Respir Res. 2025 Feb 28;26(1):80. doi: 10.1186/s12931-025-03139-3.

ABSTRACT

BACKGROUND: Supplemental oxygen therapy is commonly prescribed in clinical practice for patients with fibrosing interstitial lung disease (ILD) to reduce breathlessness and increase physical capacity. Only a few studies have evaluated the incidence of oxygen therapy use, with evidence lacking in its use among fibrosing ILD subtypes including patients with idiopathic pulmonary fibrosis (IPF) and non-IPF ILD. This study aimed to estimate incidence of oxygen therapy and factors associated with oxygen therapy initiation.

METHODS: This non-interventional study used US administrative claims and electronic health record data from 01 October 2015 to 30 June 2022. Patients aged ≥ 18 years with newly diagnosed fibrosing ILD (≥ 2 fibrosing ILD diagnoses in any position on different dates of service within 365 days) were included; the index date was the first date with ILD diagnosis. Patients were followed until the earlier of health plan disenrollment, death, or end of study period. Oxygen therapy use was evaluated among patients without evidence of oxygen therapy before the index date, stratified by the underlying fibrosing disease (i.e., IPF vs. non-IPF ILD). Factors associated with oxygen therapy use were evaluated using Cox proportional hazards regression.

RESULTS: A total of 114,921 patients (IPF n = 5,555; non-IPF ILD n = 109,366) newly diagnosed with fibrosing ILD were included in the study. The mean (standard deviation) age of patients with ILD was 66.9 (14.2) years, and 47.2% were male. Patients were followed for a mean of 24 months after ILD diagnosis, during which 38% of fibrosing ILD patients initiated oxygen therapy; a higher proportion of patients with IPF initiated oxygen therapy compared to those with non-IPF ILD (68% and 36%, respectively). Factors associated with oxygen therapy initiation included IPF, higher Charlson comorbidity scores, and comorbidities that impair respiratory capacity.

CONCLUSIONS: The study findings demonstrate a substantial proportion of patients with fibrosing ILD initiated oxygen therapy following initial ILD diagnosis, with higher rates of oxygen therapy initiation observed among patients with IPF compared with non-IPF ILD. Respiratory comorbidities were key factors associated with increased initiation of oxygen therapy.

PMID:40022082 | DOI:10.1186/s12931-025-03139-3

Respir Res. 2025 Feb 28;26(1):73. doi: 10.1186/s12931-025-03136-6.

ABSTRACT

BACKGROUND: The prognostic value of patterns and quantitative measures of lung fibrosis on high-resolution computed tomography (HRCT) in patients identified as having progressive pulmonary fibrosis (PPF) has not been established. We investigated whether HRCT patterns and quantitative scores were associated with risk of progression in patients with PPF.

METHODS: Patients enrolled in the ILD-PRO Registry had an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis, reticular abnormality and traction bronchiectasis, and met criteria for ILD progression. HRCT images taken between 24 months prior to enrollment and 90 days after enrollment were analyzed using a machine learning algorithm to derive quantitative scores. Associations were assessed between HRCT pattern (usual interstitial pneumonia [UIP]-like versus other patterns) and tertiles of quantitative scores and measures of disease severity at enrollment, and between these patterns/tertiles at enrollment and ILD progression (relative decline in forced vital capacity [FVC] % predicted ≥ 10%, lung transplant, or death) over a median follow-up of 17.3 months.

RESULTS: Among 395 patients, 178 (45.1%) had a UIP-like pattern on HRCT. A UIP-like pattern did not associate with worse disease severity at enrollment or an increased risk of ILD progression (HR 1.01 [95% CI: 0.71, 1.44]). The highest quantitative lung fibrosis (QLF) score tertile (≥ 20.5%) was associated with worse disease severity. In unadjusted analyses, patients with QLF scores in the highest tertile had a significantly increased risk of ILD progression versus the middle tertile (HR [95% CI] 1.63 [1.07, 2.49] and a numerically increased risk versus the lowest tertile (HR 1.46 [0.97, 2.18]); however, after adjustment for sex, age, FVC % predicted and oxygen use at enrollment, there were no significant differences. There were no significant associations between tertiles of quantitative ILD score, quantitative ground glass score, or quantitative honeycomb cysts score and risk of ILD progression in unadjusted or adjusted analyses.

