Low-flow extracorporeal carbon dioxide removal (ECCO2R) may be useful when severe hypercapnia limits ultra-protective ventilation but full venovenous extracorporeal membrane oxygenation (VV-ECMO) is not pursued. We describe a 68 year old man with metastatic lung adenocarcinoma who developed amivantamab-associated immune-related interstitial lung disease complicated by acute respiratory distress syndrome (ARDS) and active airway hemorrhage. After endotracheal intubation, the dominant physiologic problem was hypercapnic acidosis (pH 7.12; PaCO2 83.4 mm Hg) with very poor respiratory system compliance, whereas oxygenation impairment was moderate (PaO2/FiO2 160 mm Hg). Because of terminal malignancy and the burden of large-bore cannulation, VV-ECMO was not pursued. Electrical impedance tomography showed no benefit from prone positioning. A hybrid strategy was then initiated: inhaled nitric oxide to improve ventilation-perfusion (V/Q) matching and ECCO2R to control carbon dioxide clearance. Within 2 hours, PaCO2 fell to 60.7 mm Hg and pH rose to 7.32; oxygenation also improved. The circuit remained functional for 13 days without recurrent airway bleeding or documented circuit thrombosis. This case illustrates the feasibility of concurrently applying inhaled nitric oxide and low-flow ECCO2R as a physiology-guided, low-intensity rescue approach in a highly selected patient when VV-ECMO was not pursued.

Purpureocillium lilacinum (P. lilacinum) is a rare opportunistic mold that predominantly affects immunocompromised hosts and exhibits intrinsic resistance to several conventional antifungal agents. Pulmonary infection is uncommon, and only a limited number of cases have been reported in patients with autoimmune connective tissue diseases receiving immunosuppressive therapy. We report a 37-year-old male hospital social worker with anti-Jo-1-positive myositis-associated interstitial lung disease receiving corticosteroids and mycophenolate mofetil who presented with hemoptysis and dyspnea. Computed tomography of the thorax demonstrated bilateral ground-glass opacities, multilobar consolidation, tree-in-bud nodularity, and mediastinal lymphadenopathy. Bronchoalveolar lavage fungal culture yielded P. lilacinum, with species identification confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Because second-generation triazoles were unavailable at the time of diagnosis, treatment was initiated with oral itraconazole (200 mg twice daily) together with temporary cessation of immunosuppressive therapy. The patient experienced rapid clinical improvement, with resolution of the acute pulmonary infiltrates on follow-up computed tomography after three months and a negative follow-up sputum fungal culture after six months of therapy. Immunosuppressive treatment was subsequently reintroduced without recurrence of infection or progression of interstitial lung disease during follow-up. This case highlights the diagnostic challenge of probable pulmonary P. lilacinum infection in immunosuppressed patients with myositis-associated interstitial lung disease. It demonstrates a favorable clinical course during prolonged oral itraconazole therapy when preferred antifungal agents were unavailable. However, treatment outcomes should be interpreted with caution, as this is a single case, and concomitant antibacterial therapy, along with temporary modification of immunosuppressive therapy, may also have contributed to recovery.

Periodontitis has been linked to several respiratory diseases such as chronic obstructive pulmonary disease, asthma, and lung cancer; however, the role of periodontal health status and matrix metalloproteinases (MMPs) in interstitial lung diseases (ILDs) remains largely unexplored. The present study aimed to investigate periodontal health and evaluate serum and salivary levels of MMP-7, MMP-8, and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with ILDs. A total of 75 individuals were included and divided equally into three groups: healthy controls, patients with chronic periodontitis, and patients with ILDs. Demographic factors such as age, gender, and socioeconomic status were recorded, along with clinical parameters including plaque index, gingival index, probing pocket depth, and clinical attachment level. The findings revealed that levels of MMP-7 and MMP-8 were significantly elevated in both the periodontitis and ILD groups compared to healthy controls, while TIMP-1 did not show notable variation among groups. Clinical periodontal parameters were also higher in patients with ILDs as well as those with chronic periodontitis. These results suggest a possible link between ILD and chronic periodontitis, both from clinical and biochemical perspectives. The study provides pioneering evidence in the emerging field of oral-systemic research, emphasizing the need for further investigations with larger sample sizes and interventional designs to strengthen the evidence base and explore possible genetic associations underlying this relationship.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible interstitial lung disease characterised by excessive collagen deposition, aberrant tissue remodelling, and impaired gas exchange, ultimately leading to respiratory failure and death. IPF carries a poor prognosis, with limited therapeutic options; currently approved treatments slow disease progression but do not reverse established fibrosis, and lung transplantation remains the only definitive therapy. Moreover, the prevalence and incidence of IPF continue to rise worldwide. These challenges underscore the urgent need to better understand the pathological mechanisms driving IPF, enabling the development of more effective therapeutic strategies. Robust and appropriate animal models are essential for investigating disease pathogenesis and therapeutic response. Although multiple murine models of pulmonary fibrosis are widely used, no single model fully recapitulates the clinical, pathological and temporal features of human IPF. In this review, we systematically summarise commonly used and new murine models of pulmonary fibrosis, emphasising induction methods, technical requirements, the time course of fibrosis development and persistence of fibrosis. Additionally, we highlight the advantages and limitations of each model, discuss how they inform mechanistic and translational studies, and provide practical guidance for selecting appropriate experimental systems based on specific scientific questions, with the goal of improving rigor and relevance in preclinical pulmonary fibrosis research.

