Search Results (191)

Bronchopulmonary dysplasia (BPD) remains a significant complication of preterm birth, characterized by impaired alveolar and vascular development, chronic lung inflammation, and long-term respiratory morbidity. Corticosteroids, both systemic and inhaled, have been widely investigated as potential therapeutic agents due to their anti-inflammatory properties and their emerging role in modulating oxidative stress. This narrative review explores the current evidence regarding the use of inhaled and systemic corticosteroids in the prevention and management of BPD, analyzing their efficacy, safety profiles, and long-term outcomes. While systemic corticosteroids, particularly dexamethasone, have demonstrated benefits in reducing ventilator dependence and lung inflammation, concerns regarding adverse neurodevelopmental effects have limited their routine use. Inhaled steroids have been proposed as a safer alternative, but their role in altering the disease trajectory remains controversial. A better understanding of the optimal timing, dosage, and patient selection is essential to maximize benefits while minimizing risks. Future research should focus on optimizing dosing strategies and identifying subgroups of preterm infants who may derive the greatest benefit from corticosteroid therapy. Full article

Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and antioxidant pharmacological activities. However, no monotherapeutic formulation of ST has been developed to date. A dry powder inhaler (DPI) enables targeted pulmonary drug delivery with excellent stability profiles and high inhalation efficiency. Methods: ST was purified and prepared as inhalable dry powder particles via an antisolvent crystallization technique. The therapeutic mechanisms of ST against ALI were elucidated by network pharmacology and pharmacokinetic analyses, with the therapeutic efficacy of the ST DPI in ALI mitigation being validated using LPS-induced rat models. Results: The ST DPI showed ideal aerodynamic characteristics. Notably, ST exhibited a three-compartment (triexponential) pharmacokinetic profile following both intravenous tail vein injection and inhalation administration. Furthermore, the inhaled formulation displayed a prolonged systemic residence time, which confers therapeutic advantages for pulmonary disease management. Furthermore, the inhalation administration of ST demonstrated a 2.7-fold increase in AUC compared with oral gavage, with a corresponding enhancement in systemic exposure. The ST DPI formulation demonstrated significant therapeutic efficacy against ALI in rats by downregulating inflammatory cytokines and modulating oxidative stress levels, mechanistically achieved through the MAPK-mediated regulation of cellular apoptosis via a positive feedback loop. Conclusions: The unique triexponential plasma level profiles of an ST DPI provide a promising pharmacokinetics-based therapeutic strategy for ALI, leveraging its marked efficacy in attenuating inflammation, oxidative stress, and pulmonary injury. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

Background: Finding the optimal amount of fluid is a major challenge in burn shock. Although there is evidence that a restrictive fluid regime is beneficial, current practice shows fluid resuscitation still well above recommendations. The extent of trauma, pre-hospital care and the patient’s pre-existing conditions influence requirements. Methods: We analysed outcomes and influencing factors of fluid regimes in a retrospective cohort study including 90 severely burnt patients resuscitated with the same protocol. Results: The mean amount of fluids in the first 24 h was 6.5 mL/kg bodyweight (BW)/% total burn surface area (TBSA). A total of 14% received restrictive (<4), 34% received liberal (4–6) and 51% received excessive (>6) mL/kgBW/%TBSA fluids. There was no difference regarding mortality, age, complications, organ failure, inhalation injury or full-thickness burns in the groups. Patients with excessive fluid therapy had a significantly lower ABSI score (9 vs. 11, p = 0.05) and TBSA (35 vs. 51%, p < 0.001), while patients with a restrictive fluid therapy needed fewer incidences of surgery to cover burn wounds (3.5 vs. 9.0 vs. 7.0, p = 0.008). History of liver disease or alcohol abuse tended to indicate excessive fluid administration. Patients with pre-existing heart failure received restrictive fluid therapy (23 vs. 3 vs. 4%, p = 0.03). Conclusions: Individualised, timely therapy monitoring is as essential as identifying patients with a higher or lower fluid requirement. Excessive fluid resuscitation had fewer deleterious consequences in complications than expected but seems to influence wound healing. Awareness of circumstances that prompt deviations from recommended fluid rates remains elementary. Full article

