Longitudinal Changes and Association of Respiratory Symptoms with Preserved Ratio Impaired Spirometry (PRISm): The Nagahama Study.

Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.

Gastroesophageal reflux disease is a risk factor for sputum production in the general population: the Nagahama study.

BACKGROUND: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. METHODS: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. RESULTS: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. CONCLUSIONS: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.

Lifestyle habits associated with nocturnal urination frequency: The Nagahama study.

BACKGROUND: Nocturia is a risk factor for poor quality of life and increased mortality. This study was aimed to clarifying dietary habits, eating behaviors, and sleep characteristics associated with nocturia to identify modifiable lifestyle factors for nocturia. METHODS: This cross-sectional study included 5683 community residents (64.5 ± 7.7 years old). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. The frequency of food intake, unfavorable eating behaviors, and sleep characteristics that may have influence on salt intake and wasting were obtained using a structured questionnaire. RESULTS: The frequency of nocturnal urination was increased with age (ß = .312, P < .001). Other basic factors associated with the frequency were the male sex (ß = .090), hypertension (ß = .038), sleep apnea (ß = .030), B-type natriuretic peptide level (ß = .089), and spot urine sodium excretion (ß = -.058). Dietary factors independently associated with nocturnal urination frequency were coffee (≥1 time/day: ß = -.059, P < .001) and green vegetable consumption (≥1 time/week: ß = -.042, P = .001), whereas habitual intake of dairy products, miso soup, and alcohol were not associated with urination frequency. Later bedtime was inversely associated with nocturnal urination frequency independent of sleep duration (before 23:00: ß = -.096; before 24:00: ß = -.225; after midnight: ß = -.240; all P < .001). CONCLUSION: Coffee and green vegetable consumption and later bedtime but not sleep duration are lifestyle factors associated with nocturnal urination frequency.

Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway.

Liver metabolism undergoes robust circadian oscillations in gene expression and enzymatic activity essential for liver homeostasis, but whether the circadian clock controls homeostatic self-renewal of hepatocytes is unknown. Here we show that hepatocyte polyploidization is markedly accelerated around the central vein, the site of permanent cell self-renewal, in mice deficient in circadian Period genes. In these mice, a massive accumulation of hyperpolyploid mononuclear and binuclear hepatocytes occurs due to impaired mitogen-activated protein kinase phosphatase 1 (Mkp1)-mediated circadian modulation of the extracellular signal-regulated kinase (Erk1/2) activity. Time-lapse imaging of hepatocytes suggests that the reduced activity of Erk1/2 in the midbody during cytokinesis results in abscission failure, leading to polyploidization. Manipulation of Mkp1 phosphatase activity is sufficient to change the ploidy level of hepatocytes. These data provide clear evidence that the Period genes not only orchestrate dynamic changes in metabolic activity, but also regulate homeostatic self-renewal of hepatocytes through Mkp1-Erk1/2 signaling pathway.

Self-reported quality of sleep is associated with physical strength among community-dwelling young-old adults.

AIM: The present study examined the association between self-reported quality of sleep (QOS) and physical function in community-dwelling young-old adults. METHODS: This cross-sectional study included 737 community-dwelling older adults aged 60 years and older (498 women, 239 men); age 68.3 ± 5.2 years (range 60-79 years). Participants completed a self-administered questionnaire, which included the Pittsburgh Sleep Quality Index, as well as information regarding sociodemographic characteristics, physical activity, smoking and alcohol consumption. The χ2 -test was used to compare categorical variables stratified by QOS, and the unpaired t-test was used for continuous variables for men and women separately. Furthermore, logistic regression analyses were carried out to verify the association between QOS and physical function measures. RESULTS: The unpaired t-test showed a significant difference ((P < 0.05) in the Timed Up and Go test and physical strength outcomes, which included: handgrip, quadriceps setting, knee extension and hip flexion strength between the good QOS and poor QOS groups among the men. However, the t-test results for physical function outcomes did not show a significant difference among the women. In the logistic regression model, after adjusting for age, sex and potential confounding factors, handgrip strength remained significantly associated with QOS (OR 0.96, 95% CI 0.92-1.00). CONCLUSION: QOS was associated with physical function in young-old adults; those with good QOS were especially more likely to possess stronger grip strengths; however, further research is required to identify the temporal relationship. Geriatr Gerontol Int 2017; 17: 1808-1813.

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.

Relationship Among Chlamydia and Mycoplasma Pneumoniae Seropositivity, IKZF1 Genotype and Chronic Obstructive Pulmonary Disease in A General Japanese Population: The Nagahama Study.

