Search Results (296)

Major airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and chronic rhinosinusitis without nasal polyps (CRSsNP), frequently coexist and share inflammatory, epithelial and remodeling features. However, whether these clinically distinct airway disorders are driven by a unified genetic liability and how this shared liability maps to disease-relevant tissues, genes and immune-regulatory programs remain incompletely understood. We integrated GWAS summary statistics for COPD, asthma, bronchiectasis and CRSsNP using linkage disequilibrium score regression, local genetic correlation analysis and Genomic structural equation modeling. A latent shared airway disease factor, termed gAirwayDisease, was constructed to capture common genetic liability across the four conditions. We then applied an integrative functional genomics framework, including gsMap spatial enrichment, PoPS gene prioritization, MAGMA gene-set enrichment, GTEx v8 lung MTWAS, OneK1K and DICE immune-cell MTWAS, scMORE regulon analysis and phenome-wide Mendelian randomization. All six airway disease pairs showed positive genetic correlations, with estimates ranging from 0.508 to 0.685. Genomic SEM supported a single shared factor, with positive standardized loadings for COPD, asthma, bronchiectasis and CRSsNP and excellent model fit. Spatial mapping localized gAirwayDisease-associated signals to airway- and epithelial-associated anatomical domains. PoPS prioritized immune and airway-relevant genes, including SMAD3, GATA3, IL1R1, RUNX3 and STAT6, while MAGMA enrichment highlighted B-cell activation, T-cell activation and transcriptional regulatory pathways. Lung MTWAS identified SLC9A2 and ORMDL3 as top genetically regulated expression signals. OneK1K immune-cell MTWAS highlighted recurrent IL18R1 associations across CD4 and CD8 T-cell subsets. scMORE further identified 36 significant regulon–cell type pairs across dendritic cells, B cells, monocytes, T cells and NK cells, including BCL11A, TCF4, KLF4, RUNX1 and STAT4 regulons. MR-PheWAS linked genetically predicted gAirwayDisease to respiratory, allergic, lung function and immune-related traits. This study defines gAirwayDisease as a genetically informed latent factor capturing shared liability across major airway diseases. Integrated functional genomic analyses highlight airway epithelial and immune regulatory programs associated with shared disease susceptibility and prioritize candidate genes and regulons for future experimental validation. Full article

Advancements in pulmonary drug delivery have enabled effective treatment approaches for more severe disease conditions, such as chronic obstructive pulmonary diseases, asthma, cystic fibrosis, and other pulmonary disorders, via targeted, sustained, and immediate drug delivery routes with minimal systemic side effects. However, conventional delivery systems have many limitations, such as poor drug targeting, adherence, and deposition, which ultimately cause variations in drug profiles and therapeutic efficacy. Recent advances in artificial intelligence (AI) and machine learning (ML) have enabled the development of smart inhaler drug–device combination systems for personalized therapy using predictive formulation parameters, design variables, device performance, and inhalation pattern monitoring. Advanced AI techniques, such as artificial neural networks, deep learning, random forests, support vector machines, deep learning algorithms, and computational modeling, predict the mass median aerodynamic diameter (MMAD), fine-particle fraction (FPF), emitted dose, and regional lung deposition. Smart inhalation devices coupled with digital sensors and computing systems enable the real-time monitoring of inhalation profiles and adherence. Moreover, AI- and ML-enabled Quality by Design (QbD) and digital twin framework technologies enhance the optimization of manufacturing process parameters, consistency, robustness, and scale-up performance. Although several developments have been reported, there is still room for improvement in terms of data heterogeneity, algorithm transparency, interpretability, cybersecurity, regulations, and long-term clinical standardization. This review emphasizes the use of AI to improve the performance of pulmonary drug delivery through smart inhaler drug–device combination therapies, focusing on technological advancements, formulation optimizations, smart inhalers, regulatory issues, current limitations, and future perspectives of AI-based pulmonary drug delivery. Full article

