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DOI： 10.1093/ajrccm/aamag125

PubMed

Language：English   Publisher：Erj Open Research  

Objective Progressive pulmonary fibrosis (PPF) is a chronic interstitial lung disease (ILD) characterised by fibrotic progression and poor prognosis, with effective treatment strategies for previously untreated patients remaining unclear. This study evaluated the efficacy and safety of upfront combination therapy with anti-inflammatory and antifibrotic agents in previously untreated PPF patients. Methods This multicentre, single-arm phase 2 study enrolled 34 patients with ILD (including unclassifiable idiopathic interstitial pneumonia, idiopathic nonspecific interstitial pneumonia, fibrotic hypersensitivity pneumonitis and rheumatoid arthritis-associated ILD) all with evidence of PPF. Tacrolimus (0.0375 mg·kg⁻¹ twice daily) and prednisolone (10 mg once daily) were initiated on day 1, with nintedanib (150 mg twice daily) added on day 8. The tacrolimus dosage was adjusted to maintain blood trough levels. The primary end-point was the change in the relative decline slope for forced vital capacity % predicted (%FVC) between before and after treatment. Results The protocol treatment was associated with a substantial improvement in the relative %FVC decline slope, from −20.9% per year before to +11.2% per year after treatment. Subgroup analysis revealed greater improvement in patients with an increased lymphocyte percentage in bronchoalveolar lavage fluid or elevated blood biomarkers. Adverse events, such as diarrhoea (67.6%) and hepatic dysfunction (29.4%), were manageable, with no severe cases or treatment discontinuations. Conclusion Early combination therapy with tacrolimus, prednisolone and nintedanib was associated with improved pulmonary function and was well tolerated in previously untreated PPF patients. Our findings suggest the potential of this regimen as an initial treatment strategy, but further validation in larger randomised controlled trials is warranted.

DOI： 10.1183/23120541.00697-2025

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Endobronchial ultrasound with a guide sheath (EBUS-GS) is used to accurately position a bronchoscope in lung lesions using a guide sheath. Previous studies have focused on diagnostic success as the endpoint. The achievement of 'within' defined as reaching the lesion, is considered crucial in EBUS-GS procedures. This study investigated cases wherein 'within' is likely to be achieved and cases that can be diagnosed after achieving 'within'. </p><p><b>Methods </b>This retrospective study evaluated 258 bronchoscopic examinations using EBUS-GS. We analyzed the relationship between patient background, lesion size and characteristics, achieving 'within', definitive diagnosis after achieving 'within', and complications. </p><p><b>Results </b>A multivariate analysis revealed that a lesion size ≥20 mm [odds ratio 12; 95% confidence interval (CI): 6.0-21; p<0.01] and the presence of solid components (odds ratio 13; 95% CI: 1.3-120; p=0.03) were significantly associated with achieving a "within" status. Among cancer cases, lesions ≥20 mm had a higher diagnostic yield after achieving "within" compared with smaller lesions (odds ratio 4.23; 95% CI: 1.38-12.9; p=0.01). The occurrence of complications was also associated with lesion size ≥20 mm (odds ratio 2.7; 95% CI: 1.02-6.9; p=0.045). </p><p><b>Conclusion </b>Lesion size ≥20 mm and the presence of solid components were key factors associated with achieving "within" during bronchoscopy via EBUS-GS. Larger lesions were linked to a higher rate of definitive diagnosis. Overall, lesion size played a major role in improving diagnostic performance, both in achieving "within" and in successfully obtaining a diagnosis once "within" was achieved. </p>

DOI： 10.2169/internalmedicine.5777-25

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Language：English   Publisher：Respirology  

Background and Objective: Genetic polymorphisms have been associated with susceptibility to interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). We have now examined the relation between single nucleotide polymorphisms (SNPs) and clinical course, including acute exacerbation (AE), in addition to disease susceptibility for IPF and unclassifiable idiopathic interstitial pneumonias (IIPs). Methods: DNA samples were collected from 223 IPF patients and 160 unclassifiable IIP patients included in a prospective, multicentre observational study in Japan. Nonfibrotic control subjects (n = 379) were selected from a previous study. Genotyping of TERT rs2736100, TERC rs1881984, MUC5B rs35705950, DSP rs2076295, and AKAP13 rs62025270 was conducted with commercial assays. The association between these SNPs and disease susceptibility, prognosis, or the cumulative incidence of AE was assessed. Results: TERT rs2736100 and MUC5B rs35705950 were significantly associated with IPF risk, and DSP rs2076295 was linked to prognosis and the incidence of AE in IPF patients. TERT rs2736100 was significantly associated with prognosis in IPF patients and the incidence of AE in patients with unclassifiable IIPs. No individuals with the TT genotype of MUC5B rs35705950 were identified, and the proportion of those with the T allele was low (minor allele frequency of 0.005 in control subjects). In addition, no individuals with the minor allele (A) of AKAP13 rs62025270 were detected. Conclusion: Consideration of genetic polymorphisms has the potential to facilitate prediction not only of prognosis but also of AE in individuals with IIPs, providing a foundation for the development of personalised management strategies based on genetic profiles. (Figure presented.).

