Immune and allergenic effects of the microalga Coccomyxa sp. strain KJ in healthy humans: A pilot study.

BACKGROUND: The Coccomyxa sp. strain KJ (Coccomyxa KJ), a microalga found in Japan, has a potential function in controlling viral infections. Recently, its dry powder has been marketed as a health food product. OBJECTIVES: This pilot study investigated the effects of Coccomyxa KJ powder tablet intake on allergic reactions and immune functions in healthy participants. MATERIAL AND METHODS: Nine healthy volunteers (4 males and 5 females) who expressed interest in foods containing Coccomyxa KJ, and were willing to undergo blood tests, were recruited. Each individual was asked to take 2 Coccomyxa KJ powder tablets (0.3 g) before breakfast once a day for 4 weeks. The salivary immunoglobulin A (IgA) level and blood parameters (white blood cell (WBC) count, eosinophil and lymphocyte counts and percentages, natural killer (NK) cell activity, interleukin (IL)-6 level, and T helper (Th)1/Th2 cell ratio) were evaluated at baseline and weeks 2 and 4. RESULTS: The 4-week intake of Coccomyxa KJ did not affect salivary IgA levels, WBC count, eosinophil and lymphocyte counts and percentages, or the Th1/Th2 ratio. There were significant differences in the NK cell activity after 4 weeks, with an average increase of 11.78 (95% confidence interval (95% CI): 6.80-16.76). None of the patients experienced adverse reactions during or after the study. CONCLUSIONS: Long-term Coccomyxa KJ intake improved NK cell activity without causing adverse effects on the indicators of local immunity, systemic inflammation and immune response balance. This study suggests that Coccomyxa KJ powder tablets can induce beneficial immune modifications without causing any adverse effects.

Clinical features of relapsed connective tissue disease-associated organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) is recognized as a nonspecific lung injury response characterized histopathologically by the presence of intra-alveolar buds of granulation tissue. Most OP patients show excellent responses to corticosteroids, but relapse is frequently seen when corticosteroids are tapered or discontinued. Although several factors associated with relapse have been reported in cryptogenic OP (COP), the clinical features and risk factors associated with relapse in connective tissue disease-associated OP (CTD-OP) have yet to be fully understood. METHODS: We retrospectively reviewed data on 47 CTD-OP patients. We investigated the frequency of relapse and compared the clinical data between CTD-OP with and without relapse to clarify the risk factors for relapse. RESULTS: Eleven (23.4%) CTD-OP patients had relapses of OP during the study. In the multivariate analysis, no CTD treatment at OP diagnosis [O.R. 11.920, p = 0.012] and partial remission after steroid treatment [O.R. 35.944, p = 0.045] were independent risk factors for relapse. Among rheumatoid arthritis-associated OP (RA-OP) patients, partial remission after steroid treatment [O.R. 16.151, p = 0.047] and age at OP diagnosis [O.R. 0.899, p = 0.045] were independent risk factors for relapse. Most of the relapsed OP patients who were on no medication at OP diagnosis later developed CTD. CONCLUSION: CTD-OP patients with residual disease on HRCT after treatment and who had OP diagnosis preceding CTD diagnosis were more likely to have an OP relapse. During the clinical course of relapsed OP patients, it is necessary to pay attention to the onset of CTD.

Retrospective study on the efficacy of monocyte distribution width (MDW) as a screening test for COVID-19.

BACKGROUND: Pathogenic genetic testing for coronavirus disease 2019 (COVID-19) can detect viruses with high sensitivity; however, there are several challenges. In the prevention, testing, and treatment of COVID-19, more effective, safer, and convenient methods are desired. We evaluated the possibility of monocyte distribution width (MDW) as an infection biomarker in COVID-19 testing. METHODS: The efficacy of MDW as a screening test for COVID-19 was retrospectively assessed in 80 patients in the COVID-19 group and 232 patients in the non-COVID-19 group (141 patients with acute respiratory infection, 19 patients with nonrespiratory infection, one patient with a viral infection, 11 patients who had received treatment for COVID-19, one patient in contact with COVID-19 patients, and 59 patients with noninfectious disease). RESULTS: The median MDW in 80 patients in the COVID-19 group was 23.3 (17.2-33.6), and the median MDW in 232 patients in the non-COVID-19 group was 19.0 (13.6-30.2) (P < 0.001). When the COVID-19 group was identified using the MDW cut-off value of 21.3 from the non-COVID-19 group, the area under the curve (AUC) was 0.844, and the sensitivity and specificity were 81.3% and 78.2%, respectively. Comparison of MDW by severity between the COVID-19 group and patients with acute respiratory infection in the non-COVID-19 group showed that MDW was significantly higher in the COVID-19 group for all mild, moderate I, and moderate II disease. CONCLUSIONS: MDW (cut-off value: 21.3) may be used as a screening test for COVID-19 in fever outpatients. Trial registration This study was conducted after being approved by the ethics committee of National Hospital Organization Omuta National Hospital (Approval No. 3-19). This study can be accessed via https://omuta.hosp.go.jp/files/000179721.pdf .

