Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination.

The determinants of immunization coverage among children aged between 12 and 35 months: a nationwide cross-sectional study in Lao People's Democratic Republic.

BACKGROUND: Immunization is one of the most important public health interventions for reducing morbidity and mortality in children. However, factors contributing to low immunization coverage are not fully understood in the Lao People's Democratic Republic (Lao PDR). Therefore, this study aimed to identify factors associated with full immunization coverage among children between 12 and 35 months, providing up-to-date information for immunization programs in Lao PDR. METHODS: We analyzed the subpopulation of a nationwide cross-sectional survey using a multistage cluster sampling procedure to evaluate the measles and rubella seroepidemiology. In addition, we categorized children aged between 12 and 35 months into two groups: "fully immunized" children with a birth dose of Bacillus Calmette and Guérin vaccine, hepatitis B vaccine (Hep B), one and three doses for the measles-containing vaccine (MCV) and pentavalent vaccine and pneumococcal conjugate vaccine (PCV) and "partially immunized" children who missed any dose of vaccine. Immunization coverage was calculated as the ratio of "fully immunized" to the total. We compared the groups' demographic characteristics and health service utilization as independent variables. Multivariate logistic regression was used to assess the relationship between immunization coverage, various demographic factors, and health service utilization. RESULTS: Overall, 256 of the 416 targeted pairs were included in the analysis. In total, 67.6% of the children were fully immunized. Childbirth at hospitals or health facilities (adjusted odds ratio: 9.75, 95% confidence interval: 5.72-16.62, p < 0.001) was the predictor of full immunization coverage. The 83 children in the partially immunized groups were attributed to Hep B at birth (46, 55.4%), three doses of PCV (34, 41.0%), and the first dose of the MCV (27, 32.5%). CONCLUSION: Our study elucidated that the immunization status among children aged between 12 and 35 months in Lao PDR is satisfactory in improving access to healthcare by strengthening communication with residents regarding health service utilization, and expanding mobile outreach services may play a pivotal role in this endeavor. Further research is warranted to evaluate efforts to increase immunization coverage and target populations with limited access to healthcare.

Impact of hepatitis B vaccination programs in Vietnam evaluated by estimating HBsAg prevalence.

Background: Vietnam introduced a 3-dose hepatitis B (HBV) immunization program comprising 1 dose immediately after birth and 2 or 3 in infancy in the past 20 years, but the impact of the vaccine has not been systematically evaluated. Thus, we conducted this survey aiming to estimate the age-specific chronic HBV prevalence in the general population and to evaluate HBV immunization effectiveness. Methods: Population-based, four-stage cluster sampling was used in the South Central Coast region of Vietnam. The point-of-care Determine rapid test was used to assess hepatitis B surface antigen (HBsAg) positivity. Results: A total of 2,075 samples were included in the study. HBsAg prevalence was significantly higher among adults aged 20-39 years than in the population aged 1-19 years (8.0% [95% confidence interval 5.0-12.0] vs. 2.0% [95% confidence interval 1.0-6.0], p<0.01). HBsAg prevalence decreased after implementation of the 3-dose vaccination schedule during infancy from 1997 to 2002, whereas the change in prevalence after implementation of the birth dosing was not significant. A slight increase in HBsAg prevalence was observed for the cohort born in 2011, 2012, and 2013, when there was a vaccine shortage and media reports of immunization resistance. Conclusions: This is the first population-based assessment of the introduction of the HBV vaccine in Vietnam performed by estimating the HBsAg prevalence across a wide range of ages. The results showed that the HBV immunization policy effectively reduces HBsAg prevalence in general, although birth dosing of the vaccine and low immunization coverage should be carefully monitored.

Prevalence of hepatitis B and C virus infections in Lao People's Democratic Republic: The first national population-based cross-sectional survey.

