Search Results (216)

Background: Noninvasive echocardiographic markers are widely used to estimate left ventricular filling pressure, but their relationship with directly measured left ventricular end-diastolic pressure (LVEDP) is often modest and context-dependent. Whether routinely available noninvasive findings reflect elevated LVEDP through an intermediate invasive pulmonary hemodynamic phenotype remains insufficiently characterized. Objective: To evaluate the relationship of noninvasive echocardiographic and laboratory markers with directly measured LVEDP and to determine whether invasive pulmonary artery diastolic pressure (dPAP) functions as a hemodynamic bridge linking upstream noninvasive findings to elevated left ventricular filling pressure in a routine catheterization cohort. Methods: This retrospective single-center observational study included patients undergoing routine cardiac catheterization with available direct LVEDP measurement and invasive pulmonary artery pressure data. Elevated LVEDP was defined as LVEDP ≥ 15 mmHg, and elevated dPAP as dPAP ≥ 24 mmHg. Noninvasive, bridge, and invasive validation models were evaluated using logistic regression, receiver operating characteristic analysis, calibration assessment, and bootstrap internal validation. Results: A total of 75 patients had direct LVEDP data, 94 had invasive dPAP data, 83 had echocardiographic systolic pulmonary artery pressure (echo-sPAP), and 37 had pulmonary capillary wedge pressure (PCWP) measurements. Patients with elevated LVEDP had significantly higher creatinine (p = 0.026), dPAP (p = 0.043), and PCWP (p = 0.004). Echo-sPAP showed good discrimination for elevated dPAP, with an AUC of 0.791 (95% CI 0.695–0.888), supporting its role as an upstream noninvasive marker of invasive pulmonary hemodynamic burden. A noninvasive model combining echo-sPAP and creatinine showed modest discrimination for elevated LVEDP (AUC 0.664, 95% CI 0.522–0.806; Brier score 0.198), whereas an invasive validation model combining dPAP and creatinine showed better performance (AUC 0.734, 95% CI 0.617–0.850; Brier score 0.176). In bootstrap validation, the optimism-corrected AUCs were approximately 0.624 and 0.711, respectively. Although the invasive model performed numerically better, DeLong comparison did not show a statistically significant difference between the two models (p = 0.459). Conclusions: Routinely available noninvasive echocardiographic and laboratory findings appear to relate to directly measured left ventricular filling pressure through an intermediate invasive pulmonary hemodynamic pattern. Echo-sPAP showed its strongest signal at the level of elevated dPAP, whereas dPAP combined with creatinine provided the most informative model for elevated directly measured LVEDP. These findings support a hypothesis-generating hemodynamic framework linking noninvasive assessment to directly measured filling pressure and may help inform noninvasive hemodynamic triage and physiological risk enrichment in selected clinical settings. Full article