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.).

[Evaluation of the Clinical Validity of the Clostridioides difficile Nucleic Acid Detection Kit "Smart Gene® CD ToxinB"].

Clostridioides difficile is the most common anaerobic bacterium that causes healthcare-associated infections, and prompt diagnosis and infection control are important because it causes C. difficile infection (CDI). In this evaluation, the C. difficile nucleic acid detection reagent, Smart Gene CD Toxin B (Mizuho Medy Co., Ltd., hereinafter referred to as the "evaluation reagent") was evaluated for its clinical performance in comparison with real-time PCR and toxigenic culture (TC). Measurement of evaluation reagents and real-time PCR were performed on 157 residual stool specimens from suspected CDI patients. For TC, stool culture was performed, and colonies in which C. difficile was identified by a mass spectrometer (MALDI Biotyper) were checked for toxin production using a rapid antigen diagnostic kit. The results of the evaluation reagents showed a high concordance rate; 100% sensitivity (81/81) and 100% specificity (76/76) with real-time PCR, 89.8% sensitivity (79/88), and 97.1% specificity (67/69) with TC. The evaluation reagent enables a simple nucleic acid amplification test (NAAT) in a short time and is thought to be useful in CDI treatment, which requires rapid diagnosis and infection control.

Efficacy of steroid pulse therapy for miliary tuberculosis complicated by acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

Acute exacerbation in antineutrophil cytoplasmic antibody-associated interstitial lung disease: Clinical features and risk factors.

BACKGROUND: Acute exacerbation (AE) is a life-threatening clinical event that occurs during the clinical course of idiopathic pulmonary fibrosis (IPF). Several studies have reported that AE also occurs in interstitial lung disease (ILD) other than IPF. However, the incidence, clinical features, risk factors for AE, and major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated ILD (ANCA-ILD) patients have not been well established. METHODS: We retrospectively reviewed the data of 54 ANCA-ILD patients and 304 IPF patients. We investigated the frequency of AE, post-AE prognoses, risk factors for AE, and major causes of death in ANCA-ILD patients. We also compared the data of ANCA-ILD with that of IPF. RESULTS: Fourteen (25.9%) ANCA-ILD patients and 84 (27.6%) IPF patients developed AE. The median survival times (MSTs) after AE in ANCA-ILD and IPF patients were 35.5 and 60 days, respectively (p = 0.588, log-rank test). In a multivariate analysis, the percentage of predicted forced vital capacity (%FVC) [O.R. 0.750 (95% CI 0.570, 0.986), p < 0.01] and serum C-reactive protein (CRP) [O.R. 2.202 (95% CI 1.037, 4.674), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death in ANCA-ILD and IPF patients. CONCLUSION: ANCA-ILD patients could develop AE, and the frequency of AE in ANCA-ILD is similar to that in IPF. AE is the most frequent cause of death in ANCA-ILD patients. A low %FVC and a high serum CRP level were independent predictive factors for AE in ANCA-ILD. The prognosis after AE in ANCA-ILD was poor, as it was in IPF.

Small-cell lung cancer from the peripheral lung is frequently accompanied by emphysema and interstitial lung disease in the background.

