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IntroductionElevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD).MethodsEosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils.ResultsProteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes.DiscussionACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.

Background: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. Methods: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. Results: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. Conclusions: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

Abstract Background Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID. Methods Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. Results At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan–Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months. Conclusions In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

Reports of eosinophilic pneumonia (EP) as a side effect of dupilumab administration are limited in previous studies. Herein, we report two cases in which EP developed subsequent to the administration of dupilumab for eosinophilic chronic rhinosinusitis (ECRS). Case 1: A 55-year-old woman presented with ECRS, eosinophilic otitis media, and bronchial asthma, and was treated with dupilumab for ECRS. Five weeks later, fever and dyspnea developed, and infiltration shadows were observed in her lungs. The peripheral blood eosinophil count (PBEC) was 3848/μL (26%), bronchoalveolar lavage fluid showed eosinophilic infiltration, and EP was subsequently diagnosed. Her condition improved following prednisolone treatment. Case 2: A 59-year-old man presented with fatigue and dyspnea after receiving dupilumab for ECRS. He had infiltrative shadows throughout his left lung field, and his PBEC was 4850/μL (26.5%). Prednisolone was initiated, and his condition improved. EP developed in both patients during the period of elevated PBEC after dupilumab administration, and dupilumab was suspected to be the causative agent in their EP. Hence, EP should be considered as a differential diagnosis when fever and dyspnea appear following dupilumab administration.

We encountered a case of a 73-year-old man with acute myeloid leukemia who developed Trichosporon asahii systemic infection while on itraconazole prophylaxis during severe neutropenia. Cryptococcal antigen was useful for diagnosis. Although itraconazole was ineffective in protecting against trichosporonosis, treatment was successful with voriconazole following liposomal amphotericin B. Keywords: Trichosporon asahii, Itraconazole, Liposomal amphotericin B, Voriconazole, Cryptococcal antigen

Introduction: Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD). Methods: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multiomics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils. Results: Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes. Discussion: ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes. [ABSTRACT FROM AUTHOR]