Osimertinib is the standard first-line therapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer, but acquired resistance remains a major clinical issue. Here, we report a case of lung adenocarcinoma harboring compound EGFR L858R and E709K mutations that acquired C797S after progression on first-line osimertinib. Gefitinib achieved a durable partial response lasting approximately 15 months, despite E709K generally conferring reduced sensitivity to first-generation EGFR-tyrosine kinase inhibitors. This case highlights the importance of repeat molecular profiling and suggests gefitinib as a potential salvage option in selected C797S-positive cases.
Prevascular mediastinal lesions encompass a broad spectrum of entities, ranging from benign cysts to malignant tumors such as thymic epithelial tumors (TETs), lymphoma, and germ cell tumors (GCTs). With the increasing use of computed tomography (CT), incidentally detected, asymptomatic prevascular mediastinal nodules are encountered more frequently in daily practice. However, accurate characterization based on CT alone remains challenging because cystic lesions may exhibit soft-tissue attenuation or pseudoenhancement, resulting in substantial overlap with solid tumors and potential overtreatment. This review mainly focuses on the differential diagnosis of incidentally detected prevascular mediastinal nodules and summarizes their epidemiologic, clinical, and imaging characteristics. Particular emphasis is placed on a practical diagnostic strategy that integrates contrast-enhanced CT for lesion localization and morphologic assessment with magnetic resonance imaging (MRI) for problem-solving. Although lymphomas and GCTs usually present as large symptomatic masses rather than incidental nodules, they are also discussed because they remain important considerations in the differential diagnosis of prevascular mediastinal lesions. MRI provides superior tissue characterization, enabling reliable differentiation of cystic and solid lesions, evaluation of intratumoral architecture, assessment of tumor cellularity using diffusion-weighted imaging and apparent diffusion coefficient values, and more accurate evaluation of local invasion. The selective role of fluorine-18 fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT), particularly for lymphoma, aggressive malignancies, and disease staging, is also discussed. By integrating imaging findings with epidemiologic information, clinical presentation, and laboratory data, a stepwise diagnostic approach can improve diagnostic confidence, reduce unnecessary invasive procedures, and facilitate appropriate management of prevascular mediastinal nodules.
BACKGROUND:Computed tomography (CT)-based artificial intelligence (AI) risk models improve malignancy prediction, but their incremental value when integrated into clinician workflows has not been studied. We aimed to assess the sequential application of Bronchosolve (AI) in nodule risk stratification. METHODS:We performed a fully crossed, multi-reader, multi-case retrospective study of 296 chest CT scans from screening and incidentally detected lung nodules under three conditions: clinician, Bronchosolve (AI), and AI-aided clinician interpretation. Primary outcomes were area under the receiver operating characteristic curve (AUC) and accuracy. Secondary outcomes included sensitivity, specificity, and net reclassification improvement (NRI), with prespecified analysis of intermediate-risk nodules. RESULTS:Mean AUC increased from 0.84 (95% CI, 0.83-0.86) for clinicians to 0.87 (95% CI, 0.86-0.88) for Bronchosolve and 0.88 (95% CI, 0.86-0.89) for AI-aided clinician interpretation. Overall, readers' accuracy improved from 74.7% to 77.7% with AI assistance (p < 0.01). In the intermediate-risk subgroup, the sequential AI-assisted workflow achieved 88.2% sensitivity and 52.3% specificity, compared with 84.8% sensitivity for Bronchosolve alone. NRI for the full cohort was 0.19, driven predominantly by correct upward reclassification of malignant nodules (event NRI = 0.10). In the full cohort, there were minimal reclassification changes among initially Low- and High-Risk cases. Bronchosolve primarily reclassified Intermediate-Risk nodules into binary Low- or High-Risk final categories. Of 969 Intermediate-Risk reader case assessments, 47.8% were reassigned to Low-Risk (71.1% benign) and 52.2% to High-Risk (59.7% malignant), demonstrating clinically meaningful risk resolution. CONCLUSION:Integrating Bronchosolve with clinician assessment improved discrimination and clinically relevant reclassification of intermediate risk lung nodules.