CONCLUSIONS: In a real-world cohort of patients with PPF, QLF score associated with subsequent risk of ILD progression, while HRCT pattern did not. The QLF score did not provide additional prognostic information beyond clinical variables.

TRIAL REGISTRATION: ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www.

CLINICALTRIALS: gov .

PMID:40022059 | DOI:10.1186/s12931-025-03136-6

BMC Pulm Med. 2025 Feb 28;25(1):98. doi: 10.1186/s12890-025-03555-7.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, and fatal disease characterized by progressive interstitial lung fibrosis. Given its insidious onset and poor outcome, there is an urgent need to elucidate the molecular mechanisms underlying IPF and identify effective therapeutic targets and diagnosis and prognosis biomarkers. Ferroptosis is an iron-dependent form of programmed cell death that occurs as lipid peroxides accumulate. Growing evidence suggests that ferroptosis is important in IPF.

METHODS: Human ferroptosis PCR array was performed on IPF and control lung tissue. The differentially expressed ferroptosis-related genes (DE-FRGs) were identified, underwent functional enrichment analyses, protein-protein interaction network construction, and potential drug target prediction. The DE-FRGs were validated and their value as diagnostic and prognostic blood biomarkers were evaluated using the Gene Expression Omnibus dataset GSE28042.

RESULTS: The array identified 13 DE-FRGs. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the DE-FRGs were mainly related to iron ion transport, blood microparticles, and oxidoreductase activity, and were involved in porphyrin metabolism, necroptosis, and the p53 signaling pathway in addition to ferroptosis. The 13 DE-FRGs were analyzed using the Drug-Gene Interaction Database to explore novel IPF therapeutic agents, yielding 42 potential drugs. Four DE-FRGs (BBC3, STEAP3, EPRS, SLC39A8) in the peripheral blood of IPF patients from the GSE28042 dataset demonstrated the same expression pattern as that observed in the lung tissue array. The receiver operating characteristic analysis demonstrated that the area under the curve of STEAP3 and EPRS were > 0.75. The survival analysis demonstrated that STEAP3 and EPRS were significantly different between the IPF and control groups.

CONCLUSIONS: The FRG expression profiles in IPF and control lung tissue were characterized. The findings provided valuable ideas to elucidate the role of ferroptosis in IPF and aided the identification of novel IPF therapeutic targets and biomarkers.

PMID:40022042 | DOI:10.1186/s12890-025-03555-7

Chest. 2025 Feb 26:S0012-3692(25)00267-3. doi: 10.1016/j.chest.2025.02.018. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with lung function decline and high mortality.

RESEARCH QUESTION: What are the associations between thresholds of lung function decline and the risk of mortality in patients with IPF?

STUDY DESIGN AND METHODS: The Idiopathic Pulmonary Fibrosis-Prospective Outcomes Registry enrolled patients with IPF that was diagnosed or confirmed at the enrolling center within the prior 6 months. Associations between time to first decline in FVC or diffusing capacity of the lungs for carbon monoxide (Dlco) of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted (and ≥ 15% predicted for Dlco) and risk of subsequent death or lung transplant was assessed using Cox proportional hazards models with a time-dependent covariate. Models were unadjusted or adjusted for FVC and Dlco % predicted, age, sex, smoking status, BMI, antifibrotic treatment (yes or no), and oxygen use at enrollment.

RESULTS: Among 1,001 patients, median follow-up time was 38.4 months. Significant associations were observed between all thresholds of decline in FVC and Dlco % predicted and the risk of death or lung transplant in unadjusted and adjusted analyses. In adjusted analyses, absolute declines in FVC of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted were associated with 1.8-fold, 2.3-fold, and 2.7-fold increases in the risk of subsequent death or lung transplant, whereas absolute declines in Dlco of ≥ 2% predicted, ≥ 5% predicted, ≥ 10% predicted, and ≥ 15% predicted were associated with 2.0-fold, 1.4-fold, 1.5-fold, and 1.9-fold increases in the risk of subsequent death or lung transplantation, respectively. For Dlco, but not FVC, the increase in risk generally was greater for patients meeting a threshold based on a relative rather than an absolute decline.

