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Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.

Background: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease. Methods: In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed. Results: Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively. Conclusions: The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not., BMC Pulmonary Medicine, 22, art. no. 45; 2022

Background: Acute exacerbation of interstitial pneumonia (AE-IP) is a serious complication of pulmonary surgery in patients with IP. However, little is known about AE-IP after non-pulmonary surgery. The aim of this study was to determine the frequency of AE-IP after non-pulmonary surgery and identify its risk factors. Methods: One hundred and fifty-one patients with IP who underwent pulmonary surgery and 291 who underwent non-pulmonary surgery were retrospectively investigated.Results: AE-IP developed in 5 (3.3%) of the 151 patients in the pulmonary surgery group and 4 (1.4%) of the 291 in the non-pulmonary surgery group; the difference was not statistically significant. A logistic regression model showed that serum C-reactive protein (CRP) was a predictor of AE-IP in the non-pulmonary surgery group (odds ratio 1.187, 95% confidence interval 1.073-1.344, P = 0.002). Conclusions: This is the first study to compare the frequency of AE-IP after pulmonary surgery with that after non-pulmonary surgery performed under the same conditions. The results suggest that the frequency of AE-IP after non-pulmonary surgery is similar to that after pulmonary surgery. A high preoperative C-reactive protein level is a potential risk factor for AE-IP after non-pulmonary surgery., Respiratory Research, 20(1), art.no.154; 2019

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). We herein report three Japanese cases of anti-MDA5 antibody-positive RP-ILD without signs of CADM or DM. High-resolution computed tomography revealed patchy or subpleural distribution of consolidations and/or ground-glass opacities accompanied by traction bronchiectasis. All patients succumbed to respiratory failure within two months. Anti-MDA5 antibody-positive RP-ILD without signs of CADM or DM should be included in the differential diagnosis of acute/subacute ILD. Measurement of anti-MDA5 antibody and an intensive immunosuppressive regimen might rescue these patients from RP-ILD., Internal medicine, 58(6), pp.837-841; 2019

Background Clinical course of pleuroparenchymal fibroelastosis (PPFE) shows considerable variation among patients, but there is no established prognostic prediction model for PPFE. Methods The prediction model was developed using retrospective data from two cohorts: our single-center cohort and a nationwide multicenter cohort involving 21 institutions. Cox regression analyses were used to identify prognostic factors. The total score was defined as the weighted sum of values for the selected variables. The performance of the prediction models was evaluated by Harrell’s concordance index (C-index). We also examined the usefulness of the gender-age-physiology (GAP) model for predicting the prognosis of PPFE patients. Results We examined 104 patients with PPFE (52 cases from each cohort). In a multivariate Cox analysis, a lower forced vital capacity (FVC [defined as FVC 550 U/mL, HR, 2.56) were significantly associated with a poor prognosis. The total score was calculated as 1 × (FVC, 550 U/mL). PPFE patients were divided into three groups based on the prognostic score: stage I (0–1 points), stage II (2 points), and stage III (3–4 points). The survival rates were significantly different in each stage. The GAP stage was significantly associated with the prognosis of PPFE, but no difference was found between moderate (stage II) and severe (stage III) disease. Our new model for PPFE patients (PPFE Prognosis Score) showed better performance in the prediction of mortality in comparison to the GAP model (C-index of 0.713 vs. 0.649). Conclusions Our new model for PPFE patients could be useful for predicting their prognosis.