BACKGROUND:Concurrent chemoradiotherapy (CCRT) followed by durvalumab is standard treatment for unresectable stage III non-small cell lung cancer (NSCLC), but the clinical significance of tumor cavitation at durvalumab initiation is uncertain. METHODS:We retrospectively studied consecutive patients treated at Iizuka Hospital between February 2018 and September 2024. Eligible patients had pathologically confirmed stage III NSCLC, completed platinum-based CCRT, and started durvalumab within 56 days. Cavitation was defined as a gas- or fluid-containing cavity measuring at least 5 mm within the primary tumor on computed tomography after CCRT and before durvalumab. Progression-free survival (PFS) from the first durvalumab infusion was the primary endpoint; overall survival (OS) and pulmonary events were secondary endpoints. RESULTS:Of 36 eligible patients, 9 (25.0 %) had cavitation at durvalumab initiation; 3 had preexisting cavitation and 6 developed cavitation during or after CCRT. Median follow-up was 54.9 months. Cavitation was associated with shorter PFS (median, 3.7 vs. 19.3 months; hazard ratio [HR], 6.60; 95 % confidence interval [CI], 2.25-19.32) and OS (median, 10.6 months vs. not reached; HR, 26.46; 95 % CI, 5.24-133.75). The age-adjusted HRs were 5.62 (95 % CI, 1.79-17.66) for PFS and 12.05 (95 % CI, 2.16-67.29) for OS. Eight patients with cavitation discontinued durvalumab, and two died of grade 5 hemoptysis. CONCLUSIONS:Tumor cavitation at durvalumab initiation identified a small subgroup with poor outcomes after CCRT. The finding supports closer surveillance but requires external validation.
BACKGROUND:Nintedanib is an effective antifibrotic treatment for interstitial lung diseases. However, adverse events often lead to discontinuation. We examined whether a multidisciplinary support pathway at the initiation of treatment was associated with continued nintedanib therapy. METHODS:In this single-center observational study, patients prospectively enrolled in a 7-day multidisciplinary inpatient pathway were compared with historical controls receiving standard care. The primary analysis assessed 12-month treatment continuation after nintedanib initiation, defining discontinuation for any reason other than death as an event. Secondary analyses assessed all-cause discontinuation and repeated the primary analysis among patients with at least 12 months of potential follow-up. RESULTS:Among 113 patients, 42 received multidisciplinary support and 71 standard care. Within 12 months, treatment discontinuation occurred in 6 and 27 patients, respectively. The Kaplan-Meier-estimated 12-month treatment continuation rates were 85.3% and 59.3%, respectively (log-rank p = 0.027). Multidisciplinary support was associated with a lower discontinuation risk (hazard ratio 0.38, 95% confidence interval 0.16-0.93, p = 0.033). In the all-cause analysis, the Kaplan-Meier-estimated 12-month treatment continuation rates were 76.9% and 52.3% (log-rank p = 0.037). The association persisted in patients with sufficient potential follow-up (log-rank p = 0.035). Any adverse event occurred at similar frequencies (73.8% vs. 73.2%). CONCLUSIONS:A multidisciplinary support pathway was associated with higher 12-month treatment continuation than standard care, although confirmation in larger contemporaneous cohorts is required.
Obstructive bronchiolitis (OB) is a rare disorder characterized by progressive airflow limitation and is most commonly associated with autoimmune diseases, inhalation of toxins, lung transplantation, and hematopoietic stem cell transplantation. Thymoma is a rare mediastinal tumor frequently accompanied by autoimmune diseases, such as myasthenia gravis. We report a male patient with mild chronic obstructive pulmonary disease who developed thymoma and severe respiratory dysfunction mimicking OB. Postmortem autopsy revealed histopathological findings resembling systemic graft-versus-host disease with OB-like bronchiolar lesions. This case highlights the potential link between thymoma and severe small-airway disease and underscores the diagnostic challenges in identifying OB-like pathology.
