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Postoperative complications of pulmonary resection in patients with pulmonary aspergilloma are common. Preoperative antifungal therapy is a perioperative management strategy to reduce postoperative complications; however, the benefit of the treatment remains controversial. A retrospective cohort study was conducted using data from the Diagnosis Procedure Combination database (July 2010-March 2021), a national inpatient database in Japan. Patients with pulmonary aspergilloma with or without chronic necrotizing pulmonary aspergillosis who underwent pulmonary resection were identified and divided into two groups based on whether they received preoperative antifungal therapy. Propensity-score overlap weighting was performed to compare the occurrence of composite postoperative complications and postoperative length of hospital stay between the two groups. We identified 98 patients with pulmonary aspergilloma who received preoperative antifungal therapy and 399 patients who did not. After propensity-score overlap weighting, the preoperative antifungal therapy group had a significantly lower proportion of composite postoperative complications than the non-preoperative antifungal therapy group (6.8% vs. 14.2%, P = .038). There was no significant difference in postoperative length of stay between the groups with and without preoperative antifungal therapy (median 14.6 vs. 15.8 days, P = .41). Preoperative antifungal therapy was associated with a reduction in postoperative complications in patients with pulmonary aspergilloma. Preoperative treatment with antifungals may be beneficial in reducing the risk of postoperative complications in patients with pulmonary aspergilloma undergoing pulmonary resection., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: Our objective was to investigate trends in the treatment of patients with late-onset rheumatoid arthritis (LORA) using data from the National Database of Rheumatic Diseases in Japan (NinJa)., Methods: Patients registered in the National Database of Rheumatic Diseases in Japan were classified according to the disease onset: at <65 years (young-onset rheumatoid arthritis); at 65-74 years (early LORA); and at ≥75 years (late LORA). Chronological changes in the treatment and disease activity were compared., Results: A total of 7178, 13,171, 15,295, and 15,943 patients were evaluated in 2010, 2013, 2016, and 2019, respectively. In all groups, the use of methotrexate gradually decreased, whereas that of biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) increased; the use of tumor necrosis factor inhibitors decreased, whereas that of non-tumor necrosis factor inhibitors increased. LORA was characterized by more single DMARD use and less methotrexate and biological/targeted synthetic DMARD use. Tumor necrosis factor inhibitors and interleukin-6 inhibitors were used less frequently, whereas abatacept was utilized more frequently in late versus early LORA. Conventional synthetic DMARD (excluding methotrexate) and glucocorticoid use was higher in late versus early LORA., Conclusions: This analysis revealed chronological changes in the treatment of LORA in Japan. Differences between early and late LORA suggest that patients are not a homogeneous population., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: Rheumatoid arthritis (RA) is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA., Methods: Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415, and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses., Results: MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (p = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% confidence interval [CI] 2.05-55.37) or ILD (p = 0.0071, Pc = 0.0284, OR 7.33, 95%CI 1.52-35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (p = 0.0072, Pc = 0.0288, OR 29.55, 95%CI 1.52-574.57) or ILD (p = 0.0037, Pc = 0.0148, OR 22.95, 95%CI 1.27-416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed., Conclusions: MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75-84 years) patients with rheumatoid arthritis., Methods: Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55-84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression., Results: About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64 years) and young-old patients (65-74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients., Conclusions: Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Secretory immunoglobulin A plays an important role in the protection against exogenous pathogens and antigens, but it has also been reported to have pathogenic potential. We previously found that secretory immunoglobulin A accumulated in the peripheral lungs during idiopathic pulmonary fibrosis and that transferrin receptor/CD71 was partially involved in secretory immunoglobulin A-induced inflammatory cytokine production in A549 cells. This study aimed to identify the receptor responsible for the induction of cytokine production by secretory immunoglobulin A-stimulated airway epithelial cells. To this end, immunoprecipitation followed by time-of-flight mass spectrometry and peptide mass fingerprinting were performed and Annexin A2 was detected as a novel receptor for secretory immunoglobulin A. Enzyme-linked immunosorbent assay demonstrated binding of secretory immunoglobulin