INTERPRETATION: Even small declines in FVC and Dlco % predicted inform prognosis in patients with IPF.

PMID:40020995 | DOI:10.1016/j.chest.2025.02.018

Chem Biomed Imaging. 2025 Jan 17;3(2):85-94. doi: 10.1021/cbmi.4c00065. eCollection 2025 Feb 24.

ABSTRACT

Disease-recapitulating animal models are valuable tools in preclinical development for the study of compounds. In the case of fibrotic pulmonary diseases such as idiopathic pulmonary fibrosis (IPF), the bleomycin model of lung injury in the mouse is widely used. To evaluate bleomycin-induced changes in the lung, we employed a quantitative, multimodal approach. Using in vivo microcomputed tomography (μCT), we demonstrated radiographic changes associated with disease progression in aeration levels of the lung parenchyma. There exists an unmet need for a quantitative, high-resolution imaging probe to detect pulmonary fibrosis, particularly that can differentiate between inflammatory and fibrotic components of the disease. Matrix remodeling and overexpression of extracellular matrix (ECM) proteins such as collagen and fibronectin are hallmarks of organ fibrosis. A splice variant of fibronectin containing extra domain A (FnEDA) is of particular interest in fibrosis due to its high level of expression in diseased tissue, which is confirmed here using immunohistochemistry (IHC) in mouse and human lungs. An antibody against FnEDA was evaluated for use as an imaging tool, particularly by using in vivo single-photon emission computed tomography (SPECT) and ex vivo near-infrared (NIR) fluorescence imaging. These data were further corroborated with histological tissue staining and fibrosis quantitation based on a Modified Ashcroft (MA) score and a digital image analysis of whole slide lung tissue sections. The fusion of these different approaches represents a robust integrated workflow combining anatomical and molecular imaging technologies to enable the visualization and quantitation of disease activity and treatment response with an inhibitor of the TGFβ signaling pathway.

PMID:40018646 | PMC:PMC11863149 | DOI:10.1021/cbmi.4c00065

Eur Respir J. 2025 Feb 27;65(2):2402224. doi: 10.1183/13993003.02224-2024. Print 2025 Feb.

NO ABSTRACT

PMID:40015735 | DOI:10.1183/13993003.02224-2024

Biogerontology. 2025 Feb 26;26(2):64. doi: 10.1007/s10522-025-10208-z.

ABSTRACT

Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging and age-related lung diseases such as chronic obstructive pulmonary disease idiopathic pulmonary fibrosis and lung cancer. HIF plays a pivotal role in cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, and inflammation. Meanwhile, cellular senescence leads to irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes to chronic inflammation, tissue remodeling, and fibrosis. Dysregulation of these pathways accelerates lung aging and disease progression by promoting oxidative stress, mitochondrial dysfunction, and epigenetic alterations. Recent studies indicate that HIF and senescence interact at multiple levels, where HIF can both induce and suppress senescence, depending on cellular conditions. While transient HIF activation supports tissue repair and stress resistance, chronic dysregulation exacerbates pulmonary pathologies. Furthermore, emerging evidence suggests that targeting HIF and senescence pathways could offer new therapeutic strategies to mitigate age-related lung diseases. This review explores the intricate crosstalk between these mechanisms, shedding light on how their interplay influences pulmonary aging and disease progression. Additionally, we discuss potential interventions, including senolytic therapies and HIF modulators, that could enhance lung health and longevity.

PMID:40011266 | DOI:10.1007/s10522-025-10208-z

Pulm Pharmacol Ther. 2025 Feb 24:102346. doi: 10.1016/j.pupt.2025.102346. Online ahead of print.

ABSTRACT

BACKGROUND: Baricitinib and nintedanib can target inflammation and fibrosis respectively, which are the two most important processes in idiopathic pulmonary fibrosis (IPF). However, it is still unknown whether targeting these two processes simultaneously can synergistically improve the therapeutic effect of IPF. Therefore, it is necessary to predict the possible translational potential through preclinical studies.