Background: Chronic obstructive pulmonary disease (COPD) is frequently accompanied by psychological distress, but the relationship between GOLD stage, dyspnea, functional limitation, and depression/anxiety symptoms remains incompletely defined. This study examined clinical and psychological profiles across GOLD stages, with particular attention to GOLD stages 3 and 4. Methods: This multicenter observational study included 285 adults with spirometry-confirmed COPD evaluated in Romania between 2023 and 2026. COPD severity was classified according to GOLD stages. Clinical assessment included FEV1, peripheral oxygen saturation, smoking exposure, the COPD Assessment Test (CAT), and the modified Medical Research Council dyspnea scale (mMRC). Psychological and well-being measures included DASS depression, anxiety, and stress scores; WHO-5; major depressive disorder score, and generalized anxiety disorder score. Descriptive analyses were performed across GOLD stages, and GOLD 3 was directly compared with GOLD 4. Results: GOLD 3 was the largest subgroup (n = 106, 37.2%), followed by GOLD 4 (n = 81, 28.4%), GOLD 2 (n = 69, 24.2%), and GOLD 1 (n = 29, 10.2%). GOLD 3 patients showed marked dyspnea and symptom burden, with mean mMRC = 2.92 and CAT = 24.44. DASS depression, anxiety, and stress scores were higher in GOLD 3 than GOLD 2, but did not increase further in GOLD 4. Direct GOLD 3 versus GOLD 4 comparisons showed no significant differences in DASS depression or DASS anxiety, whereas GOLD 4 had a significantly higher mMRC, major depressive disorder score, and generalized anxiety disorder score. Conclusions: GOLD 3 COPD was associated with substantial dyspnea, functional limitation, and measurable psychological distress. However, depression and anxiety patterns varied by instrument, suggesting that psychological burden in COPD is multidimensional and not explained by spirometric severity alone. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a prevalent chronic disorder whose first-line treatment, continuous positive airway pressure (CPAP), is effective only if the patient maintains sufficient adherence. Early predictions of the risk of low adherence would make it possible to personalize follow-up and optimize healthcare resources. The aim of this study was to develop and evaluate a machine-learning-based clinical decision support system to predict CPAP adherence after one year of treatment. Methods: A cohort of 200 patients with OSA from the Sleep-Disordered Breathing Unit of Hospital Álvaro Cunqueiro in Vigo was used. The cohort was split into a training set (n = 160) and an independent test set (n = 40). Two scenarios were defined: Scenario A, with pre-treatment variables, and Scenario B, which also includes early adherence metrics. In each scenario, variables were selected through recursive feature elimination. The selected variables were apnea-hypopnea index (AHI), 3% oxygen desaturation index (ODI3%), chronic obstructive pulmonary disease and neck circumference in Scenario A, and first-month adherence, ODI3% and AHI in Scenario B. Once these subsets were defined, several classifiers were analyzed. Results: Random Forest was the model selected in both scenarios. On the test set, Scenario A reached an area under the curve (AUC) of 0.71 (sensitivity 0.83; specificity 0.45) and Scenario B an AUC of 0.91 (sensitivity 0.90; specificity 0.82). Conclusions: Early prediction of CPAP adherence using machine learning is feasible; incorporating real first-month use markedly improves discriminative ability. The system was integrated into a web prototype as a proof of concept. Given the modest sample size and the absence of external validation, these results should be interpreted as preliminary, corresponding to an exploratory, feasibility study. For future implementation, an extensive clinical validation process will be required, along with the expansion of the database, which will likely contribute to improving the system’s robustness and generalization capacity. Full article

Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous chronic airway disorders characterized by complex interactions among inflammation, immune dysregulation, environmental exposures, and tissue remodeling. Conventional clinical classifications based on symptoms, lung function, and exacerbation history often fail to fully capture the biological mechanisms underlying disease progression and therapeutic variability. Methods: This narrative review summarizes current evidence regarding the biological and clinical significance of YKL-40, mannose-binding lectin (MBL), and epigenetic remodeling in asthma and COPD, with particular emphasis on the inflammation–epigenetic axis and its potential role in disease phenotyping and precision medicine. Results: Available evidence suggests that YKL-40, MBL, and epigenetic signatures represent complementary biomarker layers reflecting tissue remodeling, innate immune variability, and cumulative inflammatory adaptation, respectively. Chronic inflammatory signaling, oxidative stress, and epigenetic remodeling may contribute to persistent molecular memory and phenotypic stabilization, providing a mechanistic framework for understanding disease heterogeneity and progression. Advances in multi-omics technologies, artificial intelligence, and machine learning are further supporting the development of integrated multimarker models. Conclusions: YKL-40, MBL, and epigenetic signatures should currently be considered complementary research variables rather than validated clinical tools. Their translation requires disease-specific assay standardization, prospective evaluation against prespecified outcomes, external validation, and evidence that biomarker-guided decisions improve patient care. Full article

