined as visceral fat area ≥100 cm(2)on computed tomography. RHI was significantly correlated with apnea hypopnea index (AHI), visceral fat area, and serum adiponectin (r=-0.24, P=0.0055, r=-0.19, P=0.031, and r=0.20, P=0.019, respectively). RHI in patients with visceral obesity was significantly decreased in the presence of severe OSA (AHI ≥30; P=0.042). On multivariate regression analysis, only severe OSA remained as an independent predictive factor of RHI (P=0.024, R(2)=5.4%). RHI in patients with severe OSA (n=44) was significantly improved after 3 months of continuous positive airway pressure (CPAP) treatment (1.78±0.40 before CPAP vs. 2.00±0.53 after CPAP, P=0.013), similarly to those with AHI <30 (P=0.45). CONCLUSIONS: Severe OSA, but not visceral fat area or serum adiponectin, was independently associated with endothelial function according to RHI. In addition, impaired endothelial function was reversible following 3 months of CPAP treatment.

Successful treatment of two consecutive cases of pulmonary pleomorphic carcinoma with platinum chemotherapy.

Pulmonary pleomorphic carcinoma (PPC) is a rare pulmonary malignant tumor that has a more aggressive clinical course and a poorer prognosis compared with non-small cell lung cancer (NSCLC) due to its resistance to chemotherapy and radiotherapy. In patients with advanced or relapsed PPC, it has been reported that the response rate to chemotherapy regimens known to be effective in patients with NSCLC is only 0-17%. The present study reports the cases of two consecutive patients with advanced PPC who exhibited marked responses to chemotherapy with carboplatin plus paclitaxel chemotherapy and long-term survival without tumor progression. This suggests that carboplatin plus paclitaxel chemotherapy is a good option for the treatment of advanced PPC.

Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels.

BACKGROUND AND OBJECTIVE: Obesity hypoventilation syndrome (OHS) prevalence was previously estimated at 9% in patients with obstructive sleep apnoea (OSA) in Japan. However, the definition of OSA in that study was based on an apnoea-hypopnoea index (AHI) of ≥ 20/h rather than ≥ 5/h. Therefore, the prevalence of OHS in OSA was not measured in the same way as for Western countries. Our study objectives were to investigate the characteristics of Japanese patients with OHS. METHODS: Nine hundred eighty-one consecutive patients investigated for suspected OSA were enrolled. At least 90% of them were from urban areas, including 162 with obese OSA (body mass index (BMI) ≥ 30 kg/m(2) and AHI ≥ 5/h). RESULTS: The prevalence of OHS (BMI 36.7 ± 4.9 kg/m(2) ) in OSA and that in obese OSA were 2.3% and 12.3%, respectively. Multiple regression analysis revealed that independent of age and BMI, arterial oxygen pressure (contribution rate (R(2) ) = 7.7%), 4% oxygen desaturation index (R(2) = 8.9%), carbon monoxide diffusing capacity/alveolar volume (R(2) = 8.3%), haemoglobin concentration (R(2) = 4.9%) and waist circumference (R(2) = 4.9%) were independently associated with arterial carbon dioxide pressure. After 12.3 ± 4.6 months of CPAP treatment, more than 60% of OHS patients no longer had hypercapnia. CONCLUSIONS: The prevalence of OHS in OSA in Japan was 2.3%. The mean BMI of patients with OHS in Japan was lower than that in Western countries (36.7 kg/m(2) vs 44.0 kg/m(2) ).

Differences in associations between visceral fat accumulation and obstructive sleep apnea by sex.

RATIONALE: The difference in mortality from obstructive sleep apnea (OSA) by sex is an important issue. Visceral fat, a significant risk factor for cardiovascular disease, was reported to be closely related to OSA. OBJECTIVES: To assess the different associations between OSA and visceral fat area (VFA) by sex, which might account for the different prognosis in men and women with OSA. METHODS: Participants were 271 men and 100 women consecutively hospitalized for examination of OSA from October 2008 to December 2010. Among the 371 participants, relationships were analyzed between fat areas by computed tomography, comorbidity, polysomnographic data, arterial blood gas, pulmonary function, and venous blood data. Multiple regression analyses were performed to identify variables independently associated with VFA and subcutaneous fat area for each sex. MEASUREMENTS AND MAIN RESULTS: Despite similar body mass index (BMI) and waist circumference, men had larger VFA, more severe OSA, and more severe dyslipidemia than women. Multiple regression analyses revealed that in men, not only age and BMI but also minimal oxygen saturation (contribution rate [R(2)], 4.6%) during sleep, and alveolar-arterial oxygen difference (R(2) = 7.6%) were independently associated with VFA. Conversely, VFA was associated only with BMI in women. CONCLUSIONS: Only in men was OSA independently associated with VFA. The lesser associations between OSA and visceral fat in women might account for the lower impact of OSA on cardiovascular disease or mortality in women.