A to Annexin A2, and flow cytometry showed robust expression of Annexin A2 on the surface of BEAS-2B cells, A549 cells, and normal human bronchial/tracheal epithelial cells. Experiments in A549 cells using Annexin A2 small interfering RNA and neutralizing antibodies suggested that Annexin A2 was partially involved in the production of interleukin-8/CXCL8 and C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 induced by secretory immunoglobulin A. Immunohistochemistry using lung sections revealed clear expression of Annexin A2 on airway epithelial cells, although the staining remained equivalent in idiopathic pulmonary fibrosis, asthma, and healthy control lungs. In conclusion, we identified that Annexin A2 expressed in airway epithelial cells is a novel receptor for secretory immunoglobulin A, which is involved in cytokine synthesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations., Objective: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization., Methods: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773)., Results: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10-5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86)., Conclusion: AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients' serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P < .0001). The median rate of change was 1.76 times (quartile 1.41-3.25). In addition, we used surgical specimens of CPA cases with high serum total IgE levels, normal serum total IgE CPA cases, and control surgical specimens and performed immunofluorescence staining with IgE, mast cell tryptase, CD138, and 4,6-diamidino-2-phenylindole. We observed multiple mast cells and plasma cells in the CPA cases regardless of the serum total IgE level. In contrast, multiple IgE-positive cells co-stained with tryptase were observed in CPA cases with high serum total IgE levels. This finding suggested that serum total IgE could serve as a biomarker for evaluating disease severity. Immunofluorescence staining suggested that IgE may play a role in pathogenesis through activation of mast cells by cross-linking in cases of CPA with high serum total IgE levels., Lay Summary: High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objective: Susceptibility genes that can account for characteristic features of SSc such as fibrosis, vasculopathy and autoimmunity remain to be determined. In mice, deficiency of Friend leukaemia integration 1 transcription factor (Fli1) causes SSc-like disease with these features. The human FLI1 gene contains (GA)n microsatellite, which has been shown to be associated with expression level. Because microsatellite polymorphisms are difficult to capture by genome-wide association studies, we directly genotyped FLI1 (GA)n microsatellite and examined its association with SSc., Methods: Genomic DNA from 639 Japanese SSc patients and 851 healthy controls was genotyped for (GA)n microsatellite using the fragment assay. The cut-off repeat number for susceptibility to SSc was determined by receiver operating characteristics (ROC) analysis. Association with susceptibility and clinical characteristics was examined using logistic regression analysis. FLI1 mRNA levels were determined using quantitative RT-PCR., Results: Based on the ROC analysis, (GA)n alleles with ≥22 repeats were collectively defined as L alleles and alleles with ≤21 repeats as S alleles. (GA)n L alleles were significantly associated with susceptibility to SSc (P = 5.0e-04, odds ratio 1.34, additive model). Significant association was observed both in diffuse cutaneous and limited cutaneous SSc. Among the SSc, (GA)n L alleles were significantly enriched in the patients with a modified Rodnan total skin thickness score ≥10 compared with those with a score <10. FLI1 mRNA levels were significantly decreased in healthy controls carrying (GA)n L alleles as compared with non-carriers., Conclusion: Extended repeat alleles of FLI1 (GA)n microsatellite may be associated with lower FLI1 mRNA levels and susceptibility to human SSc., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The human leukocyte antigen (HLA) is the strongest genetic risk factor for idiopathic inflammatory myopathy (IIM), and different HLA alleles have been reported to be associated with IIM susceptibility among different ethnic groups. In this study, we have investigated HLA alleles associated with IIM in Japanese patients. Methods: Genotyping of HLA-DRB1 and DPB1 were performed in 252 Japanese IIM patients (166 dermatomyositis [DM] and 86 polymyositis [PM] patients) and the association was analyzed with comparison to controls ( n  = 1026 for DRB1 and n  = 413 for DPB1 ). Results: DRB1*08:03 was associated with IIM ( p  = 1.60 × 10 -5 , p c = .0005, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.52-2.92) and DM ( p  = .0004, p c = .0128, OR 2.06, 95%CI 1.40-3.02). DPB1*05:01 was also associated with IIM ( p  = .0001, p c = .0021, OR 1.96, 95%CI 1.38-2.77) and DM ( p  = .0005, p c = .0075, OR 2.05, 95%CI 1.37-3.08). DRB1*09:01 ( p  = .0012, p c = .0368, OR 0.35, 95% CI 0.18-0.69) and DPB1*04:01 ( p  = .0004, p c = .0057, OR 0.05, 95% CI 0.00-0.85) were protectively associated with PM. Two locus analyses suggested that DRB1*09:01 and DPB1*04:01 were independently associated with PM. Conclusion: Protective associations of HLA were detected in Japanese PM patients.