Background: The diffusing capacity of the lung for carbon monoxide (DLCO) is a key measure of alveolar–capillary gas exchange, but its clinical significance in chronic obstructive pulmonary disease (COPD) remains incompletely defined. This study aimed to characterize the demographic, clinical, functional, and comorbid profiles of COPD patients stratified by the degree of DLCO impairment, and to evaluate the potential value of DLCO as a marker for disease severity and clinical phenotyping in a Chinese cohort. Methods: This single-center retrospective cross-sectional study enrolled 650 patients diagnosed with COPD (according to GOLD 2025 criteria) who underwent pulmonary function tests between January 2024 and February 2025 at the university-town hospital of Chongqing Medical University. Patients were stratified by predicted DLCO% into four groups: normal (≥80%), mild impairment (60–79%), moderate impairment (40–59%), and severe impairment (<40%). Demographic, clinical, laboratory, pulmonary function, echocardiographic, and chest CT data were collected. Comparisons across groups were performed using ANOVA/Kruskal–Wallis tests, chi-square or Fisher’s exact tests, and Spearman correlation analysis (IBM SPSS Statistics 25.0). Due to the exploratory nature of the study, no adjustment for multiple comparisons was applied. Results: Progressive DLCO impairment was associated with a higher proportion of male patients (69.2% to 90.9%, p = 0.018), older age (67.3 ± 9.0 to 72.9 ± 6.7 years, p < 0.001), lower BMI (median from 23.9 to 20.0 kg/m², p < 0.001), and higher smoking prevalence (58.7% to 87.5%, p = 0.001). The prevalence of pulmonary tuberculosis rose markedly (0.58% to 9.09%, p = 0.037). All spirometric parameters declined (e.g., FEV1%pred from 67.3% to 32.6%, p < 0.001). Systemic inflammatory markers (NLR, SII) increased, while hemoglobin and albumin decreased (both p < 0.001). Respiratory failure occurred in 30.0% of the severe DLCO group (predominantly type I, p <0.001). Echocardiography revealed a decline in left ventricular ejection fraction (61.2 ± 5.0% to 59.1 ± 4.0%, p = 0.012) and a trend toward higher pulmonary hypertension risk (27.8%, p = 0.056). DLCO%pred correlated positively with FEV1%pred (r = 0.394, p < 0.001) and oxygen saturation (r = 0.151, p < 0.001), and negatively with NLR (r = −0.165, p < 0.001) and SII (r = −0.149, p < 0.001). Conclusions: In COPD, DLCO impairment is associated with distinct clinical phenotypes, including male sex, advanced age, malnutrition, increased tuberculosis risk, worse lung function, systemic inflammation, and respiratory/cardiac dysfunction. These findings support DLCO as a valuable complementary marker for disease severity characterization in COPD. Longitudinal studies are needed to confirm its prognostic value. Full article

Diffuse alveolar haemorrhage (DAH) is rare but associated with high morbidity and mortality. It is underpinned by mechanisms of endothelial dysfunction, inflammation, and vascular remodelling, yet its pathogenesis remains incompletely understood. Progress in translational research is currently limited by the absence of robust animal models of this condition. Equine exercise-induced pulmonary haemorrhage (EIPH), a common and progressive disorder in racehorses, may represent a novel and underutilised translational model for studying DAH, which can be a complication of or associated with other cardiopulmonary conditions, such as pulmonary arterial hypertension (PAH). EIPH occurs spontaneously in up to 95% of thoroughbreds after repeated strenuous exercise and is characterised by haemorrhage into the alveoli, capillary stress failure, inflammatory infiltration, and subsequent parenchymal remodelling. These processes closely parallel the vascular injury and immune activation observed in DAH. Horses further offer distinct advantages as models for human respiratory disease, including large lung size, long lifespan, and comparable pulmonary architecture. The regional distribution of haemorrhage in equine lungs additionally enables within-animal control studies. By leveraging the mechanistic overlaps between equine and human pulmonary pathology, EIPH provides a unique opportunity for biomarker discovery, mechanistic insight, and therapeutic testing in pulmonary vascular disease. Full article

Unravelling the cellular and molecular mechanisms underlying lung injury and repair requires precise spatial context. Profiling cell-to-cell transcriptional variability and spatial orientation has become increasingly sophisticated, but validating results at the protein level still remains challenging, particularly for low-expressed proteins or small-scale samples. Here, we present a workflow established by our group for spatial protein analysis in the lung by combining two commercially available platforms: (1) laser-assisted microdissection (LMD) with (2) a capillary electrophoretic-based immunoassay (CEI). Using this workflow, we demonstrate a simple, accessible, and sensitive method for spatially capturing regions of interest to investigate small-scale samples or low-expressed proteins. This workflow provides an additional option for orthogonal validation for researchers using omics-based approaches. Furthermore, we validated transcriptome analysis results at the protein level by applying this workflow to a pre-clinical model of cigarette smoke (CS)-induced lung injury. In line with the previous findings, the results showed a significant downregulation of the endothelial cell marker in LMD-enriched alveolar regions, suggesting spatial capillary rarefaction, and activation of the mitogen-activated protein kinase (MAPK) signalling pathway in pulmonary vasculature of CS-exposed mice. Our approach overcomes traditional challenges and provides new opportunities for understanding complex disease pathomechanisms and identifying potential therapeutic targets. Full article

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO₂ in the first 72 h were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD. Full article

