BACKGROUND: Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis.
METHODS: Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages.
RESULTS: The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis.
CONCLUSIONS: CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides.
CONCLUSIONS: Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

Respiratory syncytial virus (RSV) usually causes acute respiratory tract infection in infants. In recent years, it has gradually become an important pathogen of lower respiratory tract infection in elderly people with an underlying disease. However, at present, the treatment of severe RSV pneumonia in adults is unclear, and organizing pneumonia (OP) after severe RSV infection has rarely been reported. We reported a 76-year-old man with multiple chronic heart and lung diseases who presented with fever, cough and progressive dyspnea. Finally, severe RSV pneumonia was diagnosed after his nasopharyngeal swabs and bronchoalveolar lavage metagenomic next-generation sequencing tests were positive for RSV. After combined treatment with oral ribavirin, intravenous immunoglobulin and corticosteroids, the patient\'s condition largely resolved, and he was discharged. However, when the corticosteroids were gradually tapered, the disease relapsed twice, and the patient experienced fever and aggravated dyspnea. Despite the lack of pathological evidence, we highly suspected organizing pneumonia secondary to severe RSV pneumonia based on the typical imaging manifestations and the clinical characteristics of a good response to corticosteroids. Finally, this patient was successfully treated with a course of corticosteroids and followed up for 14 months in total.

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

OBJECTIVE: To evaluate the performance of a clinical-radiomics model for differentiating focal organizing pneumonia (FOP) and lung adenocarcinoma (LUAD).
METHODS: We retrospectively analyzed the data of 60 patients with FOP confirmed by postoperative pathology at the First Medical Center of the Chinese PLA General Hospital from January, 2019 to December, 2022, who were matched with 120 LUAD patients using propensity score matching in a 1∶2 ratio. The independent risk factors for FOP were identified by logistic regression analysis of the patients\' clinical data. The cohort was divided into a training set (144 patients) and a test set (36 patients) by random sampling. Python 3.7 was used for extracting 1835 features from CT image data of the patients. The radiographic features and clinical data were used to construct the model, whose performance was validated using ROC curves in both the training and test sets. The diagnostic efficacy of the model for FOP and LUAD was evaluated and a diagnostic nomogram was constructed.
RESULTS: Statistical analysis revealed that an history of was an independent risk factor for FOP (P=0.016), which was correlated with none of the hematological findings (P > 0.05). Feature extraction and dimensionality reduction in radiomics yielded 30 significant labels for distinguishing the two diseases. The top 3 most discriminative radiomics labels were GraylevelNonUniformity, SizeZoneNonUniformity and shape-Sphericity. The clinical-radiomics model achieved an AUC of 0.909 (95% CI: 0.855-0.963) in the training set and 0.901 (95% CI: 0.803-0.999) in the test set. The model showed a sensitivity of 85.4%, a specificity of 83.5%, and an accuracy of 84.0% in the training set, as compared with 94.7%, 70.6%, and 83.3% in the test set, respectively.
CONCLUSIONS: The clinical-radiomics nomogram model shows a good performance for differential diagnosis of FOP and LUAD and may help to minimize misdiagnosis-related overtreatment and improve the patients\' outcomes.