DOI： 10.1111/resp.70120

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Language：English   Publisher：Scientific Reports  

There are no established biomarkers for acute exacerbations in idiopathic pulmonary fibrosis (AE-IPF). The bronchoalveolar lavage fluid of patients with IPF notably has elevations in high-mobility group box 1 protein (HMGB1), a nuclear non-histone chromosomal protein that functions as an alarmin that perpetuates the inflammatory process. This study investigated the potential of serum HMGB1 levels as a diagnostic marker for AE-IPF. This prospective, multicenter, observational cohort study included 779 HMGB1 readings from 269 Japanese patients with IPF. Diagnostic performance was assessed using four different methods of recording serial HMGB1 measurements rather than relying on a simple comparison between stable IPF and AE-IPF. Additionally, KL-6 was measured in cases of stable IPF and AE-IPF. A comparative analysis for the usefulness of HMGB1 and KL-6 as biomarkers for AE-IPF was performed. The cohort accounted for 505.6 person-years, with a mean follow-up duration of 1.88 years. A total of 46 cases with AE were recorded with their corresponding HMGB1 levels. All four diagnostic methods examined had high diagnostic accuracy (area under the curve > 0.75). HMGB1 had significantly better diagnostic performance than KL-6. HMGB1 demonstrated high diagnostic utility in AE-IPF, which can be used to facilitate earlier diagnosis and treatment.

DOI： 10.1038/s41598-025-22422-3

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Language：English   Publisher：BMC Pulmonary Medicine  

Background: Low skeletal muscle mass has been reported to associated with poor prognosis in patients with idiopathic pulmonary fibrosis (IPF). However, such associations have scarcely reported in idiopathic interstitial pneumonias (IIPs) other than IPF. Quantification of muscle mass obtained from chest computed tomography (CT) is used as a simple screening tool for sarcopenia in patients with respiratory diseases. However, the optimal thoracic site for muscle mass quantification is controversial. Moreover, there have been no reports investigating the association between muscle mass and acute exacerbations. This study aimed to evaluate optimal site for muscle mass quantification in chest CT to predict survival and acute exacerbation in IPF and non-IPF idiopathic interstitial pneumonias. Methods: This study included 528 patients diagnosed with IIP at 29 facilities between September 1, 2013, and April 30, 2016, following multidisciplinary discussions with prospective follow-up over a 5-year period. The cohort was divided into two groups: those with IPF and those with non-IPF IIPs. Skeletal muscle mass was quantified using the erector spinae muscle index (ESMI) and pectoralis muscle index (PMI), defined as the respective muscle area on chest computed tomography (CT) divided by height squared at the time of enrollment. Associations between these indices at baseline and both survival and acute exacerbation were analyzed. Results: In both IPF and non-IPF cohorts, Cox regression analysis revealed that patients with low ESMI had a poorer prognosis compared to those with normal ESMI, even after adjusting for age, sex, % forced vital capacity (FVC), and smoking exposure level. The hazard ratios were 0.62 (95% CI 0.40–0.90; p = 0.013) and 0.46 (95% CI 0.26–0.83; p = 0.009), respectively. In contrast, no significant relationship was identified between PMI and survival. Multivariable Cox regression analysis confirmed that ESMI was an independent predictor of survival in both IPF and non-IPF patients. Additionally, acute exacerbations occurred more frequently in the low ESMI group and low PMI group, particularly among non-IPF patients. Conclusions: The ESMI obtained from chest CT is associated with survival in not only in IPF patients but also in the non-IPF patients. The ESMI and PMI also associate with acute exacerbations in non-IPF patients.

