Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Risk factors for in-hospital mortality in patients with advanced lung cancer with interstitial pneumonia undergoing systemic chemotherapy: A retrospective and observational study using a nationwide administrative database in Japan.

BACKGROUND: The safety profile of systemic chemotherapy for lung cancer patients with interstitial pneumonia (IP) in clinical practice remains unclear. Using Diagnostic Procedure Combination (DPC) data from the Japanese administrative database, we investigated the mortality of hospitalized lung cancer patients with IP as they underwent a course of systemic chemotherapy nationwide. METHODS: The DPC data of patients with stage IIIB or IV lung cancer as defined by the Union for International Cancer Control Tumor-Nodes-Metastases 6th and 7th editions from April 2014 to March 2016 were obtained. Among those patients, only patients with concomitant IP and receiving systemic chemotherapy without radiotherapy were included. RESULTS: Among 1524 included patients, 70 (4.6%) died in the hospital. Multivariate analysis revealed that low activities of daily living (ADL) scores on admission (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.24-4.12, p = 0.008) and high-dose corticosteroid therapy following chemotherapy (HR 2.62, 95% CI 1.44-4.77, p = 0.002) were strongly associated with in-hospital mortality. It was determined that patients possibly received high-dose corticosteroids for IP exacerbations; these patients had a higher in-hospital mortality rate of 67.7% (21/31 patients) and a significantly shorter median survival time of 55 days (95% CI 31-69 days, p < 0.001) than those who did not receive high-dose corticosteroids. CONCLUSION: Acute exacerbation of IP treated with systemic high-dose corticosteroids is significantly associated with in-hospital mortality, and a low ADL score on admission is a risk factor for in-hospital mortality in lung cancer patients with IP who undergo systemic chemotherapy.

Exposure to PM2.5 is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case-control study.

BACKGROUND: Short-term exposure to ozone and nitrogen dioxide is a risk factor for acute exacerbation (AE) of idiopathic pulmonary fibrosis (AE-IPF). The comprehensive roles of exposure to fine particulate matter in AE-IPF remain unclear. We aim to investigate the association of short-term exposure to fine particulate matter with the incidence of AE-IPF and to determine the exposure-risk time window during 3 months before the diagnosis of AE-IPF. METHODS: IPF patients were retrospectively identified from the nationwide registry in Japan. We conducted a case-control study to assess the correlation between AE-IPF incidence and short-term exposure to eight air pollutants, including particulate matter < 2.5 µm (PM2.5). In the time-series data, we compared monthly mean exposure concentrations between months with AE (case months) and those without AE (control months). We used multilevel mixed-effects logistic regression models to consider individual and institutional-level variables, and also adjusted these models for several covariates, including temperature and humidity. An additional analysis with different monthly lag periods was conducted to determine the risk-exposure time window for 3 months before the diagnosis of AE-IPF. RESULTS: Overall, 152 patients with surgically diagnosed IPF were analyzed. AE-IPF was significantly associated with an increased mean exposure level of nitric oxide (NO) and PM2.5 30 days prior to AE diagnosis. Adjusted odds ratio (OR) with a 10 unit increase in NO was 1.46 [95% confidence interval (CI) 1.11-1.93], and PM2.5 was 2.56 (95% CI 1.27-5.15). Additional analysis revealed that AE-IPF was associated with exposure to NO during the lag periods lag 1, lag 2, lag 1-2, and lag 1-3, and PM2.5 during the lag periods lag 1 and lag 1-2. CONCLUSIONS: Our results show that PM2.5 is a risk factor for AE-IPF, and the risk-exposure time window related to AE-IPF may lie within 1-2 months before the AE diagnosis. Further investigation is needed on the novel findings regarding the exposure to NO and AE-IPF.

Temporal echocardiographic assessment of pulmonary hypertension in idiopathic pulmonary fibrosis patients treated with nintedanib with or without oxygen therapy.