METHODS: We evaluated both the in vitro and in vivo efficacy of a drug combination, nintedanib with baricitinb, a JAK1/JAK2 inhibitor. We first examined the fibroblast proliferation and myofibroblast differentiation of single agents or combinations by the MTT assay. Then we determined the migration of the fibroblasts by a wound healing assay. Meanwhile, we quantified the protein level of related growth factor or cytokines in the cell supernatant by ELISA. Finally, we investigated the therapeutic potential and mechanism in a bleomycin-induced mouse model.

RESULTS: Our results showed that the combination of nintedanib and baricitinib was more effective in suppressing fibroblast proliferation, myofibroblast transformation and fibroblast migration compared to either agent alone. In a bleomycin-induced IPF mouse model, the combination therapy resulted in a higher survival rate, increased body weight, and a lower lung/body weight ratio compared to the individual drugs. Moreover, both drugs improved lung functions in mice, but their combined administration led to superior outcomes. Histopathological analysis also revealed that the combination therapy mitigated pulmonary inflammation and fibrosis to a greater extent than the individual compounds. Mechanistically, baricitinib appears to orchestrate the effects of nintedanib in IPF by modulating the expression of genes such as il-6, tgf-β, col1α1 and fibronectin.

CONCLUSION: The synergistic targeting of inflammation by baricitinib and fibrosis by nintedanib preclinically improves IPF outcomes, thus suggesting their potential as a novel combination therapy for this condition.

PMID:40010629 | DOI:10.1016/j.pupt.2025.102346

Autoimmun Rev. 2025 Feb 24:103782. doi: 10.1016/j.autrev.2025.103782. Online ahead of print.

ABSTRACT

B cells play a key role in the pathophysiology of systemic sclerosis (SSc). While they are less characterized than their circulating counterparts, tissue-infiltrating B cells may have a more direct pathological role in tissues. In this review, we decipher the multiple evidence of B cells infiltration in the skin and lungs of SSc patients and animal models of SSc but also of other chronic fibrotic diseases with similar pathological mechanisms such as chronic graft versus host disease, idiopathic pulmonary fibrosis or morphea. We also recapitulate the current knowledge about mechanisms of B cells infiltration and their functions in tissues. Finally, we discuss B cell targeted therapies, and their specific impact on infiltrated B cells. Understanding the local consequences of infiltrating B cells is an important step for a better management of patients and the improvement of therapies in SSc.

PMID:40010623 | DOI:10.1016/j.autrev.2025.103782

Ther Adv Drug Saf. 2025 Feb 24;16:20420986251321704. doi: 10.1177/20420986251321704. eCollection 2025.

ABSTRACT

Artificial intelligence (AI) is transforming medication research and development, giving clinicians new treatment options. Over the past 30 years, machine learning, deep learning, and neural networks have revolutionized drug design, target identification, and clinical trial predictions. AI has boosted pharmaceutical R&D (research and development) by identifying new therapeutic targets, improving chemical designs, and predicting complicated protein structures. Furthermore, generative AI is accelerating the development and re-engineering of medicinal molecules to cater to both common and rare diseases. Although, to date, no AI-generated medicinal drug has been FDA-approved, HLX-0201 for fragile X syndrome and new molecules for idiopathic pulmonary fibrosis have entered clinical trials. However, AI models are generally considered "black boxes," making their conclusions challenging to understand and limiting the potential due to a lack of model transparency and algorithmic bias. Despite these obstacles, AI-driven drug discovery has substantially reduced development times and costs, expediting the process and financial risks of bringing new medicines to market. In the future, AI is expected to continue to impact pharmaceutical innovation positively, making life-saving drug discoveries faster, more efficient, and more widespread.

PMID:40008227 | PMC:PMC11851753 | DOI:10.1177/20420986251321704

Front Pharmacol. 2025 Feb 11;16:1509665. doi: 10.3389/fphar.2025.1509665. eCollection 2025.

