Search Results (372)

Obstructive sleep apnea (OSA) could increase pulmonary artery pressure. However, the clinical consequences vary, mainly depending on comorbidities. Patients with pulmonary hypertension associated with lung diseases (World Health Organization (WHO) Group 3 pulmonary hypertension) are particularly vulnerable increases in pulmonary artery pressure. Managing pulmonary hypertension in this specific patient population presents a considerable challenge. While positive airway pressure therapy for OSA has shown promise in improving pulmonary hemodynamics in patients with obesity hypoventilation syndrome and chronic obstructive pulmonary disease, evidence is lacking for similar improvements in those with other pulmonary diseases and hypoventilation disorders. Furthermore, pulmonary-artery-specific therapies may carry a risk of clinical worsening in this group. Weight management and new pharmacotherapy have together emerged as a crucial intervention, demonstrating benefits for both OSA and pulmonary hemodynamics. We reviewed key studies that provide insights into the influence of OSA on WHO Group 3 pulmonary hypertension and the clinical management of both conditions. Full article

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Pre-oxygenation is the key step prior to endotracheal intubation, particularly in a critically ill patient, to prevent life-threatening peri-procedural hypoxemia. This narrative review explores the emerging interest of Non-Invasive Positive Pressure Ventilation (NIPPV) as a pre-oxygenation modality in the intensive care unit (ICU) context. We reviewed data from randomized controlled trials (RCTs) and observational studies published from 2000 to 2024 that compare NIPPV to conventional oxygen therapy and High Flow Nasal Cannula Oxygen (HFNCO). The pathophysiological mechanisms for the successful use of NIPPV, including alveolar recruitment, the decrease of shunting, and the maintenance of functional residual capacity, were reviewed in depth. Existing studies show that NIPPV significantly prolongs the apnea time, reduces the rate of peri-intubation severe hypoxaemia in selected patients and is especially effective for patients with acute hypoxaemic respiratory failure. Nevertheless, appropriate patient selection is still crucial because some diseases can contraindicate or even be harmful with NIPPV. We further discussed the practical aspects of how to use this ventilatory support (the best ventilator settings, which interface, and when to apply it). We lastly discuss unanswered questions and offer suggestions and opportunities for future exploration in guiding the role of NIPPV use in the pre-oxygenation of the critically ill patient requiring emergent airway management. Full article

Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange but, when impaired, can result in life-threatening hypoxemia. Moreover, under conditions of generalized alveolar hypoxia, HPV can result in pulmonary hypertension. Voltage-gated K⁺ channels (K_v channels) are key to HPV: a change in the intracellular hydrogen peroxide (H₂O₂) levels during acute hypoxia is assumed to modulate these channels’ activity to trigger HPV. However, there are longstanding conflicting findings on whether H₂O₂ inhibits or activates K_v channels. Therefore, we hypothesized that H₂O₂ affects K_v channels depending on the experimental conditions, i.e., the H₂O₂ concentration, the channel’s subunit configuration or the experimental clamping potential in electrophysiological recordings. Therefore, cRNAs encoding the K_v1.5 channel and the auxiliary K_vβ subunits (K_vβ1.1, K_vβ1.4) were generated via in vitro transcription before being injected into Xenopus laevis oocytes for heterologous expression. The K⁺ currents of homomeric (Kv1.5) or heteromeric (K_v1.5/K_vβ1.1 or K_v1.5/K_vβ1.4) channels were assessed by two-electrode voltage clamp. The response of the K_v channels to H₂O₂ was markedly dependent on (a) the clamping potential, (b) the H₂O₂ concentration, and (c) the K_v channel’s subunit composition. In conclusion, our data highlight the importance of the choice of experimental conditions when assessing the H₂O₂ sensitivity of K_v channels in the context of HPV, thus providing an explanation for the long-lasting controversial findings reported in the literature. Full article

