肺胞蛋白症（自己免疫性又は先天性）

Rickettsia typhi-induced murine typhus is underrecognized in southern U.S. regions such as Texas. While typical symptoms include fever, rash, and mild pulmonary involvement, severe presentations such as pneumonia or acute respiratory distress syndrome (ARDS) can occur. The radiographic "crazy-paving" pattern is nonspecific and can be seen in a variety of infectious and inflammatory pulmonary conditions, creating diagnostic uncertainty. Because pulmonary alveolar proteinosis (PAP) typically prompts consideration of invasive diagnostic evaluation, recognizing infectious mimics has important clinical implications. A 46-year-old man with alcohol use disorder develops fatigue, cough, dysuria, dyspnea, and fever. CT imaging revealed bilateral perihilar ground-glass opacities with interlobular septal thickening ("crazy-paving"). Laboratory studies showed leukocytosis, thrombocytopenia, acute kidney injury, transaminitis, and elevated inflammatory markers. Broad-spectrum antibiotics did not provide symptom relief. Serologic testing confirmed murine typhus; doxycycline led to rapid clinical and radiographic improvement. Four-week follow-up imaging showed near-complete resolution. This is, to our knowledge, the first reported case of murine typhus presenting with radiological and clinical features that closely mimic pulmonary alveolar proteinosis. In endemic regions, murine typhus should be included in the differential diagnosis of diffuse alveolar disease with a crazy-paving pattern, as this overlap may lead to diagnostic uncertainty and potentially unnecessary invasive evaluation. Early recognition and treatment with doxycycline can result in rapid clinical and radiographic resolution.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. The efficacy of antifibrotic drugs for progressive pulmonary fibrosis (PPF) associated with sarcoidosis has not yet been sufficiently clarified. Therefore, we retrospectively examined the effectiveness and safety of nintedanib in patients with pulmonary sarcoidosis who met PPF criteria. METHODS: Participants comprised six patients with sarcoidosis complicated by pulmonary fibrosis who were treated with nintedanib for PPF between 2020 and 2023. The forced vital capacity (FVC) change rate (mL/year) before and after nintedanib initiation was compared using the Wilcoxon signed-rank test. RESULTS: Among the six patients (5 male; median age at nintedanib initiation, 59 years), two had autoimmune pulmonary alveolar proteinosis. Oral prednisolone (2-7.5 mg daily) was simultaneously administered in five patients. The initial nintedanib doses were 200 mg (n = 3) and 300 mg daily (n = 3). The median annual declines in FVC before and after nintedanib initiation were -254.0 mL/year and -65.9 mL/year, respectively. Although this difference did not reach significance, the FVC increased in two patients and the annual FVC decline rate decreased in another patient after nintedanib initiation. Consolidation with traction bronchiectasis and honeycombing on chest computed tomography (CT) suggested improved FVC change and no improvement, respectively. Nintedanib was discontinued in one patient because of death. Diarrhea was observed in two patients. CONCLUSIONS: Our exploratory study yielded two hypotheses; a potential benefit of nintedanib on the FVC annual decline and a possible role for chest CT findings predicting nintedanib efficacy. Unexpected adverse events were not observed.