ABSTRACT

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF), an interstitial lung disease of unknown etiology, remains incurable with current therapies, which fail to halt disease progression or restore lung function. However, Feibi Recipe No. 2 (FBR2), a clinically validated traditional Chinese medicine formula, exhibits potential as an IPF treatment.

OBJECTIVE: This study aimed to investigate the regulatory effect of FBR2 on ferroptosis through the SIRT3/p53 pathway and its therapeutic potential in improving IPF.

METHODS: Pulmonary fibrosis was induced in C57BL/6J mice by intratracheal instillation of Bleomycin (BLM), followed by FBR2 treatment via gavage. Assessments encompassed histopathology, ELISA for cytokine detection, IHC and Western blot for protein expression analysis, and qRT-PCR for gene expression quantification. Transmission electron microscopy (TEM) was used to observe mitochondrial morphology. The roles of Erastin and the SIRT3 inhibitor 3-TYP were also explored to elucidate FBR2's mechanisms of action.

RESULTS: FBR2 treatment significantly mitigated BLM-induced lung injury in mice, as evidenced by improved body weight and survival rates, and reduced levels of inflammatory cytokines, including IL-6 and TNF-α. FBR2 decreased collagen deposition in lung tissue, as shown by Masson's staining and IHC detection of Col-I and α-SMA, confirming its anti-fibrotic effects. It also reduced iron and MDA levels in lung tissue, increased GSH-Px activity, improved mitochondrial morphology, and enhanced the expression of GPX4 and SLC7A11, indicating its ferroptosis-inhibitory capacity. Furthermore, FBR2 increased SIRT3 levels and suppressed p53 and its acetylated forms, promoting the translocation of p53 from the nucleus to the cytoplasm where it co-localized with SIRT3. The protective effects of FBR2 were reversed by Erastin, confirming the central role of ferroptosis in pulmonary fibrosis treatment. The use of 3-TYP further confirmed FBR2's intervention in ferroptosis and cellular senescence through the SIRT3/p53 pathway.

CONCLUSION: FBR2 shows therapeutic potential in a BLM-induced pulmonary fibrosis mouse model, with its effects mediated through modulation of the ferroptosis pathway via the SIRT3/p53 mechanism. This study provides novel evidence for the targeted treatment of IPF and offers further insights into its pathogenesis.

PMID:40008127 | PMC:PMC11850536 | DOI:10.3389/fphar.2025.1509665

Respir Med Case Rep. 2025 Jan 28;54:102168. doi: 10.1016/j.rmcr.2025.102168. eCollection 2025.

ABSTRACT

INTRODUCTION: Nintedanib is a tyrosine kinase inhibitor and has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) since 2020. In Clinical trials, the antifibrotic effect of nintedanib was shown.

CASE: A 60-year-old female medical assistant, infected with COVID-19 in 10/2020, experienced a complicated course of disease leading to tracheal stenosis. Various interventions, including stent placements and tracheal surgeries, were performed. Due to recurrent restenosis, the patient was treated with nintedanib, a tyrosine kinase inhibitor used in idiopathic pulmonary fibrosis. The treatment spanned 306 days, during which the patient showed stability in pulmonary function. Nintedanib demonstrated a potential anti-inflammatory effect, reducing the frequency of interventions and prolonging stent-free intervals. The results suggest possible efficacy of nintedanib in managing scar-related granulation tissue, highlighting its potential in treating tracheal stenosis.

CONCLUSION: This case shows a decreased need for interventions, and the longer duration of stent placement may suggest a potential role for nintedanib in diminishing hypertrophic scarring, possibly through an anti-inflammatory effect. Further exploration of this potential in additional clinical trials would be valuable.

PMID:40007765 | PMC:PMC11849196 | DOI:10.1016/j.rmcr.2025.102168

Bioorg Chem. 2025 Feb 18;157:108294. doi: 10.1016/j.bioorg.2025.108294. Online ahead of print.

