Search Results (43)

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

Introduction: Difficult airway management is a critical challenge in anesthesia, often necessitating advanced techniques to ensure patient safety. A patient presented with a malignant lesion on the epiglottis, significantly altering the airway anatomy. Flexible rhinolaryngoscopy revealed a laryngeal carcinoma affecting the entire epiglottis, causing thickening and displacement, which suggested the potential for difficult intubation. Methods: Given the expected feasibility of bag-mask ventilation and front-of-neck access, an asleep intubation technique was selected. The combined use of a McGrath video laryngoscope and C-MAC video stylet allowed for fast and easy atraumatic intubation on the first attempt. The anesthetic and surgical course was uneventful. Discussion: This case report highlights the successful use of a combined approach involving a video laryngoscope and video stylet for intubation in a patient with known difficulties in airway management, providing insights into the benefits of enhanced visualization and maneuverability. The rigid design and steerable tip of the C-MAC video stylet provide advantages over traditional flexible optics, offering better maneuverability and reducing the need for a second operator. Although this technique was successful in this case, its use in patients with complex airway pathologies warrants careful preoperative assessment and collaboration with an experienced airway management team. Full article

Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway’s mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically. The mucin concentrations in BW were determined using the slot-blot technique. The immunohistochemical expression of MUC5AC and MUC5B was localized to goblet cells and submucosal glands. Smokers had higher MUC5AC and lower MUC5B goblet cell expression and higher concentrations of soluble MUC5AC in BW than never-smokers. The MUC5B expression in goblet cells correlated positively with expiratory air flows, diffusing capacity, and the dyspnoea score. Chronic bronchitis, emphysema, and the progression of chronic airflow limitation during a median follow-up time of 8.4 years were associated with higher MUC5AC and lower MUC5B expression in goblet cells. Sustainers, slow progressors, and rapid progressors of airflow obstruction differed in their MUC5B expression at baseline. Emphysema and bronchial wall thickening on CT at a follow-up visit were associated with lower MUC5B expression at baseline. Our findings strengthen the hypothesis that MUC5AC and MUC5B are yet another contributing factor to smoking-associated lung disease progression. Full article

Within the pediatric population, bronchial asthma is one of the most prevalent chronic respiratory system diseases. The number of exacerbations, severity, and duration of symptoms all have a significant impact on children’s life quality. In the last decades, the prevention and management strategies of this pathology have focused on maintaining or even increasing the pulmonary function to maximum levels in early childhood, as it has been demonstrated that functional deficits at this level occurring before school age cause pathological manifestations later, in adulthood. The epithelium of the airways and implicitly that of the lung is the first barrier against the lesions caused by pro-oxidative factors. Both oxidative and antioxidative factors can be of endogenous origin (produced by the body) or exogenous (from the environment or diet). Good functioning of antioxidant defense mechanisms from the molecular level to the tissue level, and a balance between pro-oxidative factors and anti- oxidative factors, influence the occurrence of compensatory mechanisms at the level of the respiratory epithelium, causing the delay of local responses to the stress induced by chronic inflammation (bronchial remodeling, thickening of airway smooth muscles, bronchoconstriction, bronchial hyper-reactivity). These mechanisms underlie the pathophysiological changes in asthma. Numerous studies carried out among the pediatric population inclusively have demonstrated the effectiveness of antioxidants in the prophylaxis, slowing down and preventing the progression of this pathology. This review complements the scientific articles, aiming at emphasizing the complexity of oxidative physio-pathological pathways and their importance in the occurrence, development, and therapeutic response in asthma, providing a good understanding of the relationship between oxidative and antioxidative factors, and being a source of future therapeutic strategies. Full article

This study investigated using a 160-slice multidetector computed tomography (CT) scanner for conscious image acquisition in dogs with upper airway disease, and describes findings in dogs that had previously undergone soft palate surgery. Seventeen client-owned dogs with upper airway disease were retrospectively reviewed, and classified into three groups: group I, “untreated brachycephalic obstructive airway syndrome (BOAS) patients”; group II, “previously treated BOAS patients”; and group III, “patients with respiratory disease other than BOAS”. Data included signalment, clinical history, direct laryngoscopy and endoscopy findings, previous surgeries and CT findings. CT scans in group I revealed overlong and thickened soft palates in all dogs, and signs of laryngeal collapse in four dogs. Patients in group II exhibited normal soft palate lengths, while patients in group III displayed various findings such as nasopharyngeal narrowing and tracheal collapse. Upper airway examinations under general anaesthesia confirmed most CT findings. This study demonstrates the feasibility and value of conscious CT scanning for assessing upper airway diseases in dogs, providing valuable diagnostic information while eliminating the need for chemical immobilisation, thus reducing patient stress and cost. These findings offer new insight into upper airway anatomy in awake patients, especially in brachycephalic breeds, and lay a foundation for future research. Full article

