Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study.

BACKGROUND: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma. METHODS: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS). RESULTS: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1-5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR. CONCLUSIONS: Exhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. CASE PRESENTATION: A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of "decoy cells". Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. CONCLUSIONS: BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Fast optimal entrainment of limit-cycle oscillators by strong periodic inputs via phase-amplitude reduction and Floquet theory.

Optimal entrainment of limit-cycle oscillators by strong periodic inputs is studied on the basis of the phase-amplitude reduction and Floquet theory. Two methods for deriving the input waveforms that keep the system state close to the original limit cycle are proposed, which enable the use of strong inputs for entrainment. The first amplitude-feedback method uses feedback control to suppress deviations of the system state from the limit cycle, while the second amplitude-penalty method seeks an input waveform that does not excite large deviations from the limit cycle in the feedforward framework. Optimal entrainment of the van der Pol and Willamowski-Rössler oscillators with real or complex Floquet exponents is analyzed as examples. It is demonstrated that the proposed methods can achieve considerably faster entrainment and provide wider entrainment ranges than the conventional method that relies only on phase reduction.

Synthesis of phosphabenzenes by an iron-catalyzed [2+2+2] cycloaddition reaction of diynes with phosphaalkynes.

A method for the synthesis of phosphabenzenes under iron catalysis is described. Thus, the FeI2 -catalyzed [2+2+2] cycloaddition of diynes with phosphaalkynes in m-xylene gave a variety of phosphabenzenes in good to high yields (up to 87 % yield).

An Autopsy Case of COVID-19 with New Diffuse Pulmonary Ossification.

We present the case of a 61-year-old man who developed coronavirus disease 2019 (COVID-19) and died during treatment for relapsing polychondritis. The patient was intubated and treated with steroid pulse therapy, remdecivir, antibacterial agents, baricitinib, and tocilizumab. However, his respiratory condition worsened, and he died 108 days after disease onset. An autopsy revealed diffuse alveolar damage in the fibrotic phase in all lung lobes, diffuse pulmonary ossification, and cytomegalovirus-infected cells in the middle lobe of the right lung. We herein discuss the clinical features and pathological findings of COVID-19 in immunosuppressed patients.

Effects of tiotropium on lung function in severe asthmatics with or without emphysematous changes.

The effects of tiotropium, an inhaled long-acting anti-cholinergic agent, on lung function were investigated in obstructed severe asthmatics with and without emphysematous changes despite maximal recommended treatments with high-dose of inhaled glucocorticoids and inhaled long-acting ß(2)-agonists. We conducted a double-blind, placebo-controlled study of an inhaled single-dose of tiotropium in 18 asthmatics with emphysema and 18 without emphysema in a crossover manner. The primary efficacy outcome was the relative change in forced expiratory volume in 1 s (FEV(1)) from baseline to 60 min, and the secondary outcome was a relative change in FEV(1) from baseline to 12 h. Subsequently, the patients were treated with tiotropium inhaled once daily for 12 weeks in an open label manner, and lung function and symptoms were evaluated. At baseline, patients with or without emphysema had a mean FEV(1) of 55.9% before tiotropium and 56.8% before placebo, or 77.4% before tiotropium and 77.6% before placebo of the predicted value and were taking a mean dose of inhaled glucocorticoids of 1444 or 1422 µg/day. Among patients with emphysema, the increase from baseline FEV(1) was 12.6 percentage points higher at 60 min after tiotropium than after placebo. Among patients without emphysema, the increase from baseline FEV(1) was 5.4 percentage points higher at 60 min after tiotropium than after placebo. Tiotropium resulted in improved lung function and symptoms in asthmatics with and without emphysema. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma and of overlapping asthma and COPD.

Clinical benefit of platinum doublet combination therapy in older adults with advanced non-small cell lung cancer: A prospective multicenter study by the National Hospital Organization in Japan.

BACKGROUND: Previous trials suggest that older adults with non-small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first-line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC. METHODS: Patients aged ≥75 years with advanced NSCLC treated at any of 24 National Hospital Organization institutions completed a pre-first-line chemotherapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. We evaluated whether these variables were the risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 148 patients with advanced NSCLC were treated with combination therapy (n = 90) or monotherapy (n = 58). Median PFS was 5.3 months and OS was 13.6 months. We identified that hypoalbuminemia (hazard ratio [HR] 2.570, 95% confidence interval [CI]: 1.117-5.913, p = 0.0264) was a risk factor for PFS and monotherapy (HR 1.590, 95% CI: 1.070-2.361, p = 0.0217), lactate dehydrogenase (HR 3.682, 95% CI: 1.013-13.39, p = 0.0478), and high C-reactive protein (HR 2.038, 95% CI: 1.141-3.642, p = 0.0161) were risk factors for OS. The median OS was significantly longer in patients treated with combination therapy than in those who received monotherapy (16.5 months vs. 10.3 months; HR 0.684, 95% CI: 0.470-0.995, p = 0.0453). DISCUSSION: Platinum doublet combination therapy may be beneficial in older patients with NSCLC. Identification of risk factors will assist in the development of a personalized treatment strategy.