Predictive factors for reintubation following noninvasive ventilation in patients with respiratory complications after living donor liver transplantation.

BACKGROUND: Postoperative respiratory complications are a major cause of mortality following liver transplantation (LT). Noninvasive ventilation (NIV) appears to be effective for respiratory complications in patients undergoing solid organ transplantation; however, mortality has been high in patients who experienced reintubation in spite of NIV therapy. The predictors of reintubation following NIV therapy after LT are not exactly known. METHODS: Of 511 adult patients who received living-donor LT, data on the 179 who were treated by NIV were retrospectively examined. RESULTS: Forty-three (24%) of the 179 patients who received NIV treatment required reintubation. Independent factors associated with reintubation by multivariate logistic regression analysis were controlled preoperative infections (odds ratio [OR] 8.88; 95% confidence interval (CI) 1.64 to 48.11; p = 0.01), ABO-incompatibility (OR 4.49; 95% CI, 1.50 to 13.38; p = 0.007), and presence of postoperative pneumonia at the time of starting NIV (OR 3.28; 95% CI, 1.02 to 11.01; p = 0.04). The reintubated patients had a significant higher rate of postoperative infectious complications and a significantly longer intensive care unit stay than those in whom NIV was successful (p<0.0001). Of the 43 reintubated patients, 22 (51.2%) died during hospitalization following LT vs. 8 (5.9%) of the 136 patients in whom NIV was successful (p<0.0001). CONCLUSIONS: Because controlled preoperative infection, ABO-incompatibility or pneumonia prior to the start of NIV were independent risk factors for reintubation following NIV, caution should be used in applying NIV in patients with these conditions considering the high rate of mortality in patients requiring reintubation following NIV.

Flexible positive airway pressure improves treatment adherence compared with auto-adjusting PAP.

STUDY OBJECTIVES: There are no clinical data comparing adherence and quality of life between auto-adjusting positive airway pressure (APAP) and two different flex positive airway pressure (PAP) devices (A-Flex, C-Flex) in patients with obstructive sleep apnea (OSA). DESIGN AND SETTING: Ninety-three patients in whom OSA was newly diagnosed were randomly assigned to receive 3 mo of APAP (n = 31), APAP with C-Flex (n = 31), or APAP with A-Flex (n = 31). Objective adherence was determined after 3 mo of CPAP treatment, and the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Calgary Sleep Apnea Quality of Life Index (SAQLI) were examined at baseline and after 3 mo. After 3 mo, patients in the APAP with A-Flex group and those in the APAP with C-Flex group were crossed over and those in the APAP group were switched to A-Flex for an additional 3 mo. MEASUREMENTS AND RESULTS: The groups were similar demographically. Treatment adherence during the first 3 mo was significantly greater in the APAP with C-Flex group (APAP with C-Flex: 5.19 ± 1.84 h/night versus APAP: 3.96 ± 1.66 h/night versus APAP with A-Flex: 4.27 ± 2.12 h/night, P = 0.04). There was a significant improvement in two of four of the SAQLI domain scores and in the ESS and PSQI in the APAP with C-Flex group. Adherence significantly improved among the poor compliers (< 4 h/night of use) in the APAP group after change to APAP with A-Flex (P = 0.01). CONCLUSIONS: Of these three modes of PAP delivery, adherence was greatest with APAP with C-Flex. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00873977.

Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia.

BACKGROUND: Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. OBJECTIVES: To evaluate the relationship between Ngal and OSA in clinical practice. METHODS: In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients. RESULTS: The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27). CONCLUSIONS: Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.

Impaired endothelium-dependent vasodilator response in patients with pulmonary fibrosis.

