Search Results (50)

Rituximab-induced lung disease (R-ILD) is a rare but potentially serious complication most commonly reported in patients receiving rituximab as part of combination chemotherapy for hematologic malignancies. Pulmonary toxicity associated with rituximab monotherapy in autoimmune disease remains underrecognized. We present a case of organizing pneumonia occurring in a patient with stable rheumatoid arthritis treated with rituximab monotherapy. Existing literature suggests that most reported cases occur in the setting of combination therapy, making this presentation uncommon. This case underscores the importance of maintaining a high index of suspicion for drug-induced lung disease in patients receiving rituximab who develop unexplained respiratory symptoms despite stable autoimmune disease. Early recognition and intervention may result in favorable clinical and radiographic outcomes. Full article

Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies. Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, observational studies, and expert consensus addressing incidence, pathophysiology, imaging findings, and treatment approaches. Results: Noninfectious pulmonary sequelae of anti-neoplastic therapies encompass a broad spectrum of etiologies. DILI occurs in up to 30% with variable onset and severity. The patterns can be diverse but include interstitial pneumonitis, organizing pneumonia, and diffuse alveolar damage. RILI is common and influenced by the radiation dose, volume, and concurrent therapies, and it may have both acute and chronic clinical and radiographic presentations. Pleural disease may arise from radiation and other agents, and the determination of etiology can impact management. Pulmonary vascular disease arises from many different etiologies, including therapies such as tyrosine kinase inhibitors and proteosome inhibitors, thromboembolic disease, as well as rare processes, including pulmonary veno-occlusive disease. Other conditions such as transfusion-related lung injury, cryptogenic organizing pneumonia, and interstitial lung abnormalities can also further complicate the diagnosis. Conclusions: Noninfectious pulmonary complications related to cancer therapies are diverse and often indistinguishable from infectious or malignant processes. The integration of clinical history, imaging, and selective invasive testing are needed for a timely diagnosis. Management typically involves withdrawal of the offending agent and corticosteroids, with immunosuppressive therapy reserved for severe or refractory cases. The awareness of these entities and early recognition are critical to optimizing outcomes. Full article

Background/Objectives: Trastuzumab deruxtecan (T-DXd) is an effective antibody–drug conjugate for human epidermal growth factor receptor 2-expressing solid tumors; however, interstitial lung disease (ILD) remains a clinically significant adverse event. Although both clinical characteristics and genetic susceptibility have been implicated in drug-induced ILD, the factors specifically associated with T-DXd-induced ILD remain unclear. This study aimed to evaluate clinical and genetic factors associated with the development of ILD in patients treated with T-DXd. Methods: We retrospectively analyzed the clinical data of 54 patients treated with T-DXd. The baseline clinical and treatment-related characteristics of patients with ILD and those without were compared. Genome-wide single-nucleotide polymorphism (SNP) analyses with genotype imputation and targeted candidate SNP analyses were performed to evaluate genetic susceptibility. Results: ILD occurred in 15 patients (27.8%), with a median time to onset of 215 days (range, 48–1187). None of the baseline clinical or treatment-related factors were significantly associated with ILD development. Genome-wide analyses did not reveal any significant SNPs after correcting for multiple testing. Contrarily, a targeted analysis focusing on SNPs previously associated with drug-induced ILD identified one variant rs12625311 that was significantly associated with ILD in this cohort. Conclusions: In this exploratory study, baseline clinical characteristics alone were insufficient to discriminate the risk of ILD among patients treated with T-DXd. Although no high-penetrance genetic variants were identified, candidate-based genetic analyses suggested that host genetic factors may contribute to ILD susceptibility. Integrating genetic information with clinical assessment may help refine the risk stratification for T-DXd-induced ILD in future studies. Full article

