Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

Characteristics of pleural effusion with a high adenosine deaminase level: a case-control study.

BACKGROUND: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion. METHODS: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors. RESULTS: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively. CONCLUSION: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Rapidly progressive respiratory failure with multiple halo signs on computed tomography in a patient with primary cardiac angiosarcoma derived from the right atrium: a case report.

BACKGROUND: Primary cardiac neoplasms are extremely rare, with an autopsy incidence of 0.0001-0.003%. Primary cardiac sarcoma is usually derived from the right atrium and it manifests as chest pain, arrhythmia, hemoptysis, dyspnea, and fatigue. The most common target organ for metastasis of primary angiosarcoma is the lungs, but the radiological-pathological correlation has been rarely reported. CASE PRESENTATION: A 38-year-old healthy Japanese man was admitted to our hospital with persistent hemoptysis, exaggerated dyspnea, and two episodes of loss of consciousness in the past 3 months. Non-enhanced thoracic computed tomography (CT) revealed multiple scattered nodules with halo signs. Contrast-enhanced thoracic CT revealed a filling defect in the right atrium, which corresponded to the inhomogeneously enhancing tumor in the right atrium on enhanced electrocardiogram-gated cardiac CT. On day 2, acute respiratory failure occurred, and the patient was placed on mechanical ventilation. The patient was diagnosed with primary cardiac angiosarcoma based on the urgent transcatheter biopsied specimen of the right atrium mass and was treated with intravenous administration of doxorubicin. However, his respiratory status rapidly deteriorated, and he died on day 20. Postmortem biopsy showed that the multiple lung nodules with the halo signs corresponded to the intratumoral hemorrhagic necrosis and peripheral parenchymal hemorrhage in their background, suggesting the fragility of the lung tissue where the tumor had invaded, which caused hemoptysis. Furthermore, two episodes of loss of consciousness occurred probably due to a decreased cardiac output because of a massive tumor occupying the right atrium, recognized as an inhomogeneous centripetal enhancement on enhanced electrocardiogram-gated cardiac CT. CONCLUSIONS: This case clearly demonstrated that primary cardiac angiosarcoma could expand in the right atrial cavity, which led to a decreased cardiac output resulting in repeated syncope, together with the fragility of lung tissue by tumor invasion, thereby generating a halo sign on thoracic CT.

Serum sST2 levels predict severe exacerbation of asthma.

BACKGROUND: Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. METHODS: This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. RESULTS: High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H2O2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /µl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. CONCLUSIONS: High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.

Bronchial epithelial cells produce CXCL1 in response to LPS and TNFα: A potential role in the pathogenesis of COPD.

RATIONALE: Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood. AIM OF THE STUDY: To assess the production of CXCL1 by bronchial epithelial cells in response to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α. MATERIALS AND METHODS: We measured sputum CXCL1 and CXCL8 levels in patients with COPD, asthma, and asthma-COPD overlap (ACO), and compared them to those of patients with interstitial pneumonia (IP). Using primary human bronchial epithelial cells and BEAS-2B cells, CXCL1 protein release and mRNA expression were measured after LPS or TNFα stimulation. We evaluated signal transduction mechanisms for CXCL1 production using nuclear factor-κ B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibitors, and examined the effects of anti-inflammatory agents on CXCL1 production in BEAS-2B cells. RESULTS: Sputum CXCL1 levels in COPD and ACO patients were higher than in IP patients, whereas sputum CXCL8 levels were not. Sputum CXCL1 levels were not affected by inhaled corticosteroid usage, whereas sputum CXCL8 levels tended to be affected. LPS and TNFα stimulated CXCL1 production and mRNA expression in bronchial epithelial cells. NF-kB and MAPK p38 were involved in LPS-induced CXCL1 production. Therapeutic anti-inflammatory agents minimally attenuated CXCL1 production and considerably inhibited CXCL8 production in BEAS-2B cells. CONCLUSIONS: Sputum CXCL1 levels is a potentially better diagnostic marker for COPD than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents than CXCL8 production.

Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-ß, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion.

PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-ß was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001). CONCLUSIONS: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 37.2% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation.

BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) -α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. RESULTS: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1ß and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. CONCLUSIONS: IL-17A in the combination with TNF-α or IL-1ß showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

BACKGROUND: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be ß-lactamase-non-producing ABPC-resistant and 11.0% to be ß-lactamase-producing ABPC-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Breakthrough invasive Candida glabrata in patients on micafungin: a novel FKS gene conversion correlated with sequential elevation of MIC.

Candida glabrata strains sequentially isolated from blood developed resistance to micafungin (MICs from <0.015 to 4 µg/ml). A novel mutation identified in micafungin-resistant strains at bp 262 of FKS2 (containing a deletion of F659 [F659del]) was inserted into the homologous region in FKS1.

Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan.

BACKGROUND: Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS. METHODS: Thirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups. RESULTS: In contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis. CONCLUSION: Development of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

Predictive factors of the presence of pulmonary embolism in patients with interstitial lung disease: Observational study.

In patients with interstitial lung disease (ILD), the risk of pulmonary embolism (PE) is increased; however, distinguishing between PE and ILD exacerbation can be difficult. Therefore, this study investigated the usefulness of the Wells criteria and revised Geneva score and predictive factors for diagnosing PE in ILD patients with worsening respiratory symptoms. We retrospectively collected the data of 65 patients with ILD who underwent computed tomography pulmonary angiography at Fukujuji Hospital and Kyorin University Faculty of Medicine from January 2018 to March 2023, including 18 patients in the PE group and 47 patients in the non-PE group, and the data were compared between the 2 groups. The Wells score (P = .165) and revised Geneva score (P = .140) were not useful for distinguishing between the PE and non-PE groups. Patients in the PE group showed higher D-dimer, total protein (TP), and globulin levels than those in the non-PE group (D-dimer median 24.5 µg/mL [range 3.0-79.3] vs 9.3 µg/mL [range 0.5-80.8], P = .016; TP median 7.2 g/dL [range 5.1-8.7] vs 6.4 g/dL [range 5.0-8.2], P = .002; globulin median 3.8 g/dL [range 2.6-5.5] vs 3.2 g/dL [range 3.0-5.3], P = .041). Using cutoff values of TP ≥ 7.0 g/dL and D-dimer ≥ 11.8 µg/mL, the odds ratios for predicting PE were 10.5 and 4.90, respectively. This study demonstrates that high TP and D-dimer levels are useful indicators for predicting PE in ILD patients with worsening respiratory symptoms, while the Wells score and revised Geneva score are not reliable in diagnosing PE.

Association of IL-33 in modeling type-2 airway inflammation and pulmonary emphysema in mice.

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.

Clinical Evaluation of Acute Exacerbation of Interstitial Lung Disease in a Single Tertiary Center: Perspectives before and after the Coronavirus Disease 2019 Pandemic.

Background/Objectives: Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes. Methods: We conducted a retrospective review of hospitalized adult patients with AEs of ILDs from January 2019 to February 2024. Results: A total of 93 patients were enrolled: IPF (n = 42), iNSIP (n = 37), and CTD-ILDs (n = 14). The median age was 80 years (interquartile range: 74.0-86.0 years), with males comprising 64.5% (n = 60). AEs of ILDs predominantly occurred in winter and were particularly notable after summer 2023, coinciding with the lifting of COVID-19-related travel restrictions in Japan. Patient referrals from different areas (Northern Tama, East and/or Southern Tama, and other Tokyo metropolitan areas) were evenly distributed throughout the study period. Viral infections were detected in only two patients (SARS-CoV-2), and bacterial infections included methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The Cox regression analysis identified serum lactate dehydrogenase levels ≥350 IU/L and tachypnea (respiratory rate ≥ 30 breaths per min) on admission as prognostic factors for mortality, with a hazard ratio [HR] of 2.783 (95% confidence interval [CI]: 1.480-5.235, p = 0.001) and an HR of 3.332 (95% CI: 1.710-6.492, p < 0.001), respectively. Conclusions: AEs of ILDs predominantly occur in winter, and viral and bacterial infections are infrequently detected. Elevated serum LDH levels and tachypnea are crucial prognostic markers for mortality. This study highlights the seasonal trend in the AE of ILD and emphasizes the importance of specific prognostic indicators in clinical practice.

