Interstitial Lung Disease Research Articles

Exploring the Potential Value of [68Ga]Ga-FAPI-46 PET/CT for Molecular Assessment of Fibroblast Activation in Interstitial Lung Disease: A Single-Center Pilot Study.

The aim of the study was to evaluate the association of high-resolution computed tomography (HRCT) findings with pulmonary fibrotic activity in the corresponding regions using [68Ga]Ga-fibroblast activation fibroblast inhibitor (FAPI) PET/CT in patients with interstitial lung disease (ILD). Additionally, the potential of [68Ga]Ga-FAPI-46 PET/CT for evaluating the active fibrosis process and 99mTc-MIBI scintigraphy for assessing the inflammatory process in ILD patients was also assessed. In this pilot study, 20 ILD patients underwent [68Ga]Ga-FAPI-46 PET/CT and 99mTc-MIBI SPECT/CT. Additionally, 10 patients without lung or thoracic involvement who were undergoing [68Ga]Ga-FAPI PET/CT for cancer detection were enrolled in the control group. The images were evaluated both visually and semiquantitatively and also compared with HRCT and pulmonary function tests. Multiple quantitative parameters were derived from the lung segments in the PET scan, including SUVmax, SUVmean, maximum target-to-liver ratio, mean target-to-liver ratio (TLRmean), and total lesion FAPI expression for the entire lung, as well as its lobes and zones. Additionally, the maximum Hounsfield unit (HU) and mean HU in HRCT were calculated for the whole lung as well as its lobes and zones. Furthermore, an HRCT fibrosis score (HFS) was defined according to the HRCT findings. Twenty ILD patients with a mean age of 58.70 (SD, 11.09) years were enrolled. Additionally, 10 control patients were enrolled with a mean age of 57.70 (SD, 15.19) years. Based on visual assessment, the FAPI scan was positive in 12 (60%) patients. Similarly, the MIBI scan was positive in 12 (60%) patients. In the 20 ILD cases, both scans were positive in 6 cases, and both were negative in 2 cases. Six cases showed FAPI-negative and MIBI-positive results, whereas another 6 cases showed FAPI-positive and MIBI-negative results. Comparing the control and ILD patients, there was a significant difference in SUVmax, SUVmean, total lesion FAPI expression, TLRmean, maximum HU, and mean HU (P < 0.05). When comparing HFS with PET-derived parameters in zones, a significant positive correlation was found between HFS and SUVmean, SUVmax, maximum target-to-liver ratio, and TLRmean (P < 0.05). Additionally, a significant difference was noted between FAPI results and HFS (P = 0.003). An ancillary finding, 9 of 20 (45%) ILD patients showed intense FAPI uptakes in gallbladder, whereas none of the 10 in the control group showed such uptake. The present study may suggest that combining [68Ga]Ga-FAPI PET/CT and 99mTc-MIBI SPECT/CT yields an additive effect for evaluating ILD-related fibrosis and inflammatory processes over using either modality alone. Furthermore, it appears that [68Ga]Ga-FAPI PET/CT has the potential to ascertain levels of fibrotic activity from population of resident fibroblasts, active fibroblasts, and scar maturation among ILD patients based on their HRCT patterns.

Prognostic value of myositis-specific antibodies in patients with idiopathic interstitial pneumonia

BackgroundPatients with idiopathic interstitial pneumonia (IIP) often exhibit positivity for myositis-specific antibodies (MSA). However, the significance of this finding remains unclear. In this study, we investigated the association of MSA with the prognosis and risk of acute exacerbation in patients with IIP.MethodsWe retrospectively reviewed the medical records of patients with IIP and examined the effect of each MSA subtype on survival and acute exacerbation.ResultsOf 240 patients with IIP, 48 (20%) exhibited positivity for MSA. The MSA subtypes included: PL-7 (antithreonyl; n = 16, 6.7%); signal recognition particle (n = 13, 5.4%); PL-12 (antialanyl; n = 9, 3.8%); Mi-2 (n = 8, 3.3%); OJ (anti-isoleucyl; n = 7, 2.9%). During the 382 days (382 ± 281 days) of observation, 32 (13%) patients expired, and 27 (11%) experienced an acute exacerbation. Cox proportional hazards regression analysis demonstrated that age at the initial visit (hazard ratio [HR]: 1.072; 95% confidence interval [CI]: 1.017–1.131; P = 0.01), PL-7 (HR: 4.785; 95% CI: 1.528–14.925; P = 0.007), and PL-12 (HR: 3.922; 95% CI: 1.198–12.82; P = 0.024) were independent predictors of survival time. PL-7 (HR: 3.268; 95% CI: 1.064–10; P = 0.039) and PL-12 (HR: 5.747; 95% CI: 1.894–7.544; P = 0.002) were independent predictors of time from first visit to acute exacerbation.ConclusionDetecting MSA in patients with interstitial lung disease may be useful in predicting prognosis and providing a rationale for intensive treatment.

