Satoshi Kasagi

The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis

BACKGROUND The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear. METHODS The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured. RESULTS In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve. CONCLUSION The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA.

Establishment of the Cardio-Ankle Vascular Index in Patients With Obstructive Sleep Apnea

BACKGROUND An arterial stiffness parameter, the cardio-ankle vascular index (CAVI), has been developed. CAVI is adjusted for BP and can be used to measure arterial stiffness with little influence of BP. The purpose of this study was to evaluate the reproducibility, validity, and clinical usefulness of CAVI among patients with obstructive sleep apnea (OSA), who often have elevated BP during measurement. METHODS Overall, 543 consecutive patients with OSA were studied. CAVI was automatically calculated from the pulse volume record, BP, and the vascular length from the heart to the ankle. First, CAVI was measured three times on different days in 25 patients to evaluate its reproducibility. Second, the correlation between CAVI and BP was assessed. Third, patients were classified into two groups (mild OSA or moderate-to-severe OSA), and the CAVIs of these groups were compared. Fourth, the correlation between CAVI and carotid intima-media thickness (IMT) was also assessed in 74 patients. RESULTS The mean coefficient of variation was 2.8. CAVI demonstrated weak or no correlations with BP (with systolic BP, r = 0.184; with diastolic BP, r = 0.223). Patients with moderate-to-severe OSA (n = 469) had a significantly greater CAVI than patients with mild OSA (p = 0.034). CAVI was positively correlated with IMT (r = 0.487). CONCLUSIONS The measurement of CAVI demonstrated good reproducibility and was not affected by the BP during measurement. Additionally, CAVI was positively correlated with another arteriosclerosis indicator. CAVI was higher in patients with more severe OSA and is regarded as a clinically useful index for the progression of vascular damage.

Relationship between atrial conduction delay and obstructive sleep apnea

Prolonged P-wave duration, indicating atrial conduction delay, is a marker of left atrial abnormality and is reported as a potent precursor of atrial fibrillation (AF). Several studies have shown that obstructive sleep apnea (OSA) is associated with AF. We evaluated the relationship between OSA and prolonged P-wave duration. Consecutive subjects who underwent overnight polysomnography and showed a normal sinus rhythm, had no history of AF or ischemic heart disease, and showed no evidence of heart failure were enrolled. Apnea–hypopnea index (AHI) is defined as the number of apnea and hypopnea events per hour of sleep. P-wave duration was determined on the basis of the mean duration of three consecutive beats in lead II from a digitally stored electrocardiogram. A total of 250 subjects (middle-aged, predominantly male, mildly obese, with a mean P-wave duration of 106 ms) were enrolled. In addition to age, male gender, body mass index (BMI), hypertension, dyslipidemia, and uric acid and creatinine levels, AHI (r = 0.56; P < 0.001) had significant univariable relationship with P-wave duration. Multivariate regression analysis showed that age, BMI, male gender, and AHI (partial correlation coefficient, 0.47; P < 0.001) were significantly independently correlated to P-wave duration. Severity of OSA is significantly associated with delayed atrial conduction time. Obstructive sleep apnea may lead to progression of atrial remodeling as an AF substrate.

Effects of obstructive sleep apnea and its treatment on signal-averaged P-wave duration in men.

