Granulomatous Lymphocytic Interstitial Lung Disease Associated With Common Variable Immunodeficiency Presenting With Respiratory Failure.

This case study presents a rare occurrence of acute respiratory failure in a 17-year-old male diagnosed with common variable immunodeficiency (CVID) and granulomatous lymphocytic interstitial lung disease (GLILD), which typically have a gradual onset. The patient initially exhibited nonspecific symptoms such as dry cough and fever but quickly progressed to severe respiratory failure despite conventional treatments. Imaging showed extensive lung abnormalities, and blood tests revealed significantly low immunoglobulin levels, indicating an underlying immunodeficiency. Treatment with high-dose steroids and immunoglobulin replacement therapy resulted in a rapid and remarkable recovery of lung function. Lung biopsies confirmed the dual diagnoses of CVID and GLILD, emphasizing the challenge of diagnosing and managing GLILD in CVID patients. This case underscores the importance of early and aggressive intervention in improving outcomes for GLILD patients with acute respiratory distress.

Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

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.

Potential Role of Gr-1+ CD8+ T Lymphocytes as a Source of Interferon-γ and M1/M2 Polarization during the Acute Phase of Murine Legionella pneumophila Pneumonia.

In this study, we analyzed interferon (IFN)-γ-producing cells and M1/M2 macrophage polarization in Legionella pneumophila pneumonia following anti-Gr-1 antibody treatment. Anti-Gr-1 treatment induced an M1-to-M2 shift of macrophage subtypes in the lungs and weakly in the peripheral blood, which was associated with increased mortality in legionella-infected mice. CD8+ T lymphocytes and natural killer cells were the dominant sources of IFN-γ in the acute phase, and anti-Gr-1 treatment reduced the number of IFN-γ-producing CD8+ T lymphocytes. In the CD3-gated population, most Gr-1-positive cells were CD8+ T lymphocytes in the lungs and lymph nodes (LNs) of infected mice. Additionally, the number of IFN-γ-producing Gr-1+ CD8+ T lymphocytes in the lungs and LNs increased 2 and 4 days after L. pneumophila infection, with anti-Gr-1 treatment attenuating these populations. Antibody staining revealed that Gr-1+ CD8+ T lymphocytes were Ly6C-positive cells rather than Ly6G, a phenotype regarded as memory type cells. Furthermore, the adoptive transfer of Gr-1+ CD8+ T lymphocytes induced increases in IFN-γ, M1 shifting and reduced bacterial number in the Legionella pneumonia model. These data identified Ly6C+ CD8+ T lymphocytes as a source of IFN-γ in innate immunity and partially associated with reduced IFN-γ production, M2 polarization, and high mortality in anti-Gr-1 antibody-treated mice with L. pneumophila pneumonia.

Metformin Mediates Protection against Legionella Pneumonia through Activation of AMPK and Mitochondrial Reactive Oxygen Species.

In Legionella pneumophila infection, macrophages play a critical role in the host defense response. Metformin, an oral drug for type 2 diabetes, is attracting attention as a new supportive therapy against a variety of diseases, such as cancer and infectious diseases. The novel mechanisms for metformin actions include modulation of the effector functions of macrophages and other host immune cells. In this study, we have examined the effects of metformin on L. pneumophila infection in vitro and in vivo. Metformin treatment suppressed growth of L. pneumophila in a time- and concentration-dependent fashion in bone marrow-derived macrophages, RAW cells (mouse), and U937 cells (human). Metformin induced phosphorylation of AMP-activated protein kinase (AMPK) in L. pneumophila-infected bone marrow-derived macrophages, and the AMPK inhibitor Compound C negated metformin-mediated growth suppression. Also, metformin induced mitochondrial reactive oxygen species but not phagosomal NADPH oxidase-derived reactive oxygen species. Metformin-mediated growth suppression was mitigated in the presence of the reactive oxygen species scavenger glutathione. In a murine L. pneumophila pneumonia model, metformin treatment improved survival of mice, which was associated with a significant reduction in bacterial number in the lung. Similar to in vitro observations, induction of AMPK phosphorylation and mitochondrial ROS was demonstrated in the infected lungs of mice treated with metformin. Finally, glutathione treatment abolished metformin effects on lung bacterial clearance. Collectively, these data suggest that metformin promotes mitochondrial ROS production and AMPK signaling and enhances the bactericidal activity of macrophages, which may contribute to improved survival in L. pneumophila pneumonia.

Development of a simultaneous dual-ablation apparatus and preparation of compositionally gradient (Sr(1-x)Eu(x))Al2O4 thin films.

A simultaneous dual-ablation apparatus using a pulsed laser was developed for preparation of compositionally gradient thin films to explore novel compounds. Unlike other compositionally gradient thin film preparation apparatus, two targets rotated by motors were installed in and two beams splitted from a single laser were introduced to a vacuum chamber. With this apparatus, a (Sr(1-x)Eu(x))Al2O4 compositionally gradient thin film was prepared. The phase and the photoluminescence properties were investigated. The Eu optimal composition for the emission intensity in the (Sr(1-x)Eu(x))Al2O4 system was found to be x=0.06.