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder that affects millions of people globally. Although the mechanisms of COPD pathogenesis are not completely known, oxidative stress and lung inflammation caused by chronic exposure to cigarette smoke, environmental or occupational pollutants, gas from burning biomass fuel are thought to contribute to development of COPD. Therefore, therapies aimed at reducing oxidative stress along with inflammation may be important in treating COPD. However, the current pharmacological therapies treat symptoms and reduce acute exacerbations, but do not treat the root cause of COPD. Quercetin is a plant polyphenol present in berries, apples and onions, and has potent antioxidant and anti-inflammatory properties. Quercetin inhibits oxidative stress by scavenging reactive oxidant species and promoting expression of antioxidant enzymes. It reduces inflammation by inhibiting various kinases that participate in the expression of pro-inflammatory cytokines. It also alters gene expression by functioning as an epigenetic modifier. Quercetin also acts as antiviral agent by attenuating viral entry and replication. In preclinical models of COPD, quercetin reduces oxidative stress, lung inflammation, goblet cell metaplasia, expression of matrix metalloprotease MMP-9 and MMP-12, and prevents rhinovirus-induced progression of emphysema. It also promotes normal regeneration of airway epithelium by improving cell polarization, reducing goblet cell hyperplasia and increasing number of ciliated cells. This review compiles the current understanding of the biological properties of quercetin and its potential therapeutic role in COPD. We also summarize its potential benefits over the current therapeutic drugs used to treat COPD. Full article

Background: Sickle cell disease (SCD) is the most common inherited blood disorder globally, affecting approximately 300,000 newborns annually. Cardiac remodeling, resulting from chronic anemia, vascular obstruction, and endothelial dysfunction, substantially contributes to morbidity and mortality in patients with SCD. Therefore, characterizing these patterns is essential to clinical management and outcome improvement in pediatric patients. However, a comprehensive synthesis of cardiac remodeling patterns in pediatric and adolescent patients with SCD and their associations with genotype and clinical severity is lacking. Methods: We conducted a systematic review in accordance with the PRISMA 2020 guidelines and searched five databases for studies published from January 1978 to December 2024. Of 1131 retrieved studies, 37 met the inclusion criteria; of these, 31 focused exclusively on children (Group A), while six included both children and adults (Group B). We analyzed cardiac remodeling patterns, genotype-specific findings, associations with disease severity, and imaging modalities. The 37 studies included approximately 4253 patients from 12 countries, representing diverse populations and imaging techniques. Results: Left ventricular (LV) dilation was the most frequently reported finding, noted in 33 of 37 studies (89.2%; representing study-level reporting frequency, not patient-level prevalence), followed by diastolic dysfunction (reported in 18 of 37 studies; 48.6%); elevated TRV (≥2.5 m/s) as an echocardiographic screening marker for pulmonary hypertension (PH) risk was found in 14 of 37 studies (37.8%; TRV ≥ 2.5 m/s is a screening criterion, not confirmed hemodynamic PH); myocardial fibrosis was found in three studies (8.1%, exclusively from mixed-age cohorts); and QTc prolongation/arrhythmia was found in one study (2.7%). The HbSS genotype was associated with the most severe cardiac changes. Studies that did not stratify by genotype subtype (HbS/β⁰ vs. HbS/β⁺) may underestimate cardiac severity in mixed-genotype cohorts. Markers of disease severity, such as elevated lactate dehydrogenase (LDH) expression, frequent acute chest syndrome (ACS), and increased hospitalizations, were associated with more pronounced cardiac remodeling in individual studies, but the cross-study consistency of this association varied. Study designs and imaging modalities also varied, underscoring the need for standardized assessment protocols to enhance comparability and clinical translation. This review presents a narrative synthesis; individual study statistics are reported as originally published, without formal pooled estimates. Conclusions: Cardiac abnormalities in SCD were reported from early childhood, with more advanced phenotypes being more frequently described in older adolescents and mixed-age cohorts, suggesting possible age-related progression requiring prospective confirmation. Principal limitations include retrospective PROSPERO registration (CRD420261435382), the predominance of cross-sectional study designs, the inconsistent z-score normalization of cardiac dimensions, the incomplete reporting of treatment exposure, the disproportionate contribution of mixed-age cohorts to advanced imaging findings, and inter-study heterogeneity in echocardiographic protocols. Full article