High-altitude workers in the Los Andes Mountains, known as “the Chilean miner model,” are exposed to chronic intermittent hypobaric hypoxia (CIHH). This intermittent condition differs from other models of chronic hypoxia, mainly due to the hypoxic pattern and the cardiovascular and pulmonary effects. There are reports of cardiopulmonary dysfunction and remodeling in human and animal models. However, research on some mechanisms of vascular function and the consequences of lung remodeling induced by CIHH is still lacking. Therefore, this study aims to characterize the effects of CIHH exposure on lung structure and redox status in a rat model of the Chilean miner, involving intermittent exposure to chronic cycles of normoxia/hypobaric hypoxia (96 h/96 h) in an experimental hypoxic chamber. Our results demonstrate that CIHH acts as a primary driver of pulmonary vascular remodeling by significantly increasing the medial wall thickness of small pulmonary arteries (<100 μm) and promoting a shift toward a more muscularized phenotype in previously non-muscularized vessels. Structurally, this was characterized by a marked reduction in alveolar space and a significant increase in the thickness of the alveolar-capillary barrier, suggesting impaired gas exchange capacity. These structural changes were strongly associated with a pro-oxidant state, evidenced by increased lipid peroxidation (malondialdehyde levels) and a concomitant reduction in antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT), in lung tissue. In conclusion, the CIHH model effectively replicates the complex interplay between chronic oxidative damage and structural lung remodeling, identifying the thickening of the arterial medial wall and alveolar septa as key pathological features of probably CIHH-induced pulmonary hypertension. Full article

Background/Objectives: High-altitude pulmonary edema (HAPE) remains a serious condition with limited preventive options. This study evaluated the prophylactic protective effects of nebulized human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in a rat model of hypobaric hypoxia-induced lung injury and explored potential mechanistic clues, with a focus on oxidative stress and TEK/Tie2 signaling. Methods: Rats were exposed to hypobaric hypoxia (47 kPa; 9.7% O₂) for 72 h and received prophylactic nebulized hUC-MSC-EVs (300 μg/rat). Lung injury was evaluated by histopathology, wet-to-dry ratio, and bronchoalveolar lavage fluid (BALF) protein concentration. Invasive pulmonary function indices were measured using a forced oscillation system. BALF cytokines (TNF-α, IL-6, and IL-10), reactive oxygen species (ROS), and TEK/Tie2 expression in lung tissue were assessed. In addition, transcriptome sequencing (RNA-seq) was performed to characterize global transcriptional changes. N-acetylcysteine (NAC), a classical antioxidant, was included as an auxiliary mechanistic intervention to assess the association of ROS with TEK/Tie2 changes. Results: Compared with hypoxia controls, prophylactic nebulized hUC-MSC-EVs reduced histopathological injury, pulmonary edema, and barrier leakage, and improved pulmonary function indices. hUC-MSC-EV intervention also attenuated inflammatory responses in BALF, with decreased TNF-α and IL-6 and increased IL-10. Hypobaric hypoxia increased ROS accumulation and decreased TEK/Tie2 expression, whereas nebulized hUC-MSC-EVs reduced ROS and partially preserved TEK/Tie2 expression. NAC pretreatment similarly reduced ROS and was accompanied by Tie2 preservation. Conclusions: Prophylactic nebulized hUC-MSC-EVs mitigated hypobaric hypoxia-induced lung injury, accompanied by reduced oxidative stress, improved vascular barrier integrity, and preservation of TEK/Tie2 expression. These findings support nebulized hUC-MSC-EVs as a potential lung-targeted prophylactic strategy for hypobaric hypoxia-induced lung injury and suggest that ROS imbalance may be associated with Tie2 preservation. Full article