Population-based seroprevalence of chronic hepatitis B and C infections has not been examined in Lao People's Democratic Republic (PDR). Therefore, this study aimed to estimate the seroprevalence of these infections in the general population of Lao PDR and perform subgroup analysis. A nationwide seroprevalence survey was conducted in Lao PDR in June 2019 using the multistage cluster sampling method. Dried blood spot samples were collected onto WhatmanTM 903 filter paper by finger prick. A chemiluminescent microparticle immunoassay was used to measure the levels of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab). Samples in which the HBsAg level was above 0.05 IU/ml and HCV-Ab was above the signal/cutoff ratio of 1.0 were considered positive based on comparisons with the relative light unit value of a calibration sample. A total of 1,927 samples (male: 47.3%, mean age: 23.0 years) were included in the analysis. The prevalence was estimated to be 4.2% (95% confidence interval [CI]: 2.7-6.3) for HBsAg and 1.6% (95% CI: 0.5-5.3) for HCV-Ab. Multivariable analysis revealed that those aged 20-24 years (adjusted odds ratio (AOR): 2.3, 95% CI: 1.1-4.6), those aged 25-29 years (AOR: 2.7, 95% CI: 1.3-5.6), those from the Northern region (AOR: 2.8, 95% CI: 1.2-6.6), and those who were Khmu (AOR: 3.6, 95% CI: 2.0-6.8) or Hmong (AOR: 5.0, 95% CI: 3.3-7.5) were significantly more likely to be positive for HBsAg. Although there were no statistically significant differences in the HCV-Ab prevalence according to each variable, males (2.9%, 95% CI: 0.7-10.7), those aged ≥40 years (6.1%, 95% CI: 2.1-16.8), and those from the Southern region (3.3%, 95% CI: 0.6-15.3) tended to have a higher prevalence. This novel population-based survey found differences in the prevalence of chronic hepatitis B and hepatitis C virus infections in Lao PDR according to sex, age group, region, and ethnicity; however, the results of this study should be confirmed in future studies, and relevant responses tailored for each target also need to be determined to control the transmission of hepatitis B and C infections.

Comparison between a rapid diagnostic test and dried blood spot-based immunoassay for hepatitis B surface antigen testing: Performance and cost implications in a population-based serosurvey in Vietnam.

OBJECTIVES: This study aimed to determine the agreement between a rapid diagnostic test (RDT) and a dried blood spot (DBS)-based electrochemiluminescence immunoassay (ECLIA) of hepatitis B surface antigen and to compare the costs of conducting serosurveys using RDTs and DBS in a field setting. METHODS: A serosurvey was conducted in the South Central Coast region of Vietnam in May 2019. Participants aged 1-39 years were recruited using a four-stage random sampling method and tested for hepatitis B surface antigen using an RDT kit (Alere Determine) and a DBS-based ECLIA. The agreement between the RDT and the DBS-based ECLIA was assessed using cross-tabulation and Cohen kappa. Cost data were categorized by input (personnel, transportation, field consumables, laboratory consumables, and capital item/overhead) and survey phase (survey preparation, data/biospecimen collection, laboratory testing, and coordination). RESULTS: A total of 2072 participants were analyzed. There was a 99% agreement between the RDT and the DBS-based ECLIA results, with a Cohen kappa of 0.9. The estimated cost of conducting a serosurvey by DBS was UD $75,291, whereas RDT was $53,182. CONCLUSION: RDTs and DBS-based ECLIA provide test results with high agreements. RDTs are a better option in terms of cost, whereas the DBS-based ECLIA may be useful when evaluating multiple infectious diseases.

Algorithm and hyperparameter optimizations for hetero-device classification by near-infrared spectra of falsified and substandard amoxicillin capsules.

In this work, we optimized classification algorithms and the hyperparameters for screening falsified and substandard amoxicillin capsules. The distribution of low-quality medical products is a serious problem, especially in low- and middle-income countries. Near-infrared (NIR) spectroscopy has been proposed as the first choice for a screening device. However, preparation of the reference library for the classification training is a highly difficult process. We herein propose a hetero-device classification between training and test devices. In this proposal, Fourier-transform NIR spectrometer and portable wavelength dispersive NIR spectrometer were used as training and test devices, respectively. As the classifier candidates, we examined 13 algorithms and selected 8. We then optimized the hyperparameters for these classifiers by the grid search and cross validation methods. In the final analysis, few classifiers were found to give acceptable prediction results by the hetero-device classification. When using these methods, it is crucial to examine the results by the classification probability, due to the trade-off between sensitivity and specificity. Finally, we suggest that k-nearest neighbors, extra trees, and gradient boosting classifiers are the optimal algorithms with high classification probability for the substandard and falsified amoxicillin capsules.

Effectiveness of immunization activities on measles and rubella immunity among individuals in East Sepik, Papua New Guinea: A cross-sectional study.