Pulmonary Rehabilitation for Diseases Other Than COPD.

Review the current literature regarding pulmonary rehabilitation (PR) for non-chronic obstructive pulmonary disease (COPD) diagnoses and what the evidence is regarding expected outcomes based on disease manifestations. Literature search was performed using PubMed database from March 2024 to June 2024. Terms included "pulmonary rehabilitation" and "exercise training" in conjunction with key words "interstitial lung disease (ILD)," "idiopathic pulmonary fibrosis," "asthma," "bronchiectasis," "post-acute sequalae of SARS-CoV-2 (PASC)," "long COVID," "pulmonary hypertension (PH)," and "lung cancer." Results were filtered for English language, randomized controlled trial, clinical trial, observational trial, meta-analysis, and guidelines. Emphasis was placed on more recent publications since prior reviews, where applicable. The abundance of literature involved ILD, where studies have demonstrated significant improvements in exercise capacity, health-related quality of life (HRQoL), and dyspnea, despite heterogeneity of diseases; benefits are similar to those seen with COPD. Those with milder disease have more sustained benefits longer term. Patients with asthma benefit in severe disease, lower exercise activity, elevated body mass index, or when comorbid conditions are present, and breathing exercises can improve symptoms of breathlessness. Patients with PASC have a multitude of symptoms and lack benefits in HRQoL measurements; PR improves performance on post-COVID-19 functional status scale, a more comprehensive measurement of symptoms. Those with bronchiectasis benefit from PR when airflow limitation or exacerbations are impacting symptoms and HRQoL. Those with stable PH can improve their exertional capacity without change in disease severity. PR reduces perioperative complications in those with lung cancer and preserve fitness during treatment.

Biologic Correlates of Radiologic Features of Systemic Sclerosis Interstitial Lung Disease

Background and objectivesThe extent and pattern of radiological features (e.g., fibrosis, ground glass) can influence treatment approaches for systemic sclerosis-related interstitial lung disease (SSc-ILD). However, the pathobiology underlying these radiologic features is poorly understood and warrants further investigation.MethodsSixty-eight proteins were measured in bronchoalveolar lavage (BAL) fluid from 103 SSc-ILD participants in Scleroderma Lung Study I. Quantitative image analysis calculated the extent of fibrosis (QLF) and ground glass opacity (QGG) from concurrent high-resolution computerized tomography (HRCT) scans. The relationship between BAL proteins and quantitative HRCT scores was assessed by univariate and multivariate analyses.ResultsQLF scores correlated weakly with the extent of QGG, suggesting two distinct processes. In a univariate analysis, 25 proteins from several biologic pathways correlated with QLF scores, including pro-fibrotic factors, tissue remodeling proteins, proteins involved in monocyte/macrophage migration and activation, and proteins linked to inflammation and immune regulation. In contrast, QGG scores correlated with only 6 proteins of which four were unique and related to granulocyte activation, mobilization of bone marrow mesenchymal stem cells, and activation of T cells, B cells, macrophages and eosinophils. In the multivariate models, IL-4, CCL7, receptor activator of NF-κB, and tumor necrosis factor alpha were independently associated with QLF, whereas, IFN-γ was independently associated with QGG.InterpretationQLF and QGG represent distinct radiologic features of SSc-ILD, a conclusion reinforced by the presence of different biologic pathways present within BAL fluid that associate with each. The identified proteins and related biologic pathways may represent important therapeutic targets.

Evidence for a lipofibroblast-to- Cthrc1 + myofibroblast reversible switch during the development and resolution of lung fibrosis in young mice.