BACKGROUND: It has long been thought that small-cell lung cancer (SCLC) is a central type of tumor that is located in the proximal bronchi and the mediastinum. However, several studies reported that SCLC exhibited several types of spread pattern on computed tomography (CT). The aim of this study is to investigate the relationship between CT images and clinical characteristics in patients with SCLC. METHODS: We retrospectively reviewed the CT images of 92 SCLC patients and classified them into six types of spreading patterns: central, peripheral, lymphangitic spread (LYM), pleural dissemination (PLE), lobar replacement (LOB), and air-space consolidation (AC). We also evaluated the correlation between primary tumor location and the clinical characteristics of patients. RESULTS: The most common type of imaging pattern was peripheral (n = 40, 44%), with the next most common type being central (n = 27, 29%). Atypical types of SCLC, such as LYM (n = 2, 2%), PLE (n = 4, 4%), LOB (n = 8, 9%), and AC (n = 11, 12%), were also recognized in our study. The prevalence of emphysema and interstitial lung disease (ILD) was significantly higher in the peripheral type than in the central type (p = 0.0056 and p = 0.0403, respectively). Meanwhile, no survival difference was seen between the central type and the peripheral type (median months 17.9 vs. 21.9, respectively, p = 0.720). CONCLUSIONS: The peripheral type of tumor was correlated with higher prevalence of emphysema and ILD in SCLC. Our result suggests different mechanisms of development and tumor characteristics according to tumor location.

Clinical features of acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: Comparison with idiopathic pulmonary fibrosis.

BACKGROUND: Several studies have reported that acute exacerbation (AE), which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the incidence, clinical features, and risk factors for AE, a major cause of death of RA-ILD patients, and the differences in clinical aspects of AE between RA-ILD and IPF have yet to be fully understood. METHODS: We retrospectively reviewed data on 149 RA-ILD patients and 305 IPF patients. We investigated the frequency of AE and compared the clinical data between RA-ILD with and without AE to clarify the risk factor for AE. We also compared the post-AE prognosis and cause of death between RA-ILD and IPF patients. RESULTS: Twenty-seven (18.1%) RA-ILD patients and 84 (27.5%) IPF patients developed AE. The median survival time (MST) after AE of RA-ILD and IPF was 277 days and 60 days, respectively (log rank, p = 0.038). In a multivariate analysis, hypoalbuminemia [odds ratio (O.R.) 0.090 (95%CI 0.011-0.733), p = 0.012] and % carbon monoxide diffusion capacity (%DLCO) [O.R. 0.810 (95%CI 0.814-0.964), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death of RA-ILD and IPF. CONCLUSION: RA-ILD patients could develop AE, and AE was not uncommon in RA-ILD or IPF. %DLCO and hypoalbuminemia were predictive factors of AE in RA-ILD. The prognosis after AE of RA-ILD was significantly better than that of IPF. The most frequent cause of death in RA-ILD and IPF was AE.

Combination immunotherapy of nivolumab plus ipilimumab in a lung cancer patient with Werner syndrome; a case report.

Werner syndrome (WS) is a rare progressive disorder that is characterized by premature aging of all organs. Malignancy is a frequent complication of WS, however, lung cancer patients with WS are much rare. In patients with WS, the treatment for malignancy is often limited due to other complications of severe skin ulcer, diabetes mellitus and cardiovascular disease. Currently, immune-checkpoint inhibitors (ICIs) are standard therapy for several cancer patients and the combination of nivolumab plus ipilimumab has also been approved for the treatment of non-small cell lung cancer (NSCLC). Recent studies have also reported that serious immune-related adverse events (irAEs) induced by ICIs may correlate with elderly or more vulnerable patients. However, the efficacy and safety of ICIs in NSCLC patients with WS remain unclear. To the best of our knowledge, this is the first case describing a NSCLC patient with WS receiving the combination immunotherapy of nivolumab and ipilimumab. Our case showed objective response to ICIs, however, several immune-related adverse events (irAEs) including hypothyroidism, adrenal insufficiency, hard rash and interstitial lung disease occurred, thus resulted in early treatment discontinuation. Our case suggests that immunotherapy for NSCLC patients with WS could be effective, but physicians may be aware of the possibility of multiple irAEs undergoing immunotherapy for NSCLC patients with WS.

Pleural empyema with gas formation caused by mixed infection of Edwardsiella tarda with Streptococcus constellatus.