Ricin is a highly potent toxin that causes severe lung injury upon inhalation by initiating a complex cascade of cellular responses that ultimately leads to cell death. The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in various physiological processes, including ricin-mediated toxicity. This study explores the role of LRP1 shedding in the development of ricin-induced lung injury. Analysis of bronchoalveolar lavage fluid (BALF) from ricin-intoxicated mice and swine showed a significant increase in soluble LRP1 (sLRP1) levels, whereas serum LRP1 levels remained largely unchanged, suggesting the lungs are the primary source of sLRP1 release. In vitro assays demonstrated the formation of ricin-sLRP1 complexes, indicating that sLRP1 in BALF retained ricin-binding capability. Flow cytometric analysis of lung cells revealed a reduction in both the percentage and total number of LRP1-expressing cells following ricin exposure. Further investigation of specific lung cell populations showed that alveolar epithelial type II (AT-II) cells, despite experiencing significant injury, exhibited minimal LRP1 shedding. No shedding of LRP1 occurred in neutrophils. In contrast, fibroblasts, which were resistant to ricin-induced cell death, exhibited increased shedding of LRP1 and a corresponding decrease in membrane-bound LRP1 expression. This shedding of the LRP1 ectodomain was mediated by metalloproteinases. Immunohistochemical staining further confirmed decreased LRP1 expression in fibroblasts from ricin-exposed mice. Macrophages also showed substantial LRP1 shedding, despite undergoing significant depletion. These findings highlight the complex cell-specific nature of LRP1 shedding in response to ricin intoxication and suggests the potential role of LRP1 in modulation of cellular susceptibility and resistance to ricin-induced lung injury. Full article

The term ‘vaping’ refers to the use of electronic cigarettes or other devices to inhale a variety of heated and aerosolized substances. Vaping has been promoted as a less harmful and potentially oncogenic alternative to nicotine cigarettes, particularly to help heavy smokers quit. While vaping products do not produce the same carcinogenic substances—such as polycyclic aromatic hydrocarbons—generated by the combustion of tobacco, and while their fluids lack tobacco-related carcinogens like nitrosamines, it is now well established that they still generate harmful and potentially oncogenic byproducts. Several mechanisms have been proposed to explain the potential oncogenic effects of vaping fluids, including direct chemical action, epithelial–mesenchymal transition induction, redox stress, mitochondrial toxicity, and DNA damage. In addition to cancer risk, there have been reports of adverse effects on cardiovascular health, reproductive function, and non-oncologic lung injuries. These include exogenous lipoid pneumonia, diffuse alveolar hemorrhage with proven alveolar injury, and vaping-associated bronchiolitis obliterans. The aim of this review is to examine vaping devices, their potential role in lung carcinogenesis, vaping-associated lung injury, and other clinical implications, including impacts on cardiovascular, cerebrovascular, and respiratory diseases, and also pregnancy and fetus health. Full article

Ambient ozone (O₃) pollution, which has become a global problem, is associated with damage to various biological systems, as determined by many studies. However, there is limited experimental evidence regarding the systemic damage induced by O₃ exposure, and there are few associated studies on mice. In the present investigation, we constructed a subacute C57BL/6J female mouse model involving exposure to 0, 0.5, 1, or 2 ppm O₃ for 28 days (3 h/day). Body weights, pulmonary function, hematology, serum biochemistry, inflammatory factors, and injuries to various organs were assessed for O₃-exposed mice. After O₃ exposure, especially to 2 ppm O₃, mice showed a loss of body weight, abnormal glucose and lipid metabolism, respiratory and nervous system injuries, an inflammatory response, and pathological changes, which supported the data reported for epidemiology studies. In addition, the IL-6 levels in bronchoalveolar lavage fluid (BALF), the lungs, the livers, the kidneys, and the brains were increased, which indicated that IL-6 was associated with the damage to various organs induced by O₃ exposure. The present report highlights the pathological injury to various organs and provides a basis for further studies of the molecular mechanisms associated with O₃ exposure. Full article

Face and neck burns present significant clinical challenges due to their proximity to the airway, predisposing patients to inhalation injuries and subsequent respiratory complications. In our cohort of 206 patients, facial and neck burns were associated with a markedly higher incidence of inhalation injury (34.8% vs. 2.8%), necessitating more frequent endotracheal intubation (51.9% vs. 14.1%). Furthermore, respiratory infections were significantly more common in patients with facial and neck burns (26.7% vs. 7%, p < 0.001), with respiratory secretion cultures revealing a predominance of Pseudomonas aeruginosa (39.58%), Acinetobacter baumanii (18.75%), and Klebsiella pneumoniae (6.25%). In contrast, patients without facial and neck burns primarily exhibited Pseudomonas aeruginosa (50%) in their cultures. These complications translated into a significantly increased mortality rate in patients with facial and neck burns (31.1% vs. 12.7%), with a reduced mean survival period (66.7 days vs. 84.3 days) and a 2.8-fold increase in the hazard of mortality. Additionally, older age emerged as a significant determinant for the development of respiratory infections. Multivariable model regression analysis revealed that only TBSA remained a consistent and independent predictor for adverse respiratory outcomes and increased mortality, while face and neck burns are more causally associated with TBSA. Full article