UNLABELLED: Inherited metabolic disorders (IMDs) are uncommon but clinically important causes of respiratory morbidity in children. Respiratory involvement may be the first or dominant manifestation, although it may precede, accompany, or follow systemic involvement. Because cough, dyspnea, hypoxemia, recurrent infection, abnormal chest imaging, and ventilatory failure are non-specific, affected children may initially be managed for common respiratory conditions, such as infection, asthma, aspiration, immunodeficiency, or non-metabolic diffuse lung disease, before the underlying IMD is recognized. This narrative mini-review presents a phenotype-driven approach to recognizing IMDs in pediatric respiratory practice. Rather than cataloguing rare disorders by metabolic pathway, it organizes respiratory involvement into practical clinical entry points: diffuse lung disease, pulmonary alveolar proteinosis-like disease, pulmonary vascular disease, recurrent infection or bronchiectasis, upper-airway or thoracic restriction, and neuromuscular respiratory failure and aspiration. For each pattern, we highlight extrapulmonary red flags and first-line biochemical, enzymatic, and genetic tests that may guide early etiological diagnosis. CONCLUSION: Careful recognition of respiratory phenotypes, combined with targeted metabolic and genomic evaluation, may shorten diagnostic delay and allow disease-specific treatment before irreversible pulmonary or neurological injury occurs. WHAT IS KNOWN: • IMDs can involve the respiratory system and may mimic common pediatric respiratory disorders or non-metabolic forms of childhood diffuse lung disease. • Respiratory manifestations may precede, accompany, or follow classical systemic features, and their temporal pattern varies among individual IMDs. WHAT IS NEW: • This mini-review organizes IMD-related respiratory involvement by presenting respiratory phenotype rather than by metabolic pathway. • It links respiratory entry points with extrapulmonary red flags and targeted biochemical, enzymatic, and genetic testing to support earlier diagnosis.

Secondary pulmonary alveolar proteinosis (PAP) is a rare but serious complication that can occur during immunosuppressive therapy for chronic graft-versus-host disease (GVHD). It is characterized by the intra-alveolar accumulation of surfactant due to drug-induced alveolar macrophage dysfunction. Managing PAP while maintaining control of active chronic GVHD represents a significant clinical challenge, particularly with regard to the optimal strategy for transitioning between immunosuppressive agents. A 25-year-old male with severe chronic GVHD developed a dry cough and bilateral ground-glass opacities (GGOs) after 2.8 years of ruxolitinib treatment. A lung biopsy confirmed secondary PAP. Ruxolitinib was tapered and replaced with belumosudil. Following the switch, the GGOs resolved rapidly within one month, and chronic GVHD remained stable, eventually allowing for successful corticosteroid tapering. Unlike ruxolitinib, belumosudil is thought to preserve the signaling pathways essential for alveolar macrophage activation. Transitioning to belumosudil may therefore represent a promising therapeutic strategy for managing secondary PAP in patients with chronic GVHD who require ongoing immunosuppressive therapy.

PURPOSE: This study evaluated the association of combining veno-venous extracorporeal membrane oxygenation (ECMO) with whole-lung lavage (WLL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) nebulization in pulmonary alveolar proteinosis (PAP), focusing on pulmonary function, oxygenation, lipid metabolism, and inflammatory modulation. METHODS: This retrospective cohort study included 40 PAP patients, categorized into WLL + GM-CSF (n = 20) and ECMO + WLL + GM-CSF (n = 20) groups according to the treatment they received. Outcomes included pulmonary function [diffusing capacity for carbon monoxide (DLCO%), forced vital capacity (FVC%)], arterial blood gas parameters [partial pressure of oxygen (PaO2), carbon dioxide (PaCO2), oxygen saturation (SaO2)], lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C)], inflammatory cytokines such as interleukin-6 (IL-6) and C-reactive protein, and functional assessments (Barthel Index score, 6-min walk distance). Correlations between lipids profiles, arterial blood gas parameters, pulmonary functional indicators, and inflammatory cytokines were evaluated using Pearson's or Spearman's correlation coefficients. RESULTS: The ECMO + WLL + GM-CSF group showed greater improvements in DLCO% and FVC%, significant increases in PaO2 and SaO2, and greater reductions in PaCO2, pro-inflammatory markers (IL-6, CRP), and lipid levels (TC, TG, LDL-C) compared to the WLL + GM-CSF group. In the ECMO + WLL + GM-CSF group, negative correlations were observed between serum TG and PaO2, DLCO%, and FVC%, and IL-6 inversely correlated with FVC%. The ECMO + WLL + GM-CSF group also achieved higher functional recovery based on the higher Barthel index scores and longer 6-min walk distance. CONCLUSION: ECMO-assisted WLL combined with GM-CSF was associated with greater improvements in pulmonary function and oxygenation, as well as greater reductions in serum lipid levels and inflammatory markers.