BACKGROUND: Recent epidemiological evidence indicates an association between cardiovascular diseases and pulmonary fibrosis. The vascular endothelium acts to maintain vascular homeostasis through multiple mechanisms and impaired endothelial function can contribute to the development, progression and clinical expression of atherosclerosis. METHODS: We consecutively recruited 39 newly-diagnosed chronic interstitial pneumonitis/fibrosis patients without any specific etiology. We assessed endothelium-dependent vasodilator response of patients using digital pulse amplitude tonometry and compared the reactive hyperemia index (RHI) with age-, sex- and body mass index-matched control subjects (n = 30). We further investigated the relationships between RHI and clinical characteristics, laboratory cardiovascular risk factors, disease-related factors and circulating levels of inflammatory biomarkers. RESULTS: RHI was significantly lower in patients with chronic interstitial pneumonitis/fibrosis than in control subjects (p = 0.02). While circulating levels of total cholesterol, triglycerides, HbA1c and fasting glucose did not differ significantly between groups, patients with chronic interstitial pneumonitis/fibrosis had significantly lower high density lipoprotein levels and higher low density lipoprotein levels as compared with control subjects. Regarding disease-related factors, RHI was significantly associated with the diffusing capacity for carbon monoxide, alveolar-arterial oxygen pressure difference, 6-min walk distance and end-exercise oxygen saturation. Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI. CONCLUSIONS: We confirmed a possible link between pulmonary fibrosis and cardiovascular disease by demonstrating an impairment of endothelium-dependent vasodilator response, which was significantly associated with the severity of pulmonary fibrosis and circulating levels of adhesion molecules.

Association between sleep apnea, sleep duration, and serum lipid profile in an urban, male, working population in Japan.

BACKGROUND: Dyslipidemia is often comorbid with obstructive sleep apnea (OSA), but few population-based studies have investigated their relationship. Short sleep duration is associated with hypertension and diabetes; however, its association with dyslipidemia is not well known. We investigated relationships among OSA, sleep duration, and the lipid profile in a community-based study. METHODS: We measured the respiratory disturbance index (RDI) and sleep duration by a type 3 portable device and actigraph in 275 men in a Japanese company. Fasting blood parameters were obtained from periodic inspection data. RESULTS: According to Japanese criteria, 143 subjects had dyslipidemia. Percent sleep time of oxygen saturation as measured by pulse oximetry (SpO2) < 90% and prevalence of severe OSA were greater and sleep duration and mean SpO2 during sleep were lower in subjects with dyslipidemia than in those without. Univariate analysis showed that the RDI was positively correlated with serum triglyceride (TG) levels (ρ = 0.20, P < .01), and sleep duration was negatively correlated with serum total cholesterol (TC) levels (γ = -0.13, P = .03) and serum low-density lipoprotein cholesterol levels (γ = -0.12, P = .04). Stepwise multiple regression analysis revealed that TG was correlated with RDI (ß = 0.14, P = .02), BMI (ß = 0.20, P < .01), and alcohol intake (ß = 0.20, P < .01), and that TC was correlated with sleep duration (ß = -0.13, P = .03), age (ß = 0.15, P = .02), and waist/hip ratio (ß = 0.15, P = .02). CONCLUSIONS: Short sleep duration was associated with TC levels and RDI was positively associated with TG levels among working-aged men in an urban Japanese company. Correcting the status of OSA and/or short sleep duration might improve the lipid profile and cardiovascular consequences.

A urine biomarker for severe obstructive sleep apnoea patients: lipocalin-type prostaglandin D synthase.

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin D2, has been reported to have a close connection with cardiovascular disease and sleep regulation. This study aimed to test the hypothesis that the L-PGDS level is a useful marker to identify patients with obstructive sleep apnoea. 64 subjects were enrolled in this prospective study. Urinary concentrations of L-PGDS were measured in the morning. Measurements were made every 4 h in 25 of the 64 patients. Endothelial function was assessed by the reactive hyperaemia peripheral arterial tone index. Circadian variations in L-PGDS concentrations had a significant time-dependent fluctuation (p = 0.0002). L-PGDS was higher in the subjects with severe obstructive sleep apnoea (median 784.7 ng per mg of creatinine, n = 23) than in control subjects (262.1 ng per mg of creatinine, n = 16; p = 0.004) and in those with moderate obstructive sleep apnoea (371.7 ng per mg of creatinine, n = 25; p = 0.0008). After 2 days of continuous positive airway pressure treatment, L-PGDS concentrations in severe obstructive sleep apnoea subjects (n = 12) decreased significantly (p = 0.02) to levels present in control subjects whereas endothelial function did not change significantly. Morning urinary L-PGDS concentrations had significant correlations with the apnoea/hypopnoea index (R2 = 13.9%) and serum high-density lipoprotein cholesterol (R2 = 6.2%), but not with sleepiness. Urinary L-PGDS might be a moderately useful marker to identify patients with severe obstructive sleep apnoea.