There is increasing interest in identifying drugs that can prevent or delay neurological complications following spinal cord injury, thus expanding the therapeutic window for other potential neuroprotective agents. In this context, manganese porphyrins (MnPs) have shown high antioxidant and anti-inflammatory potential in various experimental disease models, including stroke, cancer, diabetes, ischemia, and radiotherapy. However, they have been little evaluated in spinal cord injuries. This study aimed to assess the therapeutic potential of the manganese porphyrins [MnTE-2-PyP]⁵⁺ (MnPI) and [MnT(5-Br-3-E-Py)P]⁵⁺ (MnPII) in acute compressive spinal cord trauma in rats. Twenty-four animals were used (six animals/group). Following general inhalation anesthesia, acute compressive spinal cord trauma was induced in all groups except for the negative control (SHAM). Treatment commenced 60 min post-trauma, with animals receiving treatment for seven days at 24 h intervals. While no improvement in motor capacity was observed, MnPs effectively blocked the increase in oxidative stress and endoplasmic reticulum (ER) stress mediators caused by trauma, maintaining the protein expression levels of Hifα, 8-OHdG and MDA, as well as the expression of the genes Grp78, Chop, Ho1, and Perk, similar to those of the control group. Moreover, there was an increase in protein expression of SOD1, Cat, and GPX1, along with a restoration of SOD and CAT enzymatic activity. Additionally, MnPs improved the expression of IL-6, neurotrophic markers, and apoptotic factors. In conclusion, treatment with MnPs attenuated the oxidative stress and ER stress caused by acute compressive spinal cord trauma and restored spinal expression of neurotrophic mediators. Full article

Severe burns are among the most traumatic injuries, characterized by tissue damage, systemic inflammation, significant fluid shifts, and a high risk of complications such as infections, organ failure, anemia, malnutrition, and psychological trauma. This article reviews recent literature from the PubMed and Google Scholar databases to outline critical components of burn care, from initial resuscitation and stabilization through rehabilitation. Key topics include early airway management to prevent respiratory compromise, meticulous fluid resuscitation to maintain tissue perfusion while avoiding complications like fluid overload, and optimal pain management. It also discusses nutritional support tailored to the burn patient’s hypermetabolic state and surgical techniques like early debridement and skin grafting. Beyond physical recovery, the review emphasizes the importance of addressing the psychological impact of burn injuries, including depression, anxiety, and post-traumatic stress, which can significantly affect long-term outcomes. By integrating the expertise of a multidisciplinary team with a personalized approach and practical recommendations, this review aims to provide clinicians with a comprehensive framework for managing severe burns, from the initial emergency response to the challenges of inpatient care and, finally, rehabilitation. Full article

Objectives: There is a scarcity of pharmacological treatments that efficiently address lung injury in individuals experiencing acute respiratory distress syndrome (ARDS). Early inhaled corticosteroids and ipratropium may reduce pulmonary inflammation and injury of the lungs, minimizing the risk of ARDS. Method: This is a double-blinded randomized control trial conducted on patients at risk of ARDS. Patients were randomly allocated into two groups; the intervention group (63 patients) were administered aerosolized budesonide and ipratropium bromide, and the control group (56) were administered a placebo every eight hours for five days. Alteration in oxygen saturation divided by inspired oxygen (Fio2) (S/F) after five days was the primary outcome. Secondary outcomes included ARDS occurrence, mechanical ventilation (MV) requirement, hospital stay duration, and mortality rates. Results: Of the 604 screened, only 119 patients were included. The intervention group (63 patients) S/F ratio recovered versus the fall of the control group. Both groups had similar organ dysfunction and 28-day mortality. The intervention group had significantly (p < 0.001) fewer cases developing ARDS (9.5%) and MV (9.5%) than the control group (46.4% and 35.7%, respectively). Conclusions: The administration of inhaled budesonide and ipratropium bromide improved oxygenation, as assessed by the S/F ratio, and significantly reduced the rate of ARDS development and the requirement of MV versus the control group. Larger multi-center trials including diverse patient populations are needed to validate these results. Full article