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling. Full article

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa. Full article

In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management. Full article

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D₃ improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D₃ may modulate these microRNAs to improve asthma symptoms. Full article

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma’s pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR. Full article

Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the “Hematopoietic cell lineage” pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs. The differentially expressed genes (DEGs) upregulated in PBMCs reflected the disease state of non-emphysematous COPD. Upregulated DEGs such as XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 activate T lymphocytes and eosinophils. Upregulating keratan sulfate biosynthesis and metabolic processes is associated with protection against the destruction of the distal airways. ITGA3 upregulation augments interactions with extracellular matrix proteins, and COL6A1 augments the profibrotic mast cell phenotype during alveolar collagen VI deposition. Upregulating HSPG2, PDGFRB, and PAK4 contributes to the thickening of the airway wall, and upregulating SERPINF1 expression explains the better-preserved vascular bed. Therefore, gene expression and pathway analysis in PBMCs in patients with non-emphysematous COPD represented type 2 immune responses and airway remodeling features. Therefore, these patients have asthmatic potential despite no clinical signs of asthma, in contrast to those with emphysematous COPD. Full article

People with cystic fibrosis (pwCF) suffer from chronic and recurring bacterial lung infections that begin very early in life and contribute to progressive lung failure. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes an ion channel important for maintaining the proper hydration of pulmonary surfaces. When CFTR function is ablated or impaired, airways develop thickened, adherent mucus that contributes to a vicious cycle of infection and inflammation. Therapeutics for pwCF, called CFTR modulators, target the CFTR defect directly, restoring airway surface hydration and mucociliary clearance. However, even with CFTR modulator therapy, bacterial infections persist. To develop a relevant model of diseased airway epithelium, we established a primary human airway epithelium culture system with persistent Pseudomonas aeruginosa infection. We used this model to examine the effects of CFTR modulators on CFTR maturation, CFTR function, and bacterial persistence. We found that the presence of P. aeruginosa increased CFTR mRNA, protein, and function. We also found that CFTR modulators caused a decrease in P. aeruginosa burden. These results demonstrate the importance of including live bacteria to accurately model the CF lung, and that understanding the effects of infection on CFTR rescue by CFTR modulators is critical to evaluating and optimizing drug therapies for all pwCF. Full article

Small airway disease (SAD) is a pathological condition that affects the bronchioles and non-cartilaginous airways 2 mm or less in diameter. These airways play a crucial role in respiratory function and are often implicated in various pulmonary disorders. Pulmonary fibrotic diseases are characterized by the thickening and scarring of lung tissue, leading to progressive respiratory failure. We aimed to present the link between SAD and fibrotic lung conditions. The evidence suggests that SAD may act as a precursor or exacerbating factor in the progression of fibrotic diseases. Patients with fibrotic conditions often exhibit signs of small airway dysfunction, which can contribute to worsening respiratory symptoms and decreased lung function. Moreover, individuals with advanced SAD are at a heightened risk of developing fibrotic changes in the lung. The interplay between inflammation, environmental factors, and genetic predisposition further complicates this association. The early detection and management of SAD can potentially mitigate the progression of fibrotic diseases, highlighting the need for comprehensive clinical evaluation and research. This review emphasizes the need to understand the evolving connection between SAD and pulmonary fibrosis, urging further detailed research to clarify the causes and potential treatment between the two entities. Full article

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are “healthier” than tobacco cigarettes or simply “water vapour”. Third-hand e-vapour exposure is the chemical residue left behind from e-cigarette aerosols, which is of concern due to its invisible nature, especially among young children. However, there is limited information surrounding third-hand e-vapour exposure. This study aimed to investigate the pulmonary effects of sub-chronic third-hand e-vapour exposure in a murine model. BALB/c mice (4 weeks of age) were exposed to a towel containing nicotine free (0 mg) e-vapour, nicotine (18 mg) e-vapour, or no e-vapour (sham) and replaced daily for 4 weeks. At the endpoint, lung function was assessed, and bronchoalveolar lavage fluid and lungs were collected to measure inflammation and fibrosis. Mice exposed to third-hand e-vapour without nicotine had alveolar enlargement compared to sham exposed controls. Mice exposed to third-hand e-vapour with nicotine had reduced bronchial responsiveness to provocation, increased epithelial thickening in large airways, increased epithelial layers in small airways, alveolar enlargement, and increased small airway collagen deposition, compared to sham exposed controls. In conclusion, our study shows that third-hand e-vapour exposure, particularly in the presence of nicotine, negatively affects the lung health of mice and highlights the need for greater public awareness surrounding the dangers of third-hand exposure to e-cigarette vapour. Full article

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma. Full article