DOI： 10.1186/s12890-025-03942-0

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Language：English   Publisher：Journal of Thoracic Disease  

Background: Interstitial lung disease (ILD) is a heterogeneous condition that requires diagnosis and treatment through an integrated approach that combines the clinical background and radiological and histopathological findings. Transbronchial lung cryobiopsy (TBLC) has the advantage of obtaining larger tissue samples with minimal tissue damage compared to transbronchial lung biopsy, and represents a safer alternative to surgical lung biopsy. Recently, 1.7-mm single-use cryoprobes have been widely used, however, the safety and usefulness of TBLC with these probes remain unclear. The aim of this study was to evaluate the procedural details, safety, and changes in diagnostic confidence with multidisciplinary discussion (MDD) following TBLC. Methods: We conducted a retrospective study of TBLC cases at a single university hospital in Japan. Between August 2023 to June 2024, 25 patients were enrolled in this study. Biopsies were obtained using a 1.7-mm single-use probe with a freezing duration of 5 s; the mean sample area was 16.0 mm², and the mean maximum diameter was 5.47 mm. Results: Complications included moderate hemorrhage in three patients (12%) and mild pneumothorax in one patient (4%). No acute exacerbations of ILD were observed. Diagnostic confidence improved after MDD in 5 out of 6 cases (83.3%) of idiopathic pulmonary fibrosis (IPF) and 7 out of 8 cases (87.5%) of hypersensitivity pneumonitis (HP). Conclusions: The incorporation of TBLC pathological findings in the MDD improved diagnostic certainty and facilitated decisions regarding treatment strategies. TBLC using a 1.7-mm single-use probe with a freezing duration of 5 s can safely obtain sufficient tissue specimens for the diagnosis of ILD.

DOI： 10.21037/jtd-2024-2160

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Language：English   Publisher：Scientific Reports  

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, based on percent predicted forced expiratory volume in 1 s (ppFEV1), has been widely adopted for assessment of chronic obstructive pulmonary disease (COPD) severity. However, the STaging of Airflow obstruction by Ratio (STAR) system, based on the ratio of FEV1 to forced vital capacity, was recently proposed as an alternative classification. This study aimed to compare the prognostic performance of the GOLD and STAR classifications for prediction of mortality and exacerbation risk in individuals with COPD. This 5-year prospective, multicenter cohort study enrolled 370 individuals with COPD at 29 medical centers. All-cause mortality risk across GOLD and STAR stages was evaluated with Kaplan-Meier curves and Cox proportional hazards models. The risk of moderate to severe COPD exacerbations across GOLD and STAR stages was examined with cumulative incidence function (CIF) curves and Fine and Gray models. Both classification systems showed a significant association with mortality and exacerbation risk (P < 0.01 for trend). The GOLD classification provided a better separation of Kaplan-Meier and CIF curves for advanced stages, whereas the STAR classification showed a clearer distinction between stages I and II. These associations remained consistent after multivariable adjustments. The GOLD classification was superior for prediction of prognosis in advanced COPD, whereas the STAR classification provided better differentiation in early-stage disease. These findings highlight the complementary roles of the GOLD and STAR classifications in assessment of COPD severity.

DOI： 10.1038/s41598-025-05033-w

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DOI： 10.1111/iju.70090

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Language：English   Publisher：Scientific Reports  

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, effectively treats EGFR-mutated non-small cell lung cancer. Drug-induced interstitial lung disease, a potentially fatal complication of osimertinib, involves an increase in lymphocytes in the bronchoalveolar lavage fluid (BALF). As the precise role of these lymphocytes is unknown, we investigated the pathogenesis of osimertinib-induced pneumonitis using BALF obtained from patients, and an osimertinib-induced pneumonitis mouse model. Mass cytometry revealed the presence of CCR7+ CD45RA+ naïve T cells in the BALF of patients with osimertinib-induced pneumonitis. Body weight measurements, BALF analysis, histopathological evaluation and RNA sequencing of mouse lung tissue were performed to investigate immune cell involvement and the mechanisms underlying osimertinib-induced pneumonitis. In the mouse model, administration of osimertinib after naphthalene-induced damage to the bronchiolar epithelium exacerbated lung inflammation and resulted in significant weight loss. Immunofluorescence staining revealed the infiltration of CCR7+ cells into the lungs of mice treated with naphthalene and osimertinib. Bulk RNA sequencing identified an upregulation of chemokine-related biological processes, with increased expression of C–C motif chemokine ligand 21 (Ccl21) and C–C motif chemokine ligand 8 (Ccl8) in the lung tissue. Additionally, immunofluorescence staining confirmed elevated expression of Ccl21 and Ccl8 in the distal bronchiolar epithelium. This study provides insights into the mechanisms underlying osimertinib-induced pneumonitis.