Fibrosis is often associated with aberrant repair mechanisms that ultimately lead to organ failure. In the lung, idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease (ILD) to which there is currently no curative therapy. From the cell biology point of view, the cell of origin and eventual fate of activated myofibroblasts (aMYFs) have taken center stage as these cells are believed to drive structural remodeling and lung function impairment. While aMYFs are now widely believed to originate from resident fibroblasts, the heterogeneity of aMYFs and ultimate fate during fibrosis resolution remain elusive. We have previously shown that aMYFs dedifferentiation and acquisition of a lipofibroblast (LIF)-like phenotype represent a route of fibrosis resolution. In this study, we combined genetic lineage tracing and single-cell transcriptomics in mice, and data mining of human IPF datasets to decipher the heterogeneity of aMYFs and investigate differentiation trajectories during fibrosis resolution. Furthermore, organoid cultures were utilized as a functional readout for the alveolar mesenchymal niche activity during various phases of injury and repair in mice. Our data demonstrate that aMYFs consist of four subclusters displaying unique pro-alveologenic versus profibrotic profiles. Alveolar fibroblasts displaying a high LIF-like signature largely constitute both the origin and fate of aMYFs during fibrogenesis and resolution respectively. The heterogeneity of aMYFs is conserved in humans and a significant proportion of human aMYFs displays a high LIF signature. Our work identifies a subcluster of aMYFs that is potentially relevant for future management of IPF.

Interstitial lung disease associated with anti-aminoacyl-tRNA synthetase syndrome: quantitative evaluation of CT after initial treatment and long-term follow-up

Interstitial lung disease associated with anti-aminoacyl-tRNA synthetase syndrome: quantitative evaluation of CT after initial treatment and long-term follow-up

Effect of Pilates Exercise on Post Covid 19 Interstitial Lung Disease

Effect of Pilates Exercise on Post Covid 19 Interstitial Lung Disease

Chest Wall Deformities in Adults With Fibrotic Interstitial Lung Disease Related to Surfactant-Related Gene Mutations

Chest Wall Deformities in Adults With Fibrotic Interstitial Lung Disease Related to Surfactant-Related Gene Mutations

Treatment patterns and patient journey in progressive pulmonary fibrosis: a cross-sectional survey

BackgroundFor patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting.MethodsData were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive.ResultsOverall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD.ConclusionsThis real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival.Trial registrationN/a.

Children interstitial lung disease: Assessment and management.

Diffuse parenchymal lung diseases or children interstitial lung disease (chILD) in pediatrics are a heterogenous group of more than 200 rare diseases with an incidence and prevalence around 8.2 and 46.4 cases/million, respectively, higher than previously recognized, probably related to a greater understanding and increased clinical awareness of these diseases. Children under 2 years of age account for 40%-60% of cases. Diseases presenting before the age of 2 years are mainly of genetic origin or associated with disorders of lung development and are very different from those of older children and adults. In 10%-20% of cases, a genetic cause is found, and in approximately 12%, no cause (undefined chILD) is found after performing all diagnostic tests. A multidisciplinary approach in an expert center is essential for diagnosis and treatment. Tests to be performed after lung computed tomography include serological and other blood tests, bronchoscopy and bronchoalveolar lavage, genetic studies and lung biopsy. Although no approved specific treatment for most cases of chILD exists, an improved understanding of the pathophysiology of many of these diseases is facilitating the development of new treatments.

Patients with anti-small ubiquitin-like modifier activating enzyme-positive dermatomyositis resembling antisynthetase syndrome with poor prognosis: a bicentric international retrospective study and literature review.

This study aimed to describe adult Brazilian and Japanese patients with anti-small ubiquitin-like modifier activating enzyme (SEA)-positive dermatomyositis (DM), as there are few studies in the literature. A literature review was also conducted. This bicentric international retrospective study, conducted between 2012 and 2023, included patients with anti-SAE-positive DM (2017 European League Against Rheumatism/American College of Rheumatology classification criteria). All demographic features and clinical, laboratory, therapeutic, and follow-up data were collected from Brazilian and Japanese centers using pre-standardized and parameterized information. We included 17 adult patients with a median age of 65 (56-76) and a predominance of females (82.4%). Constitutional symptoms at baseline were present in 58.8% of the patients. In addition to classical cutaneous DM lesions, one-third of the patients had myalgia and significant muscle weakness, whereas half presented with dysphagia, interstitial lung disease, and joint manifestations. The first-line treatment consisted of intravenous methylprednisolone and immunoglobulin pulse therapy in 41.2% and 28.6% of the patients, respectively. The median follow-up duration was 20 (13-74) months; at the last medical evaluation, half had active disease and were still using oral glucocorticoids (median dosage, 10.0 mg/day). Approximately one-fifth to one-third of the patients were diagnosed with different types of cancer, had severe infections, or died. Patients with anti-SAE-positive DM not only resemble the phenotype of antisynthetase syndrome but are also associated with a poor prognosis.