BACKGROUND: Nintedanib is an inhibitor of receptor tyrosine kinases, including vascular endothelial growth factor receptor, but its effects on pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients with chronic hypoxia were unclear. METHODS: This study included a nintedanib prospective study and historical control study. In the nintedanib prospective study, pulmonary artery systolic pressure (PASP) measured using transthoracic echocardiography was evaluated at six points during 48 weeks in 16 IPF patients in whom nintedanib was started. In the historical control study, adjusted annual change in PASP was compared between patients treated with (n = 16) and without (n = 15) nintedanib. RESULTS: In the nintedanib prospective study, the mean PASP at 48 weeks after starting nintedanib was significantly higher compared to that at baseline. When IPF patients were divided into two groups, IPF patients with or without long-term oxygen treatment (LTOT), mean PASP at 48 weeks was significantly higher than that at baseline only in IPF patients receiving LTOT (P = 0.001). In the historical control study, adjusted annual change in PASP in IPF patients treated with nintedanib was significantly lower than that in patients treated with no antifibrotic agents when considering patients without LTOT (0.26 mmHg vs 7.05 mmHg; P = 0.011). CONCLUSIONS: We found differential effects of nintedanib on PH between IPF patients with or without LTOT. Nintedanib may have a disadvantageous effect on PH in IPF patients with LTOT. Conversely, nintedanib treatment may be beneficial to PH in IPF patients without LTOT.

The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. METHODS: Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. RESULTS: Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. CONCLUSIONS: PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

Lymphocytic focus score is positively related to airway and interstitial lung diseases in primary Sjögren's syndrome.

OBJECTIVE: Although high-resolution computed tomography (HRCT) is useful for the characterization of minute morphological changes in the lungs, no study has investigated risk factors for lung involvement detected by HRCT in patients with Sjögren's syndrome with or without respiratory symptoms. The aim of the current study was to investigate risk factors for lung involvement in patients with primary Sjögren's syndrome detected by HRCT, with a particular focus on airway and interstitial lung diseases. METHODS: We performed a retrospective cohort study of patients with primary Sjögren's syndrome and investigated risk factors for lung involvement detected by HRCT. A total of 101 patients with primary Sjögren's syndrome with initial HRCT examinations were enrolled. RESULTS: Higher age, dry mouth, and higher labial gland biopsy focus scores (≥4) were risk factors for airway diseases (odds ratio [OR] 1.064 confidence interval [CI] 1.026-1.102, OR 8.795 CI 2.317-33.378 and OR 3.261 CI 1.100-9.675, respectively) in the multivariable analysis. Higher age, male sex, and higher labial gland biopsy focus scores (≥4) were risk factors for interstitial lung diseases (OR 1.078 CI 1.032-1.127, OR 12.178 CI 1.121-132.307 and OR 3.954 CI 1.423-10.987, respectively) in the multivariable analysis. The presence of anti-T-lymphotropic virus type 1 antibodies was significantly more common in patients with airway diseases. CONCLUSIONS: This study showed significant associations of labial gland biopsy focus scores and dry mouth with pulmonary manifestations in patients with primary Sjögren's syndrome. Focus scores as well as dry mouth may reflect lymphoproliferative activity in the lungs in patients with primary Sjögren's syndrome.

Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice.

RATIONALE: Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. OBJECTIVES: To determine the role of NOSs in BM cells in PH. METHODS: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)-/-, iNOS (inducible NOS)-/-, eNOS (endothelial NOS)-/-, and n/i/eNOSs-/- mice. MEASUREMENTS AND MAIN RESULTS: In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSs-/- genotype and, to a lesser extent, in the eNOS-/- genotype as compared with the WT genotype. In the n/i/eNOSs-/- genotype exposed to hypoxia, the number of circulating BM-derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein-transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs-/--BM transplantation significantly aggravated hypoxia-induced PH in the WT genotype, and WT-BM transplantation significantly ameliorated hypoxia-induced PH in the n/i/eNOSs-/- genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs-/--BM compared with those with WT-BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia-induced PH caused by n/i/eNOSs-/--BM transplantation. CONCLUSIONS: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.

Respiratory comorbidities and risk of mortality in hospitalized patients with idiopathic pulmonary fibrosis.