Silicosis is an interstitial lung disease (ILD) caused by prolonged inhalation of silica particles. Acute lung injury (ALI) is a critical clinical syndrome involving bilateral lung infiltration and acute hypoxic respiratory failure. However, there is currently no effective treatment for these two diseases. Previous research has established that cyclic adenosine monophosphate (cAMP) is pivotal in the pathogenesis of silicosis and acute lung injury. Phosphodiesterase 4 (PDE4) is a hydrolase enzyme of cAMP, and BI 1015550, as an inhibitor of PDE4B, is expected to be a candidate drug for treating both. BI 1015550 has shown certain anti-inflammatory and anti-fibrotic properties in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF), but there is a lack of research on silicosis and acute lung injury. In this research, we successfully synthesized BI 1015550 autonomously and demonstrated that it could significantly improve lung fibrosis and inflammation in a silica-induced silicosis mouse model. Furthermore, we found that BI 1015550 could also alleviate lung inflammation in a Lipopolysaccharide (LPS)-induced acute lung injury mouse model. The mechanism of action may involve the regulation of cAMP-related signaling pathways. Full article

Nitrous oxide has a wide range of medical applications, such as being used as an analgesic in general anesthesia, dental procedures, childbirth and sedation. Lately, it has also been employed as an inhalant recreational drug to induce brief euphoria. Recent studies indicate a worldwide rise in the incidence of skin frostbites associated with nitrous oxide use. A scoping review was conducted to synthesize and summarize the existing literature published in English regarding frostbite injuries associated with the recreational use of nitrous oxide. The literature search was carried out in July 2024 using databases such as Embase, Web of Science and PubMed^®. From an initial pool of 83 publications, 8 studies were ultimately selected for full-text review as they met our inclusion criteria for analysis. Additionally, we provide a representative clinical case involving a 21-year-old male who experienced frostbite following skin exposure to nitrous oxide. Most publications on nitrous oxide induced frostbites are from recent years, primarily between 2022 and 2024, with the first case documented in 1996. These injuries are mostly observed in young adults, with a female dominance, and are typically localized to the inner thighs. According to the existing literature, the predominant treatment approach is conservative management, with excision and split-thickness skin grafting (STSG) in the second place. This study represents the first literature review summarizing frostbite injuries to the skin from nitrous oxide misuse. There is a need for enhanced preventive measures to raise public awareness and reduce the incidence of frostbite injuries associated with the recreational use of nitrous oxide. Full article

Burn injuries often lead to severe complications, including acute respiratory distress syndrome (ARDS), driven in part by systemic inflammation and glycocalyx disruption. In this study, we analyzed the sera of 28 patients after burn trauma and utilized single-cell RNA sequencing (scRNA-seq) along with microarray transcriptomic analysis to decipher the impact of burn injury on glycocalyx derangement. We observed the significant upregulation of immune cell-derived degrading enzymes, particularly matrix metalloproteinase-8 (MMP8), which correlated with increased immune cell infiltration and glycocalyx derangement. Serum analyses of burn patients revealed significantly elevated levels of shed glycocalyx components and MMP8, both correlating with the presence of inhalation injury. Consequently, the treatment of human in vitro lung tissue models with MMP8 induced significant glycocalyx shedding in alveolar epithelial cells. Together, based on these findings, we propose that MMP8 plays a previously unrecognized role in glycocalyx disruption and subsequent lung injury post-burn, which implies that inhibiting MMP8 may represent a promising therapeutic strategy for alleviating lung injury after burn trauma. Full article

Background/Objectives: Wildland firefighters (WFFs) are subjected to significant physical and physiological demands that expose them to substantial occupational risks, including thermal stress, prolonged physical exertion, and exposure to harmful substances. These factors not only affect their immediate performance but also have long-term implications for their health. This narrative review seeks to analyze the main factors influencing the health and performance of WFFs, with a particular focus on physical, environmental, and psychological challenges. Methods: A narrative review was performed, synthesizing data from diverse sources. The analysis centered on studies addressing the physiological, environmental, and psychological aspects of WFF performance. Specific topics included physical workload, exposure to environmental stressors, use of protective equipment, hydration, sleep patterns, and mental health. Results: The review highlights several critical challenges faced by WFFs, including the extreme physical demands of carrying heavy equipment during extended interventions, elevated physiological strain induced by protective gear, and significant health risks associated with smoke inhalation and dehydration. Additionally, inadequate sleep and heightened mental stress were found to impair both cognitive and physical performance. Variations in injury prevalence and patterns of chronic pain were observed, often influenced by factors such as sex, age, and professional experience. Conclusion: To mitigate these risks and enhance the health and performance of WFFs, targeted interventions are essential. These include tailored physical training programs, heat acclimatization strategies, and improved resource management. Future research should aim to integrate these measures comprehensively and address existing knowledge gaps to ensure the long-term well-being of these professionals. Full article