Objectives: Interstitial lung disease (ILD) is a life-threatening extra-articular manifestation of rheumatoid arthritis (RA). We aimed to clarify the relationship between chronic ILD with a pattern of usual interstitial pneumonia (UIP) or non-UIP and mortality in RA patients. Methods: We retrospectively surveyed information of consecutive RA patients who visited our hospital from 2009 to 2014. The relationship between their mortality and chronic ILD (UIP or non-UIP) detected by high-resolution computed tomography was examined. Results: Of 2702 patients enrolled, 261 (9.7%) had chronic ILD and among these 120 had a UIP pattern. At the onset of RA, the prevalence of chronic ILD was 6%. Patients with chronic ILD had a higher mortality than those without. The most frequent cause of death was pneumonia including acute exacerbation (AE) of chronic ILD. Lung cancer death was frequently identified in deceased patients with chronic ILD with a UIP pattern compared with the other decedents ( p =.062). The estimated mortality of lung cancer in patients with chronic ILD with a UIP pattern was five times higher than the general population. Conclusion: RA patients with ILD with a UIP pattern have a high mortality rate and are prone to die of AE or lung cancer.

Species of Aspergillus section Nigri are generally identified by molecular genetics approaches, whereas in clinical practice, they are classified as A. niger by their morphological characteristics. This study aimed to investigate whether the species of Aspergillus section Nigri isolated from the respiratory tract vary depending on clinical diagnosis. Forty-four Aspergillus section Nigri isolates isolated from the lower respiratory tracts of 43 patients were collected from February 2012 to January 2017 at the National Hospital Organization (NHO) Tokyo National Hospital. Species identification was carried out based on β-tubulin gene analysis. Drug susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) M38 3rd edition, and the clinical characteristics were retrospectively reviewed. A. welwitschiae was isolated most frequently, followed by A. tubingensis. More than half of the A. tubingensis isolates exhibited low susceptibility to azoles in contrast to only one A. welwitschiae isolate. Approximately three quarters of the patients from whom A. welwitschiae was isolated were diagnosed with colonization, whereas more than half the patients from whom A. tubingensis was isolated were diagnosed with chronic pulmonary aspergillosis (CPA). More attention needs to be given to the drug choice for patients with CPA with Aspergillus section Nigri infection because A. tubingensis, which was found to be frequently azole-resistant, was the most prevalent in these patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-β and IL-8., (© 2019 British Society for Immunology.)

Objective: To evaluate the difference between adult juvenile idiopathic arthritis (JIA, starting at <16 years) and rheumatoid arthritis (RA). Methods: Data on 128 adult JIA patients were from the National Database of Rheumatic Diseases in Japan (NinJa), 2014, divided into 4 groups by period of disease onset (Group 1: 2000-2013, n  = 32; Group 2: 1981-1999, n  = 32; Group 3: 1966-1980, n  = 31; Group 4: ∼1965, n  = 33). Disease activity, treatment and long-term prognosis of adult JIA patients were compared with RA patients matched for sex- and disease duration in each era. Results: In Groups 1 and 2, adult JIA patients had significantly lower clinical disease activity indices (CDAI) (Group 1: adult JIA 1.5 [0.4-6.9]-vs-RA 5.3 [2.5-10.3], p  = .001, Group 2: 2.6 [0.6-9.0]-vs-6.9 [3.5-11.0], p  = .001, shown as median [quartile range], p -value, respectively), and had higher CDAI remission rates than RA patients (Group 1: 54.8%-vs-28.2%, p  = .002, Group 2: 51.7%-vs-17.0%, p  < .001). More adult JIA than RA patients in Group 1 used biologics (62.5%-vs-24.7%, p  < .001). However, there were no adult JIA-vs-RA differences in joint destruction and physical function in any group. Conclusions: Adult rheumatologists must recognize that adult JIA patients are different from RA patients even when disease duration is the same.