Survival and acute exacerbation for patients with idiopathic pulmonary fibrosis (IPF) or non-IPF idiopathic interstitial pneumonias: 5-year follow-up analysis of a prospective multi-institutional patient registry.

OBJECTIVE: Few prospective cohort studies with relatively large numbers of patients with non-idiopathic pulmonary fibrosis (non-IPF) of idiopathic interstitial pneumonia (IIP) have been described. We aimed to assess disease progression and cause of death for patients with non-IPF IIPs or IPF under real-life conditions. METHODS: Data were analysed for a prospective multi-institutional cohort of 528 IIP patients enrolled in Japan between September 2013 and April 2016. Diagnosis of IPF versus non-IPF IIPs was based on central multidisciplinary discussion, and follow-up surveillance was performed for up to 5 years after patient registration. Survival and acute exacerbation (AE) were assessed. RESULTS: IPF was the most common diagnosis (58.0%), followed by unclassifiable IIPs (35.8%) and others (6.2%). The 5-year survival rate for non-IPF IIP and IPF groups was 72.8% and 53.7%, respectively, with chronic respiratory failure being the primary cause of death in both groups. AE was the second most common cause of death for both non-IPF IIP (24.1%) and IPF (23.5%) patients. The cumulative incidence of AE did not differ significantly between the two groups (p=0.36), with a 1-year incidence rate of 7.4% and 9.0% in non-IPF IIP and IPF patients, respectively. We found that 30.2% and 39.4% of non-IPF IIP and IPF patients, respectively, who experienced AE died within 3 months after an AE event, whereas 55.8% and 66.7% of such patients, respectively, died within 5 years after registration. CONCLUSION: Closer monitoring of disease progression and palliative care interventions after AE are important for non-IPF IIP patients as well as for IPF patients.

Estimating asymptotic phase and amplitude functions of limit-cycle oscillators from time series data.

We propose a method for estimating the asymptotic phase and amplitude functions of limit-cycle oscillators using observed time series data without prior knowledge of their dynamical equations. The estimation is performed by polynomial regression and can be solved as a convex optimization problem. The validity of the proposed method is numerically illustrated by using two-dimensional limit-cycle oscillators as examples. As an application, we demonstrate data-driven fast entrainment with amplitude suppression using the optimal periodic input derived from the estimated phase and amplitude functions.

Differences in the spectrum of respiratory viruses and detection of human rhinovirus C in exacerbations of adult asthma and chronic obstructive pulmonary disease.

BACKGROUND: Viral respiratory infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma. We conducted a multicenter prospective study to determine the differences in the spectrum of viruses between adults with asthma exacerbations and AECOPD and assessed the prevalence and impact of human rhinovirus (HRV)-C in adults, which is more pathogenic in children with asthma than other HRV species. METHODS: Nasopharyngeal and serum samples and clinical information were collected from 64 outpatients with adult asthma exacerbations and 44 outpatients with AECOPD between April 2018 and March 2020. Viral pathogens and HRV strains were identified from nasal samples by multiplex PCR and VP4/VP2 nested PCR. RESULTS: Viral pathogens were identified in 31 patients with asthma exacerbations (48.4%) and 17 patients with AECOPD (38.6%). The most commonly detected viruses were HRV/enterovirus followed by human metapneumovirus (hMPV) in patients with asthma exacerbations, and hMPV followed by parainfluenza virus in patients with AECOPD. HRV-C was the HRV species most commonly associated with both asthma exacerbations and AECOPD. Clinical characteristics, baseline lung function, serum inflammatory chemokines, hospitalization, and systemic steroid use did not differ between HRV-C-positive patients and those positive for other HRV species. CONCLUSIONS: Exacerbation-associated spectrum of viruses differed between adults with asthma exacerbations and AECOPD. HRV-C was the HRV species most often observed in adult asthma exacerbations and AECOPD, although it did not worsen patients' clinical outcomes relative to those of patients with other HRVs. Underlying disease-specific factors may be responsible for susceptibility to respiratory viruses. TRIAL REGISTRATION: UMIN-CTR UMIN000031934.

Predicting systemic therapy toxicity in older adult patients with advanced non-small cell lung cancer: A prospective multicenter study of National Hospital Organization in Japan.