DOI： 10.1038/s41598-025-95271-9

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal of Clinical Medicine  

Background: Lung malignancies, including cancerous lymphangitis and lymphomas, can mimic interstitial lung diseases like cryptogenic organizing pneumonia (COP) on imaging, leading to diagnostic delays. We aimed to identify potential biomarkers to distinguish between these conditions. Methods: We analyzed bronchoalveolar lavage fluid from 8 patients (4 COP, mean age 59.8 ± 13.5 years; 4 lung malignancies including 2 cancerous lymphangitis, 1 MALT lymphoma, and 1 diffuse large B cell lymphoma, mean age 67.8 ± 4.5 years) using mass cytometry with 35 T cell markers. Data were analyzed using principal component analysis (PCA) and unsupervised Citrus clustering. Results: PCA of T cell marker intensities effectively separated the two groups, with IL-2Rα, PD-L2, CD45RA, CD44, and OX40 being the top discriminating markers. Citrus analysis showed a significant increase in the CD16+ CD4+ and CD16+ CD8+ T cell populations in the COP group compared to lung malignancies. Conclusions: Our findings reveal distinct T cell immunophenotypes in COP versus lung malignancies, particularly increased CD16+ T cells in COP, which could serve as potential diagnostic biomarkers.

DOI： 10.3390/jcm14020316

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal for Immunotherapy of Cancer  

Background The immune-related adverse event (irAE), pneumonitis, is a potentially fatal complication of immune checkpoint inhibitors (ICIs). Preventing its progression is crucial, emphasizing the need for effective screening tests. We evaluated the feasibility of using Krebs von den Lungen-6 (KL-6), a marker for interstitial pneumonitis, as a screening tool for pneumonitis. Methods We examined 500 patients with cancer divided into two groups: those with cancer other than non-small cell lung cancer (NSCLC) (Group 1, n=382) and those with NSCLC (Group 2, n=118). KL-6 levels were monitored before and during ICI treatment and analyzed for their correlation with pneumonitis. Results In Group 1, 37 patients (9.7%) developed pneumonitis. KL-6 levels were significantly elevated at irAE onset (pre: 222.0 U/mL, post: 743.0 U/mL, p<0.0001). Receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.903 (sensitivity 81.1%, specificity 91.6%) with a cut-off value 1.52 times pre-KL-6 levels, indicating that KL-6 is a reliable biomarker for pneumonitis. In these patients, the KL-6 level increased regardless of pneumonitis severity and was significantly elevated in patients with both symptomatic (pre: 205.0 U/mL, post: 674.5 U/mL, p<0.0001) and asymptomatic pneumonitis (pre: 314.0 U/mL, post: 743.0 U/mL, p<0.0001) at irAE onset. After irAE treatment, KL-6 levels in steroid-responsive patients remained unchanged; however, steroid-unresponsive patients had a significant increase in KL-6 levels at 1 month (1078 U/mL, p=0.031) compared with at irAE onset (678.0 U/mL). In Group 2, 24 patients (20.3%) developed irAE pneumonitis, with KL-6 levels elevated (pre: 360.5 U/mL, post: 506.5 U/mL, p=0.029) and an AUC of 0.683, indicating that KL-6 was less reliable in patients with NSCLC. Conclusions KL-6 is a viable screening biomarker in ICI-induced pneumonitis, particularly in patients without NSCLC. In patients with NSCLC, the significance of KL-6 monitoring is limited as it is not effective for detecting ICI-induced pneumonitis; their treatment is typically managed by pulmonary specialists. Early detection through KL-6 monitoring facilitates timely intervention for ICI-induced pneumonitis, potentially preventing treatment interruptions and reducing the need for immunosuppressants.

DOI： 10.1136/jitc-2024-010114

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p>Nodal T-follicular helper cell lymphoma (nTFHL), a hematologic neoplasm originating from T-follicular helper (TFH) cells, occasionally presents with pulmonary radiographic abnormalities, without neoplastic cellular infiltration. However, the precise mechanisms underlying non-neoplastic pulmonary opacities in patients with nTFHL remain unclear. Previous reports have shown that TFH cell abnormalities are associated with collagen disease and interstitial pneumonia with autoimmune features (IPAF). We herein report a patient with nTFHL accompanied by interstitial pneumonia diagnosed via lung and lymph node biopsies. These findings suggest the need to rule out nTFHL before diagnosing IPAF. </p>

DOI： 10.2169/internalmedicine.3601-24

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CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：(一社)日本内科学会  