Pulmonary hypertension is a progressive syndrome characterised by pulmonary vascular dysfunction, inflammation, maladaptive remodelling, and progressive right-ventricular strain. Translational progress remains limited because experimental models reproduce only selected aspects of the complexity of human disease. This narrative review evaluates naturally occurring canine disease as a comparative and spontaneous model of human pulmonary hypertension within a One Health framework. To achieve this, we synthesise recent human and veterinary literature, international consensus statements, and key registry and imaging studies. We outline current human definitions and diagnostic pathways based on right-heart catheterisation, together with the veterinary probability-based approach centred on echocardiography; compare epidemiology across species; and summarise contemporary mechanisms spanning vascular dysfunction, immune and metabolic signalling, and right-ventricular adaptation. We then examine canine conditions that parallel major human pulmonary hypertension phenotypes, including left-heart disease due to myxomatous mitral valve degeneration, fibrotic interstitial lung disease in West Highland White Terriers, sleep-related airway obstruction in brachycephalic breeds, and rare venous and capillary disorders. When combined, these spontaneous models provide opportunities to investigate disease-modifying techniques other than vasodilation and allow for the longitudinal, real-world evaluation of imaging, functional assessments, and circulating biomarkers. To improve care for both veterinary and human patients, we conclude by outlining priorities for mechanism-based clinical trials, shared outcome measures, prospective registries and biobanks, and harmonised definitions. Full article

Background: Severe lung compromise from COVID-19, ARDS, and recently AH3N2 can progress to life-threatening hypoxia. Past experience led to standardized protocols that assumed similarity to SARS-CoV. Methods: COVID-19 pathophysiology and histopathological lung biopsy photomicrographs are analyzed. Results: Pneumolysis is defined as progressive alveolar–capillary destruction resulting from SARS-CoV-2 attack on pneumocytes. In the final stages preceding pneumolysis, molecular mechanisms in the lungs include apoptosis in alveolar epithelial type I and II cells, compromising alveolar regeneration, and necrosis, resulting in leakage of intracellular contents and amplifying inflammation. Pyroptosis, driven by inflammasome activity, further disrupts alveolar integrity in ARDS. Histopathological findings include Masson bodies, alveolar-coating cells with nuclear atypia, reactive pneumocytes and reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates and abscesses, microthrombi, hyaline membrane remnants, and emphysema. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are shown. Conclusions: Silent hypoxemia rapidly progresses to critical hypoxemia. This progression results from progressive pneumolysis, inflammation, immune overexpression, autoimmunity, and HAPE-type edema, leading to acute pulmonary insufficiency. Long-lasting COVID-19 can result in fibrosis and, as a compensatory mechanism, polierythrocythemia. The proposed treatment (based on tolerance to hypoxia and the hemoglobin factor) includes prompt oxygen administration, control of inflammatory and immune responses, antibiotics, rehydration, erythropoietin and platelet aggregation inhibitors. Full article

Acute respiratory distress syndrome (ARDS) remains a leading cause of morbidity and mortality in critically ill patients despite advances in supportive care and lung-protective ventilation. The syndrome is characterized by biological heterogeneity involving epithelial and endothelial injury, dysregulated inflammation, surfactant dysfunction, and impaired alveolar–capillary barrier integrity. This review integrates experimental, translational, and clinical evidence to examine the biological and molecular basis underlying ARDS, with particular emphasis on alveolar–capillary architecture, immune dysregulation, pulmonary mechanics, and the temporal evolution of diffuse alveolar damage. We further discuss emerging concepts in ARDS phenotyping and biomarker-based stratification as tools to address therapeutic heterogeneity and improve prognostic precision. Collectively, the evidence supports a shift from syndromic management toward biologically informed, precision-based approaches that may enable targeted interventions and improved clinical outcomes in ARDS. Full article