Background—Prolonged P-wave duration, indicating atrial conduction delay, is a potent precursor of atrial fibrillation. Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation development. We investigated the association of P-wave duration with OSA and its treatment. Methods and Results—We enrolled 80 consecutive men with normal sinus rhythms who underwent polysomnography, had no history of atrial fibrillation or ischemic heart disease, and no evidence of heart failure. Signal-averaged P-wave duration (SAPWD) was measured in all participants. Multivariable regression analysis showed that age, hypertension, and log-transformed apnea–hypopnea index were significantly and independently correlated with SAPWD. SAPWD was repeatedly measured after 1 month of continuous positive airway pressure (CPAP) therapy in 62 patients with moderate-to-severe OSA. As controls, 18 patients with moderate-to-severe OSA were enrolled. Their SAPWD was also measured at baseline and after 1 month without CPAP therapy. No significant change in SAPWD was found between baseline and after 1 month in the controls. However, SAPWD was significantly shortened after 1 month of CPAP therapy (from 137.5±8.6 to 129.7±8.5 ms; P<0.001), and the SAPWD change was significantly different in patients with CPAP therapy compared with controls (P<0.001). In addition, the SAPWD change in patients with CPAP therapy correlated inversely with nightly CPAP usage (r=−0.52; P<0.001). Conclusions—OSA severity was significantly associated with prolonged SAPWD. CPAP therapy significantly shortened SAPWD in patients with moderate-to-severe OSA. Thus, OSA may cause atrial conduction disturbances, leading to an increased risk of atrial fibrillation development, which may be modifiable by alleviating OSA with CPAP therapy.

Change in cardio-ankle vascular index by long-term continuous positive airway pressure therapy for obstructive sleep apnea.

BACKGROUND It has been reported that patients with obstructive sleep apnea (OSA) have an elevated arterial stiffness, and alleviation of OSA by continuous positive airway pressure (CPAP) might attenuate this. Recently, the cardio-ankle vascular index (CAVI) has been reported to be a highly reproducible arterial stiffness parameter in OSA patients. However, the change in CAVI that occurs following long-term CPAP treatment for OSA remains unclear. METHODS Patients with moderate-to-severe OSA were enrolled. Changes in CAVI at 1 and 12 months after CPAP initiation (ΔCAVI(1) and ΔCAVI(12), respectively) were assessed. Factors associated with ΔCAVI(1) and ΔCAVI(12) were determined by multivariable regression analyses. RESULTS Thirty subjects were assessed. CAVI was significantly reduced at 1 month compared with the baseline from 7.80 ± 1.19 to 7.56 ± 1.08 (p = 0.013). A non-significant reduction was observed at 12 months (7.72 ± 1.18, p = 0.365 versus baseline) and CAVI had actually increased compared with that measured at 1 month. In multivariable analyses, ΔCAVI(1) was inversely correlated with CPAP usage (coefficient: -0.500, p = 0.006) and was directly correlated with the change in the ratio of low frequency to high frequency in heart rate variability (coefficient: 0.607, p < 0.001), whereas ΔCAVI(12) was related to the use of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II-receptor blockers (ARB; coefficient: 0.464, p = 0.013), was directly correlated with the change in hemoglobin A1c levels (coefficient: 0.644, p < 0.001), and was inversely correlated with the change in CPAP usage (coefficient: -0.380, p = 0.046). CONCLUSIONS CAVI was significantly reduced by short-term CPAP and then slightly increased from 1 to 12 months, which was probably due to natural progression associated with the aging process. However, long-term CPAP treatment had the beneficial effect of maintaining CAVI below baseline levels when associated with the use of ACE-I/ARB, the control of blood glucose and the CPAP compliance.

Effects of olmesartan on blood pressure and insulin resistance in hypertensive patients with sleep-disordered breathing.

The increased risk of cardiovascular morbidity and mortality among patients with sleep-disordered breathing (SDB) has been linked to arterial hypertension and insulin resistance. However, an effective antihypertensive agent for patients with SDB has not been identified. We investigated the effect of the angiotensin II subtype 1 receptor blocker olmesartan in hypertensive patients with SDB. This prospective, one-arm pilot study included 25 male patients with untreated SDB (mean age, 52.7 ± 11.4 years). We measured blood pressure, oxygen desaturation index (ODI), cardiac function using echocardiography, and insulin resistance using the homeostasis model assessment (HOMA) before and after 12 weeks of olmesartan therapy (mean dose, 17.6 ± 4.4 mg/day). Olmesartan significantly decreased systolic blood pressure (151.4 ± 8.0 vs 134.0 ± 7.4 mmHg; P < 0.001), diastolic blood pressure (93.4 ± 7.1 vs 83.9 ± 6.3 mmHg; P < 0.001), and HOMA index (3.7 ± 2.9 vs 2.8 ± 1.9; P = 0.012). Furthermore, left ventricular ejection fraction significantly increased at 12 weeks (68.1 ± 5.1 vs 71.6 ± 5.4%; P = 0.009). However, body mass index (BMI) and degree of SDB did not change (BMI, 26.6 ± 4.0 vs 26.6 ± 4.2 kg/m2, P = 0.129; 3% ODI, 29.5 ± 23.1 vs 28.2 ± 21.0 events/h, P = 0.394). Olmesartan significantly reduced blood pressure and insulin resistance in hypertensive patients with SDB without changing BMI or SDB severity.