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring. Full article

Idiopathic pulmonary fibrosis is a chronic, progressive, interstitial lung disease for which specific and effective drug therapies are still lacking. Lathyrol is a diterpene compound with broad pharmacological activities that can be extracted from the traditional Chinese medicine Leptochloa chinensis (L.) Nees. To investigate the anti-pulmonary fibrosis effect of lathyrol and its underlying mechanism. In vivo, a mouse model of pulmonary fibrosis was induced by bleomycin, treated with intraperitoneal injections of lathyrol. In vitro, myofibroblast conversion was induced in three fibroblast cell lines by stimulating them with TGF-β1, followed by treatment with lathyrol. Transcriptomic analysis was performed to assess the regulation of signaling pathways and gene expression patterns modulated by lathyrol. The effects of lathyrol on PPARγ activation, as well as on the nuclear translocation and ubiquitination of phosphorylated Smad3, were examined. The interaction among Nedd4, PPARγ, and phosphorylated Smad3 was detected. In vivo, lathyrol ameliorated pathological fibrosis in the lungs of mice with pulmonary fibrosis and this effect was blocked by a PPARγ inhibitor. In vitro, lathyrol inhibited the transdifferentiation of fibroblasts into myofibroblasts, and these effects were suppressed by either inhibiting PPARγ activation or specifically silencing the PPARγ gene. Lathyrol inhibited the nuclear translocation of phosphorylated Smad3 and promoted its ubiquitination, while also enhancing the interaction among Nedd4, PPARγ, and phosphorylated Smad3. These effects were abolished following the specific silencing of either PPARγ or Nedd4. In conclusion, Lathyrol inhibits myofibroblast transformation by suppressing TGF-β/Smad pathway activation through PPARγ activation, thereby exerting its anti-pulmonary fibrosis effects. Full article

Inflammatory bowel disease (IBD) management traditionally focuses on intestinal inflammation, yet extraintestinal manifestations can substantially impair patient quality of life. In this perspective, we emphasize the broad systemic impact of IBD—from highly prevalent conditions such as anemia, metabolic dysfunction-associated steatotic liver disease, or fatigue to rare but severe complications like interstitial lung disease and drug-induced glomerulonephritis. We review underlying mechanisms linking gut inflammation to distant organs, including immune dysregulation, microbial translocation, and metabolic derangements. Advances in diagnostics—such as biomarker panels, high-resolution imaging, and genomic/microbiome profiling—enable early detection and risk stratification. Emerging therapies, including targeted biologics (anti-TNF, anti-integrin, anti-IL-23), JAK and S1P modulators, precision nutrition, and microbiome modulation, offer new opportunities to address systemic inflammation. A multidisciplinary framework integrating gastroenterology with hepatology, hematology, neurology, nephrology, endocrinology, dermatology, pulmonology, and cardiology is essential to recognize hidden complications, facilitate timely intervention, and deliver personalized, comprehensive care for IBD. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease (ILD) with a poor prognosis. The prognosis of ILDs showing progressive pulmonary fibrosis (PPF) is poor, similar to that of IPF. Diarrhea is the most frequently observed adverse event in ILDs treated with nintedanib. Managing diarrhea is important for maintaining nintedanib use and improving the prognosis of ILDs. Methods: Between October 2022 and March 2025, we enrolled patients with severe nintedanib-induced diarrhea that was uncontrolled by loperamide and/or probiotics. Other drugs were administered to control diarrhea, and the patients were prospectively observed to evaluate stool frequency, stool form score (scores 3, 2, and 1 for watery stool, soft stool without form, and soft stool with form, respectively), quality of life (QOL) using the Japanese version of the irritable bowel syndrome (IBS)-QOL questionnaire, adverse events, and laboratory findings. Results: Eleven patients (IPF, n = 5; PPF, n = 6) were enrolled, and all patients were treated with ramosetron, a 5-hydroxytryptamine type 3 receptor (5-HT₃) antagonist. Ramosetron was terminated within 3 weeks, before sufficient evaluation, because of insufficient efficacy (n = 1) and the discontinuation of nintedanib due to pneumothorax (n = 1). Stool frequency and stool form scores decreased significantly after the initiation of ramosetron therapy; however, IBS-QOL did not improve significantly. IBS-QOL correlated with shortness of breath scores but not with stool frequency. No prominent adverse events were associated with ramosetron administration. Conclusions: Ramosetron, a 5-HT₃ antagonist, improved stool frequency and stool form in patients with severe nintedanib-induced diarrhea. Full article

