Search Results (223)

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

Pulmonary fibrosis (PF) is characterized by excessive collagen deposition and impaired lung function. Pulmonary surfactant may modulate fibroblast activity and offer therapeutic benefits. We developed a natural porcine pulmonary surfactant (NPPS) enriched with 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) and evaluated its biophysical and biological properties. Biophysical analysis showed that PE improved surfactant performance by increasing surface pressure and stability. In vitro, NPPS-PE reduced collagen expression and induced apoptosis in normal human lung fibroblasts; in addition, it decreased proliferation in fibroblasts stimulated with TGF-β. In vivo, NPPS-PE improved gas exchange and significantly reduced collagen deposition in bleomycin-treated mice. These findings suggest that NPPS-PE may be a promising therapeutic strategy for fibrosing lung diseases. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2^−ΔΔCt method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Results: Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients (p < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (p < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases (p < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (p < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. Conclusions: COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity. Full article

Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of K. pneumoniae. Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against K. pneumoniae in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm² of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% m/v) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log₁₀) in K. pneumoniae viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against K. pneumoniae, even in the presence of lung surfactant, a necessary step before the in vivo experiments. Full article

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

Background: Children’s interstitial and diffuse lung diseases, commonly referred to as “chILDs”, include around 200 rare conditions that disrupt normal lung function. They are classified, based on etiopathogenesis, into several subgroups, having a varied and multifaceted clinical presentation depending on the type of genetic mutation present. Methods and Results: We describe the case of a late preterm newborn presenting soon after birth with respiratory distress syndrome poorly responsive to surfactant administration, in whom a targeted gene panel analysis for pulmonary congenital diseases, performed using next-generation sequencing (NGS), revealed a novel compound heterozygous variant of the ATP-Binding-Cassette-Subfamily-A-Member-3 (ABCA3) gene. A review of the literature on the subject completes our work. Conclusions: Molecular genetic analysis has become crucial for a more targeted therapeutic treatment, along with the only current curative treatment option that is lung transplantation. Full article

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that worsen patients’ prognosis. This growth of malignant cells on a fibrotic background has also been called scar-cinoma. For this reason, not only an early diagnosis but also personalized decisions on the best treatment approach should be considered for each patient in a multidisciplinary discussion, since in some cases chemotherapy or surgery could be detrimental for patients with pulmonary fibrosis. LC and lung fibrosis may share common pathogenetic mechanisms like an altered healing process in response to repeated tissue damage from environmental exposure in genetically susceptible individuals. Smoking history and air pollution together with mutations in telomere and surfactant protein genes lead to the production of cytokines and nitro derivatives in the microenvironment that facilitate the carcinomatous transformation during fibrogenesis. The evolution of LC therapy and the implementation of immunotherapy acting on targetable immune checkpoints have raised interest in evaluating ILD-LC actionable mutations. The main pathogenetic mechanisms, clinical presentations and treatment implications are presented in this review. Full article

Background/Objectives: The usefulness of presepsin, which is released from macrophages, in acute exacerbation of interstitial lung diseases (AE-ILDs) is unknown. We aimed to investigate the utility of monitoring presepsin with other AE-ILD markers before and after steroid pulse therapy in AE-ILDs. Methods: This pilot single-center retrospective observational study involved 16 patients with AE-ILDs, including the AE of idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia and rapidly progressive connective tissue disease-associated ILD. Patients who survived 90 days were assigned to the survival group (n = 9). The remaining patients were classified in the non-survivor group (n = 7). To evaluate the therapeutic efficacy of steroid pulse therapy, specific serum markers were selected—presepsin, as a novel AE-ILD marker, and surfactant protein D, C-reactive protein, and lactate dehydrogenase (LDH), as classical AE-ILD markers. Results: Thirteen out of sixteen patients with AE-ILDs showed high presepsin levels (presepsin ≥ 470 pg/mL) before steroid pulse therapy. The post-/pre-presepsin ratio and the post-/pre-LDH ratio, calculated by dividing the presepsin and LDH levels after therapy by the levels before therapy, respectively, showed a positive correlation (r = 0.579, p = 0.021). As a result of this correlation, the post-/pre-presepsin–LDH index was created, obtained from the “post-/pre-presepsin ratio” multiplied by the “post-/pre-LDH ratio”. In a receiver operating characteristic curve analysis for non-survival, the post-/pre-presepsin–LDH index showed good discrimination as a prognostic marker for a poor outcome (AUC: 0.873, 95% confidence interval: 0.655–0.999). Conclusions: Tracking presepsin and LDH simultaneously may be useful for determining treatment response to steroid pulse therapy in the clinical management of AE-ILDs. Full article

Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). Methods: The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. Results: The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of −15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC₅₀ (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. Conclusions: The inhalable NE-Cela formulation improved Cela’s physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment. Full article

Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD. Full article

Background/Objectives: Critical lung infection affects alveolar cells and probably also their ability to perform surfactant procedures, but bedside tools for monitoring lung surfactants are lacking. In this descriptive exploratory study, we aimed to evaluate lung surfactant levels in bronchial aspirate (BA) from patients admitted to the intensive care unit due to severe respiratory failure. Methods: Bronchial aspirates were collected from nine patients (median age: 72 years, range: 52–85) who required orotracheal intubation. Samples were obtained within 24 h of mechanical ventilation initiation (T1), after three days on a ventilator (T2), and on day seven (T3) for four patients. The concentration of dipalmitoylphosphatidylcholine (DPPC), a key surfactant component, was assessed in the lamellar body precipitate. Results: Across the nine patients at T1, the DPPC level was 12 µM (range: 3–20 µM). By T2, the DPPC level declined to 8 µM (range: 2–22 µM), with a statistically significant decrease from T1 (p = 0.0039). At T3, the DPPC level in four patients ranged from 2 to 5 µM, though the difference from T2 was not statistically significant. A surfactant biomarker would assist clinical decision-making when dealing with patients in severe respiratory failure where exogenous surfactant therapy may be considered. Conclusions: DPPC levels obtained from bronchial aspirate can be measured in patients with severe respiratory failure and may serve as a useful biomarker for lung surfactant status, which suggests the potential for bedside assessment in clinical practice with a dedicated test device. Full article

Lung ultrasound (LUS) has become a crucial part of the investigative tools available in the management of critically ill patients, both within the intensive care unit setting and in prehospital medicine. The increase in its application, in part driven by the COVID-19 pandemic, along with the easy access and use of mobile and handheld devices, allows for immediate access to information, reducing the need for other radiological investigations. LUS allows for the rapid and accurate diagnosis and grading of respiratory pathology, optimisation of ventilation, assessment of weaning, and monitoring of the efficacy of surfactant therapies. This, however, must occur within the framework of accreditation to ensure patient safety and prevent misinterpretation and misdiagnosis. This narrative review aims to outline the current uses of LUS within the context of published protocols, associated pathologies, LUS scoring systems, and their applications, whilst exploring more novel uses. Full article

Respiratory diseases are major health concerns worldwide. Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide and some of the most common are chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases, and pulmonary hypertension. Despite having different etiology and characteristics, these diseases share several features, such as a persistent inflammatory state, chronic oxidative stress, impaired mucociliary clearance, and increased alveolar surface tension. CRDs are not curable; however, various forms of treatment, that help restore airway patency and reduce shortness of breath, can improve daily life for people living with these conditions. In this regard myo-inositol may represent a valid therapeutic adjuvant approach due to its properties. Being a redox balancer, an inflammation modulator, and, most importantly, a component of pulmonary surfactant, it may improve lung function and counteract symptoms associated with respiratory diseases, as recently evidenced in patients with COPD, COVID-19, asthma, and bronchiectasis. The aim of this review is to evaluate the potential therapeutic role of myo-inositol supplementation in the management of patients with respiratory diseases. Full article

Neonatal respiratory distress syndrome (RDS) is a common and potentially life-threatening condition in preterm infants, primarily due to surfactant deficiency. Early and accurate diagnosis is critical to guide timely interventions such as surfactant administration and respiratory support. Traditionally, chest X-rays have been used for diagnosis, but lung ultrasound (LUS) has gained prominence due to its non-invasive, radiation-free, and bedside applicability. Compared to chest X-rays and CT scans, LUS demonstrates superior sensitivity and specificity in diagnosing RDS, particularly in identifying surfactant need and predicting CPAP failure. Additionally, LUS offers real-time imaging without radiation exposure, an advantage over other modalities. However, its broader adoption is limited by challenges in standardizing training, ensuring diagnostic reproducibility, and validating scoring systems, especially in resource-limited settings. This narrative review aims to evaluate the role of LUS in the diagnosis and management of neonatal RDS over the past decade, focusing on its clinical utility, scoring systems, and emerging applications. We reviewed the literature from 2013 to 2023, focusing on studies evaluating LUS’ diagnostic accuracy, scoring systems, and its potential role in guiding surfactant therapy and predicting CPAP failure. Despite its benefits, addressing the variability in operator expertise and integrating artificial intelligence to enhance usability are crucial for ensuring LUS’ efficacy across diverse clinical environments. Future research should prioritize standardizing training and scoring protocols to facilitate wider implementation and optimize neonatal respiratory care outcomes. Full article