Chronic pulmonary aspergillosis (CPA) is a common subtype of pulmonary aspergillosis and a life-threatening disease. However, its diagnosis remains difficult due to the lack of specific clinical features and radiologic findings, as well as the difficulty of isolating Aspergillus spp. We developed a novel species-specific detection method of medically important aspergilli using a loop-mediated isothermal amplification (LAMP) for CPA. Specific LAMP primer sets for Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, and Aspergillus nidulans were designed. The use of the LAMP assay was validated using respiratory specimens (CPA cases, n = 21; nonaspergillosis cases, n = 23). A total of 15 cases were positive in the CPA group (A. fumigatus, n = 5; A. flavus, n = 1; A. niger, n = 1; A. terreus, n = 7; A. nidulans, n = 1), but only three in the non-CPA group (A. niger, n = 2; A. terreus n = 1). The sensitivity and specificity of the diagnosis of CPA by the LAMP system were 71.4% and 87.0%, respectively. In conclusion, we developed a species-specific detection approach for five medically important aspergilli using the LAMP method. The system showed high sensitivity and specificity for diagnosis of CPA., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition., Methods: We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP)., Results: Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not., Conclusions: Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality., Clinical Trials Registration: JMA-IIA00146., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Immunoglobulin (Ig)A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first-line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)-β, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real-time quantitative polymerase chain reaction (PCR) revealed that sIgA enhanced production of α-smooth muscle actin (α-SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co-cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be due partially to its binding to CD71 or the secretory component., (© 2018 British Society for Immunology.)

Objectives: The number of octogenarian lung cancer patients undergoing radical surgery has been increasing recently. However, knowledge regarding the risk factors for postoperative complications and reliable predictive factors for long-term survival is limited. This study aimed to investigate the risk factors of postoperative complications, and reliable prognostic factors, in lung cancer patients older than 80 years., Methods: Lung cancer patients aged 80 years or older who underwent radical surgery were retrospectively studied; a multi-institutional analysis was conducted from January 1998 to December 2015. Preoperative and postoperative clinical data, including age, gender, smoking history, body mass index, respiratory function, Charlson Comorbidity Index, Glasgow Prognostic Score, surgical procedure, cancer histology, clinical and pathological stage, surgical result and survival time, were collected., Results: A total of 337 patients, comprising 216 (64.1%) men and 121 (35.9%) women were enrolled. The median age was 82 (range 80-92) years. Of the 337 patients, 205 (60.8%) had preoperative comorbidities. Postoperative complications were observed in 119 (35.3%) patients; postoperative mortalities occurred in 6 (1.8%) patients. Univariate and multivariate analyses showed that male gender (P = 0.01) and operation time (P = 0.047) were associated with postoperative complications; in contrast, pathological Stage III (P < 0.001), male gender (P = 0.01), Charlson Comorbidity Index ≥2 (P = 0.03) and Glasgow Prognostic Score = 1/2 (P = 0.04) were independent prognostic factors for overall survival., Conclusions: The risk factors for postoperative complications (male gender and operation time) and the predictive factors affecting long-term survival (male gender, Charlson Comorbidity Index, Glasgow Prognostic Score and P-stage) should be taken into account for the effective management of patients older than 80 years with lung cancer, undergoing surgery.

Objectives: Chronic pulmonary aspergillosis (CPA) is an emerging complication after lobectomy for lung cancer. This retrospective study aimed to determine the incidence, main risk factors and clinical features of postoperative CPA in lung cancer patients., Methods: This study included lung cancer patients treated by lobectomy and with no previous history of thoracic surgery or coexistent aspergillosis at the time of surgery. The cumulative incidence of CPA was determined using death as a competing risk. Furthermore, the identified lung cancer patients were divided into CPA and non-CPA groups to compare their preoperative clinical features and to identify the risk factors of postoperative CPA by univariable and multivariable analyses. We also analysed the clinical features of CPA patients after diagnosis., Results: We included 475 lung cancer patients. Of these, 17 patients (3.6%) developed CPA after the lobectomy. The cumulative postoperative incidence rate of CPA was 2.3% [95% confidence interval (CI), 0.8-3.8%] at 5 years and 7.9% (95% CI, 3.0-13.0%) at 10 years. There were significantly more men (P = 0.007), smokers (P = 0.002) and comorbid chronic obstructive pulmonary disease (COPD) (P = 0.008) and interstitial lung disease (ILD) (P = 0.009) patients in the CPA group than in the non-CPA group. Multivariable analysis identified comorbid COPD (P = 0.0019) and ILD (P = 0.0003) as significant risk factors. An antifungal treatment response was obtained in 6 patients (35%). The 1-year survival rate was 47% (follow-up periods, interquartile range: 3-78 months), and 5 of the total of 11 deaths were due to CPA., Conclusions: Through the present retrospective study, CPA seems to be a common sequel to lobectomy in lung cancer patients, and COPD and ILD represent strong risk factors of postoperative CPA. Because of the poor clinical outcome of lung cancer patients who develop CPA after lobectomy, careful follow-up using several examinations and chest radiographs to make CPA diagnosis may be essential., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens., Methods: Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology. Culture was performed for 18 h with fluid mononuclear cells in the supernatant of the effusion together with saline or Mycobacterium tuberculosis-specific antigenic peptides, early secretory antigenic target 6 and culture filtrate protein 10. IFN-gamma concentrations in the culture supernatants were measured., Results: In patients with active tuberculous serositis, antigen-specific IFN-gamma responses of cavity fluid samples were significantly higher than those of nontuberculous effusion samples. Area under the receiver operating characteristic (AUROC) curve was significantly greater for cavity fluid IFN-gamma response (AUROC curve, 0.996) than for cavity fluid adenosine deaminase and whole-blood IFN-gamma responses (AUROC curve, 0.882 and 0.719, respectively; P = .037 and P < .001, respectively). Although the AUROC curve was greater for cavity fluid IFN-gamma response than for background cavity fluid IFN-gamma level (AUROC curve, 0.975), the AUROC curves were not statistically significantly different (P = .74). However, multivariate logistic regression analysis revealed that cavity fluid IFN-gamma responses were significantly associated with the diagnosis, even after adjustment for background IFN-gamma level (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P < .001)., Conclusions: The cavity fluid IFN-gamma assay could be a method for accurately and promptly diagnosing active tuberculous serositis.