Objectives: This study aimed to assess measles and rubella immunity by measuring virus-specific immunoglobulin G (IgG) prevalence among individuals and evaluate the effectiveness of recent supplementary immunization activities (SIAs) by comparing the antibody positivity rates of the SIA target age groups in 2015 with those in 2019 as measles and rubella are endemic in Papua New Guinea. Methods: A cross-sectional study. The measles- and rubella-specific IgG levels of patients aged ≥1 year at two clinics in East Sepik province, Papua New Guinea were assessed with commercially available virus-specific IgG EIA kits. Results: In total, 297 people participated in the study and 278 samples with sufficient volume, relevant information, and age inclusion criteria were analyzed. The overall IgG prevalence rates were 62.6% for measles and 82.0% for rubella. The age groups targeted in the 2019 SIAs had a higher IgG prevalence than those targeted in the 2015 SIAs for both the infectious diseases. Moreover, the IgG prevalence for rubella was higher than measles in these groups. Conclusions: The anti-measles and anti-rubella IgG prevalence in the target groups were lower than those required for herd immunity. The immunization program should be emphasized to eliminate measles and rubella. Further population-based studies are warranted.

Device-Independent Discrimination of Falsified Amoxicillin Capsules Using Heterogeneous Near-Infrared Spectroscopic Devices for Training and Testing of a Support Vector Machine.

The objective of this work is to demonstrate the potential of near-infrared spectroscopy for common screening of falsified medicines in the field by means of a device-independent universal discrimination approach. In order to provide a useful discrimination tool to protect people from low-quality medical products, not only is a low-cost and portable screening device necessary, but a reference library is also essential. The authors believe that a device-dependent reference library inhibits near-infrared spectroscopy from becoming a popular screening tool. In this study, to develop a device-independent method, discrimination performance is evaluated using different devices for training and testing. The training data sets for the reference library were prepared using a bench-top Fourier transform near-infrared spectrophotometer, and predictive discrimination was performed using the spectral data by a low-cost and portable wavelength dispersive near-infrared spectrophotometer. A near-infrared spectrum-based support vector machine was used for these purposes, but the screening resulted in low accuracy thought to be caused by the intrinsically device-dependent features of the spectra data. Thus, principal component analysis was performed to collect the proper components to discriminate low-quality products from standard products. The principal component score-based support vector machine was able to produce highly accurate results, identifying falsified products with no false positive cases.

Infectious Disease Emergency Specialist (IDES) Training Program in Japan: an innovative governmental challenge to respond to global public health emergencies.

In 2015, Japan created a unique governmental program to train experts in health emergencies called Infectious Disease Emergency Specialist (IDES). This is a concept paper to set out the goal and structure of the program, and to describe the achievement and the way forward to further contribute to global health security. The IDES program background, mission, structure, achievement, and future directions were reviewed and discussed by the IDES trainees, graduates, and program coordinators/supervisors. Since 2015, thirteen Japanese medical doctors have graduated from the program while five are currently in training. The IDES core competencies were identified in the context of a wide range of skillsets required for health emergencies. A large national and global network has been created through the training. Coordinated work with surge capacity of experts is of paramount importance to prepare for and respond to public health emergencies. The IDES program can be a good model to many other governments, and contribute to global health security.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: A systematic review.

BACKGROUND: Balloon pulmonary angioplasty (BPA) has been performed for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual pulmonary hypertension after pulmonary endarterectomy (PEA). We performed a systematic review to assess the efficacy and safety of BPA, especially compared to medical treatment or PEA. METHODS: We reviewed all studies investigating pre- and post-treatment pulmonary hemodynamics, mortality, or complications from three electronic databases (PubMed, Cochrane Library, Japan Medical Abstracts Society) prior to February 2017. From 26 studies retrieved, we selected 13 studies (493 patients): the 10 most recent ones including complete data from each institution, one study of residual pulmonary hypertension, and two studies comparing BPA with medical treatment or PEA. RESULTS: No randomized controlled or prospective controlled studies comparing BPA with medical treatment or PEA were reported. The early mortality of BPA ranged from 0% to 14.3%; lung injury occurred in 7.0% to 31.4% (average sessions, 2.5-6.6). Mean pulmonary arterial pressure decreased from 39.4-56 to 20.9-36 mm Hg, and the 6-min walk distance increased from 191-405 to 359-501 m. The 2-year mortality of 80 patients undergoing BPA was significantly lower compared to 68 patients receiving medical treatment (1.3% vs. 13.2%); the risk ratio was 0.14 (95% confidence interval: 0.03-0.76). No significant difference was observed in the 2-year mortality between BPA (n=97) and PEA (n=63) patients. CONCLUSIONS: This systematic review suggests that BPA improves hemodynamics, has acceptable early mortality, and may improve long-term survival compared with medical treatment in inoperable CTEPH patients.

The effects of pirfenidone in patients with an acute exacerbation of interstitial pneumonia.