BACKGROUND: Respiratory comorbidities are frequently associated with idiopathic pulmonary fibrosis (IPF). However, little is known about their prognostic impact in hospitalized patients with IPF. We examined the impact of respiratory comorbidities on the mortality rates of hospitalized patients with IPF using a Japanese nationwide database. METHODS: We identified 5665 hospitalized patients diagnosed with IPF between April 2010 and March 2013. The primary outcome was defined as the in-hospital mortality at 30 days after admission. The impact of respiratory comorbidities was assessed using a Cox proportional hazards model that incorporated clinically relevant factors. RESULTS: In hospitalized patients with IPF, the prevalence of bacterial pneumonia, pulmonary hypertension, and lung cancer were 9.5%, 4.6%, and 3.7%, respectively. Among patients with bacterial pneumonia, the four most common pathogens were Streptococcus pneumoniae (31.6%), methicillin-resistant Streptococcus aureus (18.4%), Klebsiella pneumoniae (9.2%), and Pseudomonas aeruginosa (9.2%). Lung cancer was more commonly found in the lower lobes (60.1%) than in other lobes. The survival at 30 days from admission was 78.4% in all patients and significantly lower in IPF patients with bacterial pneumonia (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.63; p < 0.023) and patients with lung cancer (adjusted HR, 1.99; 95% CI, 1.47-2.69; p < 0.001) than in others. Pulmonary hypertension was not associated with mortality. IPF patients with one or more of these three respiratory comorbidities had a poorer survival than others (p < 0.05). CONCLUSIONS: Respiratory comorbidities, especially bacterial pneumonia and lung cancer, influence mortality in hospitalized patients with IPF.

Immune-mediated thrombocytopenia and hypothyroidism in a lung cancer patient treated with nivolumab.

Patients treated with immune checkpoint inhibitors can develop various immunological complications; however, few cases of immune thrombocytopenia occurring in association with the administration of these agents have so far been reported. We herein report the case of a 62-year-old Japanese man with non-small-cell lung cancer who developed immune thrombocytopenia and hypothyroidism during nivolumab therapy. After the second administration of the drug, his peripheral blood platelet count rapidly decreased to 1.6 × 104/µl with a petechial rash and symptoms associated with a low thyroid function. Nivolumab-induced immune thrombocytopenia and hypothyroidism were suspected based on the presence of platelet-associated IgG, an increased level of autoantibodies to thyroglobulin and thyroid peroxidase and an enlarged thyroid gland. The patient eventually made a full recovery after treatment with oral prednisolone and levothyroxine. Further investigations and the accumulation of data are necessary to elucidate the precise mechanisms underlying the autoimmune responses that occur in patients treated with immune checkpoint inhibitors.

Bilateral Tuberculous Pleurisy with Subsequent Upper Lobe Predominant Pulmonary Fibrosis Mimicking Pleuroparenchymal Fibroelastosis.

Although the majority of patients with Mycobacterium tuberculosis have pulmonary involvement, some cases have pleural involvement as extra-pulmonary sites of infection. We herein report a case of upper lobe-predominant pulmonary fibrosis that developed in a 47-year-old male with a history of bilateral tuberculous pleurisy. Based on his chest radiological findings, pleuroparenchymal fibroelastosis (PPFE) was most strongly suspected, and a surgical lung biopsy (SLB) was performed to obtain a pathological diagnosis. The SLB specimens showed interstitial pneumonia with pleural involvement without any characteristic findings of PPFE. Careful discretion in obtaining a precise diagnosis of this condition should be practiced in such cases.

The utility of electron microscopy in detecting asbestos fibers and particles in BALF in diffuse lung diseases.

BACKGROUND: In patients with diffuse lung diseases, differentiating occupational lung diseases from other diseases is clinically important. However, the value of assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated the utility of EM in detecting asbestos fibers and particles in patients with diffuse lung diseases. METHODS: The BALF specimens of 107 patients with diffuse lung diseases were evaluated. First, detection of asbestos by EM and light microscopy (LM) were compared. Second, the detection of asbestos using surgically obtained lung tissues of 8 of 107 patients were compared with the results of EM and LM in BALF. Third, we compared the results of mineralogical components of particles in patients with (n = 48) and without (n = 59) a history of occupational exposure to inorganic dust. RESULTS: BALF asbestos were detected in 11 of 48 patients with a history of occupational exposure by EM; whereas asbestos as asbestos bodies (ABs) were detected in BALF in 4 of these 11 patients by LM. Eight of 107 patients in whom lung tissue samples were surgically obtained, EM detected BALF asbestos at a level of >1,000 fibers/ml in all three patients who had ABs in lung tissue samples by LM at a level of >1,000 fibers/g. The BALF asbestos concentration by EM and in lung tissue by LM were positively correlated. The particle fractions of iron and phosphorus were increased in patients with a history of occupational exposure and both correlated with a history of occupational exposure by a multiple regression analysis. CONCLUSIONS: EM using BALF seemed to be superior to LM using BALF and displayed a similar sensitivity to LM using surgically-obtained lung tissue samples in the detection of asbestos. Our results also suggest that detection of elements, such as iron and phosphorus in particles, is useful for evaluating occupational exposure. We conclude that the detection of asbestos and iron and phosphorus in particles in BALF by EM is very useful for the evaluation of occupational exposure.