Acute lung injury (ALI), a life-threatening clinical syndrome with multifactorial origins, is characterized by uncontrolled pulmonary inflammation and disrupted alveolar–capillary barrier integrity, leading to progressive hypoxemia and respiratory failure. In this hypoxic setting, hypoxia-inducible factor (HIF)-1 is activated, acting as a central regulator of the inflammatory response and reparative processes in injured lung tissue during ALI. The role of HIF-1 is distinctly dualistic; it promotes both anti-inflammatory and reparative mechanisms to a certain extent, while potentially exacerbating inflammation, thus having a complex impact on disease progression. We explore the latest understanding of the role of hypoxia/HIF-mediated inflammatory and reparative pathways in ALI and consider the potential therapeutic applications of drugs targeting these pathways for the development of innovative treatment strategies. Therefore, this review aims to guide future research and clinical applications by emphasizing HIF-1 as a key therapeutic target for ALI. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition marked by persistent airflow limitation and is currently the fourth leading cause of death worldwide, accounting for 3.5 million deaths in 2021. While its physical manifestations such as dyspnea, chronic cough, and sputum production are well known, its psychological impact, particularly the high prevalence of depression among patients, remains under-recognized. Objectives: This narrative review aims to summarize the existing data on the association between COPD and depression, analyze their pathophysiological connections, explore treatment possibilities, and highlight the interrelationships between these conditions. Methods: A non-systematic literature search was conducted using PubMed, Scopus, and Google Scholar. Studies, reviews, and key publications addressing the relationship between COPD and depression were selected based on clinical relevance. Findings were synthesized thematically to provide a comprehensive and critical overview. Results: Depression in patients with COPD is linked to worse quality of life, increased functional impairment, higher suicide risk, and poorer adherence to treatment. Contributing mechanisms include chronic systemic inflammation, hypoxemia, oxidative stress, and psychosocial risk factors such as low educational level, socioeconomic disadvantage, and comorbidities. Despite evidence of this strong association, treatment strategies remain limited and underutilized, and no unified approach has yet been established. Conclusions: Depression represents a major comorbidity in COPD that exacerbates both disease burden and patient suffering. Further research is essential to clarify the underlying mechanisms and to develop integrated therapeutic approaches. Enhancing our understanding and management of this comorbidity holds promise for significantly improving patient outcomes and overall quality of life. Full article

Background and Objectives: Chronic obstructive pulmonary disease (COPD) significantly impacts morbidity and mortality, often due to cardiovascular comorbidities that are frequently overlooked. This study examines the prevalence of left ventricular dysfunction in COPD patients and its association with disease severity, hypoxemia, and exacerbation frequency. Materials and Methods: COPD patients (n = 114) were evaluated using spirometry and transthoracic echocardiography. Statistical analysis utilized Student’s t-test, chi-square test, and multivariable logistic regression with 1000 bootstrapping iterations, considering p < 0.05 as significant differences. Results: Most patients were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III (40.4%) and stage IV (44.7%). Diastolic dysfunction was present in 67.5% of the patients (Grade 1: 53.5%, Grade 2: 13. 2%, Grade 3: 0.0.9%), while 18.4% exhibited systolic dysfunction (LVEF < 50%). The prevalence of diastolic dysfunction increased significantly, from 41.2% in GOLD stage II to 92. 2% in GOLD stage IV (p < 0.001). Independent predictors of diastolic dysfunction included GOLD stage IV (Odds Ratio [OR]: 5.39, 95% Confidence Interval [CI]: 1. 42–23.35, p < 0.001), older age (OR: 1.02 per year, 95% CI: 1.01–1.04, p = 0.025), and a history of frequent exacerbations (OR: 1.09 per event, 95% CI: 1.01–1.17, p = 0.039). Systolic dysfunction correlated significantly with GOLD stage IV (OR: 1.83, p = 0.014), oxygen saturation below 88% (OR: 3.12, p = 0.036), and having three or more exacerbations (OR: 4.18, p = 0.008). Conclusions: This study reveals a high prevalence of left ventricular dysfunction in COPD patients, linked to disease severity, hypoxemia, and frequent exacerbations. It supports incorporating complementary echocardiographic assessments in managing advanced COPD, especially for those with frequent exacerbations or oxygen desaturation. Full article

