Cystic Fibrosis

2. CysticFibrosis Molecular data : differenttypes of mutations Therapeutic perspectives

3. CFTR gene • On chromosome 7, long arm (q31). • Code for an ion chanel thatconduceschlorideacrosscellmembrane. • More than a thousand mutations have been described.

4. Mutation ΔF508 • This is the main frequentmutation : approximately70% of cases. • Deletion of threenucleotides, removing a phenylalanine in positition 508 • preventing it from reaching the cell membrane

5. Otherfrequently mutations • G542X : nonsense mutation, 12% of cases, causing partial reduction of synthesis. • G551D : missense mutation, 3% of cases, causingdysregulation of the channel. • R117H : missense mutation, 3% of cases

6. It isreallydifficult to predict the phenotypeeven if we know the genotype. • Manyfactorscan influence the occurrence and the severity of the disease: - the type of mutation - the associations of mutations (for heterozygotescomposed) - the differentsvariants of poly-T tract in intron 8 (which influence the splicing of exon 9)

7. An Overview of Cystic Fibrosis Treatment • Although there is still no a definitive cure for Cystic Fibrosis (CF), but treatment has improved greatly patients life in last years. • The goals of CF treatment include: • Preventing and controlling lung infections • Loosening and removing thick, sticky mucus from the lungs • Preventing or treating blockages in the intestines • Providing enough nutrition

8. Medications People with cystic fibrosis will have to take medications for the rest of their lives. Some of the common medications are: Antibiotics:Taken to prevent or cure an infection. Anti-inflammatory: An anti-inflammatory is a drug that reduces irritation and swelling. They are used toreduce the swelling in the lungs and breathing passages. Enzymes:One of the problems caused by CF is that the thick secretions in the pancreas prevent it from releasing the enzymes the body needs to digest food. People with CF need to take pills that contain the necessary enzymes before each meal. Mucolytics:Mucolytics are medicines that help to thin mucus and make it easier to cough out. They are often prescribed to cystic fibrosis patients to help them clear their airways of the thick, sticky mucus that CF causes..

9. Airway Clearance • An essential part of cystic fibrosis treatment is the use of a variety of techniques to help loosen and remove mucus. The therapy will involve one or more of these techniques: Chest Physical Therapy (CPT): • This therapy uses a technique called percussion that involves rhythmic tapping of the hands on strategic areas of the chest. • Mechanical devices also can help loosen lung mucus. The options include: • Chest clapper :a hand-held device that mimics the effect of cupped hands clapping over the ribs • Inflatable vest :a device worn around the chest that vibrates at high frequency • Breathing devices :usually a tube or mask through which the patient exhales while performing breathing exercises

10. Physical activities • Physical activity has both short-term and long-term benefits for people with cystic fibrosis. • The immediate benefit is that exercise forces more air through the lungs and helps loosen mucus. The long-term benefit of exercise is that it helps improve cardiovascular health and endurance. Diet People with cystic fibrosis don’t absorb nutrients properly from the food that they eat, and the work of breathing causes them to burn extra calories, so itcauses malnutrition and poor growth. Doctors suggest to: - Eat 3 meals and 2-3 snacks per day - Eat foods high in protein and fat - Drink nutrition shakes once or twice a day - Take vitamin supplements, especially vitamins A, D, E, and K

11. Surgical and other procedures Nasal polyp removal:Your doctor may recommend surgery to remove nasal polyps that obstruct breathing. Oxygen therapy: If blood-oxygen level declines, the doctor may recommend breathe pure oxygen to prevent high blood pressure in the lungs (pulmonary hypertension). Endoscopy and lavage:Mucus may be suctioned from obstructed airways through an endoscope. Feeding tube : it is used to deliver extra nutrition while sleeping. It may be threaded through a tube fromnose to stomach or surgically implanted into the abdomen. Bowel surgery:If a blockage develops in bowel, the patientmay need surgery to remove it. • Lung Transplantation • Lung transplantation requires surgery to replace one or both of lungs with healthy lungs from a human donor. • Factors that determine whether patientscan undergo lung transplantation include: • The type of bacteria in lungs • Your age and weight • The medications taking • Other medical conditions, including osteoporosis • How lungs function.

12. Pulmonary Rehabilitation Doctor may recommend PR as part of treatment plan. PR is a broad program that helps improve the well-being of people who have chronic (ongoing) breathing problems. PR doesn't replace medical therapy. Instead, it's used with medical therapy and may include: • Exercise training • Nutritional counseling • Education on lung disease or condition and how to manage it • Energy-conserving techniques • Breathing strategies • Psychological counseling and/or group support PR has many benefits. It can improve patient’sability to function and quality of life. The program also may help relieve breathing problems.

13. Thankyou for your attention ! • MariarosariaMagaldi • Corentin Bessy

14. References Emery’sElement of genetic, Peter Turnpenny, Sian Ellard, chap 19. http://ghr.nlm.nih.gov/gene/CFTR, 10/09/14 • http://cysticfibrosis.about.com/od/treatment/a/CFtreatment.htm • http://www.nhlbi.nih.gov/health/health-topics/topics/cf/treatment.html • http://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/basics/definition/con-20013731 • http://cystic-fibrosis.emedtv.com/cystic-fibrosis/treatment-for-cystic-fibrosis-p2.html https://www.youtube.com/watch?v=DMt2JQgOVZY