High-flow nasal cannula (HFNC) therapy is an established modality for noninvasive respiratory support in acute hypoxemic respiratory failure. More recently, its use has expanded beyond acute care to home, rehabilitation, and palliative settings. This narrative review summarizes the current evidence on the long-term and non-acute applications of HFNC in adult patients.A PubMed search (2010–2025) identified studies on domiciliary HFNC for chronic respiratory failure as well as its use in rehabilitation and palliative care. In chronic obstructive pulmonary disease (COPD), multiple randomized controlled trials have shown that long-term HFNC use reduces exacerbation frequency and improves quality of life (QOL), although effects on hospitalizations and mortality remain uncertain. In bronchiectasis, available studies suggest reduced exacerbations and symptom improvement despite limited high-quality evidence. In interstitial lung disease (ILD), findings are heterogeneous, with some low-certainty studies reporting benefits for dyspnea, cough, and exercise tolerance.During exercise and pulmonary rehabilitation, HFNC may reduce dyspnea, improve endurance, particularly in COPD, and attenuate oxygen desaturation in ILD. In palliative care, HFNC effectively relieves dyspnea and may improve comfort, communication, and QOL in patients with advanced diseases.Overall, HFNC appears to be a versatile respiratory support modality in chronic and non-acute settings. However, further high-quality studies are needed to define optimal indications and long-term outcomes. Careful patient selection, clear therapeutic goals, and multidisciplinary preparation are essential for safe and effective implementation.
BACKGROUND:Patients with hematologic malignancies frequently require diagnostic bronchoscopy for the evaluation of pulmonary complications, but thrombocytopenia complicates procedural safety and decision-making. We aimed to identify a platelet count threshold associated with increased intraprocedural bleeding risk during bronchoscopy with biopsy or brushing in this population. METHODS:We conducted a single-centre retrospective cohort study of adults with hematologic malignancies who underwent diagnostic bronchoscopy between 2010 and 2023. Bleeding was graded according to the Nashville Bleeding Scale (grade 1-4). Among procedures including transbronchial lung biopsy (TBLB) and/or endobronchial brushing, receiver operating characteristic (ROC) curve analysis was used to identify the platelet count cut-off associated with grade 2-4 bleeding. RESULTS:Overall, 122 bronchoscopies were performed in 117 patients; 16 procedures (13.1%) were complicated by grade 2-4 bleeding. Among the 89 procedures involving TBLB and/or brushing, the optimal platelet count cut-off for predicting grade 2-4 bleeding was 8.2 × 104/μL (area under the ROC curve 0.73, 95% CI 0.59-0.88; sensitivity 85.7%; specificity 65.7%). No procedure-related deaths occurred. TBLB yielded a pathological diagnosis in 22.4% (17/76) of procedures, while brushing cytology was diagnostic in 3.6% (2/55). Organizing pneumonia was the most frequent histopathological diagnosis, followed by lung cancer and fungal infection. CONCLUSIONS:In patients with haematologic malignancies and thrombocytopenia, bronchoscopy with biopsy or brushing provides clinically useful diagnostic information but carries an increased bleeding risk at lower platelet counts. A platelet count of approximately 8.2 × 104/μL may serve as a reference point indicating increased bleeding risk at lower counts during TBLB and brushing, rather than a definitive "safe" threshold. However, given the limited number of bleeding events, this should be regarded as an exploratory finding requiring validation in larger, prospective studies.