Objectives: Endometrial cancer is the most common gynaecologic malignancy, and its mortality rate is rising. Advanced or recurrent disease remains challenging because historically there have been limited therapeutic options. We aim to describe a complete and durable response to the HER2-directed antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in a heavily pretreated patient with HER2-positive, mismatch-repair-deficient metastatic serous endometrial cancer. Methods: A 72-year-old woman underwent hysterectomy, bilateral salpingo-oophorectomy, and staging procedures for FIGO stage IIIA, high-grade serous papillary endometrial carcinoma. Tumour profiling revealed dMMR, a p53 abnormal pattern, and HER2 overexpression (IHC 3+). She received carboplatin/paclitaxel plus avelumab, followed by pegylated liposomal doxorubicin and weekly paclitaxel. After progression on paclitaxel, off-label T-DXd was initiated. Molecular data (FoundationOne CDx) were collected, along with and serial imaging and CA125 assessments. Results: The patient developed cough after two cycles of T-DXd; interstitial lung disease was excluded, and treatment resumed with steroid cover. By December 2024, PET/CT demonstrated complete metabolic response, with resolution of vaginal-vault and para-aortic lesions and normalisation of CA125. Real-world progression-free survival exceeded eight months, with ongoing symptom improvement. Treatment was generally well tolerated; the principal adverse event was grade 3 neutropenia requiring dose reduction. No cardiotoxicity or interstitial lung disease occurred. Conclusions: This case illustrates that T-DXd can induce deep and durable remission in HER2-positive, dMMR metastatic serous endometrial cancer after multiple lines of therapy. It adds real-world evidence supporting further investigation of HER2-directed antibody–drug conjugates in gynaecologic malignancies, and underscores the need for confirmatory trials and refined biomarker-driven patient selection. Full article

Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates glycolytic pathways in oncogenesis, its specific contributions to fibroblast activation and therapeutic potential in PF pathogenesis remain undefined. This study elucidates the functional role of SIK2 in PF and assesses its viability as a therapeutic target. Methods: SIK2 expression/localization in fibrosis was assessed by Western blot and immunofluorescence. Fibroblast-specific Sik2 KO mice evaluated effects on bleomycin-induced fibrosis. SIK2’s role in fibroblast activation and glucose metabolism impact (enzyme expression, metabolism assays, metabolites) were tested. SIK2 inhibitors were screened and evaluated therapeutically in fibrosis models. Results: It demonstrated significant SIK2 upregulation, specifically within activated fibroblasts of fibrotic lungs from both PF patients and murine models. Functional assays demonstrated that SIK2 is crucial for fibroblast activation, proliferation, and migration. Mechanistically, SIK2 enhances fibroblast glucose metabolism by increasing the expression of glycolysis-related enzymes. Additionally, this study demonstrated that the SIK2 inhibitor YKL06-061 effectively inhibited PF in both bleomycin and FITC-induced PF mouse models with the preliminary safety profile. Furthermore, we identified a novel therapeutic application for the clinically approved drug fostamatinib, demonstrating it inhibits fibroblast activation via SIK2 targeting and alleviates PF in mice. Conclusions: Our findings highlight SIK2 as a promising therapeutic target and provide compelling preclinical evidence for two distinct anti-fibrotic strategies with significant potential for future PF treatment. Full article

Background: Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by chronic inflammation and excessive extracellular matrix deposition, with fibrocytes playing a pivotal role in fibrotic remodeling. This study aimed to identify upstream molecular mechanisms regulating fibrocyte recruitment and activation, focusing on the SPHK1 pathway as a potential therapeutic target. Methods: We utilized Mendelian Randomization and phenome-wide association analyses on genes involved in sphingolipid metabolism to identify potential regulators of idiopathic pulmonary fibrosis (IPF). A bleomycin-induced mouse model was employed to examine the role of the SPHK1-S1P axis in fibrocyte recruitment, using SKI-349 to target SPHK1 and FTY720 to antagonize S1PR1. Results: Our analyses revealed SPHK1 as a significant genetic driver of IPF. Targeting SPHK1 and S1PR1 led to a marked reduction in fibrocyte accumulation, collagen deposition, and histopathological fibrosis. Additionally, PAXX and RBKS were identified as downstream effectors of SPHK1. Our protein–protein interaction mapping indicated potential therapeutic synergies with existing anti-fibrotic drug targets. Conclusions: Our findings establish the SPHK1-S1P-S1PR1 axis as a key regulator of fibrocyte-mediated pulmonary fibrosis and support SPHK1 as a promising therapeutic target. Full article

Nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, has been associated with rare but potentially serious pulmonary toxicity, which can present in acute, subacute, or chronic forms. Acute toxicity typically manifests in the form of hypersensitivity pneumonitis, which is characterized by fever, dyspnea, and eosinophilia, often resolving rapidly after drug discontinuation. However, chronic toxicity can lead to interstitial lung disease with progressive fibrosis, causing significant and sometimes irreversible pulmonary impairment. The pathophysiology of nitrofurantoin-induced lung injury is thought to involve oxidative stress, immune-mediated mechanisms, and direct cytotoxic effects; however, the exact pathways remain incompletely understood. Clinical diagnosis is challenging due to nonspecific symptoms that often resemble other respiratory conditions, leading to delays in recognition and treatment. Radiographic findings vary, with acute cases showing diffuse ground-glass opacities, while chronic cases may demonstrate reticular interstitial changes and fibrosis. The discontinuation of nitrofurantoin is the primary intervention, but corticosteroids may be beneficial, particularly in chronic cases with persistent inflammation or fibrosis, though their efficacy remains uncertain. Given the risk of long-term respiratory complications, heightened awareness among healthcare providers is essential for early diagnosis and intervention. Future research is needed to better define risk factors, improve diagnostic criteria, and explore alternative treatment strategies that mitigate the potential for pulmonary toxicity while maintaining effective antimicrobial therapy. This review explores the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for nitrofurantoin-induced pulmonary toxicity. Full article

Silicosis is an interstitial lung disease (ILD) caused by prolonged inhalation of silica particles. Acute lung injury (ALI) is a critical clinical syndrome involving bilateral lung infiltration and acute hypoxic respiratory failure. However, there is currently no effective treatment for these two diseases. Previous research has established that cyclic adenosine monophosphate (cAMP) is pivotal in the pathogenesis of silicosis and acute lung injury. Phosphodiesterase 4 (PDE4) is a hydrolase enzyme of cAMP, and BI 1015550, as an inhibitor of PDE4B, is expected to be a candidate drug for treating both. BI 1015550 has shown certain anti-inflammatory and anti-fibrotic properties in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF), but there is a lack of research on silicosis and acute lung injury. In this research, we successfully synthesized BI 1015550 autonomously and demonstrated that it could significantly improve lung fibrosis and inflammation in a silica-induced silicosis mouse model. Furthermore, we found that BI 1015550 could also alleviate lung inflammation in a Lipopolysaccharide (LPS)-induced acute lung injury mouse model. The mechanism of action may involve the regulation of cAMP-related signaling pathways. Full article

Background: The degree of exercise-induced oxygen desaturation and outcomes following antifibrotic drug therapy in asymptomatic patients with fibrosing interstitial lung disease (FILD) remain unclear. Methods: We compared clinical data, incidence of annual FILD progression, overall survival, and tolerability after initiating nintedanib between 58 patients with dyspnea and 18 patients without. Annual FILD progression was defined as >10% decrease in forced vital capacity (FVC), >15% decrease in diffusing capacity of the lungs for carbon monoxide (D_LCO), developing acute exacerbations, or FILD-related death within 1 year of starting nintedanib. Outcomes between the two groups were adjusted for covariates, including age, gender, FVC, D_LCO, and diagnosis of idiopathic pulmonary fibrosis, all known prognostic factors for FILD. Results: In 6-min walk test, incidence of decrease to <90% of SpO₂ was significantly lower in non-dyspnea group than in dyspnea group (24% vs. 55%, p = 0.028), but incidence of >4% decreases showed no significant difference (71% vs. 89%, p = 0.11) The incidence of annual progression was significantly lower in non-dyspnea than in dyspnea group (17% vs. 53%, adjusted p = 0.026). The relative change in D_LCO was significantly slower in non-dyspnea group (adjusted p = 0.036), but FVC was not (adjusted p = 0.067). Overall survival was longer in non-dyspnea group (adjusted p = 0.0089). The discontinuation rate and therapeutic period of nintedanib were not significantly different between the groups. Conclusions: Asymptomatic patients with FILD have severe exercise-induced oxygen desaturation and better outcomes after nintedanib therapy than symptomatic patients. Antifibrotic drug therapy should not be avoided solely because of a lack of symptoms. Full article