Analysis of systemic and airway inflammation in obstructive sleep apnea.

PURPOSE: The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA. METHODS: This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry. RESULTS: In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum. CONCLUSIONS: Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.

Measurement of dyspnea in patients with obstructive sleep apnea.

PURPOSE: Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA. METHODS: We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI. RESULTS: Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale. CONCLUSIONS: Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.

Use of noninvasive ventilation for pediatric patients after liver transplantation: decrease in the need for reintubation.

Noninvasive ventilation (NIV) refers to ventilation delivered through a noninvasive interface (a nasal or face mask) rather than an invasive interface (an endotracheal tube or tracheostomy). The role of NIV in preventing reintubation after abdominal surgery in pediatric patients is uncertain. Therefore, we evaluated the role of NIV for this purpose in pediatric patients after liver transplantation. We successfully started using NIV for respiratory complications (RCs) in pediatric patients undergoing liver transplantation in 1999. For this report, we screened all medical records of patients under the age of 12 years who underwent liver transplantation between 2001 and 2009, and we retrieved data for cases at high risk of extubation failure. We retrospectively compared the clinical outcomes of patients who received NIV during their intensive care unit (ICU) stay and patients who did not. Data for 94 cases (92 patients) were included in this analysis. NIV was used in 47 patients during their ICU stay. The rate of reintubation for RCs was significantly lower in NIV patients versus non-NIV patients [3/47 (6.4%) versus 11/47 (23.4%), P = 0.02]. Furthermore, the discharge rate from the ICU was significantly better for NIV patients versus non-NIV patients. The use of NIV after extubation prevented the worsening of atelectasis and stabilized respiratory conditions in this cohort. No major changes in operative procedures or other treatments during the examined period were found. In conclusion, NIV is acceptable and promising for the respiratory management of pediatric patients undergoing liver transplantation. Its use may stabilize respiratory conditions and decrease the need for reintubation in pediatric liver transplant patients, and it may also facilitate an early ICU discharge.

Analysis of anatomical and functional determinants of obstructive sleep apnea.

PURPOSE: Craniofacial abnormalities have an important role in the occurrence of obstructive sleep apnea (OSA) and may be particularly significant in Asian patients, although obesity and functional abnormalities such as reduced lung volume and increased airway resistance also may be important. We conducted simultaneous analyses of their interrelationships to evaluate the relative contributions of obesity, craniofacial structure, pulmonary function, and airway resistance to the severity of Japanese OSA because there are little data in this area. METHODS: A cross-sectional observational study was performed on 134 consecutive Japanese male patients. A sleep study, lateral cephalometry, pulmonary function tests, and impulse oscillometry (IOS) were performed on all patients. RESULTS: Age, body mass index (BMI), position of the hyoid bone, and proximal airway resistance on IOS (R20) were significantly related to the apnea/hypopnea index (AHI) (p < 0.05) in multiple regression analysis. Subgroup analysis showed that, for moderate-to-severe OSA (AHI ≥ 15 events/h), neck circumference and R20 were predominantly related to AHI, whereas for non-to-mild OSA (AHI < 15 events/h), age and expiratory reserve volume were the predominant determinants. In obese subjects (BMI ≥ 25 kg/m(2)), alveolar-arterial oxygen tension difference, position of the hyoid bone, and R20 were significantly associated with AHI, whereas age alone was a significant factor in nonobese subjects (BMI < 25 kg/m(2)). CONCLUSIONS: Aside from age and obesity, anatomical and functional abnormalities are significantly related to the severity of Japanese OSA. Predominant determinants of AHI differed depending on the severity of OSA or the magnitude of obesity.