Impact of Cough Severity on the Diagnostic Yield of Endobronchial Ultrasonography Transbronchial Biopsy with Guide Sheath: A Retrospective Observational Study.

Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated. Bronchoscopists assessed the cough severity upon completion of the procedure using a four-point cough scale. Cough severity was included as a predictive factor along with those reportedly involved in bronchoscopic diagnosis, and their impact on diagnostic yield was evaluated. Predictors of cough severity were also examined. A total of 275 patients were enrolled in this study. In the multivariate analysis, the diagnostic group (n = 213) had significantly more 'within' radial endobronchial ultrasound findings (odds ratio [OR] 5.900, p < 0.001), a lower cough score (cough score per point; OR 0.455, p < 0.001), and fewer bronchial generations to target lesion(s) (OR 0.686, p < 0.001) than the non-diagnostic group (n = 62). The predictive factors for severe cough include the absence of virtual bronchoscopic navigation (VBN) and prolonged examination time. Decreased cough severity was a positive predictive factor for successful EBUS-GS-TBB, which may be controlled using VBN and awareness of the procedural duration.

Serum Derivatives-Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma-COPD Overlap: A Prospective Study.

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives-reactive oxygen metabolites (d-ROMs) in serum. Results: The d-ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d-ROMs levels between the COPD and ACO groups. In BA, d-ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George's Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d-ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d-ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d-ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO.

High-resolution computed tomography findings for patients with drug-induced pulmonary toxicity, with special reference to hypersensitivity pneumonitis-like patterns in gemcitabine-induced cases.

BACKGROUND: Gemcitabine (GEM) is widely used as a chemotherapeutic agent. However, pulmonary toxicity has been rarely observed with GEM use. This article aims to determine the incidence and causes of drug-induced pulmonary toxicity, and to classify the high-resolution computed tomography (HRCT) findings for antitumor therapy-associated pulmonary toxicity based on characteristic patterns and pathological considerations, with a special focus on GEM-associated pulmonary toxicity (GAPT). METHODS: Medical records of all patients with drug-induced pulmonary toxicity seen at Kyorin University hospital between April 2006 and December 2011 were retrospectively reviewed. The study examined correlations between HRCT and the assessed pathological or clinical findings, with a specific focus on antitumor drugs. RESULTS: We identified 66 patients with drug-induced pulmonary toxicity. Among the antitumor drugs, GEM was the primary offending agent (n = 8) for pulmonary toxicity followed by docetaxel and gefitinib. HRCT patterns for the eight GAPT patients included the non-specific interstitial pneumonia (NSIP; n = 5) and the hypersensitivity pneumonitis (HP)-like pattern (n = 3). In contrast, four patients in the study were found to have the HP-like pattern, with three cases associated with GEM and one case associated with imatinib mesylate. The transbronchial lung biopsy or video-assisted thoracic surgery specimens for these patients showed granuloma or organizing tissue with a random distribution that was independent of the respiratory bronchiole. These results appeared to correspond to the HRCT-determined centrilobular nodules. CONCLUSION: GEM was the leading cause of drug-induced pulmonary toxicity in the patients examined in this study. This toxicity appears as NSIP or an HP-like pattern during HRCT examinations. This HP-like pattern may be useful for diagnosing GEM-induced pulmonary toxicity, as well as demonstrating granuloma or organizing tissue during lung pathology examinations.