症例は72歳男性で、夜間の乾性咳嗽と3ヵ月で5kgの体重減少を認めた。免疫グロブリン(Ig)G、IgG4、IgE、可溶性インターロイキン-2受容体の血清レベルが高値で、抗核抗体、リウマトイド因子、ミエロペルオキシダーゼ抗好中球細胞質抗体が陽性であった。高解像度CTの所見では、可能性の高い通常型間質性肺炎パターンが示された。FDG-PET検査で、両側肺門および縦隔リンパ節を包囲する全身性リンパ節腫脹が判明した。気管支肺胞洗浄、経気管支針生検、皮膚生検、胸腔鏡下気管分岐部リンパ節生検および右下葉部分切除術を行い、節性濾胞性ヘルパーT細胞リンパ腫(nTFHL)・非特定型と診断した。右下葉生検の所見では、部分的器質化肺炎を伴う非特異性間質性肺炎パターンが認められた。複数の組織学的パターンの重複が認められ、特異的組織病理型が決定できなかったことから、肺症状はnTFHLに伴う続発性間質性肺炎であると考えられた。診断後に胸水が悪化したため、リンパ腫の節外浸潤の可能性を考慮してプレドニゾロン治療を開始すると、間質性肺炎が改善し、リンパ節サイズが縮小し、胸水量が減少した。

Language：English   Publisher：BMC Pulmonary Medicine  

Background: We conducted a prospective observational study to elucidate the long-term prognosis and management of chronic obstructive pulmonary disease (COPD) in clinical practice in Japan in the mid-2010s. Methods: This prospective cohort study included 29 facilities. Data from 427 patients clinically diagnosed with COPD, enrolled between September 2013 and April 2016, were analyzed. Interstitial pneumonia was excluded through a central multidisciplinary discussion. Follow-up data were collected for up to 5 years after patient registration. Results: At the time of registration, 53 patients clinically diagnosed with COPD did not have airflow limitation (AFL). In the cohort with AFL (n = 374), 232 patients completed a 5-year follow-up, while 49 patients died during the 1576.6 person-years of observation. The mean age was 71.7 years with an overall 5-year survival rate of 85.4%. Stratified by % forced expiratory volume in one second (FEV1), survival rates were 93.6% in the mild and moderate AFL group, 82.5% in the severe AFL group, and 66.1% in the very severe AFL group. The prognosis of the subpopulation without AFL was poor with a 5-year survival of 81.6%. This subpopulation exhibited respiratory symptoms, low vital capacity and total lung capacity, and emphysematous changes. Conclusions: Our study presents the 5-year survival and real-world clinical practice scenario of a prospective cohort of patients clinically diagnosed with COPD in Japan in the mid-2010s. The survival rates of our cohort were numerically better than the Japanese cohort in the 1990s, regardless of the high median age of this cohort. Overall, 12.4% of the patients in this cohort with no AFL at registration exhibited respiratory symptoms and distinct spirometric patterns, and had a poor prognosis.

DOI： 10.1186/s12890-024-03347-5

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scandinavian Journal of Rheumatology  

Objective: This study aimed to analyse whether initiating nintedanib treatment at a reduced dose could improve the treatment continuation rate while maintaining efficacy in patients with connective tissue disease (CTD)-associated interstitial lung disease. Method: In total, 51 patients (age 61.6 ± 13.2 years; 38 women, 13 men) were retrospectively analysed. The primary endpoint was the cumulative discontinuation rate due to adverse events. Secondary endpoints included changes in drug dosage, efficacy evaluated based on annual changes in forced vital capacity (FVC), and safety assessed based on the frequency of adverse events. Results: Eighteen patients who started treatment at the standard dose of 300 mg (standard dosage group) were compared with 33 patients who started treatment at a reduced dose (reduced dosage group). Systemic sclerosis was the most common CTD (n = 32), followed by idiopathic inflammatory myopathies and, rarely, rheumatoid arthritis. Both groups exhibited comparable cumulative discontinuation rates due to adverse events and similar frequencies of adverse events. No significant differences were observed in maintenance doses between the two groups; however, patients in the reduced dosage group had a lower cumulative dose for up to 52 weeks than those in the standard dosage group. No significant differences were observed in changes in FVC between the two groups. Conclusion: There was no evidence for a difference between the two groups in terms of discontinuation rates, efficacy, and safety. To provide further evidence, future studies using more precise dose-escalation protocols are warranted.