In chronic respiratory diseases (CRDs), oxidative stress and inflammation are closely linked, driving disease onset, progression, and comorbidities. Oxidative stress activates inflammatory pathways, while chronic inflammation promotes further reactive oxygen species (ROS) production, creating a vicious cycle leading to airway remodeling, reduced lung function, and exacerbations. This review highlights the central roles of inflammation and oxidative stress in chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). In COPD, chronic hypoxemia associates with emphysema, appearing with disease progression. In OSA, beyond systemic consequences, pulmonary inflammation and oxidative stress contribute to lung injury as well. Although COPD and OSA are distinct conditions, some patients present with “overlap syndrome”, a term used in this review to describe the coexistence of both. This combination poses unique diagnostic and therapeutic challenges. We also examine the role of hypoxia and its transcriptional effects via hypoxia-inducible factors (HIFs) in promoting oxidative stress and inflammation. Finally, we explore how artificial intelligence (AI) offers promising tools to improve diagnosis, monitoring, and management of CRDs and may help elucidate mechanistic links between hypoxia, inflammation, and oxidative stress, contributing to more personalized therapeutic strategies. Full article

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder, primarily characterized by recurrent episodes of upper airway obstruction during sleep. Individuals affected by OSA are at increased risk for a variety of adverse health outcomes, particularly neurocognitive impairments and cardiovascular complications, highlighting the clinical significance of this condition. A defining feature of OSA is intermittent hypoxemia, which contributes to the excessive production of reactive oxygen species (ROS) and the subsequent development of oxidative stress. The primary objective of this narrative review was to comprehensively investigate the intricate mechanisms of oxidative stress and elucidate their complex interplay in the development and progression of OSAS. Subsequently, we examined the current literature to identify the most promising biomarkers and pharmacological treatments related to OSA and oxidative stress. We found that biomarkers of oxidative stress have shown potential in assessing disease severity and tracking individual responses to therapy. However, none have yet to be incorporated into standard clinical practice. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Nevertheless, antioxidant therapy has emerged as a potential adjunctive approach that may help address residual dysfunctions not fully resolved by CPAP alone. Both the use of oxidative stress biomarkers and antioxidant-based therapies require further validation through robust clinical studies before they can be routinely implemented in clinical settings. 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/Objectives: Obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) are two highly prevalent and interconnected conditions with significant implications for morbidity and mortality. Emerging evidence suggests a bidirectional relationship between the two disorders, mediated by shared pathophysiological mechanisms such as intermittent hypoxia, systemic inflammation, and autonomic dysfunction. Methods: A structured narrative review of the literature was conducted using a comprehensive PubMed search of clinical and observational studies published between 2020 and 2024. Studies evaluating the association between OSA and diabetes, including its effects on glycemic control, diabetic complications, and treatment outcomes, were included. Results: Thirty-three studies met our inclusion criteria. OSA is independently associated with impaired glucose metabolism, increased insulin resistance, and a higher risk of diabetic complications, including nephropathy, retinopathy, and neuropathy. Continuous positive airway pressure (CPAP) therapy has shown variable effects on metabolic outcomes, largely dependent on adherence. Traditional OSA severity metrics, such as the apnea–hypopnea index (AHI), did not consistently predict metabolic burden. Factors such as sleep quality, nocturnal hypoxemia, and comorbid insomnia have emerged as the most relevant predictors. Sex-specific differences and the roles of pharmacological and behavioral interventions were also noted. Conclusions: OSA is a modifiable and under-recognized risk factor for poor glycemic control and diabetes complications. Routine screening and individualized treatment strategies are warranted, particularly for patients with T2DM and suboptimal metabolic control. Future research should focus on defining the phenotypes at the greatest risk and developing integrated treatment pathways. Full article

Background/Objectives: This review aims to identify existing protocols and evaluate the effects of prone positioning on oxygenation and clinical outcomes in pediatric patients with hypoxemia. Methods: A systematic review was conducted in accordance with the PRISMA guidelines and registered in PROSPERO (CRD42023457270). Literature research was performed in Scopus, PubMed, Web of Science, and ScienceDirect. The final search was completed in January 2025. Results: A total of 2033 studies were identified, with 5 meeting inclusion criteria. Forty percent applied prone positioning for 12 to 20 h, improving pulmonary function. Combined with alveolar recruitment, prone positioning increased functional residual capacity and reduced atelectasis, with SpO₂ improvements from 13% to 38% and atelectasis reduction from 8% to 47%. Another 40% focused on oxygenation, reporting PaO₂ increases from 52 to 59 mmHg and SpO₂ improvements from 93.2% to 96.2% within 2 to 4 h. One study found a significant SpO₂ difference between prone (98.3%) and supine (96.2%) positions (p = 0.003). Protocols commonly included facial tilt and pillows to reduce compression. Safety measures involved checking catheter and tube placement, suspending enteral nutrition 30 min before repositioning, and hemodynamic monitoring. Adverse events were rare, including two cases of tube obstruction and one hypercapnia. No significant differences were observed in ventilation duration, oxygen therapy length, or 28-day survival between groups. Conclusions: Prone positioning improves pulmonary function and addresses refractory hypoxemia in pediatric patients. However, the optimal duration remains unclear, underscoring the need for further research to establish standardized guidelines. Full article