INTRODUCTION: The prognosis of patients with an acute exacerbation of interstitial pneumonia (AE-IP) is poor. Pirfenidone (PFD) reduces the disease progression in idiopathic pulmonary fibrosis. OBJECTIVES: The purpose of this study was evaluating whether the administration of PFD improved the outcomes of AE-IP. METHODS: We conducted a retrospective study of 31 patients with AE-IP who did not recover between 7 and 14 days after an initial treatment. Fourteen patients received PFD within 2 weeks (PFD group) of the AE, while 17 patients were treated without PFD (non-PFD group). The patients' clinical data and computed tomography (CT) scores were analyzed. RESULTS: The survival rate in the PFD group was not significantly different from non-PFD group at 30 (78.6% vs 64.7%, P = .46) and 90 days (64.3% vs 52.9%, P = .72). The white blood cell counts in the PFD group were significantly lower on PFD day 14 than on PFD days 1 and 7. The C-reactive protein levels in the PFD group were also significantly lower on PFD day 7 than on PFD day 1. There were no significant differences regarding the changes of the CT scores. CONCLUSIONS: PFD may reduce the inflammation in AE-IP patients undergoing corticosteroid treatment.

Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease.

AIMS: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data. METHODS AND RESULTS: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4+ cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis. CONCLUSIONS: Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube.

Predictive factors for the effect of pirfenidone in idiopathic pulmonary fibrosis.

Background: Pirfenidone is one of the anti-fibrotic drugs used for patients with idiopathic pulmonary fibrosis. Pirfenidone exerts anti-inflammatory effects by inhibiting the influx of inflammatory cells. Objectives: The purpose of this study was to clarify the differences in the baseline parameters in responsive and unresponsive patients, and to assess the clinical and radiological changes after pirfenidone therapy. Methods: Patients with idiopathic pulmonary fibrosis who were treated with pirfenidone from April 2009 to March 2014 were retrospectively analyzed. The enrolled patients were classified into a good response group if they showed inhibition of progression, or were classified into a slowly progressive group on the basis of a decline in the vital capacity over a six-month interval after beginning treatment. The parameters of pulmonary function tests and laboratory findings were compared before and after treatment. The chest computed tomography findings were evaluated using the Sumikawa score. Results: Twenty patients were classified into seven good responders and eight cases with inhibition of progression. These groups had higher antinuclear antibody and autoimmune antibody values, and less ground glass attenuation at baseline. A chest computed tomography assessment at six-months after beginning pirfenidone administration showed a reduction of the ground glass attenuation findings in the good response group and an increase in airspace consolidation in the slowly progressing group compared with the baseline. Conclusions: Higher positive values for antinuclear antibodies and autoimmune antibodies at baseline and the location of ground glass attenuation at baseline, which indicates inflammatory lesions, may predict the efficacy of pirfenidone. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 290-299).

Efficacy of thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: a nonrandomized prospective study.

PURPOSE: Acute exacerbation (AE) is an important outcome of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Recombinant human soluble thrombomodulin (rhTM) is a new drug for the treatment of disseminated intravascular coagulation in Japan. The objective of this study was to evaluate the efficacy of rhTM for AE of IPF/NSIP. METHODS: Twenty-two patients with AE-idiopathic interstitial pneumonia (16 patients with IPF and six patients with NSIP) were enrolled in our study. Among them, eleven patients were treated with rhTM (rhTM group), and eleven patients were treated without rhTM (non-rhTM group). Patients admitted to our hospital prior to December 2013 were treated with rhTM, while those admitted after January 2014 were treated without rhTM. The primary endpoint was mortality at 90 days after AE treatment. The secondary endpoint was the safety of rhTM for AE-IPF/AE-NSIP. In addition, we examined prognostic factors of AE-IPF/AE-NSIP. RESULTS: The mortality rate was significantly lower in the rhTM group than in the non-rhTM group (mortality rate at 90 days: 36% vs 90%, P=0.023; median survival time: not reached vs 15.0 days, P=0.019). A univariate analysis revealed the respiratory rate (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.00-1.18, P=0.039) and rhTM administration (HR 0.21, 95% CI 0.06-0.77, P=0.013) as predictors of mortality at 90 days, and a multivariate analysis identified rhTM administration (HR 0.025, 95% CI 0.0006-0.94, P=0.046) as an independent predictor of mortality at 90 days. No serious adverse events were observed. CONCLUSION: The administration of rhTM is associated with reductions in mortality in patients with AE-IPF/NSIP, without causing adverse events.

Estimation using the impulse oscillation system in patients with pulmonary sarcoidosis.

