Fractional exhaled nitric oxide distribution and its relevant factors in the general adult population and its healthy subpopulation.

Background: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its "healthy" subpopulation would contribute to the interpretation of Feno in clinical practice. Objective: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. Methods: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). Results: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite-specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. Conclusion: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study.

Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

Combined Fat Mass and Fat-free Mass Indices and Lung Function Among Japanese Population: The Tohoku Medical Megabank Community-based Cohort Study.

BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other, since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 was 3.0 (standard deviation [SD], 0.7) L for men and 2.3 (SD, 0.5) L for women. The mean FVC was 3.8 (SD, 0.7) L for men and 2.8 (SD, 0.5) L for women. FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSION: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study.

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5±0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.

Carotid Intima Media Thickness and Risk Factor for Atherosclerosis: Tohoku Medical Megabank Community-Based Cohort Study.

AIM: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline. METHODS: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height. RESULTS: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT. CONCLUSIONS: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.

Association between lung function and hypertension and home hypertension in a Japanese population: the Tohoku Medical Megabank Community-Based Cohort Study.

BACKGROUND: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population. INDIVIDUALS AND METHODS: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV 1 ) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension. RESULTS: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV 1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women. CONCLUSION: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension.

The Association of Lung Function and Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

AIM: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. METHODS: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. RESULTS: After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). CONCLUSIONS: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

Associations between the Combined Fat Mass Index and Fat-Free Mass Index with Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

AIM: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT. METHODS: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend). CONCLUSIONS: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.

Association between fat mass index, fat-free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

AIMS/INTRODUCTION: Fat mass and fat-free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat-free mass index with HbA1c. MATERIALS AND METHODS: We carried out a cross-sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat-free mass index were calculated as fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into sex-specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat-free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat-free mass index, entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat-free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat-free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend). CONCLUSIONS: Fat mass index was positively related to HbA1c levels. The fat-free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes.

Association between the combined fat mass and fat-free mass index and hypertension: The Tohoku Medical Megabank Community-based Cohort Study.

BACKGROUND: A  higher body fat percentage is associated with hypertension, even in non-obese individuals. The difference in body composition may be related to hypertension. The fat mass index (FMI) and fat-free mass index (FFMI) are proposed indicators of body composition. This study aimed to examine the relationship of a combination of FMI and FFMI with hypertension. METHODS: We conducted a cross-sectional study of 5,058 men and 11,842 women aged ≥ 20 years in the Miyagi Prefecture, northeastern Japan. The FMI and FFMI were calculated as the fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into quartiles and combined into 16 groups. Hypertension was defined as casual blood pressure ≥ 140/90 mmHg and/or self-reported treatment for hypertension. Multivariable logistic regression models, adjusted for potential confounders, were used to assess the relationship of a combination of FMI and FFMI with hypertension. RESULTS: Higher FMI was associated with hypertension in most of the FFMI subgroups. Similarly, a higher FFMI was associated with hypertension in most of FMI subgroups. For men, the association between FFMI and hypertension in the lowest FMI group was not significant. CONCLUSIONS: Reducing the FMI and FFMI may be important in preventing hypertension. For men, the relationship between the FFMI and hypertension in the lowest FMI group might be weak.

Change during an 8-Year Period in Streptococcus Pyogenes emm Types in Pharyngeal Isolates from Children with Noninvasive Infections.

BACKGROUND: Streptococcus pyogenes, or group A streptococcus (GAS), is one of the most common bacterial pathogens in children. GAS can cause such nonserious and noninvasive diseases as pharyngitis and skin infection, as well as serious, invasive diseases like streptococcal toxic shock syndrome. One factor that makes GAS pathogenic is the type-specific M protein on its cell surface. To identify emm types and their characteristics, we previously examined GAS strains isolated from children with noninvasive infections at our hospital. The present study was conducted 8 years later, for comparison. METHODS: The 23 participants were inpatients and outpatients at Nippon Medical School Tama Nagayama Hospital during 2016 and 2017. A pharyngeal swab specimen was obtained from each child, and genes encoding M proteins were amplified by polymerase chain reaction. RESULTS: emm type analysis identified emm1 in 11 of the 23 strains and emm12 in 4. Three group G streptococcus (GGS) strains carried M-like protein genes. CONCLUSIONS: The predominant emm type was emm12 in our previous report and emm1 in this study. This study also identified 3 GGS strains among the isolates, which carried either the stg245, stg6795, or stg840 M-like protein gene. One GAS strain carried stg485, a gene associated with GGS rather than GAS.