BACKGROUND:Chronic ischemia in patients with chronic obstructive pulmonary disease (COPD) can increase the risk of inner ear diseases, such as sudden sensorineural hearing loss (SSNHL), Bell's palsy, and Meniere's disease. However, the impact of COPD on these diseases has not been estimated. This study aimed to estimate the risk of SSNHL, Bell's palsy, and Meniere's disease in patients with COPD. METHODS:A total of 582,406 COPD patients were matched with 2,063,063 control participants. The overlap weighted hazard ratios (HRs) of COPD for SSNHL, Bell's palsy, and Meniere's disease were calculated using a propensity score overlap weighted Cox proportional hazard regression model. Secondary analyses were conducted in subgroups according to demographic factors and comorbidities. RESULTS:Overall, 1.00% (5838/582,406), 0.71% (4133/582,406), and 0.75% (4340/582,406) of the COPD patients had SSNHL, Bell's palsy, and Meniere's disease, respectively. The risks of SSNHL, Bell's palsy, and Meniere's disease were 1.06 (95% confidence intervals [CI] = 1.03 - 1.08), 1.05 (1.02 - 1.08), and 1.13 (1.10 - 1.17) times greater, respectively, in COPD patients than in control participants. The increased risk of three diseases in COPD patients was consistent in most of the subgroups. CONCLUSION:Patients with COPD had greater risks of SSNHL, Bell's palsy, and Meniere's disease than did those without COPD. Meniere's disease showed the highest risk related to the presence of COPD.
BACKGROUND:The current state of respiratory physical therapy for adult pneumonia in Japan is insufficiently characterized. This study aimed to elucidate the current practices of respiratory physical therapy in Japan, including its implementation specifics, clinical frameworks, and medical reimbursement, with the aim of optimization respiratory physical therapy for adult pneumonia. METHODS:A cross-sectional questionnaire survey comprising 21 questions was administered to members of the Japanese Society of Respiratory Physical Therapy. The survey items encompassed basic institutional information, existence of protocols, timing of rehabilitation prescriptions, clinical and educational systems for respiratory physical therapy (such as training systems), and content of respiratory physical therapy. RESULTS:The timing of rehabilitation prescriptions for adult pneumonia "varies depending on clinical decision-making by attending physicians" in 35.4% of institutions, and only 8.3% of facilities had established rehabilitation protocols. Furthermore, the most pressing issue concerning respiratory physical therapy for adult pneumonia was identified as "the lack of guidelines for respiratory physical therapy (pulmonary rehabilitation) for pneumonia," with 92 institutions citing this as the most significant problem. CONCLUSIONS:The practice of respiratory physical therapy for adult pneumonia in Japan varies across institutions, with a lack of reference materials, including clinical practice guidelines, potentially contributing to this variability. These findings highlight the need for further research and the development of optimized clinical guidance.
Primary pulmonary angiosarcoma is a rare malignancy with limited therapeutic options. We report a case of primary pulmonary angiosarcoma in which tumor regression was achieved with immune checkpoint inhibitor (ICI) rechallenge following pazopanib therapy. The tumor showed strong PD-L1 expression and infiltration of CD3+, CD4+, and CD8+ T cells without CD20+ B cells. After disease control with atezolizumab, pazopanib induced tumor shrinkage but was followed by disease progression. Pembrolizumab rechallenge resulted in tumor regression and sustained benefit. This case suggests that sequential VEGF-targeted therapy and PD-1 blockade may contribute to renewed sensitivity to ICI in tumors with a T-cell-inflamed microenvironment.
BACKGROUND:Coughing during bronchoscopy causes patient discomfort and may compromise procedural stability. However, its relationship with oxygen desaturation remains unclear. This study was conducted to identify factors associated with severe cough and oxygen desaturation (peripheral oxygen saturation [SpO2] ≤85%) during standalone endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS:We retrospectively reviewed 192 stand-alone EBUS-TBNA procedures performed between March 2019 and March 2024. Cough severity was assessed using a 4-point operator-rated scale and categorized as mild (scores of 0-1 point) or severe (scores of 2-3 points). Oxygen desaturation was defined as minimum SpO2 of ≤85% during the EBUS-TBNA phase after convex-probe EBUS bronchoscope insertion. Multivariable logistic regression identified independent predictors of severe cough and desaturation while considering relevant clinical and procedural variables. RESULTS:Severe cough occurred in 78 (40.6%) patients, and SpO2 ≤85% occurred in 25 (13.0%). SpO2 ≤85% was independently associated with severe cough (odds ratio [OR] 6.45, 95% confidence interval [CI] 2.26-18.40; p < 0.001). For desaturation, female sex (OR 7.73), hypertension (OR 4.05), and station #11s sampling (OR 4.50) were independently associated with SpO2 ≤85% (p < 0.05). The #11s association did not remain significant after multiple testing corrections in the exploratory station-wise analyses. CONCLUSIONS:Clinically relevant desaturation during EBUS-TBNA was strongly associated with severe cough. Female sex and hypertension were also associated with desaturation, and #11s sampling showed a clinically relevant but exploratory signal. These findings may support individualized risk assessment and procedural planning.