Background Heat shock protein 47 (HSP47), a collagen-binding protein, has a specific role in the intracellular processing of procollagen production. HSP47 expression is associated with cancer growth and metastasis in several types of cancers. However, none of the studies have assessed whether HSP47 expression is associated with the risk of postoperative recurrence of lung cancer until now. Therefore, we aimed to assess this association. Methods The study population consisted of a cohort of consecutive patients who underwent surgery for lung cancer at Nagasaki University Hospital, Nagasaki, Japan, from January 2009 to December 2010. Patient characteristics, survival and disease-free survival (DFS), and laboratory findings were compared between patients who tested positive and negative for HSP47 expression in lung cancer cells and between those who showed high and low numbers of HSP47-positive fibroblasts in cancer stroma. Results A total of 133 patients underwent surgery for lung cancer. Sixty-seven patients (50.4%) had HSP47-positive cancer cells, and 91 patients (68.4%) had a higher number of HSP47-positive fibroblasts. The patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with a low number of HSP47-positive fibroblasts. Multivariate analysis identified only the presence of a high number of HSP47-positive fibroblasts as an independent risk factor for recurrence of lung cancer after surgery (odds ratio, 4.371; 95% confidence interval, 1.054–29.83; P = 0.042). Conclusion The present study demonstrated that the presence of a high number of HSP47-positive fibroblasts in the cancer stroma was a risk factor for recurrence of lung cancer after surgery.

A 65-year-old Japanese man was referred to our hospital for the further assessment of cough and dyspnea. He had a history of ulcerative colitis for which he was receiving treatment. Chest computed tomography showed a crazy-paving pattern. His bronchoalveolar lavage fluid had a milky appearance, and a transbronchial lung biopsy specimen revealed acellular periodic acid-Schiff stain-positive bodies. The serum anti-granulocyte macrophage-colony stimulating factor (GM-CSF) antibody titer was elevated. The diagnosis was autoimmune pulmonary alveolar proteinosis (PAP). There are few reports of autoimmune PAP in patients with ulcerative colitis. Some reports suggest that PAP and inflammatory bowel disease might have a common pathogenesis involving the anti-GM-CSF antibody., Internal Medicine, 57(18), pp.2705-2708; 2018

Purpose Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD. Methods The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients. Results One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862–9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581–10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392–11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763–37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis. Conclusion HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis.

Background Anti-aminoacyl-tRNA synthetase (ARS) antibodies have been detected in patients with polymyositis/dermatomyositis (PM/DM) and are especially correlated with interstitial lung disease (ILD). The aim of this study was to clarify the clinical features of patients with anti-ARS antibody positive idiopathic interstitial pneumonias (IIPs). Methods Patients were classified into three groups: 1) IIP with anti-ARS antibodies (ARS(+)IIP), 2) IIP without anti-ARS antibodies (ARS(−)IIP), and 3) PM/DM-associated ILD with anti-ARS antibodies (ARS(+)PM/DM-ILD). Clinical characteristics were compared retrospectively between the ARS(+)IIP group and the ARS(−)IIP group or ARS(+)PM/DM-ILD group. Results Eighteen ARS(+)IIP, 284 ARS(−)IIP, and 20 ARS(+)PM/DM-ILD patients were enrolled. The ARS(+)IIP group was significantly older and the male sex was predominant, had a lower prevalence of signs of connective tissue disease, differences in HRCT findings and patterns, and higher KL-6 levels compared to the ARS(+)PM/DM-ILD group. The findings in the bronchoalveolar lavage fluid (BALF) showing lymphocytosis and a lower CD4/CD8 ratio were similar between the two groups. However, the ARS(+)IIP group had significantly lower percentage of sputum, higher prevalence of mechanic's hand, higher KL-6 levels, lower percentage of vital capacity in the pulmonary function test, and lower CD4/CD8 ratio in BALF, compared to the ARS(−)IIP group. Conclusions The present study demonstrated that features of pulmonary involvement were similar to those in the ARS(+)PM/DM-ILD group; however, some differences including HRCT findings and higher KL-6 levels suggest that ARS(+)IIP has severe ILD compared with ARS(+)PM/DM-ILD. Further prospective studies with a larger number of patients will elucidate the exact role of anti-ARS antibodies in IIPs.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy., Tohoku Journal of Experimental Medicine, 248(3), pp.209-216; 2019

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 Sjogren'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 Sjogren'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 Sjogren's syndrome and investigated risk factors for lung involvement detected by HRCT. A total of 101 patients with primary Sjogren'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 Sjogren's syndrome. Focus scores as well as dry mouth may reflect lymphoproliferative activity in the lungs in patients with primary Sjogren's syndrome.