Estudio del estrés oxidativo en el epitelio nasal ciliado de pacientes con Discinesia Ciliar Primaria
Background: Primary ciliary dyskinesia (PCD) is a rare disease with an estimated prevalence of 1:20.000 births. It is characterized by an alteration of the mobility pattern of cilia and flagella, causing lack of mucociliary clearance and subsequent infection and chronic inflammation of the airways. An inefficient inflammatory process increases the production of reactive oxygen and nitrogen species (ROS and RNS), which derives in a higher risk of diseases. In PCD, a study demonstrated that oxidative stress is increased in exhaled breath condensate from paediatric patients. Although oxidative stress had not been determined in the affected tissue yet, we hypothesized that patients with PCD have a pro-oxidative status in respiratory epithelial cells. Aims: To study the oxidative status of nasal epithelial cells from patients with PCD, compare it with healthy controls, and determine their role on the disease pathophysiology. Methods: Levels of ROS, RNS, glutathione (GSH), intracellular Ca2+, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and the mitochondrial function were analysed by flow cytometry in nasal epithelial cells. Two groups took part in the study: 35 healthy subjects and 35 patients diagnosed of PCD. 7 Results: Patients with PCD have levels of apoptosis, NO, ONOO-, total O2-, mitochondrial H2O2 and mitochondrial O2- in their nasal epithelial cells lower than those of healthy individuals. There are no differences between the groups of patients and controls in the rest of the parameters measured. When comparing within the group of patients, there are no differences between adults and children in any compared parameter, nor is there any difference depending on the different ciliary mobility pattern; women with PCD have lower levels of mitochondrial H2O2 and O2- than men with the disease; patients with atelectasis, and those with situs inversus have higher intracellular peroxides levels than those who do not; patients with chronic rhinosinusitis have lower levels of ONOO- than those who do not, and no differences have been found depending on the other symptoms. A tree has been designed to classify individuals as patient or healthy control based on the levels of certain parameters of the oxidative profile measured in their nasal epithelial cells.