A Prospective Study Of Histo-Pathological Changes In Lungs, Liver And Kidneys In Burns Cases Autopsied At A Tertiary Care Hospital

Introduction: Medico legal deaths including burns claim a substantial number of lives in central Karnataka.‘A Prospective Study of Histo-Pathological changes in Lungs, Liver and Kidneys in Burns Cases’ was carried out at the Department of Forensic Medicine &amp; Toxicology, SS hospital, SSIMS &amp; RC, Davangere. Material &amp; methods: The present study was carried out for the period of 3 years from January 2021 to December2023. Totally 100 cases with burns and scalds injuries brought to the mortuary for autopsy was the material for study and collection of tissues for histopathological examination. Observations &amp; Results: In the present study, histopathological changes in lungs showed congestion, pulmonary edema, Diffuse alveolar damage or ARDS changes, bronchopneumonia, interstitial pneumonitis, anthracotic pigment, carbon laden macrophages, intravascular thrombi, septic emboli, interstitial &amp; intra alveolar hemorrhage. Histopathological changes in liver showed congestion, fatty change, centrilobular necrosis, cloudy swelling, focal hemorrhage, necrosis, portal inflammation. Histopathological changes in kidneys showed ATN in majority of cases, cloudy degeneration, congestion, tubular casts and acute pyelonephritis in rest of the cases. Conclusion: The effect of burns on vital organs can be assessed through histopathological examination, which helps in determining the post burn complications and which aid in better treatment outcome of the burn’s patients.

Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis

Objective Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. Methods We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). Results Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%–92%), with moderate heterogeneity (I 2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05–1.71, I 2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). Conclusion The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Diagnosis of pulmonary sarcoidosis comorbid with non-specific interstitial pneumonia: a case report

BackgroundAlthough the imaging manifestations of pulmonary sarcoidosis have been described in detail in previous studies, a consensus has not been reached on the imaging presentation of non-specific interstitial pneumonia (NSIP) lookalike pattern as a distinct pattern in the diagnosis of pulmonary sarcoidosis in high-resolution computed tomography (HRCT). No cases of pulmonary sarcoidosis comorbid with NSIP have been reported.Case presentationA 53-year-old male presented to the hospital with a five-year history of recurrent coughing up sputum and a four-year history of shortness of breath. In addition to the typical features of pulmonary sarcoidosis, the patient’s HRCT also showed unexpected interstitial changes in the lower lobes of both lungs, suggesting an NSIP pattern. Histopathology of the lung tissue in this region confirmed well-formed noncaseating epithelioid granulomas and pathological modifications of NSIP. After a rigorous exclusion diagnosis combining the patient’s clinical features, radiological and pathological findings, we diagnosed this patient with pulmonary sarcoidosis comorbid with NSIP.ConclusionsThis suggests that NSIP may act as a rare comorbidity of pulmonary sarcoidosis thereby resulting in the patient’s HRCT presenting differently from routine sarcoidosis imaging.

Interplay between Lung Diseases and Viral Infections: A Comprehensive Review.

The intricate relationship between chronic lung diseases and viral infections is a significant concern in respiratory medicine. We explore how pre-existing lung conditions, including chronic obstructive pulmonary disease, asthma, and interstitial lung diseases, influence susceptibility, severity, and outcomes of viral infections. We also examine how viral infections exacerbate and accelerate the progression of lung disease by disrupting immune responses and triggering inflammatory pathways. By summarizing current evidence, this review highlights the bidirectional nature of these interactions, where underlying lung diseasesincrease vulnerability to viral infections, while these infections, in turn, worsen the clinical course. This review underscores the importance of preventive measures, such as vaccination, early detection, and targeted therapies, to mitigate adverse outcomes in patients with chronic lung conditions. The insights provided aim to inform clinical strategies that can improve patient management and reduce the burden of chronic lung diseases exacerbated by viral infections.

The Validity and Reliability of the Turkish version of Modified Medical Research Council Dyspnea Scale in Systemic Sclerosis Patients with Interstitial Lung Disease

The Validity and Reliability of the Turkish version of Modified Medical Research Council Dyspnea Scale in Systemic Sclerosis Patients with Interstitial Lung Disease