INTRODUCTION: Previous studies have developed risk stratification schemas to assess systemic therapy toxicity. However, it is controversial which geriatric assessment variables should be used to assess the individual risk of severe treatment-associated toxicity in older adult patients. MATERIALS AND METHODS: Patients aged ≥70 years with advanced non-small cell lung cancer (NSCLC) treated at 24 National Hospital Organization institutions completed a pre-first-line systemic therapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. Patients were followed through one cycle of systemic therapy to assess grade 3 (severe) to grade 5 (death) adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: In total, 348 advanced NSCLC patients with a median age of 76 years (range, 70 to 95 years) joined this prospective study. Severe adverse events ≥grade 3 occurred in 136 patients (39.1%). Predictors of hematologic toxicity were treatment variables, body mass index, body weight loss, and limitation in daily living due to dementia. These predictors provided the predictive model of hematologic toxicity ≥grade 3; 0 point (22.2%), 1 point (33.8%), 2 points (59.6%), ≥3 points (73.3%). Sex, daily living independence level, and lactate dehydrogenase levels were associated with non-hematologic toxicity ≥grade 3 in multivariate analysis. A scoring system using these predictors distinguished the risk levels of non-hematologic toxicity ≥grade 3; 0 point (6.6%), 1 point (12.2%), 2 points (39.0%), 3 points (75.0%). DISCUSSION: A stratification using individual extracted risk factors may be useful to predict the vulnerability to systemic therapy in older adult NSCLC patients.

[A case of alveolar hemorrhage caused by gefitinib].

Although drug-induced interstitial pneumonitis caused by gefitinib is well recognized in Japan, reports of alveolar hemorrhage caused by gefitinib are very rare. We encountered a case of alveolar hemorrhage thought to be caused by gefitinib. A 74-year-old woman with non-small cell lung cancer (adenocarcinoma; cT4NOM0, stage IIIB) had been receiving gefitinib as second-line therapy from January 2009. However, bloody sputum and nasal bleeding were observed 2 weeks after the initiation of gefitinib therapy. Chest radiography and computed tomography revealed ground-glass opacities predominantly in the lower lung fields. Bronchoscopy was performed, and the bronchoalveolar lavage fluid obtained from the right B8 was bloody. Her symptoms and chest ground-glass opacities improved after the withdrawal of gefitinib. Based on these clinical findings, we diagnosed alveolar hemorrhage caused by gefitinib. If chest radiography or computed tomography findings of gefitinib-treated patients show ground-glass opacities, the possibility of not only interstitial pneumonitis, but also alveolar hemorrhage should be considered in the differential diagnosis.

Correlation of 4-meter gait speed with clinical indicators of chronic obstructive pulmonary disease.

BACKGROUND: Measuring daily physical activity and exercise capacity is recommended in the routine care of patients with chronic obstructive pulmonary disease (COPD). The 4-m gait speed (4mGS) is simple and effective in stratifying patients according to exercise performance, dyspnea, health status, and prognosis. We assessed the reliability of the 4mGS as a clinical marker by examining its association with established clinical indicators among hospitalized patients with COPD. METHODS: This retrospective study included 78 patients hospitalized with COPD (mean age: 76.3 ± 0.9 years; males, n = 69) between January 2016 and June 2018 who were assessed using the 4mGS and divided into slow (<0.8 m/s) and normal (≥0.8 m/s) 4mGS groups. Clinical characteristics were compared, including death during the observation period, time to first exacerbation, and long-term oxygen therapy requirement. RESULTS: There were strong relationships between 4mGS performance, the 6-min walk test (R = 0.70; p < 0.0001), and the modified Medical Research Council dyspnea scale (R = 0.68; p < 0.0001) among the 78 patients. The slow 4mGS group had a higher frequency of death during the observation period (p = 0.0095) and a greater requirement for long-term oxygen therapy (p = 0.0063). The 4mGS correlated with inspiratory capacity (IC) and IC/total lung capacity ratios, which are respiratory failure indicators. CONCLUSIONS: The 4mGS is a simple and easy method of assessing the physical condition as well as estimating the prognosis of patients with COPD, and may serve as a useful marker in home medical treatment or clinical settings.

[A case of pulmonary actinomycosis mimicking chronic necrotizing pulmonary aspergillosis].

A 60-year-old man was admitted to our hospital with fever, appetite loss, and fatigue. Chest X-ray films and computed tomography scans showed fungus-ball-like lesions in the thoracic cavity, and pleural thickening with surrounding infiltration in the left upper lobe, developing over several months. The white blood cell count (WBC) and serum C-reactive protein (CRP) levels of the patient at the time of admission were 8800/microl and 2.7 mg/dl, respectively. He showed a negative reaction for the serum Aspergillus precipitating antibody, and a positive reaction for the serum Aspergillus antigen (Pletelia Aspergillus) according to the new cut-off index (the result was 0.8). From these clinical findings, we diagnosed this lesion as chronic necrotizing pulmonary aspergillosis (CNPA) and administered anti-fungal drugs (itraconazole plus micafungin, voriconazole) for several months. Despite medication, his condition appeared to deteriorate, and Aspergillus was never confirmed from frequent sputum cultures and bronchial lavage specimens. Finally, a pneumectomy was performed. Histopathological findings revealed a Gram-positive, filament-form Actinomyces cluster inside the cavity, which we diagnosed pulmonary actinomycosis. In this case, there was a possibility that the serum aspergillus antigen showed a false-positive reaction. Case must be taken in the evaluation of serum Aspergillus antigen testing.