BACKGROUND:Chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis (PF) represent divergent respiratory pathologies, yet their systemic metabolic drivers remain poorly understood. This study aimed to identify systemic lipidomic signatures characterizing the pathophysiological heterogeneity of these conditions. METHODS:We conducted a cross-sectional lipidomic analysis of peripheral plasma from age- and sex-matched patients with COPD (n = 25) and PF (n = 27, serum KL-6 >1000 U/mL) using liquid chromatography-tandem mass spectrometry. RESULTS:Twenty-eight lipid species were significantly differentially expressed. COPD was characterized by systemic ceramide depletion and enhanced lysophosphatidylethanolamine - phosphatidylethanolamine - phosphatidylserine (LPE-PE-PS) metabolic cycling, reflecting distinct membrane remodeling processes compared to PF. The correlation between lysophosphatidic acid (LPA) 16:0 levels and forced expiratory volume at 1 s/forced vital capacity (FEV1/FVC) was divergent: inverse in COPD and positive in PF. This metabolic mirror effect highlights how plasma lipid signatures reflect contrasting mechanical environments, airflow obstruction in COPD versus radial traction-induced airway patency in PF. CONCLUSIONS:These findings suggest that systemic lipidomic profiles provide a molecular framework for identifying disease-specific treatable traits offering a foundation for advancing personalized clinical management in chronic respiratory diseases. TRIAL REGISTRATION:Registry for UMIN, Lipidomic analysis on plasma in idiopathic pulmonary fibrosis patients. Trial registry number, UMIN000020872.
BACKGROUND:Mycobacterium avium complex lung disease (MAC-LD) is a chronic pulmonary infection associated with significant long-term morbidity and mortality. The Geriatric Nutritional Risk Index (GNRI) is a simple nutritional indicator derived from serum albumin levels and the actual-to-ideal body weight ratio. Although host nutritional status is thought to influence the prognosis of patients with MAC-LD, the clinical importance of the GNRI in this population remains unclear. METHODS:This multicenter retrospective cohort study included 588 patients diagnosed with MAC-LD between 2006 and 2020. Patients were categorized into four groups according to GNRI: ≥98 (no risk), 92-<98 (low risk), 82-<92 (moderate risk), and <82 (high risk). Furthermore, the association between the GNRI and clinical outcomes was evaluated. RESULTS:The 5-year survival rates in the no-, low-, moderate-, and high-risk groups were 94%, 78%, 65%, and 46%, respectively (p < 0.01). In the multivariable Cox model, a higher-risk group based on GNRI was independently associated with a higher risk of all-cause mortality (hazard ratio 1.89, 95% confidence interval 1.45-2.44), and the GNRI category-based model yielded a Harrell's C-index of 0.888 (95% confidence interval, 0.841-0.920) for all-cause mortality. In the multivariable Fine-Gray model, a higher-risk group based on GNRI was significantly associated with a higher risk of respiratory-related mortality (subdistribution hazard ratio 2.08, 95% CI 1.52-2.86). CONCLUSION:These findings suggest that the GNRI is a useful prognostic marker for all-cause and respiratory-related mortalities in patients with MAC-LD.