Valproate-Induced Polycystic Ovary Syndrome in a Girl with Epilepsy: A Case Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common ovulatory disorder that can be induced by sodium valproate (VPA). PATIENT: We report a case of PCOS that developed in a 15-year-old girl with idiopathic epilepsy after she took VPA. VPA administration stopped her seizures, but it also led to weight gain and amenorrhea, and the patient was diagnosed with PCOS on the basis of diagnostic imaging and serological examination results. Cessation of VPA administration led to reduced weight gain and restored menstruation. CONCLUSIONS: The risk of PCOS developing in patients with epilepsy is known to be high, and the association of VPA with PCOS is well established, so if physicians feel this is the best drug to prescribe for female patients with epilepsy, they should carefully monitor the patients' weight and menstruation, and immediately perform ovarian imaging and hormonal examinations if any abnormalities are observed.

A Girl with Idiopathic Epilepsy Showing Forced Normalization after Levetiracetam Administration.

BACKGROUND: Forced normalization has been reported in association with almost all anti-epileptic drugs. PATIENT: We report on a 9-year-old girl with idiopathic epilepsy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with generalized tonic-clonic seizures when she was 4 years old. Diffuse sharp and slow wave complexes (SWCs) were observed on electroencephalography (EEG). We prescribed sodium valproate (VPA) and benzodiazepines, but the seizures and EEG findings worsened gradually. Although subsequent administration of LEV stopped the seizures, the patient became subject to episodes of rage and violent behavior. Forced normalization was confirmed by the disappearance of SWCs on EEG. We reduced the dose of LEV and tried in various ways to resolve the situation, but finally we had to abandon LEV. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with idiopathic epilepsy but without disabilities in everyday life showing forced normalization associated with LEV administration.

Normative Data and Predictive Equation of Interrupter Airway Resistance in Preschool Children in Japan.

Measurement of interrupter airway resistance (Rint) is a convenient alternative to standard spirometry for assessing respiratory function in uncooperative young children. The aim of the present prospective study was to establish the normative data and predictive equation of Rint in Japanese preschool children. A total of 214 children were enrolled from a single kindergarten; however, 129 were excluded because they met at least 1 of the exclusion criteria, such as wheezing history or recent common cold. Expiratory Rint values were assessed in 85 of the children, but technically unsatisfactory measurements were obtained in 5 of them. Thus, 80 healthy Japanese children (39 boys and 41 girls) without any history or symptoms of respiratory tract diseases were evaluated. Their age, body height, and body weight ranges (median) were 1.67 to 6.42 (4.38) years, 79.8 to 120.9 (102.5) cm, and 10.4 to 24.9 (15.8) kg, respectively. The mean Rint was 0.93±0.25 kPa/L/s (range=0.46-1.49 kPa/L/s). The Rint tended to decrease with increasing age and body height (r=-0.65; P<0.01), but sex played no significant role (P=0.71). The predictive equation based on body height derived by linear regression was expiratory Rint (kPa/L/s) =2.513-0.01567×body height (cm) (multiple correlation coefficient=0.653). Because 79 of the 80 measured Rint values were within 140% of the predictive Rint value, we calculated a 140% cut-off for predicting bronchoconstriction. Our results provide a reference value for evaluating the degree of airway obstruction in young Japanese children.

Development of reference equations for spirometry in Japanese children aged 6-18 years.

BACKGROUND: Spirometry is the most widely used pulmonary function test and the measured values of spirometric parameters need to be evaluated using reference values predicted for the corresponding race, sex, age, and height. However, none of the existing reference equations for Japanese children covers the entire age range of 6-18 years. The Japanese Society of Pediatric Pulmonology had organized a working group in 2006, in order to develop a new set of national standard reference equations for commonly used spirometric parameters that are applicable through the age range of 6-18 years. METHODS: Quality assured spirometric data were collected through 2006-2008, from 14 institutions in Japan. We applied multiple regression analysis, using age in years (A), square of age (A(2)), height in meters (H), square of height (H(2)), and the product of age and height (AH) as explanatory variables to predict forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), peak expiratory flow (PEF), forced expiratory flow between 25% and 75% of the FVC (FEF(25-75%)), instantaneous forced expiratory flow when 50% (FEF(50%)) or 75% (FEF(75%)) of the FVC have been expired. RESULTS: Finally, 1,296 tests (674 boys, 622 girls) formed the reference data set. Distributions of the percent predicted values did not differ by ages, confirming excellent fit of the prediction equations throughout the entire age range from 6 to 18 years. Cut-off values (around 5 percentile points) for the parameters were also determined. CONCLUSIONS: We recommend the use of this new set of prediction equations together with suggested cut-off values, for assessment of spirometry in Japanese children and adolescents.

