Search Results (145)

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. Pseudomonas aeruginosa is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. P. aeruginosa exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, P. aeruginosa undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic P. aeruginosa infections in CF. Full article

Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of a 66-year-old immunocompetent woman with a history of breast cancer in remission and NCFB, who presented with chronic cough and dyspnea. Chest CT revealed bilateral bronchiectasis with new pseudonodular opacities. Bronchoalveolar lavage cultures identified E. dermatitidis, along with Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Given clinical stability and the absence of systemic signs, initial therapy included oral voriconazole, levofloxacin, doxycycline, and inhaled amikacin. Despite persistent fungal isolation on repeat bronchoscopy, the patient remained asymptomatic with stable radiologic and functional findings. Antifungal therapy was discontinued, and the patient continued under close monitoring. The patient exhibited clinical and radiological stability despite repeated fungal isolation, reinforcing the hypothesis of persistent colonization rather than active infection. Discussion: This case underscores the diagnostic challenges in distinguishing fungal colonization from true infection in structurally abnormal lungs. In NCFB, disrupted mucociliary clearance and microbial dysbiosis may facilitate fungal persistence, even in the absence of overt immunosuppression. The detection of E. dermatitidis should prompt a comprehensive evaluation, integrating clinical, radiologic, and microbiologic data to guide management. Voriconazole is currently the antifungal agent of choice, though therapeutic thresholds and duration remain undefined. Conclusions: This report highlights the potential role of E. dermatitidis as an under-recognized respiratory pathogen in NCFB and the importance of a multidisciplinary, individualized approach to diagnosis and treatment. This case underscores the need for further research on fungal colonization in NCFB and the development of evidence-based treatment guidelines. Further studies are needed to clarify the pathogenic significance, optimal management, and long-term outcomes of E. dermatitidis in non-CF chronic lung diseases. Full article

Background/Objectives: In hospital settings, the wide variability of acute and complex chronic conditions—among both adult and pediatric patients—requires advanced approaches to detect early signs of clinical deterioration and the risk of transfer to the intensive care unit (ICU). Nursing diagnoses (NDs), standardized representations of patient responses to actual or potential health problems, reflect nursing complexity. However, most studies have focused on the total number of NDs rather than the individual role each diagnosis may play in relation to outcomes such as ICU transfer. This study aimed to identify and rank the specific NDs most strongly associated with ICU transfers in hospitalized adult and pediatric patients. Methods: A retrospective, monocentric observational study was conducted using electronic health records from an Italian tertiary hospital. The dataset included 42,735 patients (40,649 adults and 2086 pediatric), and sociodemographic, clinical, and nursing data were collected. A random forest model was applied to assess the predictive relevance (i.e., variable importance) of individual NDs in relation to ICU transfers. Results: Among adult patients, the NDs most strongly associated with ICU transfer were Physical mobility impairment, Injury risk, Skin integrity impairment risk, Acute pain, and Fall risk. In the pediatric population, Acute pain, Injury risk, Sleep pattern disturbance, Skin integrity impairment risk, and Airway clearance impairment emerged as the NDs most frequently linked to ICU transfer. The models showed good performance and generalizability, with stable out-of-bag and validation errors across iterations. Conclusions: A prioritized ranking of NDs appears to be associated with ICU transfers, suggesting their potential utility as early warning indicators of clinical deterioration. Patients presenting with high-risk diagnostic profiles should be prioritized for enhanced clinical surveillance and proactive intervention, as they may represent vulnerable populations. Full article

Aging affects all tissues in an organism, including the tracheobronchial tree, with structural and functional changes driven by mechanisms such as oxidative stress, cellular senescence, epigenetic modifications, mitochondrial dysfunction, and telomere shortening. Airway aging can be accelerated by intrinsic or extrinsic factors. This review brings together information from the literature on the molecular changes occurring in all layers of the tracheobronchial airway wall. It examines the biomolecular changes associated with aging in the mucosa, submucosa, cartilage, and smooth muscle of the airways. At the mucosal level, aging reduces ciliary function and disrupts mucin homeostasis, impairing mucociliary clearance and contributing to chronic respiratory diseases such as COPD (Chronic Obstructive Pulmonary Disease). Cellular senescence and oxidative stress drive extracellular matrix remodeling and chronic inflammation. Airway cartilage undergoes age-related changes in collagen and fibronectin composition, leading to increased stiffness, while heightened MMP (Matrix Metalloproteinases) activity exacerbates ECM (extracellular matrix) degradation. In airway smooth muscle, aging induces changes in calcium signaling, hypertrophy, and the secretion of pro-inflammatory mediators, further perpetuating airway remodeling. These changes impair respiratory function and increase susceptibility to chronic respiratory conditions in the elderly. By consolidating current knowledge, this review aims to provide a comprehensive overview of the molecular changes occurring in the respiratory tract with aging and to highlight new molecular perspectives for future research on this topic. Full article