The therapeutic landscape for lung cancer has been transformed by the introduction of molecular targeted therapies, immune checkpoint inhibitors (ICIs), and antibody-drug conjugates (ADCs). However, this expansion of treatment options has been accompanied by an increasing incidence of drug-induced interstitial lung disease (DIILD), which can significantly impact clinical outcomes. This review provides a comprehensive overview of DIILD in lung cancer management. Distinct clinical features and management strategies for various classes of antineoplastic agents are discussed. A high incidence of epidermal growth factor receptor-tyrosine kinase inhibitor-associated ILD in the Japanese population and emerging risks associated with sequential therapy using osimertinib following ICIs are highlighted. Unique "off-target" pulmonary toxicities of newer ADCs and the complex "two-hit" interactions between systemic therapies and local interventions like pleurodesis are also examined. Furthermore, a standardized five-step diagnostic approach based on systematic exclusion and multidisciplinary team consensus is proposed. Vigilant monitoring, early detection, and integrated management involving patient education and shared decision-making remain essential for optimizing patient safety in the era of precision oncology.
BACKGROUND:Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and invasive pneumococcal diseases in older adults. Although pneumococcal vaccination is effective in preventing severe disease, adult vaccination recommendations have become increasingly complex with the introduction of multiple vaccine types and poor dissemination among healthcare professionals. METHODS:A questionnaire survey was conducted among medical institutions in Shimane Prefecture across three survey periods: early (2017), middle (2019), and late (2023). The survey assessed institutional characteristics, clinical specialties, awareness of pneumococcal vaccination-related knowledge, and vaccination practices. Multivariate logistic regression analysis evaluated the association between awareness and vaccination implementation. RESULTS:Response rates were 43.5%, 38.0%, and 36.8% in the early, middle, and late survey periods, respectively. In the late period, 80.1% of the institutions were aware that two classes of pneumococcal vaccines were recommended for older adults. The proportion was significantly lower than that observed in the middle period (p = 0.041). Awareness that PPSV23 can be administered as a routine vaccination even after prior PCV vaccination was limited (47.6%) and declined from the middle to the late period (p = 0.001). Multivariate analyses demonstrated that the awareness of pneumococcal vaccine types and the benefits of sequential vaccination were markedly associated with vaccination practices. CONCLUSIONS:The dissemination of accurate information on pneumococcal vaccine types and vaccination recommendations may contribute to improving vaccination coverage. Strengthening continuous education and awareness activities targeting a broad range of healthcare professionals is warranted.
BACKGROUND:Progressive pulmonary fibrosis (PPF) encompasses non-IPF fibrosing interstitial lung diseases that progress despite conventional management. Nintedanib is the only licensed antifibrotic for non-IPF PPF, yet real-world populations differ substantially from INBUILD trial participants, particularly in near-universal concomitant immunosuppressive therapy (IST) use. METHODS:A systematic search of PubMed/MEDLINE, EMBASE, and Cochrane Library (inception-May 2026) identified observational studies, registries, and open-label trial extensions evaluating antifibrotics in adults with non-IPF PPF. Studies reporting lung function, disease progression, or safety with ≥6 months follow-up were eligible. Data were narratively synthesized per PRISMA 2020 and SWiM guidelines; formal meta-analysis was precluded by substantial heterogeneity. Risk of bias and certainty of evidence were assessed using ROBINS-I and GRADE. RESULTS:Ten studies were included (N = 3228; 9 countries; 2014-2025). Real-world patients showed greater disease severity at initiation, with 55-100% receiving concomitant IST. Nintedanib was associated with attenuated FVC decline in uncontrolled pre-post analyses (-72 to -89 mL/year on treatment vs. -188 to -240 mL/year pre-treatment); these estimates are hypothesis-generating only. Diarrhea occurred in 29-77%; permanent discontinuation in 9-29%. Nintedanib combined with mycophenolate, rituximab, or tocilizumab was not associated with excess serious adverse events. Pirfenidone evidence comprised a single 11-patient case series. CONCLUSIONS:Very low-certainty real-world evidence suggests nintedanib may attenuate disease progression and is generally tolerable across diverse ILD subtypes and IST backgrounds. Pirfenidone evidence remains insufficient. Prospective controlled studies and registries examining antifibrotic-IST combinations and long-term patient-centered outcomes are an urgent priority.