Edwardsiella tarda is an anaerobic, gram-negative rod bacterium associated with freshwater and marine life. Human E. tarda infections are rare, and most infections in humans cause gastroenteritis. Extraintestinal infections of E. tarda such as pleural empyema are particularly rare. A 72-year-old man was admitted with cough and purulent sputum. His medical history included periodontal disease and gastric cancer for which he had undergone total gastrectomy. Chest computed tomography showed left pleural effusion with foci of gas, and both E. tarda and Streptococcus constellatus were cultured from the pleural effusion. Thus, he was diagnosed with gas-forming empyema. He was successfully treated with therapeutic thoracentesis and antibiotics. Our case suggests that a dietary habit of raw fish, undernutrition, gastrectomy and oral infection may be predisposing factors for empyema caused by E. tarda.

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.

Complete Genome Sequencing of Mycobacterium heckeshornense Strain JMUB5695, Isolated from Necrotizing Granulomatous Lesions.

We report the complete genome sequence of Mycobacterium heckeshornense strain JMUB5695, which was isolated from necrotizing granulomatous lesions in a lung cancer patient. The complete genome consists of a 4,865,109-bp chromosome with a GC content of 65.9% and contains no plasmids.

Comfort and safety of bronchoscopy performed under sedation and local anesthesia in elderly patients.

Although sedation for bronchoscopy improves patient comfort, there is a risk of oversedation in elderly patients. Only a few studies have evaluated the efficacy and safety of sedation for bronchoscopy in elderly patients.This study retrospectively analyzed records of 210 patients who underwent transbronchial brushing and/or biopsy under midazolam sedation at National Hospital Organization Omuta National Hospital between June 2017 and October 2019. Patients were administered 1 mg midazolam following 10 mL 4% lidocaine inhalation. When sedation was insufficient, 0.5 mg midazolam was administered additionally. Diagnostic yield, incidence of complications, amount of oxygen supplementation, decreases in percutaneous oxygen saturation (SpO2), changes in blood pressure, and degree of comfort were analyzed.Patients were divided into the elderly (n = 102) and non-elderly (n = 108) groups. No significant differences were observed in diagnostic yield and procedure time between the 2 groups, and no severe adverse events were noted in the elderly group. The degree of comfort during bronchoscopy was significantly higher in the elderly group. In patients administered < 2 mg midazolam, the amount of oxygen supplementation and decreases in SpO2 were significantly smaller in the elderly group compared to the non-elderly group.The risk of adverse events related to midazolam sedation in bronchoscopy does not increase with age, and sedation improves comfort during flexible bronchoscopy in elderly patients. Moreover, a total dose of midazolam <2 mg is safe for elderly patients undergoing bronchoscopy.

Indium kinetics in an indium exposed worker before and after bilateral lung transplantation.

BACKGROUND: A male worker with indium-tin oxide (ITO)-induced pneumoconiosis underwent bilateral lung transplantation (LT). METHODS: Post-LT histopathological investigations of the isolated lungs and hilar lymph nodes were performed and indium concentration in serum (In-S) and serum Krebs von den Lungen-6 (KL-6) were tracked for 122 weeks. RESULTS: He has attained the ultimate treatment goal of > 2-year survival. The main histopathological characteristics were pan-lobular emphysematous change, interstitial fibrosis, and lymphocytic infiltration in the peribronchiolar/perivascular portions, and numerous cholesterol clefts and giant cells containing brown particles. These findings support the conclusion that the lung injury was caused by the inhalation of ITO. Metal element mapping and indium in the isolated lungs revealed that inhaled ITO particles in humans migrate to the lymph nodes. In-S remained at remarkably high levels (≥30 ng/mL) and showed wide fluctuation with bimodality until 46 weeks after LT, but KL-6 remained in the normal range for almost the entire period. The indium concentration in the donor's resection lung at 10 weeks after LT was 143.5 ng/g wet-weight, which was only one one-thousandth of the recipient's lung (161 µg/g wet-weight). After 48 weeks of LT, the recipient's In-S had gradually decreased; the biological half-life was 1.2 years. These results clearly suggest that indium remaining in the recipient's tissues did not adversely influence the transplant donor's lungs. CONCLUSIONS: The transplanted donor's lungs were not influenced by indium in the recipient's organs. Bilateral LT is thus an effective treatment option in severe indium lung disease cases.

Trends in the prevalence of COPD in elderly individuals in an air-polluted city in Japan: a cross-sectional study.