ABSTRACT

PDE4 inhibitors have been developed as anti-inflammatory medications primarily used in the clinical treatment of pulmonary inflammations such as asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. However, the application of these drugs is usually restricted by obvious side effects, such as nausea and vomiting. Our previous study found that several natural PDE4 inhibitors or their modified derivatives showed minimal side effects, particularly reduced incidence of nausea and vomiting, which aroused our interest in searching for natural PDE4 inhibitors. In this study, a chemical investigation of an active fraction of Piper betle L. leaves led to the characterization of 23 hydroxychavicol derivatives, including 18 hydroxychavicol-type lignans. Compounds 1-9 were new lignans, with three of them being racemates that were eventually resolved into isolated (+)- and (-)-enantiomers. Compounds 1-5 and 10, neolignans characterized by a dioxane moiety, were unique to this species within the genus Piper. Compounds 5 and 10 were the sole sesquineolignans found in the genus Piper. Compounds 5, 7-14, 16, 17, and 21 exhibited considerable inhibition towards PDE4 with IC50 values ranging from 1.8 to 10 μM, with hit 7 exhibiting remarkable activity (1.8 μM). Further anti-inflammatory assays revealed that compounds 5, 7, 9, and 16 decreased the expression of several key inflammatory mediators in LPS-stimulated RAW 264.7 cells. Notably, 16 was comparable to the positive control rolipram at the same concentration of 10 μM. A primary study of the mechanism of action revealed that 16 may exert anti-inflammatory effect by inhibiting the NF-κB signaling pathway, displaying significant inhibition of the phosphorylation of IκB-α and p65 at concentrations of 5 and 10 μM. These findings suggest that hydroxychavicol derivatives from P. betle L. leaves may serve as new PDE4 inhibitors, offering promising leads for the development of anti-inflammatory medications.

PMID:40007350 | DOI:10.1016/j.bioorg.2025.108294

Pharmaceutics. 2025 Feb 14;17(2):253. doi: 10.3390/pharmaceutics17020253.

ABSTRACT

Background/Objectives: The identification of inflammatory mediators and the involvement of CD206 macrophages in anti-inflammatory responses, along with the synthesis of fibrotic mediators, are crucial for the diagnosis and treatment of Idiopathic Pulmonary Fibrosis (IPF). Methods: In this study, the assessment of 68Ga-labeled linear and cyclic forms of the RP832c peptide, which demonstrate a specific affinity for CD206 macrophages, was performed to evaluate efficacy for CD206 imaging through PET/CT, biodistribution studies, and CD206 staining in a bleomycin-induced lung injury mouse model (BLM). This model serves as a representative framework for inflammation and fibrosis. Results: The findings reveal significant peak PET/CT signals (SUV means), ID/gram values, and CD206 staining scores in lung tissues at one week post bleomycin instillation, likely due to the heightened expression of CD206 in the bleomycin-induced lung injury model. In contrast, the healthy mice exhibited no detectable CD206 staining, lower PET signals, and reduced radiopharmaceutical accumulation in lung tissues at the same timepoint. Conclusions: These findings suggest that both linear and cyclic [68Ga]Ga-RP832c may function as promising PET imaging agents for CD206 macrophages, and thereby a strategy to non-invasively explore the role of macrophages during fibrogenesis.

PMID:40006620 | DOI:10.3390/pharmaceutics17020253

Medicina (Kaunas). 2025 Feb 6;61(2):283. doi: 10.3390/medicina61020283.

ABSTRACT

Background and Objectives: The aim of our study is to compare the effects of pirfenidone and nintedanib on lung function and radiologic findings in Idiopathic Pulmonary Fibrosis and to identify which drug is more appropriate for which patient group. Materials and Methods: The data of patients who were treated in our department for at least one year between 1 January 2010 and 31 December 2022 and who were started on pirfenidone or nintedanib treatment with the diagnosis of Idiopathic Pulmonary Fibrosis were retrospectively reviewed. The patients were divided into two groups-the nintedanib and pirfenidone groups-and both groups were compared in terms of progression in lung function tests (changes in FEV1, FVC, 6 MWT and DLCO values at the 3rd, 6th, 9th and 12th months compared to baseline values) and radiological findings (the presence of progression in findings such as ground-glass opacity, reticulation, honeycomb and traction bronchiectasis) within 1 year after diagnosis. Results: The study included 109 patients. The number of patients treated with pirfenidone (IPF patients) was 82 (75.2%) and the number of patients treated with nintedanib was 27 (24.8%). When the PFT values at 3, 6, 9 and 12 months were compared with the baseline values in both groups, there was no statistically significant difference in any parameter between the two groups. No significant difference was found in terms of radiological progression at the end of 1 year in both groups. Conclusions: The results of our study show that pirfenidone and nintedanib are equivalent in their effectiveness in preventing disease progression in patients with IPF.

