Facultad de Ciencias de la Salud

Primary Ciliary Dyskinesia (PCD) represents a rare condition marked by an abnormal mobility pattern of cilia and flagella, resulting in impaired mucociliary clearance. This deficiency leads to recurrent infections and persistent inflammation of the airways. While previous studies have indicated heightened oxidative stress levels in the exhaled breath condensate of pediatric PCD patients, the assessment of oxidative stress within the affected respiratory tissue remains unexplored. Aims: To assess the oxidative status of human nasal epithelial cells (NECs) in PCD patients. Methods: Thirty-five PCD patients and thirty-five healthy control subjects were prospectively included in the study. Levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), intracellular Ca2+, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and mitochondrial function were analyzed by flow cytometry in NECs. Results: NECs from PCD patients showed reduced levels of apoptosis (p = 0.004), superoxide anion (O2 −, p = 0.018), peroxynitrite (ONOO−, p = 0.007), nitric oxide (NO, p = 0.007), mitochondrial hydrogen peroxide (mtH2O2, p < 0.0001), and mitochondrial superoxide anion (mtO2 −, p = 0.0004) and increased mitochondrial mass (p = 0.009) compared to those from healthy individuals. No significant differences were observed in oxidized proteins (p = 0.137) and the oxidized/reduced lipid ratio (p = 0.7973). The oxidative profile of NEC cells in PCD patients, according to their ciliary motility, recurrent otitis, recurrent pneumonia, atelectasis, bronchiectasis, and situs inversus, showed no statistically significant differences in the parameters studied. Conversely, patients with chronic rhinosinusitis exhibited lower levels of ONOO− than PCD patients without this condition, with no significant differences related to other symptoms. Conclusions: Our findings strongly suggest the presence of a redox imbalance, specifically leaning toward a reductive state, in PCD patients.

Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient’s clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.