###### Created: 2023-09-12 09:27 ###### Areas & Topics: #medicine #respiratory #paediatrics ###### Note Type: #permanent ###### Connected to: [[Iontophoresis]] - Cystic Fibrosis (CF) is an autosomal recessive genetic disorder. - It is caused by a defect in the cystic-fibrosis transmembrane conductance regulator (CFTR) gene, found on chromosome 7. - This gene is responsible for controlling cAMP chloride channels, which draw fluid into mucous to reduce its viscosity. ### Epidemiology - Diagnosed in 1 in 2500 new-borns, with 193 people newly diagnosed in the UK in 2019. ### Pathophysiology - There are multiple different variants of the CFTR mutation which lead to pathological changes. - All these variants lead, in some way, to chloride being moved into cellular spaces, thereby drawing sodium with it and away from mucus covering epithelial surfaces. - This then draws water out of mucus and into cellular spaces, causing the mucus to thicken and become significantly more viscous. - The lack of water and increased viscosity of mucus causes dysfunction of the cilia and issues with the mucociliary escalator. - Since mucus cannot be effectively cleared, the airways become obstructed and bacteria and other infective organisms aren't effectively cleared leading to increased and recurrent infections. - Increased mucous viscosity also affects other organs such as the pancreas and bile ducts, leading to issues there as well. ### Clinical Features - Younger people commonly have infections as a result of Staphylococcus Aureus and Haemophilus Influenza - Adults are commonly infected by Pseudomonas Aeruginosa - Severe cases have a strong, purulent, 'wet' cough - Examination will typically show chest hyperinflation and coarse inspiratory crepitations (and expiratory wheeze and finger clubbing in some cases) **New-Born** - The lungs before birth, during birth and directly after birth are normal in CF patients as pathological changes have not yet begun to take place - There is however clinical evidence of CF due to increased mucous viscosity - The main features in new-borns include [[Meconium Ileus]] and diagnosis through the new-born screening test **Infant** - Prolonged Neonatal Jaundice (likely due to biliary obstruction from thickened secretions) - Faltering Growth/Malabsoprtion/Steatorrhea (due to issues with absorption and pancreatic function) - Recurrent Chest Infections **Young Children** - [[Bronchiectasis]] - Rectal prolapse (likely caused due to bowel movements having more volume and poor nutrition) - [[Nasal Polyps]] (likely caused due to frequent infections and sinusitis from mucociliary dysfunction) - Sinusitis (likely due to the same reasons as above) **Everyone Else** - Diabetes (due to thickened secretions leading to pancreating inflammation and scarring) - Cirrhosis and Portal Hypertension (likely due to issues with the biliary system leading to scarring and thereby fibrosis and cirrhosis) - Infertility (in males) ### Diagnosis **Heel-Prick/Newborn Blood Spot Testing** - The Newborn blood spot test/heel prick test is a new-born test used 5 days after birth to screen for nine different conditions. - The pancreatic enzyme Immunoreactive Trypsinogen (IRT) is used to screen for cystic fibrosis. - This is because if you have CF then you will have thicken secretions leading to obstruction of exocrine pancreatic enzymes (which includes IRT). - This will then cause IRT levels in your blood to become elevated (although they can also be elevated in prematurity/stress in new-borns) **Sweat Test** - In CF patients, increased levels of chloride are seen in patient sweat due to higher levels in cellular spaces - Therefore measuring chloride levels in sweat is the gold standard for CF diagnosis - Clinicians apply pilocarpine to the skin of the patient's forearm - They then use a low-voltage current which imbibes (absorbs) the pilocarpine into the patient's sweat glands (this process is known as [[Iontophoresis]]) - The pilocarpine is a muscarinic receptor agonist, causing contraction of the sweat glands and allowing for sweat to be collected and then measured ### Management - Management is complex with an MDT approach being incredibly important - The main aim of management is to prevent lung disease progression and allow for adequate nutrition and growth ### Medications Medications for CF can be broadly grouped into 3 classes: 1. CFTR Potentiators - Allows CFTR Protein to function more effectively as a chloride channel (e.g. ivacaftor) 2. CFTR Correctors - Help the CFTR protein to fold correctly and get to the cell surface (e.g. elexacaftor) 3. Combination Therapy - Use of a mix of potentiators and correctors (e.g. Kaftrio) ![[3-s2 6.jpeg]] ### Resources https://www.ncbi.nlm.nih.gov/books/NBK493206/ https://app.pulsenotes.com/medicine/respiratory/notes/cystic-fibrosis https://www-clinicalkey-com.ezproxy.lancs.ac.uk/student/content/book/3-s2.0-B9780702081804000176#hl0001328