PMID:40005400 | DOI:10.3390/medicina61020283

Medicina (Kaunas). 2025 Jan 31;61(2):244. doi: 10.3390/medicina61020244.

ABSTRACT

Background and Objectives: Acute exacerbation of idiopathic pulmonary fibrosis (IPF-AE) often results in severe respiratory distress requiring treatment in the intensive care unit and has a high mortality rate. Identifying prognostic markers and assessing disease severity are crucial for clinicians to gain detailed insights. The mean platelet volume-to-platelet count ratio (MPR) is an inflammatory marker commonly used in malignancies. This study aimed to evaluate MPR and other factors affecting mortality in patients with IPF-AE who were monitored in the intensive care unit (ICU). Materials and Methods: This retrospective study was conducted on patients monitored in the ICU for IPF-AE between 2017 and 2023. Demographic characteristics, vital signs, laboratory and imaging findings, and administered treatments were reviewed. MPR was calculated by dividing the mean platelet volume by the platelet count. The primary endpoint was defined as 1-month in-hospital mortality. Results: A total of 59 patients monitored in the ICU for IPF-AE were included in the study. The mean age of the patients was 62.75 years, and 81.4% of the participants were male. During the 30-day follow-up period, 62.7% of the patients died. The need for invasive mechanical ventilation (IMV) was significantly associated with increased mortality (p < 0.001). The optimal cutoff value for MPR was determined to be 0.033, with a sensitivity of 83.7% and specificity of 63.64%, indicating its predictive value for mortality (AUC: 0.764; 95% CI: 0.635-0.864; p < 0.001). Conclusions: In this study, the need for IMV emerged as a critical parameter in predicting mortality in patients with IPF-AE. Additionally, the use of the MPR as a prognostic biomarker may offer a novel approach in the management of IPF patients. These findings could contribute to the development of strategies aimed at early intervention in IPF patients. Further studies with larger sample sizes are needed to validate these results. This study has demonstrated that MPR is a significant prognostic biomarker for predicting mortality in patients with IPF-AE who are managed in the intensive care unit. The potential use of MPR as a biomarker in clinical decision-making may provide new approaches to the management of IPF patients. Additionally, the need for IMV in IPF-AE emerges as a critical parameter for predicting mortality. These findings may contribute to the development of early intervention strategies for IPF patients. Further studies with larger cohorts are needed to validate these results.

PMID:40005361 | DOI:10.3390/medicina61020244

J Clin Med. 2025 Feb 17;14(4):1317. doi: 10.3390/jcm14041317.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a relatively common progressive fibrotic interstitial lung disease associated with significant morbidity and mortality. The available medications for IPF only slow down the disease process, with lung transplantation the only option for a cure. Non-pharmacological therapies are significant adjuncts that can improve symptom burden and quality of life with minimal or no side effects. Supplemental oxygen can improve exercise capacity and the sensation of dyspnea in a significant portion of patients with resting or exertional hypoxemia and has been supported by several professional societies. Pulmonary rehabilitation is a comprehensive program that includes education and therapeutic exercises to improve patient stamina and strength. It is one of the few interventions that have been shown to produce a meaningful increase in a patient's exercise capacity, but its wide adoption is limited by availability, especially in rural areas. Sleep optimization with supplemental oxygen and positive airway pressure therapy should actively be investigated for all patients diagnosed with IPF. Although gastroesophageal reflux control with non-pharmacological means is still controversial as an intervention to reduce the rate of lung function decline, it can help control reflux symptoms and improve cough intensity. IPF patients should be educated on the importance of balanced nutrition and the potential benefits of screening for lung transplantation. Palliative medicine can help with symptom control and should be considered for all patients regardless severity, but especially in those in the later stages of disease.