Chronic obstructive pulmonary disease (COPD) is a possible risk factor for cardiovascular disease. The association of COPD with the pathogenicity of infection with Chlamydia pneumoniae and Mycoplasma pneumoniae is controversial. We conducted a cross-sectional study to clarify the association between atypical pneumoniae seropositivity and COPD in a general population. We also investigated genetic polymorphisms conferring susceptibility to a pneumonia titer. The study included 9040 Japanese subjects (54 ±â€Š13 years). COPD was defined as a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 70%. Serum levels of IgA and IgG antibodies to C pneumoniae were determined using an enzyme-linked immunoassay, and M pneumoniae seropositivity was assessed by a particle agglutination test. Subjects seropositive for C pneumoniae (26.1%) had a higher prevalence of COPD (seropositive, 5.8%; seronegative, 3.1%; P < 0.001) after adjustment for age, sex, height, weight, and smoking status. The association between M pneumoniae seropositivity (20.4%) and COPD was also significant in covariate-adjusted analysis (P < 0.001). A genome-wide association analysis of the C pneumoniae IgA index identified a susceptible genotype (rs17634369) near the IKZF1 gene, and the seropositive rate of C pneumoniae significantly differed among genotypes (AA, 22.5; AG, 25.3; GG, 29.7%, P < 0.001). On multiple regression analysis, seropositivity for both C pneumoniae (odds ratio = 1.41, P = 0.004) and M pneumoniae (odds ratio = 1.60, P = 0.002) was an independent determinant for COPD, while no direct association was found with the rs17634369 genotype. Seropositivity for both C pneumoniae and M pneumoniae is an independent risk factor for COPD in the general population.

Obstructive sleep apnea and abdominal aortic calcification: Is there an association independent of comorbid risk factors?

BACKGROUND: No studies have addressed the relationship between obstructive sleep apnea (OSA) and abdominal aortic calcification (AAC), a marker for subclinical atherosclerosis and future cardiovascular events. OBJECTIVES: To investigate 1) the association between OSA severity and AAC, and 2) whether OSA can impact the extent of AAC independent of comorbid atherogenic risk factors. METHODS: 390 participants aged 40-70 years underwent polysomnography and abdominal computed tomography. AAC was separately quantified in the upper and lower abdominal aorta using the modified Agatston scoring method, and the total AAC score was calculated as a sum of the two scores. OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 87), moderate (AHI 15-30, n = 129), and severe (AHI ≥30, n = 174). RESULTS: Log-transformed total AAC score adjusted for age and body mass index (BMI) was greater in participants with an elevated AHI (3.4 for none/mild OSA, 3.7 for moderate OSA, and 4.2 for severe OSA, p = 0.04). Multivariate linear regression analysis including age and BMI as covariates showed that severe OSA was associated with higher scores for the lower and total AAC (ß = 0.15 and 0.14, p = 0.01 and 0.01, respectively). The association did not persist after additionally adjusting for traditional atherogenic risk factors including visceral fat, smoking, hypertension, dyslipidemia, and diabetes. CONCLUSIONS: Severe OSA was associated with a greater extent of AAC, which was dependent on coexisting atherogenic risk factors. Comorbid cardiometabolic disorders may largely mediate the association of OSA with subclinical atherosclerosis.

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.

Successful allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by severe pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. We report herein a rare case of myelodysplastic syndrome (MDS-RAEB) complicated by severe PAP, and successful allogeneic bone marrow transplantation (BMT) for both disorders. An unrelated BMT was planned for a 48-year-old male with advanced MDS-RAEB. Just before the initiation of the conditioning regimen for unrelated BMT in March 2007, he developed dyspnea. A diagnosis of PAP was made based on findings of chest X-ray, CT scanning, and the fluid obtained by bronchoalveolar lavage. To improve his dyspnea and improve BMT safety, whole lung lavage (WLL) was performed twice, with the partial improvement of PAP. Unrelated allogeneic BMT was performed in September 2007. We had to perform a third WLL because of the worsening of PAP on day 26 after BMT. Despite many infectious complications after BMT, GVHD was relatively mild. PAP had almost disappeared 6 months after BMT. He was well with favorable hematopoiesis 20 months after the BMT without any specific treatment. There has been no report of an MDS patient with PAP in whom 3 WLL procedures were performed before and after allogeneic BMT.

[An autopsy case of racemose hemangioma of bronchial arteries associated with neovascularization from the chest wall after ligation and frequent embolizations].

We report an autopsied 33 year old pregnant woman with racemose hemangioma of the bronchial arteries. She was first given a diagnosis of racemose hemangioma of the bronchial arteries at age 19 and underwent surgical ligation. Nevertheless, she had to be admitted to the hospital for bronchial artery embolizations every time hemoptysis recurred. In her 21st gestational week, she was admitted to our hospital because of her 9th recurrent massive hemoptysis and dyspnea. Bronchial artery embolizations were repeatedly performed under intubation to ventilate the healthy left lung separately. We succeeded in temporarily stopping the hemoptysis, but her case was complicated by bacterial pneumonia and septic shock. Her baby was born dead on day 11 and she died on day 12. The autopsy revealed abnormal convoluted and dilated arteries branching from the right intercostal and subclavian arteries and intruding into the lung parenchyma through adhesion caused by her previous thoracostomy. The connections of these abnormal arteries with pulmonary arteries and veins, which had been shown by angiography, were confirmed by autopsy. The autopsy findings suggest that temporal surgical procedures with thoracostomy in this condition can induce abnormal neovascularization via pleural adhesion.