BACKGROUND: Limitations in airflow are detected in some patients with sarcoidosis in association with a poor prognosis. The impulse oscillation system (IOS) is used to treat patients with obstructive lung disease, as it can sensitively detect increased airway resistance. OBJECTIVES: To investigate the characteristics of parameters obtained with IOS in patients with sarcoidosis. METHODS: Forty-six pulmonary sarcoidosis patients at Chiba University Hospital and 20 healthy controls were enrolled. The subjects underwent IOS, pulmonary function testing and multidetector computed tomography. We evaluated the correlations between these indices in the pulmonary sarcoidosis patients and compared the pulmonary sarcoidosis patients with the healthy controls. RESULTS: The ratio of V50/V25, percentage of wall area (WA%), resistance at 5 Hz (R5) and difference between the R5 and R20 (R5-R20) values of the patients with pulmonary sarcoidosis were significantly increased compared to those observed in the controls. Inverse weak correlations were observed between the R5-R20 values and the forced expiratory volume in one second (r = -0.56; p <0.001). The R5-R20 values were correlated with the V50/V25 (r = 0.42; p < 0.005) and WA% (r = 0.43; p < 0.05) values. The WA% values were also significantly correlated with the V50/V25 (r = 0.32; p < 0.05) and R5 (r = 0.33; p < 0.05) values. CONCLUSIONS: IOS parameters were found to be significantly correlated with pulmonary function parameters and the airway wall thickness in pulmonary sarcoidosis patients. IOS is considered to be useful for detecting early manifestations of airflow limitation in pulmonary sarcoidosis patients.

Thrombomodulin for acute exacerbations of idiopathic pulmonary fibrosis: a proof of concept study.

INTRODUCTION: The mortality of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is high. Anticoagulation therapy (recombinant human soluble thrombomodulin (rhTM)) is recognized as a potential new strategy for treating disseminated intravascular coagulation in Japan. This preliminary study was to evaluate whether the coagulation factors increase or decrease in AE-IPF-patients, and whether the additional administration of rhTM for AE-IPF-patients has any beneficial effects on inflammatory mediators and activated coagulation. METHODS: We retrospectively compared the clinical data of AE-IPF-patients, idiopathic pulmonary fibrosis (IPF) with pneumonia-patients and slowly progressive IPF-patients. As a subsequent study, AE-IPF-patients were prospectively treated with a bolus of rhTM intravenously for six days under mechanical ventilation. We historically investigated the improvement of the serial clinical data in both oxygenation and intravascular coagulation disturbance between treated AE-IPF-patients and untreated AE-IPF-patients. RESULTS: Eleven AE-IPF, 21 IPF with pneumonia and 16 slowly progressive IPF-patients were enrolled, and the coagulatory levels of the AE-IPF-patients were found to be significantly higher than in the other patients. In 20 treated AE-IPF-patients, the 28-day mortality and in-hospital mortality were 35% and 45%, respectively. The levels of oxygenation rapidly increased on day 1 and continued to improve until day 7 in the survival AE-IPF-patients. The thrombin-antithrombin complex levels and inflammatory cytokine levels in the survivors on day 7 were significantly different from those observed in the nonsurvivors. CONCLUSION: AE-IPF-patients were found to have significantly higher levels of coagulation. The rhTM administration in the surviving AE-IPF-patients led to significant differences in the oxygenation and intravascular coagulation disturbance.

Effect of lifestyle on asthma control in Japanese patients: importance of periodical exercise and raw vegetable diet.

BACKGROUND: The avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients. METHODS: The study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted. RESULTS: The proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis. CONCLUSIONS: Periodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients.

A case of yellow nail syndrome with dramatically improved nail discoloration by oral clarithromycin.

An 80-year-old woman was admitted to our hospital with pneumonia and exacerbation of sinobronchial syndrome (SBS). She presented with yellow discoloration of the nail beds of all fingers and toes, and her nails were recognized as growing slowly. Chest X-ray revealed bronchiectasis in the bilateral lower lobe and bilateral pleural effusion. We diagnosed her as having yellow nail syndrome (YNS), based on the triad of yellow nails, lymphedema, and lung disease. After treatment with antibiotics [ampicillin/sulbactam and clarithromycin (CAM)] for pneumonia and SBS, her general condition improved, and the yellow nails disappeared in some fingers. When she was previously treated with 200 mg CAM for SBS, her yellow nails had not shown improvement. This time, her yellow nails improved after treatment with 400 mg CAM. The literature reports vitamin E, zinc, and topical corticosteroid plus active vitamin D3 to be effective in the treatment of yellow nails. Two studies have reported treatment for YNS using CAM, though they found a lack of efficacy. Thus, the present case is the first to report improved yellow nails using CAM alone. We conclude that not only SBS and lung disease but also YNS were improved by treatment with 400 mg CAM.