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.

Risk factors for an acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis are major causes of morbidity and mortality among patients with idiopathic pulmonary fibrosis. However, acute exacerbations remain unpredictable. The aim of this study was to investigate risk factors for acute exacerbations of idiopathic pulmonary fibrosis. METHODS: We performed a retrospective cohort study of patients with idiopathic pulmonary fibrosis who visited our institutions from January 1999 to September 2014. We investigated risk factors for acute exacerbations in patients with idiopathic pulmonary fibrosis diagnosed retrospectively based on the official 2011 idiopathic pulmonary fibrosis ATS/ERS/JRS/ALAT Update Statement. RESULTS: The idiopathic pulmonary fibrosis study cohort included 65 subjects. The median follow-up period was 2.6 years. During follow-up, 24 patients (36.9 %) experienced acute exacerbations. A Kaplan-Meier curve demonstrated that the 1-year, 2-year, and 3-year incidences of acute exacerbation were 9.6, 19.2 and 31.0 %, respectively. Acute exacerbation exerted a significant impact on overall survival among those with the disease. A log-rank test showed that baseline cardiovascular diseases, higher GAP (gender, age, physiology) stage (≥II), higher serum lactate dehydrogenase level (≥180 U/L), higher serum surfactant protein-D level (≥194.7 ng/mL), higher neutrophil (≥1.77 %) and eosinophil (≥3.21 %) percentages in bronchoalveolar lavage fluid samples, and treatment with an immunosuppressive agent after diagnosis were associated with poor acute exacerbation-free probability. In the Cox analysis adjusted for treatment with an immunosuppressive agent, baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were predictors of an acute exacerbation of idiopathic pulmonary fibrosis. CONCLUSIONS: This study demonstrated that baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were associated with the onset of an acute exacerbation of idiopathic pulmonary fibrosis.

Efficacy of concurrent treatments in idiopathic pulmonary fibrosis patients with a rapid progression of respiratory failure: an analysis of a national administrative database in Japan.

BACKGROUND: Some IPF patients show a rapid progression of respiratory failure. Most patients are treated with high-dose corticosteroids. However, no large clinical studies have investigated the prognosis or efficacy of combined treatments including high-dose corticosteroids in IPF patients with a rapid progression of respiratory failure. METHODS: We enrolled IPF patients who received mechanical ventilation and high-dose corticosteroids between April 2010 and March 2013. Records were extracted from a Japanese nationwide inpatient database. We conducted a retrospective epidemiologic and prognostic analysis. RESULTS: Two hundred nine patients receiving an average of 12.8 days of ventilatory support were enrolled. There were 138 (66 %) fatal cases; the median survival was 21 days. The short-term (within 30 days) and long-term (within 90 days) survival rates were 44.6 and 24.6 %, respectively. The average monthly admission rate among the IPF patients with the rapid progression of respiratory failure in the winter was significantly higher than that in spring (p = 0.018). Survival did not differ to a statistically significant extent in the different geographic areas of Japan. Survivors were significantly younger (p = 0.002) with higher rates of mild dyspnea on admission (p = 0.012), they more frequently underwent bronchoscopy (p < 0.001), and received anticoagulants (p = 0.027), co-trimoxazole (p < 0.001) and macrolide (p = 0.02) more frequently than non-survivors. A multivariate logistic analysis demonstrated that two factors were significantly associated with a poor prognosis: >80 years of age (OR = 2.94, 95 % Cl 1.044-8.303; p = 0.041) and the intravenous administration of high-dose cyclophosphamide (OR = 3.17, 95 % Cl 1.101-9.148; p = 0.033). Undergoing bronchoscopy during intubation (OR = 0.25, 95 % Cl 0.079-0.798; p = 0.019) and the administration of co-trimoxazole (OR = 0.28, 95 % Cl 0.132-0.607; p = 0.001) and macrolides (OR = 0.37, 95 % Cl 0.155-0.867; p = 0.033) were significantly associated with a good prognosis. The dosage of co-trimoxazole significantly correlated with survival. CONCLUSIONS: Co-trimoxazole and macrolides may be a good addition to high-dose corticosteroids in the treatment of IPF patients with a rapid progression of respiratory failure.