Background/Objective: Obesity is a documented risk factor for impaired pulmonary function and abnormal oxyhaemoglobin levels during sleep. This functional impairment becomes more significant when there are additional respiratory pathologies, such as obstructive sleep apnea (OSA) and/or chronic obstructive pulmonary disease (COPD). Overnight pulse oximetry may offer an effective evaluation of nocturnal oxyhaemoglobin levels/waveform patterns. We evaluated the correlation between obesity, overnight pulse oximetry (parameters, waveform patterns) and pulmonary function in patients diagnosed with moderate–severe OSA and normal oxyhaemoglobin saturation levels during waking hours. We also compared the overnight oxyhaemoglobin saturation levels between patients with OSA alone and those with associated COPD. Methods: This was a retrospective, transversal, non-interventional study on consecutive patients with moderate–severe OSA diagnosed using overnight cardiorespiratory polygraphy over a period of 18 months. After analyzing the study population’s characteristics, the patients were divided into two subgroups: one consisting of patients with OSA alone (Group A), and the second with coexisting OSA and COPD (Group B). Results: Seventy-six patients were included in the study, and 18% were diagnosed with COPD. A higher body mass index (BMI) correlated with a higher number of ≥3% SpO₂ drops/h (ODI3) and percentage of time with oxyhaemoglobin saturation < 90% (t90) and a lower average nocturnal oxyhaemoglobin saturation (avgSpO₂). ODI3 correlated negatively with avgSpO₂ and positively with t90. After eliminating BMI as a confounding factor, lower values of forced expiratory volume in the first second (FEV1) were associated with lower avgSpO₂ and higher t90. FEV1 did not corelate with ODI3. After dividing the study population into the two subgroups, patients from Group B had a tendency towards lower average nocturnal SpO₂ levels compared to Group A. Conclusions: Different phenotypes/patterns of nocturnal hypoxemia can be identified using quantitative and qualitative analyses of overnight pulse oximetry: repetitive, consecutive obstructive respiratory events with a characteristic intermittent (saw-tooth) hypoxemia pattern and alveolar hypoventilation, resulting in a continuous (plateau) hypoxemia pattern. According to our findings, nocturnal hypoxemia is more important at lower FEV1 values (correlating with lower avgSpO₂/higher t90, but not with ODI3). The presence of a continuous hypoxemia pattern in patients with OSA may suggest that pulmonary function tests should be performed in order to differentiate patients with alveolar hypoventilation secondary to obesity (restrictive syndrome) from those with associated COPD (obstructive syndrome). This can have an impact on the management of the case and the therapeutic approach (positive pressure therapy with/without supplemental oxygen). Full article

Diffuse alveolar hemorrhage (DAH), a catastrophic complication of connective tissue disorders (CTDs), manifests as rapid-onset hypoxemia, alveolar infiltrates, and progressive bleeding into the airways. While immune-mediated alveolar–endothelial injury primarily drives its pathophysiology, diagnosis is based on bronchoscopy and chest imaging. The clinical urgency lies in securing the compromised airway and stabilizing respiratory failure, a challenge increased by CTD-specific anatomical alterations such as cervical spine instability, cricoarytenoid arthritis, and subglottic stenosis. High-dose corticosteroids and immunosuppression are essential, while severe cases require extracorporeal membrane oxygenation or plasmapheresis. This comprehensive review introduces two novel approaches to address fundamental gaps in the management of CTD-induced DAH: a structured algorithm for a CTD-specific airway risk stratification tool, integrating anatomical screening and the application of lung ultrasounds (LUSs) for post-intubation CTD-induced DAH ventilation management. The need for a multidisciplinary team approach is also discussed. Despite aggressive care, mortality remains high (25–50%), underscoring the necessity for improved early recognition and intervention strategies for these high-risk patients. Full article