Micronodular Pattern of Organizing Pneumonia or Hypersensitivity Pneumonia Induced by an Immune Checkpoint Inhibitor?

Takimoto, Takayuki

doi:10.1164/rccm.202005-2104le

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…There were no typical features of HP, such as granuloma, and were non-specific features of inflammation. It is difficult to completely discriminate pathological HP from the micronodular pattern of organizing pneumonia, which shows radiographically similar manifestations to HP but pathologically indicates organizing pneumonia [ [35] , [36] , [37] ]. In the clinical setting, bronchoscopy or surgical lung biopsy is not always performed because of respiratory failure.…”

Section: Discussionmentioning

confidence: 99%

Drug-related pneumonitis with radiographic hypersensitivity pneumonitis pattern: Three case series

Nakamura

Takimoto

Kobayashi

et al. 2021

Respiratory Medicine Case Reports

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Novel therapies have recently emerged for various diseases, and the management of drug-related pneumonitis (DRP) has become increasingly important. In particular, the hypersensitivity pneumonitis (HP) pattern of DRP has been increasingly recognized due to development of new therapeutic strategies, such as immunotherapy. However, literature describing detailed clinical cases is still lacking. Herein, we report three cases of DRP with typical HP radiographic pattern. These patients were treated with different drugs, namely nano albumin-bound (nab)-paclitaxel, everolimus, or nivolumab, but had common clinical features, including a good prognosis.

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Section: Discussionmentioning

confidence: 99%

Drug-related pneumonitis with radiographic hypersensitivity pneumonitis pattern: Three case series

Nakamura

Takimoto

Kobayashi

et al. 2021

Respiratory Medicine Case Reports

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“…The innate and adaptive immune systems defend the host against diseases through different mechanisms, thus facilitating the emergence of simultaneous immunotherapies against OP. 7 Innate immunity relies on a diverse array of immune cells, such as macrophages, neutrophils, monocytes, eosinophils, basophils and natural killer (NK) cells, which collectively safeguard the body's equilibrium through their inherent defensive capabilities. The function of these immune cells influences the progression of OP, as revealed by the typical severe OP that develops after COVID‐19 in an immunocompromised teenager.…”

Section: Introductionmentioning

confidence: 99%

Integrated multi‐omics profiling landscape of organising pneumonia

Tang,

Chu,

et al. 2024

Clinical & Translational Med

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BackgroundOrganising 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.MethodsComprehensive 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.ResultsThe 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.ConclusionsCD36 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.HighlightsOur 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.

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“…Recently, immunotherapy has become a standard of care in oncology [ 7 , 11 ], and DRP-HP induced by immune checkpoint inhibitors (ICIs) has been reported up to 16–22% of all ICI-related pneumonitis [ 11 , 12 ]. Thus, in terms of the clinical management of the disease, it is important to distinguish DRP-HP from other diseases, including common non-fibrotic (inhalation) or infectious diseases [ 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Biomarkers in a Radiological Pattern of Non-Fibrotic Hypersensitivity Pneumonitis: Implications for Mechanistic Difference and Differential Diagnosis

Takimoto

Nakamura

2022

Diseases

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Hypersensitivity pneumonitis (HP) is a consequence of immune-mediated reactions caused by recurrent exposure to environmental agents. Recently, clinical practice guidelines for the diagnosis of HP were published and increased interest in HP. On the other hand, novel therapies have recently emerged for various diseases, and the management of drug-related pneumonitis (DRP) has become increasingly important. Among DRP, the HP pattern (DRP-HP) shows small, poorly defined centrilobular nodules with or without widespread areas of ground-glass opacity or lobular areas of decreased attenuation and vascularity. A similar radiological pattern of non-fibrotic HP can be induced, irrespective of inhalation (non-fibrotic HP) or intravenous administration (DRP-HP). However, their difference has not been well described, although the distribution of lesions in the lungs was slightly different between these two conditions. In this review, we focus on serum biomarkers of lung epithelial cells in order to investigate the difference between DRP-HP and non-fibrotic HP (common-HP). Serum levels of Krebs von den Lungen 6 (KL-6) might be relatively lower (occasionally normal) in DRP-HP than in common-HP, implying a mechanistic difference. KL-6 could be useful in discriminating between DRP and non-fibrotic HP (common type).

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Micronodular Pattern of Organizing Pneumonia or Hypersensitivity Pneumonia Induced by an Immune Checkpoint Inhibitor?

Cited by 3 publications

References 6 publications

Drug-related pneumonitis with radiographic hypersensitivity pneumonitis pattern: Three case series

Drug-related pneumonitis with radiographic hypersensitivity pneumonitis pattern: Three case series

Integrated multi‐omics profiling landscape of organising pneumonia

Serum Biomarkers in a Radiological Pattern of Non-Fibrotic Hypersensitivity Pneumonitis: Implications for Mechanistic Difference and Differential Diagnosis

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