Background/Objectives: Accurate diagnosis of lymph node pathology is essential for the management of both malignant and benign diseases. This study compares the diagnostic performance of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a real-world cohort. Methods: A single-center retrospective observational study was conducted, including 91 patients who underwent both cryobiopsy and EBUS-TBNA for lymph node evaluation. EBUS-TBNA was performed with a 19-G needle and cryobiopsy with a 1.1 mm flexible cryoprobe. Clinical characteristics, positron emission tomography–computed tomography (PET–CT) findings, ultrasonographic characteristics of the lymph nodes, diagnostic yield, and procedure-related complications were analyzed. Diagnostic accuracy, sensitivity, specificity, and factors associated with correct diagnosis were assessed. Results: The median age of the cohort was 65 years [interquartile range-IQR-56–74], 63.7% were male, and 74.7% were former or current smokers. Malignant disease was ultimately diagnosed in 60 patients (65.9%), of whom 78.3% had non-lymphoproliferative tumours and 21.7% had lymphoproliferative malignancies. The diagnostic accuracy of cryobiopsy was 89%, compared with 82.4% for EBUS-TBNA. The paired comparison between the two techniques did not reach statistical significance. After exclusion of non-diagnostic samples, sensitivity was numerically higher for cryobiopsy (96.4%, 95% CI 90.7–100) than for EBUS-TBNA (88.9%, 95% CI 79.6–98.2). Factors associated with correct diagnosis included chronic obstructive pulmonary disease for cryobiopsy, cardiovascular comorbidities, and maximum SUV for EBUS-TBNA. In malignant lesions, cryobiopsy showed higher diagnostic accuracy than EBUS-TBNA (90% vs. 80% accuracy), particularly in lymphoproliferative diseases. In benign lesions, both techniques agreed in 17 (54%) of cases, with cryobiopsy showing a higher yield for sarcoidosis and contributing to the diagnosis of tuberculosis. Complications were infrequent and minor, with no major adverse events reported. Conclusions: Cryobiopsy showed numerically higher diagnostic accuracy and sensitivity compared with EBUS-TBNA, particularly in malignant and lymphoproliferative disorders, with a favorable safety profile. These findings support its role as a valuable complement—or alternative—to conventional EBUS-TBNA in the assessment of mediastinal lymph nodes. Full article

Occupational chronic obstructive pulmonary disease (O-COPD) represents a lung disorder attributable to occupational exposures that are characterized by early development of airway remodeling and pulmonary fibrosis. O-COPD is poorly recapitulated by existing preclinical models. This study aimed to perform comparative characterization of an O-COPD patient cohort exposed to industrial aerosols and to develop a relevant murine model that accurately mirrors the human pathology. In the patient cohort, it was shown that the O-COPD phenotype is associated with the chemical composition of industrial aerosols and mediated by a specific inflammatory pattern with predominant obstructive changes and increased bronchial reactivity upon exposure to metal particles, as well as irreversible fibrotic changes in the lungs upon exposure to silicon dioxide. In the murine model, silica nanoparticles (SiNPs) or magnetic nanoparticles (MNPs) were utilized. Repeated intranasal SiNP administrations have been shown to reflect one of the main features of O-COPD—progressive airway remodeling and fibrosis, observed even after elimination of SiNPs. Administration of MNPs in the same regimen did not result in fibrotic changes in the lungs, partially recapitulating the human pathology resulting from exposure to the complex composition of industrial aerosols as well as the specific properties of chemically synthesized nanoparticles. Thus, the integrative data from the human cohort and animal model provides a reflective platform to advance the investigation of O-COPD mechanisms and development of interventions for fibrotic lung pathology. Full article

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive respiratory disorder characterized by airflow limitation, chronic inflammation, and structural lung alterations. Despite advances in clinical monitoring, current approaches such as spirometry, symptom scores, and imaging remain limited in capturing disease complexity and early pathophysiological changes. In this context, microRNAs (miRNAs) have emerged as promising molecular biomarkers due to their involvement in key inflammatory and immune pathway regulation. Sputum is gaining attention as a non-invasive and informative matrix for studying COPD. As a surrogate of airway mucus, sputum reflects local pathological processes, including inflammation and tissue damage, and contains biomarkers such as miRNAs. Compared to circulating miRNAs, sputum-derived miRNAs appear to more accurately represent lung-specific alterations. In this review, we focus on works published so far about the identification of miRNAs in COPD sputum. Several miRNAs have been associated with COPD diagnosis, severity, and exacerbations. These findings, including the possible correlation of some miRNAs with sputum biophysical properties, support the value of integrated biomarker approaches. While further large-scale and standardized studies are required to validate the role of COPD miRNAs assessed in sputum, their evaluation in sputum represents a promising tool for improving the diagnosis, phenotyping and monitoring of COPD. Full article