Background: Neonates and young infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) are highly vulnerable to pulmonary dysfunction, systemic inflammation, capillary leak, and fluid overload, which may lead to acute kidney injury (AKI) and the need for peritoneal dialysis (PD). Lung ultrasound (LUS) is a bedside, radiation-free tool that allows real-time assessment of lung aeration and pulmonary congestion. However, its role in predicting postoperative renal support remains limited. This study aimed to evaluate whether early postoperative LUS scores could predict the need for PD in neonates after congenital heart surgery with CPB. Methods: In this prospective single-center study, 53 neonates undergoing cardiac surgery with CPB between June 2025 and January 2026 were included. LUS was performed preoperatively and at 0–2 h, 24–48 h, 72 h, 120 h, and 168 h postoperatively using a standardized six-zone scoring system (0–18). The primary outcome was postoperative PD requirement. ROC analysis assessed predictive performance, and multivariable logistic regression identified independent predictors. Results: Total LUS scores significantly increased in the early postoperative period, remained elevated for 24–72 h, and gradually declined by days 5–7. Infants requiring PD (n = 16) had significantly higher LUS scores at 0–2 h, 24–48 h, and 72 h (p < 0.05). The 24–48 h (AUC = 0.784; sensitivity 87%, specificity 62% at cut-off ≥ 11.5) LUS score showed the best predictive value for PD (AUC = 0.831; sensitivity 86%, specificity 74% at cut-off ≥ 13). In multivariable analysis, higher LUS scores at 0–2 h (OR 1.625, p = 0.048) and 24–48 h (OR 1.621, p = 0.048) independently predicted PD. Conclusion: Postoperative LUS is a reliable, noninvasive tool that can aid in predicting the need for PD in neonates undergoing cardiac surgery with CPB, supporting timely fluid and renal management. Full article

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms by which uremic toxins affect lung tissue. Methods: A narrative review was conducted using keywords related to uremic toxins and lung injury to search the PubMed database. An advanced literature review was conducted in PubMed to identify studies explaining the mechanisms underlying lung pathophysiology in chronic kidney disease (CKD), with particular focus on CKD-induced pulmonary epithelial and endothelial dysfunction. Additionally, to highlight the pathological processes of lung congestion in CKD, studies on CKD-induced dysfunction of the alveolar-capillary barrier were retrieved. Studies published up to November 2025 were evaluated. Results: A total of 148 articles were reviewed in full text. Uremic toxins negatively impact lung tissue structure and function through multiple mechanisms, including oxidative stress, inflammation, and direct effects. Uremic toxins appear to share signaling pathways in endothelial cells, including those linked to Mitogen-activated protein kinases (MAPK), the Aryl Hydrocarbon Receptor (AhR), the receptor for advanced glycation end products (RAGE), and pro-inflammatory transcription factors such as nuclear factor κB (NF-κB). Additionally, oxidative stress acts as a pro-inflammatory signal shared by several uremic toxins. The mechanisms behind the harmful interactions between CKD and lung disease are mostly unknown, although more evidence exists for acute kidney injury (AKI). Conclusions: Chronic kidney disease, which leads to the buildup of uremic toxins, negatively affects the lungs. Overall, the accumulation of uremic toxins in CKD impairs endothelial and epithelial cells and the alveolar capillary barrier. Further research is needed to understand the specific mechanisms underlying these effects and to identify therapeutic options to protect the lungs in these patients. Full article

The vertebrate respiratory system arose under evolutionary pressures that linked increasing atmospheric oxygen levels to the metabolic demands of mitochondria. This transition—from ancestral gill-based exchange to the highly alveolated mammalian lung—was accompanied by the emergence of a hormonal regulatory axis centered on the glucocorticoid receptor alpha (GRα). Over time, GRα became deeply integrated into the architecture and function of the respiratory system, aligning pulmonary performance with organismal homeostasis across different developmental stages, environmental challenges, and disease states. This review combines evolutionary, embryological, and molecular evidence to explain how GRα shapes respiratory structure and function. We trace the evolution from ancient oxygen-sensing systems to mammalian alveoli and endothelial adaptations, demonstrating how conserved developmental pathways (including WNT, FGF, BMP, and SHH) are repurposed during both organogenesis and repair. Genetic models show that GRα is essential for preparing the lung for postnatal life, coordinating the reciprocal signaling between mesenchyme and epithelium that drives branching, septation, extracellular matrix organization, and the development of functional alveolar units. In the mature lung, GRα maintains the stability of the alveolar–capillary interface and coordinates immune, vascular, and metabolic functions to support efficient gas exchange. Its actions also extend to red blood cell biology and the regulation of stress erythropoiesis, linking pulmonary oxygen management with systemic oxygen delivery. Mechanistically, GRα interacts with circadian and hypoxia pathways and activates mitochondrial programs that enhance energy production and redox homeostasis during stress. By integrating these regulatory layers across developmental and physiological contexts, this review reframes GRα not simply as a stress-response receptor but as a non-redundant system-level integrator of respiratory homeostasis. Understanding this layered control not only explains the benefits of antenatal corticosteroids but also highlights the therapeutic value of phase-specific, precision modulation of the GC–GRα axis—along with strategies that support GC–GR signaling—to reestablishing and maintaining homeostasis in acute and chronic pulmonary disorders. Full article