DOI： 10.1080/03009742.2024.2327159

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DOI： 10.7759/cureus.61470

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Language：English   Publisher：Respirology Case Reports  

We report the first case of drug-induced interstitial lung disease attributed to lemborexant. A 66-year-old man reported to our hospital with the acute onset of cough and breathlessness with ground-glass opacity on radiological examination. Symptoms were identified after taking lemborexant for 2 consecutive days. The patient had undergone lemborexant treatment 2 years prior and had exhibited no symptoms at that time. The drug-induced lymphocyte stimulation test for lemborexant was positive. He showed rapid improvement upon treatment with steroid. With the rise in prescriptions of lemborexant for insomnia, lemborexant should be considered as a possible cause of drug-induced interstitial lung disease.

DOI： 10.1002/rcr2.1334

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Language：English   Publisher：eLife  

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

DOI： 10.7554/eLife.87288

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scientific Reports  

Mucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, but whether it also exerts direct effects on airway epithelial cells has remained unclear. Therefore, we sought to investigate the inhibitory role of SP-D on mucin production in airway epithelial cells. We prepared air–liquid interface (ALI) cultures of human primary bronchial epithelial cells (HBECs), which recapitulated a well-differentiated human airway epithelium. Benzo(a)pyrene (BaP), a key toxicant in cigarette smoke, induced mucin 5AC (MUC5AC) production in ALI-cultured HBECs, airway secretory cell lines, and airway epithelia of mice. Then, the protective effects of SP-D against the BaP-induced mucin overproduction were examined. BaP increased MUC5AC production in ALI cultures of HBECs, and this effect was attenuated by SP-D. SP-D also suppressed the BaP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and MUC5AC expression in NCI-H292 goblet-like cells, but not in NCI-H441 club-like cells. Signal regulatory protein α (SIRPα) was found to be expressed in HBECs and NCI-H292 cells but absent in NCI-H441 cells. In NCI-H292 cells, SP-D activated SH2 domain-containing tyrosine phosphatase-1 (SHP-1), downstream of SIRPα, and knockdown of SIRPα abolished the suppressive effects of SP-D on BaP-induced ERK phosphorylation and MUC5AC production. Consistent with these in vitro findings, intratracheal instillation of SP-D prevented the BaP-induced phosphorylation of ERK and Muc5ac expression in airway epithelial cells in a mouse model. SP-D acts directly on airway epithelial cells to inhibit mucin secretion through ligation of SIRPα and SHP-1-mediated dephosphorylation of ERK. Targeting of SIRPα is therefore a potential new therapeutic approach to suppression of mucin hypersecretion in chronic airway diseases such as COPD and asthma.

DOI： 10.1038/s41598-024-52328-5

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：American Journal of Respiratory and Critical Care Medicine  

DOI： 10.1164/rccm.202309-1562LE

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DOI： 10.1183/13993003.congress-2023.PA1232

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DOI： 10.1183/13993003.congress-2023.PA2887

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DOI： 10.1093/jjco/hyad053

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DOI： 10.1111/1759-7714.15005.

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Language：English   Publisher：Respiratory Medicine Case Reports  

Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonitis. Although most cases of PPFE are idiopathic, some cases of PPFE occur secondary to stem cell transplantation. We report a 41-year-old woman developed pneumonia after autologous peripheral blood system cell transplantation (PBSCT). Eleven years after PBSCT, she presented with dyspnea. A computed tomographic scan showed pleuroparenchymal thickening and predominantly in the upper lobes. She was diagnosed with PPFE secondary to PBSCT. She was started nintedanib and administered oxygen therapy. Most cases of PPFE secondary to stem cell transplantation have been reported. However, we experienced the case of PPFE post-autologous PBSCT.

DOI： 10.1016/j.rmcr.2023.101845

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Language：English   Publisher：Chest  

Case Presentation: An 85-year-old Japanese man, who was taking aspirin and edoxaban for previous myocardial infarction and atrial fibrillation, came to our hospital with a chief complaint of dyspnea for 3 weeks. Chest radiography showed a massive left pleural effusion (Fig 1A). Analysis of pleural fluid showed an elevated hematocrit level at 32.8% (blood hematocrit level, 32.0%), and he was diagnosed with hemothorax. However, he had neither coagulation disorder nor thrombocytopenia, and the pleural effusion was negative for atypical cells. These findings suggested that the antithrombotic and anticoagulant medications might have induced the hemothorax.

DOI： 10.1016/j.chest.2021.09.012

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Event date： 2024.10

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Venue：オンライン   Country：Japan  

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Venue：東京   Country：Japan  

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