PMID:40004847 | DOI:10.3390/jcm14041317

J Clin Med. 2025 Feb 15;14(4):1300. doi: 10.3390/jcm14041300.

ABSTRACT

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate IPF and to identify the main determinants of AA dilatation. Methods: All IPF patients without severe pulmonary hypertension who underwent a multi-instrumental evaluation, comprehensive of high-resolution computed tomography (HRCT) and transthoracic echocardiography (TTE), between September 2017 and November 2023, were retrospectively analyzed. The primary endpoint was the composite of "all-cause mortality or re-hospitalization for all causes", over a medium-term follow-up. The secondary endpoint was to evaluate the independent predictors of AA dilatation. Additionally, Bland-Altman analysis was used to assess the accuracy and precision of echocardiography-derived AA diameters compared with non-ECG gated HRCT measurements. Results: A total of 105 IPF patients and 102 age-, sex-, and CV risk factor-matched controls without IPF were evaluated retrospectively. Over a follow-up of 3.9 ± 1.9 yrs, 31 patients died and 47 were re-hospitalized. AA/height (HR 1.15, 95% CI 1.06-1.25, p < 0.001) was independently associated with the primary endpoint, whereas unindexed AA (HR 1.01, 95% CI 0.96-1.06, p = 0.83) and AA/BSA (HR 1.00, 95% CI 0.89-1.11, p = 0.39) were not. An AA/height > 20 mm/m showed 100% sensitivity and 63% specificity (AUC = 0.78) for predicting the primary endpoint. C-reactive protein (OR 1.87; 95% CI 1.21-2.89, p = 0.005) and left ventricular mass index (OR 1.13, 95% CI 1.04-1.24, p = 0.006) were independently associated with an AA/height > 20 mm/m in the whole study group. The Bland-Altman analysis revealed a bias of +2.51 mm (with the 95% limits of agreement ranging from -3.62 to 8.65 mm) for AA estimation, suggesting a general overestimation of the AA diameter by TTE in comparison to HRCT. Conclusions: AA dilatation is predictive of poor outcomes in IPF patients without advanced lung disease over a mid-term follow-up. The AA/height assessment may improve the prognostic risk stratification of IPF patients.

PMID:40004830 | DOI:10.3390/jcm14041300

J Clin Med. 2025 Feb 8;14(4):1093. doi: 10.3390/jcm14041093.

ABSTRACT

Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders marked by inflammation and/or fibrosis of the lung parenchyma, often leading to progressive shortness of breath and end-stage respiratory failure. In the U.S., ILDs affect approximately 650,000 individuals and cause approximately 25,000-30,000 deaths annually. Lung transplantation (LTx) offers definitive treatment for advanced ILD, with improved survival attributed to advancements in immunosuppression, organ preservation, surgical techniques, and postoperative care. However, disease recurrence in transplanted lungs remains a significant concern. Understanding the risk factors and mechanisms underlying recurrence is critical for refining recipient selection and improving outcomes. This review examines ILD recurrence post LTx and its implications for lung transplantation success.

PMID:40004625 | DOI:10.3390/jcm14041093

Diagnostics (Basel). 2025 Feb 16;15(4):474. doi: 10.3390/diagnostics15040474.

ABSTRACT

Hyperpolarized xenon-129 MRI (129XeMRI) has emerged as a powerful tool in the identification, evaluation, and assessment of disease endotyping and in response to interventions for a myriad of pulmonary diseases. Growing investigative efforts ranging from basic science to application in translational research have employed 129XeMRI in the evaluation of pulmonary conditions such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and cystic fibrosis (CF). The novel feature of 129XeMRI is its ability to generate anatomic and physiologic readouts of the lung with resolution from the whole lung down to the lobar level. Additional advantages include being non-invasive and non-radioactive, and utilizing an inexpensive and ubiquitous noble gas as an inhalation contrast agent: xenon-129. In this review, we outline the clinical advances provided by 129XeMRI among common pulmonary diseases with high healthcare burdens in recent decades.

PMID:40002625 | DOI:10.3390/diagnostics15040474