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease with unknown etiology, characterized by chronic inflammation and tissue scarring. Although, Pirfenidone and Nintedanib slow the disease progression, no currently available drugs or therapeutic interventions address the underlying cause, highlighting the unmet medical need. A matricellular protein, Wnt-1-induced secreted protein 1 (WISP1), also referred to as CCN4 (cellular communication network factor 4), is a secreted multi-modular protein implicated in multi-organ fibrosis. Although the precise mechanism of WISP1-mediated fibrosis remains unclear, emerging evidence indicates that WISP1 is profibrotic in nature. While WISP1-targeting therapy is applied in the clinic for fibrosis, detailed interrogation of WISP1-mediated fibrogenic molecular and biological pathways is lacking. Here, for the first time, using NanoString^® technology, we identified a novel WISP1-associated profibrotic gene signature and molecular pathways potentially involved in the initiation and progression of fibrosis in primary human dermal and lung fibroblasts from both healthy individuals and IPF patients. Our data demonstrate that WISP1 is upregulated in IPF-lung fibroblasts as compared to healthy control. Furthermore, our results confirm that WISP1 is downstream of the transforming growth factor-β (TGFβ), and it induces fibroblast cell proliferation. Additionally, WISP1 induced IL6 and CCL2 in fibroblasts. We also developed a novel, combined TGFβ and WISP1 in vitro system to demonstrate a role for WISP1 in the progression of fibrosis. Overall, our findings uncover not only similarities but also striking differences in the molecular profile of WISP1 in human fibroblasts, both during the initiation and progression phases, as well as in disease-specific context. Full article

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting and detecting DIILD are limited. Therefore, we aimed to evaluate the feasibility of ¹⁸F-FDG PET/CT, PET radiomics, and machine learning in distinguishing DIILD in an explorative pilot study. Methods: Eighteen Hodgkin’s lymphoma (HL) patients, of whom 10 developed DIILD after treatment with bleomycin, were retrospectively included. Five diffuse large B-cell lymphoma (DLBCL) patients were included as a control group since they were not treated with bleomycin. All patients underwent ¹⁸F-FDG PET/CT scans before (baseline) and during treatment (interim). Structural changes were assessed by changes in Hounsfield Units (HUs). The ¹⁸F-FDG PET scans were used to assess metabolic changes by examining the feasibility of 504 radiomics features, including the mean activity of the lungs (SUVmean). A Random Forest (RF) classifier evaluated the identification and prediction of DIILD based on PET radiomics features. Results: HL patients who developed DIILD showed a significant increase in standard SUV metrics (SUVmean; p = 0.012, median increase 37.4%), and in some regional PET radiomics features (texture strength; p = 0.009, median increase 101.6% and zone distance entropy; p = 0.019, median increase 18.5%), while this was not found in HL patients who did not develop DIILD and DLBCL patients. The RF classifier correctly identified DIILD in 72.2% of the patients and predicted the development of DIILD correctly in 50% of the patients. There were no significant differences in HUs over time within all three patient groups. Conclusions: Our explorative longitudinal pilot study suggests that certain regional ¹⁸F-FDG PET radiomics features can effectively identify DIILD in HL patients treated with bleomycin, as significant longitudinal increases were observed in SUVmean, texture strength, and zone distance entropy after the development of DIILD. The metabolic activity of these features did not significantly increase over time in DLBCL patients and HL patients who did not develop DIILD. This indicates that ¹⁸F-FDG PET radiomics, with and without machine learning, might serve as potential biomarkers for detecting DIILD. Full article