Characteristics of tobacco-related lung diseases in Fukuoka Prefecture, Japan: A prospective, multi-institutional, observational study.

BACKGROUND: Tobacco smoking causes a variety of smoking-related diseases, death, and economic damage. Despite targeted anti-smoking campaigns, tobacco-related deaths are expected to increase in Japan. We investigated the current state of non-cancerous lung diseases such as idiopathic interstitial pneumonias (IIPs), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), which are known to be highly related to tobacco smoking. METHODS: This prospective multi-institutional observational study involved 29 major hospitals within the Fukuoka Prefecture area (Fukuoka tobacco-related lung disease registry study group). Patients diagnosed with IIPs, including CPFE and COPD, registered from September 1, 2013 to April 30, 2016 were included. Clinical background information, laboratory and pulmonary function test results, findings of imaging tests, including chest radiography and chest computed tomography, and DNA isolated from peripheral blood were collected from each patient. Follow-up surveillance involved collection of data regarding the exacerbation of disease and death until 5 years of registration. In the present study, we report the baseline characteristics of the patients registered in this surveillance study. RESULTS: Overall, 1016 patients (524 with IIPs, including 145 CPFE and 492 with COPD) were enrolled. Among the patients with COPD, 96.8% were current or former smokers. Among the patients with IIPs, 69.9% were current or former smokers. CONCLUSION: This study revealed the current status of lung diseases potentially related to tobacco smoking in Fukuoka Prefecture. Both COPD and CPFE were highly related to tobacco smoking, whereas 30% of patients with IIPs had never smoked.

Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.

Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis.

BACKGROUND AND OBJECTIVE: The usefulness of two tests in the serodiagnosis of chronic pulmonary aspergillosis (CPA) was compared. The tests were the serum Aspergillus galactomannan antigen test (Platelia (R) Aspergillus) by enzyme-linked immunoassay (EIA) using old and new cut-off indexes, and the Aspergillus precipitating antibody test. METHODS: Both Aspergillus-precipitating antibody and Platelia Aspergillus EIA positivity were measured in the sera of 28 patients at the time of diagnosis of CPA. RESULTS: Serum Aspergillus precipitating antibody positivity was 89.3% (25/28) in CPA patients. Serum Platelia Aspergillus EIA positivity was 21.4% (6/28) using the old cut-off index (> or =1.5) and 50% (14/28) using the new cut-off index (> or =0.5)-still less than that for Aspergillus precipitating antibody. Three of the 28 CPA patients had positive reactions in the Platelia Aspergillus EIA using the old cut-off index but not in the Aspergillus precipitating antibody test. Positivity for (1,3) beta-d glucan was 15.4%, and that for culture on CHROMagar Candida was 17.9%. One patient with pulmonary actinomycosis had a false-positive reaction in the Platelia Aspergillus test with the new cut-off index. CONCLUSIONS: For the diagnosis of CPA, Aspergillus precipitating antibody testing is more sensitive than the Platelia Aspergillus EIA, even with the new cut-off index. False-positive reactions are observed with the Platelia Aspergillus EIA in patients with conditions such as pulmonary actinomycosis. Results should be interpreted with care when patients are positive for the Platelia Aspergillus EIA but negative for Aspergillus precipitating antibody.

[Two familial cases of optic nerve hypoplasia including superior segmental optic hypoplasia].

PURPOSE: To report two familial cases of optic nerve hypoplasia including superior segmental optic hypoplasia (SSOH). CASES: In Family 1, case 1 and case 2 were sisters. In Family 2, case 3 was the mother of case 4 and the younger sister of case 5. The cases in Family 1 had SSOH in one eye, whereas Family 2 showed various patterns of SSOH, as well as nasal optic nerve hypoplasia, and a wide range of optic nerve hypoplasia. Case 1 and case 3 were diagnosed as normal tension glaucoma and treated with eye drops at a previous hospital. None of the cases had any systemic illness. The father of cases 1 and 2, and the father of Cases 3 and 5 were under treatment for type 2 diabetes mellitus. CONCLUSION: In this study, SSOH seemed to be prevalent among family members. In addition, as the cases in Family 2 illustrate, hypoplasia of the optic nerve showed various patterns in the superior segment, nasal segment, and over a wide range of the optic nerve. Therefore SSOH was just one part of the overall optic nerve hypoplasia.