Impact of Trikafta on P2X7R and Clinical Outcomes in Cystic Fibrosis

The aim of this study is to assess the response of the ETI on P2X7R level as inflammatory marker and clinical outcomes including respiratory outcomes, gastrointestinal outcomes, anthropometric measurements in patients with cystic fibrosis. Written consent will be obtained from the legal guardians of the patients or the patients.The study will be 35 CF patients before starting ETI and same patients after 12 months of therapy .The data will be collected as Clinical parameters:Complete history taking including:sociodemographic data ( date of birth, gender, consanguinity and residency), age of diagnosis ,medication history,family history of sibling affection and history of sibling death,history of presenting symptoms as:respiratory symptoms(productive cough, expectoration, dyspnea , wheezes, chest pain),pancreatic function(failure to thrive, steatorrhea, thirst, and polyuria),gastrointestinal symptoms(abdominal pain, bloating and vomiting),symptoms of fat-soluble vitamins deficiency,detailed dietetic history, comorbidities(CF-related diabetes, GIT complications as constipation,and rectal prolapse, respiratory complications as hemoptysis, or pulmonary hypertension).Clinical examination including :complete general examination of the patients especially:respiratory rate, oxygen saturation by pulse oximetry on room air, clubbing,anthropometric measurements: including weight (kg), height (cm), body mass index (BMI) (kg/m²) will be measured and their Z-scores will be calculated according CDC growth charts at 6 and 12 months follow up and Full chest examination for signs of respiratory distress and the auscultatory findings.

• laboratory parameters:CBC,CRP,Liver function tests, sputum culture ,genotype (Homozygous or heterozygous Phe508del or any eligible genes for ETI( from medical records )), Human Purinergic Receptor P2X, Ligand Gated Ion Channel 7 (P2RX7), radiological assessment : low dose high-resolution CT (HRCT) of the chest,Pulmonary Function Test:Forced spirometry for cooperative patients with with comment mainly on FEV1 % Predicted and FEF25-75%Predicted and nutritional plan as macronutrients ,micronutrients and Pancreatic Enzyme Replacement Therapy.All of the following data will be collected before ETI and after 12months of treatment: presenting symptoms,all clinical assessment measures that were mentioned before,all laboratory investigations,pulmonary function tests and radiological assessment.

Inclusion criteria

• Confirmed diagnosis of Cystic Fibrosis according to CF Foundation guidelines (based on positive sweat chloride test and/or presence of disease-causing mutations in homozygous state or compound heterozygous state in CFTR gene).
• Patients eligible for ETI therapy (having at least one F508del mutation or a mutation known to be responsive to ETI).
• Age above 5 years old.

Exclusion criteria

• Known allergy or hypersensitivity to ETI or any of its components.
• Moderate hepatic impairment (Child-Pugh Class B) or severe hepatic impairment (Child-Pugh Class C).
• Presence of chronic inflammatory diseases unrelated to CF (e.g., Crohn's disease, glomerulonephritis, or thrombotic disorders) that could confound P2X7R levels.