Interferon Causes Endothelial Injury in Humans

Therapy with exogenous interferon and human conditions that feature endogenous interferon upregulation may be associated with endothelial damage that primarily involves small blood vessels. Endothelial injury associated with interferon may display different clinical expression, including thrombotic microangiopathy, Raynaud’s phenomenon, vasculopathy of dermatomyositis and atrophic papulosis, interferon-associated skin angiopathy, systemic capillary leak syndrome, collapsing glomerulopathy, interstitial lung disease, pulmonary hypertension, and retinopathy. Interferon- induced endothelial damage involves complement-mediated injury, although pathogenic mechanisms by which interferon promote abnormal complement activation on endothelial cells are not fully understood. Human interferon-γ (type II interferon) binds to heparan sulfate on the endothelial surface, suggesting that overproduction of interferon-γ may hinder factor H attachment to the same location. Absence of factor H on self surfaces promotes activation of the alternative pathway of complement and complement-mediated endothelial damage. Type I interferon typically induces the generation of antibodies. Type I interferon upregulation may elicit the formation of autoantibodies against factor H. These autoantibodies block factor H binding to endothelial surfaces, abolishing the protective effect of factor H on complement-mediated damage. In addition, interferon induces insulin resistance which is associated with reduced heparan sulfate in the extracellular matrix, including the endothelial surface. Decreased amount of heparan sulfate suppresses factor H attachment, promoting activation of the alternative pathway of complement. Complement blockade with eculizumab (a monoclonal antibody against C5) improves endothelial damage in patients with thrombotic microangiopathy and other situations associated with interferon upregulation and interferon-induced endothelial injury, suggesting that complement-mediated injury is clinically relevant under conditions that feature interferon overproduction.

EVALI SYNDROME IN A PATIENT WITH HYPERSENSITIVITY PNEUMONITIS

Smoking electronic cigarettes, or vaping, is considered by many to be a safe alternative to smoking tobacco. It was only relatively recently that reports began to appear about the development of lung damage caused by electronic cigarettes - EVALI syndrome. Currently, the morphological manifestations of this syndrome have not been studied sufficiently due to the small number of cases described in the literature. These facts, as well as the fact that the changes that occur are not specific, and may vary in different patients, make it difficult to diagnose the disease in a timely manner. We have described a clinical case of death in a patient who has repeatedly received inpatient treatment for interstitial lung disease, who was admitted to the pulmonology department with signs of decompensated respiratory failure after prolonged and intensive use of electronic cigarettes. The autopsy revealed and substantiated clinical and morphological signs of chronic hypersensitive pneumonitis in combination with EVALI syndrome. The article also provides a brief literature review of the literature on EVALI and hypersensitive pneumonitis with their diagnostic criteria. Like EVALI, hypersensitive pneumonitis is difficult to recognize and diagnose by doctors, which is often associated with low awareness, as well as the absence of pathognomonic symptoms.

Pulmonary rehabilitation in patients with fibrotic interstitial lung disease

Cough, progressive exertional dyspnea, and exercise limitation are the main presenting symptoms in fibrotic interstitial lung disease (F-ILD). F-ILD is usually progressive, leading to heavy disease and socioeconomic burden. In addition to the drug therapy, pulmonary rehabilitation is an important part of comprehensive treatment in F-ILD patients. In recent years, the application of pulmonary rehabilitation in F-ILD patients has attracted the attention of clinicians and society. Meanwhile, pulmonary rehabilitation has widely applicated in F-ILD patients as it is beneficial to improve their symptoms, functional exercise and quality of life. This article provides a comprehensive review of pulmonary rehabilitation in F-ILD and proposes the principles and strategies, to prevent the progression or acute exacerbation of F-ILD and improve its application in F-ILD patients.

Luteolin-Loaded Hyaluronidase Nanoparticles with Deep Tissue Penetration Capability for Idiopathic Pulmonary Fibrosis Treatment.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by sustained fibrotic lesions. Orally administered drugs usually fail to efficiently penetrate the interstitial tissue and reach the lesions, resulting in low treatment efficiency. Luteolin (Lut)is a natural flavonoid, active metabolites of which possess antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. In this study, a nano-formulation is developed by loading Lut into hyaluronidase nanoparticles (Lut@HAase). These Lut@HAase nanoparticles (NPs) exhibit small size and good stability, suitable for noninvasive inhalation and accumulation in the lungs, and hyaluronidase at the site of lesions can degrade hyaluronic acid in the interstitial tissue, enabling efficient penetration of Lut. Lut's therapeutic effect, when administered via NPs, is studied both in vitro (using MRC5 cells) and in vivo (using IPF mice models), and its anti-fibrotic properties are found to inhibit inflammation and eliminate reactive oxygen species. Conclusively, this study demonstrates that Lut@HAase can improve lung function and enhance survival rates while reducing lung damage with few abnormalities during IPF treatment.