Cardiogenic pulmonary edema (CPE) is a life-threatening manifestation of acute heart failure characterized by rapid accumulation of fluid in the interstitial and alveolar spaces, leading to severe dyspnea, hypoxemia, and respiratory failure. The condition arises from elevated left-sided filling pressures that increase pulmonary capillary hydrostatic pressure, disrupt alveolo-capillary barrier integrity, and impair gas exchange. Neurohormonal activation further perpetuates congestion and increases myocardial workload, creating a vicious cycle of hemodynamic overload and respiratory compromise. Respiratory support is a cornerstone of management in CPE, aimed at stabilizing oxygenation, reducing the work of breathing, and facilitating ventricular unloading while definitive therapies, such as diuretics, vasodilators, inotropes, or mechanical circulatory support (MCS), address the underlying cause. Among available modalities, non-invasive ventilation (NIV) with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) has the strongest evidence base in moderate-to-severe CPE, consistently reducing the need for intubation and providing rapid relief of dyspnea. High-flow nasal cannula (HFNC) represents an emerging alternative in patients with moderate hypoxemia or intolerance to mask ventilation, and should be considered an adjunctive option in selected patients with less severe disease or NIV intolerance, although its efficacy in severe presentations remains uncertain. Invasive mechanical ventilation is reserved for refractory cases, while extracorporeal membrane oxygenation (ECMO) and other advanced circulatory support modalities may be necessary in cardiogenic shock. Integration of respiratory strategies with hemodynamic optimization is essential, as positive pressure ventilation favorably modulates preload and afterload, synergizing with pharmacological unloading. Future directions include personalization of ventilatory strategies using advanced monitoring, novel interfaces to improve tolerability, and earlier integration of MCS. In summary, respiratory support in CPE is both a bridge and a decisive therapeutic intervention, interrupting the cycle of hypoxemia and hemodynamic deterioration. A multidisciplinary, individualized approach remains central to improving outcomes in this high-risk population. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar-capillary membrane remodeling and impaired gas diffusion. The diffusing capacity of the lung for nitric oxide (DLNO) has been proposed as a physiological parameter reflecting membrane diffusing capacity and pulmonary vascular involvement, potentially providing complementary information to diffusing capacity of the lung for carbon monoxide (DLCO). This study aimed to evaluate the role of DLNO in the functional assessment of patients with IPF and its correlation with clinical and echocardiographic outcomes. Materials and Methods: This observational, retrospective study included 35 consecutive IPF patients receiving antifibrotic therapy between February and December 2023. All participants underwent plethysmography, combined single-breath DLNO and DLCO testing, six-minute walk test (6MWT), mMRC dyspnea scale assessment, and echocardiography for the estimation of a higher probability of pulmonary hypertension (PH). Results: DLNO was significantly lower in males compared to females (49.3 ± 16.7% vs. 74.6 ± 16.1%, p < 0.001), with a reduced DLNO/DLCO ratio in men. DLNO correlated with oxygen therapy requirement (p = 0.010) and lower oxygen saturation during the 6MWT (p = 0.021). Patients with higher echocardiographic probability of PH showed markedly reduced DLNO values (17.6 ± 7.6%, p = 0.016) and higher FVC/DLNO ratios (2.31 ± 0.85 vs. 1.65 ± 0.64, p = 0.023), together with lower DLCO levels (p = 0.037). Conclusions: DLNO may complement DLCO in the evaluation of gas exchange and alveolar-capillary dysfunction in IPF. Although preliminary, these findings support the potential clinical utility of DLNO as an adjunct parameter in the functional characterization of IPF. Further multicenter studies are warranted to confirm these results. Full article