Fatal tracheo-innominate artery fistula after tracheostomy in a patient with Pelizaeus-Merzbacher disease.

Tracheo-innominate artery fistula (TIF) is a serious, life-threatening complication following tracheostomy. We report a fatal TIF in a 15-year-old girl with Pelizaeus-Merzbacher disease. She received a tracheostomy for prolonged translaryngeal intubation due to acute respiratory failure without a trial of noninvasive ventilatory support before intubation. Severe hemorrhage from the TIF occurred 6 months after tracheostomy; immediate resuscitation failed. Antemortem fiberoptic bronchoscopy showed tracheal stenosis accompanied by granulation tissue, and postmortem examination revealed TIF with ulcerative granulation. Preventive intervention is required to avoid catastrophic TIF due to its high mortality rate. Moreover, to avoid prolonged translaryngeal intubation leading to tracheostomy, noninvasive ventilatory support before translaryngeal intubation, if applicable, is beneficial.

Epidemiologic survey of patients with congenital central hypoventilation syndrome in Japan.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by hypoventilation during sleep. This study discusses the first epidemiologic survey of patients with CCHS in Japan. METHODS: The first survey was conducted between September and December 2006 and involved 507 registered institutes for pediatric training in Japan. The second survey was conducted between January and April 2007 and involved only those institutes that confirmed diagnosis of CCHS in the first survey or reported on CCHS at a conference during the preceding decade. RESULTS: Thirty-seven patients with CCHS were reported from 23 hospitals. Patient characteristics were as follows: 18 were male, 19 were female; and age range 4 months to 34 years. Diagnosis was based on clinical symptoms in 37/37 patients; blood gas analysis in 25/37; ventilatory response to inhaled CO(2) in 14/37; and genetic analysis (paired-like homeobox gene 2B) in 11/37. Complications included Hirschsprung's disease in 13/37 and central nervous system disorders in 15/37. Prognoses were as follows: 3/37 died in hospital, 1/37 remained in hospital, 33/37 were on home mechanical ventilation (died 4/33, survived 29/33), and 0/37 were cured. Ventilation methods included tracheostomy (21/37), use of a nasal mask (9/37), use of a facemask (5/37), and diaphragmatic pacing (1/37). CONCLUSIONS: There is currently no consensus on the most appropriate methods for diagnosing and treating patients with CCHS in Japan. More CCHS-related data need to be collected in the near future in order to enable appropriate diagnosis and management of patients with CCHS.

A neonate with reduced cytomegalovirus DNA copy number and marked improvement of hearing in the treatment of congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection can cause severe permanent disabilities. A mother who is seronegative before conception but acquires infection during pregnancy is a risk factor for congenital infection. We describe a neonate in whom congenital CMV infection was diagnosed at birth and confirmed with DNA quantitation by means of the polymerase chain reaction, was accompanied by cerebral ventriculomegaly and severe hearing loss, and was treated with ganciclovir/valganciclovir for 6 weeks. Initially, cerebral ventriculomegaly and calcification were also found with computed tomography, and severe hearing loss was detected with auditory brainstem response testing. After treatment, CMV DNA decreased in copy number and became undetectable. No marked side effects occurred after treatment. Surprisingly, 1 year after treatment, neurological and motor development was equivalent to that in a healthy infant. Audiometry indicated that auditory ability would improve with rehabilitation, speech and language therapy, and cochlear implantation. Single-photon emission computed tomography showed marked improvement 6 months after treatment. This case provides compelling evidence that a reliable diagnosis of congenital CMV infections coupled with a prompt and appropriate treatment program can prevent permanent disability. It is, therefore, important to establish a more effective strategy for the management of congenital CMV infection.