We evaluated an enzyme-linked immunosorbent assay (ELISA) for detecting anti-Jo-1 antibodies in patients with polymyositis (PM) or dermatomyositis (DM) by use of the recombinant fusion protein Jo-1. Sera from 64 patients with PM or DM, from 80 patients with other connective tissue diseases, and from 64 healthy subjects matched for age, sex and race, were studied by the ELISA and by the double immunodiffusion (DID) method. Eight patients with myositis (six PM, one DM and one DM with malignancy) with positive anti-Jo-1 by DID also showed positive results by the ELISA method, whereas five patients with positive anti-Jo-1 by this ELISA showed negative results on DID. One of the five had non-specific results. The incidence of positive results for anti-Jo-1 with the ELISA (18.8%) was greater than that for DID (12.5%), but the difference was not statistically significant. All patients with positive results for anti-Jo-1 by DID were also positive by the ELISA. The ELISA system with the recombinant Jo-1 antigen was useful in the detection of anti-Jo-1 antibodies in patients with PM/DM.

We determined the extent to which chronic fatigue syndrome (CFS) patients with sicca symptoms fulfil the diagnostic criteria for Sjögren's syndrome (SS). Three sets of diagnostic criteria for SS, formulated by the Japanese, Europeans and Fox, were used. One-third of the CFS patients with sicca symptoms fulfilled the diagnostic criteria for SS. However, they were 'seronegative', differing from the ordinary primary SS.

The relationship between calcinosis and the anticentromere antibody (ACA) was studied from a clinical, radiological and immunogenetic standpoint. Ten ACA-positive scleroderma patients, 34 ACA-negative scleroderma patients, 31 ACA-positive patients without sclerodermatous skin changes and 140 ACA-negative patients with various rheumatic diseases were compared with regard to the incidence of calcinosis as measured by radiographs of hand and/or foot. Calcinosis was found in 10 (100%), 12 (35%), 13 (42%) and eight (6%) patients in each group respectively. Frequent sites for calcinosis in the ACA-positive patients were foot (24%), hand (21%) and leg (19%). The forearm was not usually involved (6%). During the follow-up term (1.0-9.5 years; mean 4.5 years) of 11 ACA-positive patients without calcinosis, four (36%) developed new calcinosis and this incidence was significantly higher (P less than 0.02) than that in the ACA-negative control group (2/42; 4.8%). As a whole, 23 (59%) of 39 patients with ACA showed calcinosis. In the ACA-positive patients with calcinosis, sclerodactyly (P less than 0.005) and CREST syndrome (P less than 0.001) were found more frequently than in ACA-positive patients without calcinosis. HLA-A2 was found more frequently (67%) in the ACA-positive patients with calcinosis when compared to normal subjects (41%) (P less than 0.02). We concluded that calcinosis seems closely related to scleroderma, especially those with ACA, and that the development of calcinosis requires a certain genetic background.