The mucociliary clearance system is an innate defense mechanism in the human respiratory tract, which plays a crucial role in protecting the airways from infections. The clearance system secretes mucus from the goblet cells, which scatters in the respiratory epithelium to trap foreign particles entering the airway, and then the mucus is removed from the body via the movement of cilia residing under the mucus and above the epithelium cells. The layer containing cilia is called the periciliary layer (PCL). This layer also contains an incompressible Newtonian fluid called PCL fluid. This study aims to determine the velocity of the PCL fluid driven by the cilia movement instead of a pressure gradient. We consider bundles of cilia, rather than an individual cilium. So, the generalized Brinkman equation in a macroscopic scale is used to predict the fluid velocity in the PCL. We apply a mixed finite element method to the governing equation and calculate the numerical solutions in a two-dimensional domain. The numerical domain is set up to be the shape of a fan blade, which is similar to the motion of the cilia. This problem can be applied to problems of fluid flow propelled via moving solid phases. Full article

Previous studies suggest that nursing diagnoses (NDs) could predict clinical outcomes, such as mortality, among patients with non-communicable diseases. However, evidence in patients with COVID-19 is still scarce. Objective: To evaluate the association between NDs and COVID-19 mortality among hospitalized patients. Methods: A retrospective cohort study was conducted on 498 paper clinical records of patients hospitalized for at least 72 h in the internal medicine unit for COVID-19 from June to December 2020. The interest association was assessed using logistic regression models. Results: NDs focused on COVID-19 pulmonary responses, such as impaired gas exchange (OR = 3.04; 95% CI = 1.87, 4.95), impaired spontaneous ventilation (OR = 3.67; 95% CI = 2.17, 6.21), or ineffective airway clearance (OR = 2.47; 95% CI = 1.48, 4.12), were significant predictors of mortality. NDs on COVID-19 extrapulmonary responses, such as risk for unstable blood glucose level (OR = 2.45; 95% CI = 1.45, 4,15), risk for impaired liver function (OR = 2.02; 95% CI = 1.11, 3.63), hyperthermia (OR = 2.08; 95% CI = 1.29, 3.35), decreased cardiac output (OR = 2.95; 95% CI = 1.42, 6.11), or risk for shock (OR = 3.03; 95% CI = 1.28, 7.13), were associated with a higher risk of in-hospital mortality. Conversely, patients with NDs of fear (OR = 0.56; 95% CI = 0.35, 0.89) and anxiety (OR = 0.44; 95% CI = 0.26, 0.77) had a lower risk of death. Conclusions: NDs on pulmonary and extrapulmonary responses to COVID-19 were associated with in-hospital mortality, suggesting that they are indicators of the severity of these patients. Therefore, NDs may help nursing staff identify individuals who require closer monitoring and guide early interventions for their recovery. Full article

Pseudomonas aeruginosa, a multidrug-resistant pathogen, significantly impacts patients with chronic respiratory conditions like cystic fibrosis (CF) and non-CF chronic suppurative lung disease (CSLD), contributing to progressive lung damage and poor clinical outcomes. This bacterium thrives in the airway environments of individuals with impaired mucociliary clearance, leading to persistent infections and increased morbidity and mortality. Despite advancements in management of these conditions, treatment failure remains common, emphasising the need for alternative or adjunctive treatment strategies. Bacteriophage therapy, an emerging approach utilising viruses that specifically target bacteria, offers a potential solution to combat P. aeruginosa infections resistant to conventional antibiotics. This review examines the prevalence and disease burden of P. aeruginosa in CF and CSLD, explores the mechanisms behind antibiotic resistance, the promising role of bacteriophage therapy and clinical trials in this sphere. Full article