Interstitial lung diseases (ILDs) comprise a heterogeneous group of lung disorders marked by progressive fibrosis and increased vulnerability to respiratory infections, which can trigger sudden outbreaks and worsen outcomes. Vaccination is a key preventive strategy in ILD patients to reduce infection-related morbidity and mortality. This review examines the importance of immunisation in individuals with ILDs, with particular emphasis on influenza, pneumococcal and severe acute respiratory syndrome coronavirus 2 vaccines endorsed by major health organisations. Despite evidence of their effectiveness, vaccination rates among patients with ILD remain low. Tailored vaccine strategies may enhance protection in this group. Additionally, although data are limited, immunisations against respiratory syncytial virus, Haemophilus influenzae, varicella-zoster virus, and pertussis may provide additional protection, particularly in older adults and those receiving immunosuppressive therapy. Hepatitis B vaccination should also be considered for patients on immunosuppressive therapies to prevent infection. Healthcare providers should actively encourage vaccination and address obstacles to immunisation in ILD patients. More research is necessary to assess the safety, effectiveness and optimal vaccination approaches for this vulnerable group. Ultimately, implementing systematic vaccination programmes and clear clinical guidelines is essential to improve preventive care and health outcomes for those with ILDs.

Alveolar regeneration failure due to alveolar stem cell senescence is a defining feature of idiopathic pulmonary fibrosis (IPF), yet the epithelial mechanisms underlying this dysfunction remain incompletely understood. Recent single-cell and lineage-tracing studies have identified distinct transitional epithelial states, such as pre-alveolar type-1 transitional cells, damage-associated transient progenitors, and alveolar-basal intermediates, which normally serve as intermediates during type 2 alveolar cell (AT2) to type 1 alveolar cell (AT1) differentiation. While these states are transient and successfully resolved during acute lung injury, these populations persist abnormally in IPF lungs, exhibiting features of senescence, cell-cycle arrest, and impaired differentiation.We review recent evidence showing how premature alveolar epithelial senescence, suppression of developmental regenerative programmes, and sustained transforming growth factor-β signalling within the fibrotic niche contribute to this disruption. These factors promote the accumulation of dysfunctional transitional cells, such as cytokeratin (KRT)8[+]/KRT17[+] basaloid cells, which fail to regenerate alveolar epithelium and instead contribute to fibrosis and bronchiolisation through pathological crosstalk with macrophages and fibroblasts. Notably, similar transitional states appear in COVID-19-associated acute respiratory distress syndrome, but they typically exhibit minimal features of senescence and resolve during regeneration, underscoring the pathological importance of accelerated epithelial senescence in IPF.Understanding the molecular checkpoints that regulate transitional cell fate may offer novel strategies to restore regenerative capacity in fibrosing lung diseases.

Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by repetitive alveolar injury leading to parenchymal thickening, scarring, and respiratory impairment. Current rodent models, particularly those utilizing bleomycin (BLEO), have limited translational relevance to human idiopathic pulmonary fibrosis (IPF) due to anatomical differences such as the absence of respiratory bronchioles. To address this limitation, we developed a large-animal model of pulmonary fibrosis in ferrets, which possess respiratory bronchioles similar to those in humans. Three-month-old wild-type ferrets received intratracheal instillation of BLEO. Lungs were harvested 8 weeks post-treatment for micro-computed tomography (micro-CT) and histological evaluation. Owing to the limited spatial resolution of multidetector CT (MDCT) in visualizing the ferret small airways, excised lungs were imaged ex vivo using a micro-CT scanner at controlled airway pressures (0 cmH2O and 25 cmH2O) to simulate expiratory and inspiratory conditions. Micro-CT imaging revealed distinct structural differences between normal and BLEO-treated ferret lungs. Normal lungs displayed low attenuation and preserved architecture, whereas BLEO-treated lungs showed markedly increased attenuation consistent with fibrosis. Features characteristic of human fibrotic lung disease, including honeycombing with cystic spaces, thickened interlobular septa, and ground-glass opacities indicative of early fibrotic or inflammatory changes, were evident. Using quantitative micro-CT analysis, it was observed that airways in BLEO-treated ferret lungs exhibited significantly reduced radial expansion, longitudinal stretching, and volume change at both applied air pressures. Furthermore, generation-matched analysis revealed significant thickening of airway walls in regions with visually apparent fibrosis. Histological assessment, including Masson's trichrome staining, confirmed extensive collagen deposition and fibrosis. This study demonstrates that BLEO-treated ferrets develop radiologic, mechanical, and histopathologic features resembling human pulmonary fibrosis. Furthermore, micro-CT enables high-resolution assessment of fibrotic distribution, airway dynamics, and lung volume changes. These findings highlight the potential of the ferret as a translational model for studying PF pathogenesis and evaluating novel therapeutic strategies.

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic lung disease with an unclear etiology, and the contribution of glycosylation-related genes (GRGs) to its pathogenesis remains poorly understood. This study focuses on elucidating the potential mechanisms of GRGs in IPF, identifying key biomarkers, and developing a diagnostic model using bioinformatics and machine learning. Transcriptomic data from the GEO database were integrated with GRGs to investigate their role in IPF. Differentially expressed genes (DEGs) were identified and subjected to functional enrichment and protein-protein interaction (PPI) analyses. A machine learning workflow combining LASSO regression, support vector machine-recursive feature elimination (SVM-RFE), and XGBoost was applied to identify key genes and construct a diagnostic model using the GSE150910 training dataset. Model performance was subsequently evaluated in four independent validation datasets. Additional analyses, including gene set enrichment analysis (GSEA), immune infiltration analysis, drug-gene interaction analysis, molecular docking, and RT-qPCR validation using peripheral blood samples from IPF patients and healthy controls, were performed to investigate the biological relevance of the identified genes. A total of 126 glycosylation-related DEGs were identified, and 10 key genes were selected. The diagnostic model achieved area under the curve (AUC) values of 0.963 and 0.814 on lung tissue datasets, and 0.681 and 0.706 on blood datasets. Immune infiltration analysis revealed differences in B-cell abundance between patient subgroups, and RT-qPCR validation confirmed the differential expression of selected genes in clinical samples. These findings provide insight into the potential involvement of GRGs in IPF and support their relevance as candidate diagnostic genes.

BackgroundThe classification of idiopathic inflammatory myopathies (IIMs) has evolved substantially with the identification of myositis-specific autoantibodies (MSAs). However, how contemporary classification frameworks are applied in routine clinical practice remains variable. This study provides a clinicopathological and serological characterization of IIMs from a national neuromuscular referral center in Cyprus.MethodsWe conducted a retrospective, single-center cohort study of adult patients diagnosed with IIM between 2007 and 2025. Patients were classified using a clinicopathological and serological approach into dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASyS), overlap myositis (OM), inclusion body myositis (IBM), and polymyositis (PM), with the 2017 EULAR/ACR criteria used as a reference framework and historical diagnoses re-evaluated.Results36 patients were included. Final subtype distribution: IMNM in 14 patients (39%), DM in 7 (19%), IBM in 4 (11%), OM in 5 (14%), ASyS in 3 (8%), PM in 2 (6%). Only one patient remained non-classifiable. Autoantibody testing was performed in 26/36 patients; MSAs were detected in 19/26 tested (73%; 53% of the total cohort), most commonly anti-HMGCR, while anti-NT5C1A antibodies were detected in three additional patients. Muscle biopsy was performed in the majority of patients, reflecting historical diagnostic practices.ConclusionThis study demonstrates real-world application of contemporary IIM classification, enabling accurate disease subtyping with direct implications for malignancy surveillance and interstitial lung disease monitoring, as well as reclassification of cases, most notably those previously labelled as PM. The findings further underscore the role of muscle biopsy, particularly when serology is negative, discordant, or unavailable.