Comparison of clinical features and polysomnographic findings between men and women with sleep apnea

BACKGROUND There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan. METHODS We conducted a case-matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age ±4 years, (II) AHI ± 4 h of sleep, and (III) BMI ±2 kg/m(2). This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA. RESULTS Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI [men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001], lower supine AHI [men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004], longer total sleep time (TST), and non-rapid eye movement (NREM) sleep stage 3 (N3), %TST [TST in men: 356.3 (IQR, 319.5-392.3); women: 372.0 (IQR, 327.8-404.5); P=0.007; N3, %TST in men: 8.8 (IQR, 3.0-14.6); women: 14.4 (IQR, 8.3-20.4); P<0.001], and better sleep efficiency [men: 80.9 (IQR, 71.0-88.0); women: 83.2 (IQR, 74.5-90.0); P=0.011]. CONCLUSIONS This study revealed that women with SA had a significantly longer TST and N3, %TST, which represents deep sleep. Future prospective studies must be conducted together with polysomnography tests including electromyography of pharyngeal muscle expansion and electroencephalography.

Craniofacial anatomical risk factors in men with obstructive sleep apnea and heart failure: a pilot study.

PurposeObstructive sleep apnea (OSA) is complicated with heart failure (HF); however, the reason for this is not well understood. Craniofacial anatomic risk factors may contribute to OSA pathogenesis in HF patients. However, there are no data about cephalometric findings among OSA patients with HF.MethodsConsecutive patients with HF and OSA (defined as total apnea–hypopnea index (AHI) ≥15/h) were enrolled. As controls, OSA patients without HF but matching the test group in age, BMI, and obstructive AHI were also enrolled.ResultsOverall, 17 OSA patients with HF and 34 OSA patients without HF were compared. There are no significant differences in the characteristics or polysomnographic parameters between 2 groups. In the cephalometric findings, compared with patients without HF, patients with HF showed a significantly greater angle between the line SN to point “A” (SNA) and a longer inferior airway space and greater airway area. However, the tongue area of patients with HF was more than those without HF.ConclusionsThe craniofacial structures of OSA patients with HF were different from those without HF. OSA patients with HF had an upper airway anatomy that is more likely to collapse when sleeping while recumbent, despite having a larger airway space.

Conversion from predominant central sleep apnea to obstructive sleep apnea following valvuloplasty in a patient with mitral regurgitation.

A few reports have shown that cardiac valve repair may improve central sleep apnea (CSA) in patients with valvular heart disease. It has been suggested that such improvements are associated with the improvement of cardiac function. We report the case of a 67-year-old man with mitral regurgitation, whose CSA converted to predominant obstructive sleep apnea following mitral valvuloplasty in association with a shortening of lung-to-finger circulation time.

Histological types and localizations of lung cancers in patients with combined pulmonary fibrosis and emphysema

Most patients with combined pulmonary fibrosis and emphysema (CPFE) are males, and heavy smokers. CPFE is more prevalent than fibrosis in patients with lung cancer, and patients with CPFE usually have a poor prognosis. This study reviewed the differences in the prevalence of lung cancer among patients with normal, fibrosis, emphysema and CPFE via chest computed tomography (CT), and the relationship between histopathology and the localizations of lung cancer.