Purpose: The aim of this study was to examine the effects of exposure to air pollution and cigarette smoke on respiratory function, respiratory symptoms, and the prevalence of COPD in individuals aged ≥50 years. Patients and methods: We used spirometry and medical questionnaires to screen 433 individuals from Omuta City, Japan, an area with high levels of air pollution. Results: Non smokers had a high estimated COPD prevalence rate of 16%. Among smokers, the estimated prevalence of COPD was 29% in seniors (50- to 74-years group) and 37% in the elderly (>75 years group). We also found a correlation between levels of suspended particulate matter and COPD. Conclusion: Both smoking and chronic exposure to air pollution (>5 years) decreased respiratory function, exacerbated respiratory symptoms, and increased the prevalence of COPD. We strongly recommend periodic screening for the elderly patients to facilitate early detection of respiratory disease.

Procalcitonin-Guided Antibiotic Discontinuation Might Shorten the Duration of Antibiotic Treatment Without Increasing Pneumonia Recurrence.

BACKGROUND: The optimal duration of antibiotic treatment has not been established for pneumonia patients. Some investigators reported procalcitonin (PCT)-guided antimicrobial stewardship reduces the duration of antibiotic use without increasing mortality in pneumonia patients. MATERIAL AND METHODS: We prospectively enrolled hospitalized community-acquired pneumonia or healthcare-associated pneumonia patients with PCT levels >0.20 ng/mL on admission, who were admitted between 2014 and 2017. PCT levels were measured on days 5, 8 and 11 and every 3 days thereafter if needed. Physicians were encouraged and strongly encouraged to discontinue antibiotics when PCT levels decreased below 0.20 ng/mL and 0.10 ng/mL, respectively. Those admitted between 2010 and 2014 were included in the study as historical controls. Primary endpoints were duration of antibiotic treatment and recurrence of pneumonia within 30 days after antibiotic discontinuation. RESULTS: The PCT-guided and control groups consisted of 116 patients each. Background factors including pneumonia severity and PCT levels did not differ between the 2 groups. Median duration of antibiotic treatment was 8.0 and 11 days in the PCT-guided and control groups, respectively (P < 0.001). Multivariable regression analysis revealed that PCT-guided antibiotic discontinuation (partial regression coefficient [PRC] -1.9319, P < 0.001), PCT (PRC 0.1501, P = 0.0059) and albumin (PRC -1.4398, P = 0.0096) were significantly related to duration of antibiotic treatment. Pneumonia recurrence within 30 days after antibiotic discontinuation was not statistically different between the 2 groups (4.3% vs. 6.0%, P = 0.5541). CONCLUSIONS: PCT-guided antibiotic discontinuation might be useful for shortening the duration of antibiotic treatment without increasing pneumonia recurrence.

Prognostic factors in patients with miliary tuberculosis.

BACKGROUND AND PURPOSE: Acute respiratory distress syndrome (ARDS) complication has long been considered a factor associated with poor prognosis in patients with miliary tuberculosis. However, few reports exist on the prognostic factors of miliary tuberculosis including those complicating ARDS. SUBJECTS AND METHODS: We retrospectively examined prognoses and other clinical information obtained from medical records of a total of 68 patients diagnosed with miliary tuberculosis. Clinical findings were compared between patients who died within three months (non-survivor group) and those who survived beyond three months (survivor group), and risk factors for death within three months of diagnosis were examined using logistic regression analysis. RESULTS: Fifteen of 68 patients diagnosed with miliary tuberculosis died within three months. Most patients were aged 60 years or older (63 patients; 91.2%), with a peak in the 80 s (32 patients; 47.1%). Of the 68 patients with miliary tuberculosis, 13 (19%) had ARDS. The risk of death within three months increased with increasing age and ARDS onset during the disease course. The results of multivariate analysis revealed that, in addition to age (odd ratio (OR): 15.5) and the presence/absence of ARDS (OR: 12.0), consciousness disturbance (OR: 81.53) and high BUN levels (OR: 5.71) were independent factors for death within three months. CONCLUSION: In patients with miliary tuberculosis, old age, ARDS, consciousness disturbance, and high BUN levels were factors associated with poor prognosis.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS: Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION: Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

An advanced case of indium lung disease with progressive emphysema.

OBJECTIVES: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. CASE REPORT: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 µg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 µg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). CONCLUSIONS: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option.