Background/Objective: Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) are among the most prevalent respiratory disorders worldwide and frequently coexist in the same patient. However, the contribution of active TB and post-tuberculosis lung disease to COPD exacerbations and long-term prognosis remains incompletely defined. This paper aim to evaluate the prevalence, clinical correlates, and prognostic significance of tuberculosis and its sequelae in patients with COPD. Materials and methods: We conducted a population-based retrospective cohort study using de-identified data from the regional healthcare information system. The cohort included all adults aged 18 years or older with a recorded diagnosis of COPD (ICD-10 code J44). Tuberculosis was identified by codes A15–A19 and B90. The primary outcomes were COPD exacerbations and all-cause mortality. Group comparisons, cluster analysis, Kaplan–Meier survival analysis, Cox proportional hazards modeling, and multivariable logistic regression were performed. Results: Tuberculosis and/or its sequelae were identified in 267 of 16,714 patients (1.60%): post-TB sequelae (B90) in 197 (73.8%), active TB (A15–A19) in 22 (8.2%), and both in 48 (18.0%). Compared with patients without TB, those with COPD-TB were younger (63.5 ± 14.2 vs. 65.7 ± 14.7 years; p = 0.018), more often male (75.3% vs. 52.0%; p < 0.001), and had higher mortality (16.5% vs. 10.6%; p = 0.003). COPD-TB was associated with bronchiectasis (OR = 6.07; 95% CI, 3.03–12.16), pulmonary fibrosis (OR = 5.67; 95% CI, 3.40–9.45), and pneumonia (OR = 2.01; 95% CI, 1.50–2.71), but with lower prevalences of obesity, diabetes mellitus, and hypertension. Patients with TB experienced more COPD exacerbations, including recurrent exacerbations. In multivariable models, tuberculosis was associated with COPD exacerbations after adjustment for age and sex (adjusted OR = 1.43; 95% CI, 1.05–1.96); this association was attenuated and lost significance after further adjustment for post-tuberculosis structural lung disease, indicating that it is largely mediated by post-TB sequelae. Tuberculosis remained associated with mortality after adjustment for available covariates, both in logistic regression (adjusted OR = 1.61; 95% CI, 1.14–2.28) and in Cox analysis (hazard ratio = 1.37; 95% CI, 1.01–1.85). Conclusions: Tuberculosis and post-tuberculosis lung disease are clinically accessible risk markers associated with COPD exacerbations and mortality. These findings support recognizing patients with COPD and a history of TB as a high-risk subgroup requiring intensified follow-up, proactive exacerbation prevention, and prioritized vaccination counseling. In the context of personalized medicine, a documented history of tuberculosis and post-tuberculosis lung changes represents a clinically accessible marker that can be used to stratify individual risk and to tailor monitoring and prevention in patients with COPD. Full article

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted in response to food intake that acts biologically by binding to GLP-1 receptors. The primary function of GLP-1 is to stimulate insulin secretion and inhibit glucagon secretion, which helps limit after-meal spikes in blood glucose. GLP-1 reduces intestinal contractility, slows down gastrointestinal motility and emptying, and also acts directly on the hypothalamus, thereby regulating appetite and food intake. Due to its metabolic effects, GLP-1 forms the basis of medications currently used to treat type 2 diabetes (T2DM) and obesity. However, it has also been observed that the use of GLP-1 agonists in the treatment of obesity or diabetes has a beneficial effect on comorbid respiratory conditions. This narrative review analyzes the scientific literature and describes the most recent information on the impact of GLP-1 receptor agonist (GLP-1 RA) therapies on the most common respiratory disorders—both the beneficial and undesirable effects. We discuss evidence that acute lung injury, COVID-19, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea can benefit from therapies with various GLP-1 RAs. They can complement existing lung-targeted treatments, but as research progresses, they are likely to play an ever more important role in the treatment of respiratory diseases. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline. Full article

Burden of diseases measured as disability-adjusted life years (DALYs) per 100,000 people can be mined from public domain data, when they are made available by population health surveillance systems. This can be analysed to allow insightful comparisons with the national average, and to understand differences in trends between the sexes, age groups, time periods, geographic regions, and sub-regions. In this illustrative case study, we have analysed the Scottish burden of disease database to understand what ailed the population of the Grampian region before the COVID-19 pandemic. We have identified that selected cancers, ischaemic heart disease, Alzheimer’s disease and other dementias are amongst the highest contributors to the burden; that drug use disorders and colorectal cancer are showing worsening trends and require health promotion and disease prevention measures from ages 15 and 25, respectively, especially in Aberdeen City; and that males are more vulnerable to atrial fibrillation and flutter, diabetes mellitus, oesophageal cancer, and self-harm, while females are more vulnerable to cerebrovascular and chronic obstructive pulmonary diseases. We demonstrate the usefulness of our analysis and methodology for the wider health system, allowing targeted medical research investments and coordinated response from public health and health service delivery. We also show the need for up-to-date surveillance data, forecasts, and evidence on the impact of interventions to be made available widely. Full article

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions. Full article