Background/Objectives: In vitro models play a crucial role in preclinical respiratory research, enabling the testing and screening of mucosal formulations, dosage forms, and inhaled drugs. Mucociliary clearance (MCC) is an essential defense mechanism in mucosal drug delivery but is often impaired in respiratory diseases. Despite its importance, standardized in vitro MCC assays are rarely reported. Furthermore, many published methods primarily measure cilia beat frequency (CBF), which requires high-speed cameras that are not accessible to all laboratories. Therefore, this study aimed to develop a physiologically relevant, differentiated in vitro model of the respiratory epithelium that incorporates both beating cilia and functional MCC. We chose porcine airway mucosa as an alternative to human tissue due to ethical considerations and limited availability. The established model is designed to provide a reproducible and accessible method for a broad range of research laboratories. Methods: The previously published tracheal mucosal primary cell (TMPC DS) model, derived from porcine tissue, lacked the presence of beating cilia, which are crucial for effective MCC analysis. For accurate MCC assessment, beating cilia are essential as they play a key role in mucus clearance. To address this limitation, the here-described ciliated tracheal mucosal primary cell (cTMPC) model was developed. cTMPCs were isolated from porcine tissue and cultured under air–liquid interface (ALI) conditions for 21 days to promote differentiation. This model was evaluated for cell morphology, tight junction formation, ciliated and mucus-producing cells, barrier function, gene expression, and tracer/IgG transport. MCC and the model’s suitability for standardized MCC assays were assessed using an inverted microscope. In contrast to the TMPC DS model, which lacked beating cilia and thus could not support MCC analysis, the cTMPC model allows for comprehensive MCC studies. Results: The developed differentiated in vitro model demonstrated key structural and functional features of the respiratory epithelium, including well-differentiated cell morphology, tight junction integrity, ciliated and mucus-producing cells, and effective barrier function. Functional MCC was observed, confirming the model’s potential for standardized clearance assays. Conclusions: This differentiated in vitro model closely replicates the structural and functional characteristics of in vivo airways. It provides a valuable platform for studying mucociliary clearance, toxicology, drug uptake, and evaluating mucosal formulations and dosage forms in respiratory research. Full article

Micro- and nanoplastics (MPs and NPs) are pervasive environmental pollutants detected in aquatic ecosystems, with emerging evidence suggesting their presence in airborne particles generated by water body motion. Inhalation exposure to airborne MPs and NPs remains understudied despite documented links between occupational exposure to these particles and adverse respiratory outcomes, including airway inflammation, oxidative stress, and chronic respiratory diseases. This study explored the effects of acute NP exposure on a fully differentiated 3D human airway epithelial model derived from 14 healthy donors. Airway epithelium was exposed to aerosolized 50 nm polystyrene NPs at concentrations ranging from 2.5 to 2500 µg/mL for three minutes per day over three days. Functional assays revealed no significant alterations in tissue integrity, cell survival, mucociliary clearance, or cilia beat frequency, suggesting intact epithelial function post-exposure. However, cytokine and chemokine profiling identified a significant five-fold increase in CCL3 (MIP-1α), a neutrophilic chemoattractant, in NP-exposed samples compared to controls. This was corroborated by increased neutrophil chemotaxis in response to conditioned media from NP-exposed tissues, indicating a pro-inflammatory neutrophilic response. Conversely, levels of interleukins (IL-21, IL-2, IL-15), CXCL10, and TGF-β were significantly reduced, suggesting immunomodulatory effects that may impair adaptive immune responses and tissue repair mechanisms. These findings demonstrate that short-term exposure to NP-containing aerosols induces a distinct pro-inflammatory response in airway epithelium, characterized by enhanced neutrophil recruitment and reduced secretion of key immune modulators. These findings underscore the potential for aerosolized NPs to induce oxidative and inflammatory stress, raising concerns about their long-term impact on respiratory health and redox regulation. 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

Mucociliary clearance, the ability of the respiratory tract to protect the integrity of the airways through the mechanical removal of potentially harmful substances, is of enormous importance during intensive care treatment. The present study aimed to evaluate the influence of clinically relevant inotropic agents on mucociliary clearance. The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance in the presence of dobutamine, epinephrine, and milrinone. Inhibitory substances were applied to elucidate the signal transduction cascades and the value and origin of calcium ions which provoke alterations in mucociliary clearance function. Dobutamine, epinephrine, and milrinone increased the PTV in a dose-dependent manner with half maximal effective concentrations of 75.7 nM, 87.0 nM, and 13.7 µM, respectively. After the depletion of intracellular calcium stores, no increase in PTV was observed after administering any of the three inotropic agents. While dobutamine and epinephrine activated β-adrenergic receptors, epinephrine used both the phospholipase C (PLC) and protein kinase A (PKA) pathway to promote the release of intracellular Ca²⁺. However, dobutamine primarily acted on the PKA pathway, having only a minor influence on the PLC pathway. The induced changes in PTV following milrinone administration required both the PKA and PLC pathway, although the PKA pathway was responsible for most of the induced changes. In conclusion, the common inotropic agents dobutamine, epinephrine, and milrinone increase murine PTV in a concentration-dependent manner and ultimately release Ca²⁺ from intracellular calcium stores, suggesting the function of changes in mucociliary clearance in the respiratory tract. Full article