OBJECTIVE: Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM) clinical phenotypes. The aim of this study is to explicate the clinical and immunological features of MSAs-negative DM patients.
METHODS: A total of 515 individuals diagnosed with DM was screened from 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed.
RESULTS: MSAs-negative DM patients were categorized into two groups: MAAs-negative (MSAs (-)/MAAs (-)) group and MAAs-positive (MSAs (-)/MAAs (+)) group. The percentage of Raynaud\'s phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positive DM patients and MSAs (-)/MAAs (-) DM patients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumonia and usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among total CD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onset age, higher level of carcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients.
CONCLUSIONS: Compared with MSAs-positive group, MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DM patients:   • The MSAs (-)/MAAs (+) DM patients demonstrated a higher prevalence of organizing pneumonia (OP) and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid.   • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients.   • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negative patients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients.   • MSAs-negative DM patients had a more favorable prognosis than MSAs-positive DM patients. A multivariable regression analysis revealed the advanced onset age, high CEA levels, and RP-ILD were risk factors for mortality in DM patients.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare acute or subacute interstitial lung disorder characterized by the deposition of fibrin within the alveoli and organizing pneumonia with a patchy distribution. The clinical features of AFOP are nonspecific, and it is often misdiagnosed as pneumonia, cancer, tuberculosis, or other lung disorders.
METHODS: In this case report, a 58-year-old woman presented with chest tightness, shortness of breath, cough and sputum. A chest CT scan showed multiple patchy shadows in both lungs. She was initially diagnosed with community-acquired pneumonia. Her purified protein derivative skin test was positive, but sputum was negative for acid-fast bacilli.
METHODS: AFOP was diagnosed by bronchoscopic lung biopsy and histopathology.
METHODS: Following AFOP diagnosis, all anti-infective drugs were discontinued, and replaced by methylprednisolone and prednisone.
RESULTS: After 1 week of treatment with methylprednisolone 40 mg daily, the patient chest CT and clinical symptoms improved. After 1 month, the patient symptoms had demonstrated dramatic improvement and CT scan revealed complete absorption of lesions in both lungs. After 5 months of follow-up, the patient symptoms completely disappeared.
CONCLUSIONS: Acute AFOP is an uncommon lung condition with poor prognosis; hence, early diagnosis and identification are particularly important. Definitive diagnosis requires histopathological findings. Currently, there is no unified treatment guideline for AFOP, and treatment must be tailored based on the etiology and severity of each individual patient disease. Subacute AFOP shows a good response to corticosteroid treatment.

BACKGROUND: Organizing pneumonia (OP) is a rare interstitial lung disease. Secondary organizing pneumonia (SOP) caused by Mycobacterium tuberculosis (MTB) is extremely rare. Migratory MTB-associated SOP is more deceptive and dangerous. When insidious tuberculosis (TB) is not recognized, SOP would be misdiagnosed as cryptogenic organizing pneumonia (COP). Use of steroid hormone alone leads to the progression of TB foci or even death. Clues of distinguishing atypical TB at the background of OP is urgently needed.
METHODS: A 56-year-old female patient was hospitalized into the local hospital because of cough and expectoration for more than half a month. Her medical history and family history showed no relation to TB or other lung diseases. Community-acquired pneumonia was diagnosed and anti-infection therapy was initialized but invalid. The patient suffered from continuous weigh loss. More puzzling, the lesions were migratory based on the chest computed tomography (CT) images. The patient was then transferred to our hospital. The immunological indexes of infection in blood and pathogenic tests in sputum and the bronchoalveolar lavage fluid were negative. The percutaneous lung puncture biopsy and pathological observation confirmed OP, but without granulomatous lesions. Additionally, pathogen detection of the punctured lung tissues by metagenomics next generation sequencing test (mNGS) were all negative. COP was highly suspected. Fortunately, the targeted next-generation sequencing (tNGS) detected MTB in the punctured lung tissues and MTB-associated SOP was definitely diagnosed. The combined therapy of anti-TB and prednisone was administrated. After treatment for 10 days, the partial lesions were significantly resorbed and the patient was discharged. In the follow-up of half a year, the patient was healthy.
CONCLUSIONS: It is difficult to distinguish SOP from COP in clinical practice. Diagnosis of COP must be very cautious. Transient small nodules and cavities in the early lung image are a clue to consider TB, even though all pathogen tests are negative. tNGS is also a powerful tool to detect pathogen, ensuring prompt diagnosis of TB-related SOP. For clinicians in TB high burden countries, we encourage them to keep TB in mind before making a final diagnosis of COP.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of \"fibrin balls\" distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease.
METHODS: We present the case of a 44-year-old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis.
CONCLUSIONS: Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient\'s symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy.

We report the case of a 59-year-old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C-reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen-B27 were unremarkable. Whole body bone scintigraphy via technetium 99m-methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.