Profibrotic role of WNT10A via TGF-ß signaling in idiopathic pulmonary fibrosis.

BACKGROUND: WNT/ß-catenin signaling plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the role of WNT10A via transforming growth factor (TGF)-ß signaling remains unclear. METHODS: We evaluated the expression of WNT10A and TGF-ß in bleomycin (BLM)-treated mice and the interactions between TGF-ß or BLM and WNT10A in vitro. Additionally, we investigated IPF patients who underwent video-assisted thoracoscopic surgery to determine whether the WNT10A expression is related to the survival. RESULTS: Increased WNT10A and TGF-ß expressions were noted in the BLM-treated mice. Real-time PCR and luciferase reporter assays demonstrated the levels of WNT10A and collagen in the fibroblasts cells to increase after TGF-ß administration. Conversely, WNT10A siRNA treatment inhibited the synthesis of collagen in the transfected fibroblasts cells. A Kaplan-Meier survival analysis demonstrated a tendency toward a poor survival among the IPF patients with a WNT10A-positive expression compared to those with a negative expression (Hazard ratio 5.351, 95 % CI 1.703-16.82; p = 0.0041). An overexpression of WNT10A was found to be significantly predictive of an acute exacerbation of IPF (AE-IPF) (Odds ratio 13.69, 95 % CI 1.728-108.5; p = 0.013). CONCLUSIONS: WNT10A plays an important role in the pathogenesis of IPF via TGF-ß activation and it may also be a sensitive predictor for the onset of an AE-IPF.

A serious mediastinum abscess induced by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): a case report and review of the literature.

A 75-year-old man with interstitial pneumonia and enlarged mediastinal lymph nodes underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). He developed a high-grade fever seven days after EBUS-TBNA was performed; laboratory and radiologic findings showed intense inflammatory reactions, with swelling of the mediastinal lymph nodes on chest computed tomography. Mediastinal lymph node abscess was diagnosed, and it worsened in spite of systemic antibacterial treatment. Surgical treatment using a median sternotomy was performed, and the cultivation of surgically obtained mediastinal lymph node abscess fluid revealed Streptococcus intermedius. Combined treatment with antibiotics and surgical treatment was effective, leading to remission.

Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection.

BACKGROUND AND OBJECTIVE: Recent advances in cultivation-independent molecular biological modalities for detecting bacterial species have indicated that several bacterial species may play a role in the pathogenesis of certain infectious diseases. The aim of this study was to evaluate the role of bacterial flora in the pathogenesis of nontuberculous mycobacteriosis (NTM) using a bacterial floral analysis of bronchoalveolar lavage fluid (BALF) with 16S rRNA gene sequencing in patients with bronchiectasis. METHODS: Fifty-eight patients with bronchiectasis evaluated using chest computed tomography were enrolled. BALF obtained from the most affected lung lesions was evaluated using culture and culture-independent methodologies. Approximately 600 bp of the bacterial 16S rRNA gene (E341F-E907R) was amplified via polymerase chain reaction using universal primers, and clone libraries were constructed. Nucleotide sequences of 96 randomly chosen clones for each specimen were determined, and the homology was searched using a basic local alignment search tool to determine the bacterial phylotypes and their proportions (bacterial floral analysis) in each specimen. RESULTS: Twenty-nine patients with bronchiectasis were diagnosed with NTM based on culture-based methods using Ogawa medium. The molecular method showed a significantly high rate of anaerobes among the patients with NTM compared with that observed in the bronchiectasis patients without NTM. In addition, findings of collapse/consolidation were significantly related to the proportion of Prevotella species in the BALF samples determined using the molecular method (P < 0.001). CONCLUSION: Given the results of the present study, anaerobes may play an important role in the pathogenesis of bronchiectasis in patients with NTM.