Background: Airway clearance techniques are a key element in the daily treatment of people with bronchiectasis. There are several methods and devices to assist in effective airway clearance. We investigated LibAirty, a novel medical device, and compared it with the common practice performed today. Methods: Twenty adults enrolled, and each one had three different treatments in a randomized order: a human respiratory physiotherapist, a High-Frequency Chest Wall Oscillator, and LibAirty with BiPAP. The outcome parameters were mucus weight and a questionnaire. Further studies were performed to investigate LibAirty with hypertonic saline (HS) inhalation and using the device as a standalone. Results: No adverse events were recorded. The sputum amount expectorated in all arms using LibAirty was 14.4 ± 11.1 g with BIPAP, 16.4 ± 7 g with HS, and 11.3 ± 4.1 g for the standalone treatment. For HFCWO, 4.45 ± 3.28 g was obtained, and for CPT, 15.9 ± 11.1 g was obtained. The amount obtained by LibAirty (all arms) was significantly higher than HFCWO. Conclusions: All arms of LibAirty were superior to HFCWO and similar to the human physiotherapist. Further studies should be performed to investigate the long-term effects of LibAirty. Full article

Over recent years, advances in medical care have significantly improved the survival of children with severe chronic conditions. These children, referred to as children with medical complexity (CMC), present unique and demanding healthcare challenges. Although definitions of CMC remain inconsistent, these patients are typically characterized by chronic, often severe conditions requiring daily specialized treatments and the use of various medical devices. CMC represent a substantial burden for healthcare systems due to their high medical costs, and place considerable strain on caregivers, who must provide continuous assistance. Airway colonization by pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Haemophilus influenzae is common in CMC and contributes to recurrent respiratory infections, increased hospitalizations, and progressive lung damage. The management of airway colonization in this population is a topic of ongoing debate, often involving a combination of airway clearance techniques (ACT) and antibiotic therapies. Antibiotics may be administered systemically, nebulized, or in combination, depending on the clinical context and severity of the condition. This review highlights the complexities of managing airway colonization in CMC, emphasizing the need for tailored therapeutic approaches to mitigate respiratory complications and improve outcomes. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, characterized by chronic mucus hypersecretion (CMH) that exacerbates airway obstruction and accelerates disease progression. Effective airway clearance techniques are essential to improve respiratory function and reduce exacerbations. Temporary Positive Expiratory Pressure (T-PEP) is a novel airway clearance device that has shown promise in managing COPD. Objectives: This meta-analysis aimed to evaluate the efficacy of T-PEP in a standard pulmonary rehabilitation program. Methods: Following PRISMA guidelines, a comprehensive search of randomized controlled trials (RCTs) was conducted in the MEDLINE and PEDro databases. Data from 162 subjects, including those with severe COPD and bronchiectasis, were analyzed. Key outcomes assessed were changes in lung function (FVC, FEV1, TLC), inspiratory and expiratory pressures (MIP, MEP), gas exchange (PaO₂, PaCO₂), exercise capacity (6MWT), symptom severity (mMRC, CAT, BCSS), and exacerbation rates. Results: T-PEP significantly improved FVC, FEV1, TLC, MIP, MEP, and DLCO compared to baseline, with heterogeneity noted across studies. Improvements in gas exchange and physical capacity were observed, with PaO₂ increasing and PaCO₂ decreasing. T-PEP also reduced symptoms of cough and dyspnea, improving quality-of-life scores. Additionally, a notable reduction in acute exacerbations of COPD was seen after one month and three months of treatment. Conclusions: T-PEP therapy shows substantial benefits in improving lung function, exercise capacity, and quality of life while reducing exacerbation rates in COPD patients. Although promising, these findings require further confirmation through randomized clinical trials to establish the optimal application of T-PEP in various clinical settings and patient phenotypes. Full article