MANAGEMENT OF CYSTIC FIBROSIS<br />DR.KARTIK SOOD<br />JUNIOR RESIDENT <br />DEPARTMENT OF PULMONARY MEDICINE<br />
<ul><li>Nearly 1000 mutations have been identified in the CYSTIC FIBROSIS gene.
Worldwide Most common mutation is (delta)F508 where there is deletion of 508 th amino acid of CFTR.
Mutations have been divided into FIVE SEQUENTIAL CLASSES broadly based in the molecular fate of the CFTR.</li></ul> (reviewed by zeitlin ) <br />( from- adc.bmj.com feb 2009) <br />
CLASS 1 MUTATIONS CAUSE DEFECTS IN CFTR SYNTHESIS RESULTING IN ABSENCE OF CFTR PRODUCTION.<br />IN CLASS 2 MUTATIONS , WHICH INCLUDE DELTA F 508, THERE IS PRODUCTION OF ABNORMAL CFTR, WHICH THEN FAILS TO ESCAPE THE ENDOPLASMIC RETICULUM.<br />CLASS 3 MUTATIONS HAVE CFTR PRODUCTION AND INTRACELLULAR TRAFFIKING, BUT THERE IS DISRUPTION OF ACTIVATION AND REGULATION AT THE CELL MEMBRANE.<br />
IN CLASS 4 MUTATIONS CFTR IS EXPRESSED AT THE CELL MEMBRANE BUT CHLORIDE CONDUCTANCE IS REDUCED.<br />CLASS 5 MUTATIONS DECREASE MEMBRANE CFTR FUNCTION BY DECREASING SPLICING OF NORMAL CFTR .<br />(recent advances in cf adc.com(arch this child )by lolojmdoull)<br />
Diagnosis Criteria<br />Positive Sweat Test: >70 mEq/L Na and Cl<br />Presence of:<br />Chronic Lung disease<br />Failure to Thrive<br />Malabsorption<br />Or<br />Family History of CF<br />
Diagnosis Methods<br />Newborn screening: measures immunoreactivetrypsinogen concentration in dried blood spots ( GURTHIE TEST)<br />SWEAT TEST : GOLD STANDARD test for diagnosis .Sweat is stimulated by<br />pilocarpineiontophoresis(a weak electric current aids the penetration of pilocarpine into the skin) and collected on filters. Atleast 100 mg of sweat should be analysed. . <br />
<ul><li>Ion concentration of greater than 70 mmol/l is indicative of CF.
Concentration of less than 50 mmol/l is normal.
b/w 50 to 70 requires further consideration by genotyping. (crofton)
Peripheral airway involvement resulting from CF manifests as an obstructive defect with airtrapping and hyperinflation</li></li></ul><li><ul><li>. In the early stages,(FEV1) may be normal and forced expiratory flow (FEF) after 25-75% of vital capacity has been expelled (FEF 25-75) is reduced, suggesting small airway involvement. As the disease progresses, FEV1 is also reduced.
CHEST X RAY-</li></ul>Mild hyperinflation and peribronchialthikening<br />Bronchiectactic changes (fishman)<br />
PERIBRONCHIAL THIKENING IN UPPER LOBES</li></li></ul><li><ul><li>SPUTUM CULTURE – (Helps in establishing diagnosis and in guiding antimicrobial therapy)</li></ul> commonly isolated organisms are-pseudomonas and staph aureus.<br /><ul><li>STOOL FAT CONTENT-malabscoffecient of more than 7 %is considered abnormal.
TRYPSIN AND CHYMOTRYPSIN IN STOOl-activity is low in stool bcoz of delayed transit time that causes partial inactivation of enzymes.
Semen analysis – to rule out azoospermia(found in 98% of cf male pts)
Mutation analysis</li></li></ul><li>Current Treatments<br />Treatment for Lung Problems<br />Antibiotics<br />Chest physical therapy (like percussion)<br />Exercise <br />Other medications <br />Anti-inflammatory medications<br />Bronchodilators, <br />Mucus-thinning drugs <br />Oxygen Therapy<br />Lung Transplantation<br />Management of Digestive Problems<br />Oral pancreatic enzymes<br />Fat-soluble vitamins A, D, E, and K <br />Feeding tube<br />Enemas and mucus-thinning medications to treat intestinal blockages <br />
antibiotics<br />Currently useful agents for treating STAPHYLOCOCCAL infections include DICLOXACILLIN, CEPHALEXIN, the newer CEPHALOSPORINS, CLAVULANIC ACID combinations, and macrolides. Early in the course of the pulmonary disease, a small fraction of PSEUDOMONAS STRAINS may be sensitive to TETRACYCLINE, TRIMETHOPRIM-SULFAMETHOXAZOLE, OR CHLORAMPHENICOL. CIPROFLOXACIN, is initially effective against many strains of pseudomonas and has gained widespread use in the outpatient management of CF<br />
Most popular antibiotic combination currently in use is TOBRAMYCIN and CEFTAZIDIME. (tobramycin, 10 mg/kg per day in three divided<br />Doses) patients begin to show improvement after 5 to 7 days,continue antibiotics intravenously or at least 2 weeks in order to decrease the relapse rate and to avoid a decrease in the interval between exacerbations<br />AZITHROMYCIN, 250 mg or 500 mg thrice weekly, was evaluated in CF patients colonized with P. aeruginosa. After 6 months of therapy, patients had an improvement in FEV1 (6.2 percent), increased weight gain, and decreased rates of pulmonary exacerbations. (fishman)<br />
MIST AND MUCUS THINNING DRUGS<br /><ul><li>dissolving mucin components and in decreasing the viscosity of sputum
BRONCHODILATORS</li></ul> (INHALATIONAL OR ORAL)<br /><ul><li> CORTICOSTEROIDS can also be used</li></li></ul><li>Physiotherapy<br />Prevents sticky lung secretions that build up in the small airways.<br /> Gravity Assisted Position<br /> The use of different body positions to achieve drainage of secretions from an area of the lung.<br />
Percussion and Vibration<br />Percussion: Clapping with hand in a cupped position loosens secretions<br />Mechanical Vibrations <br /> ( shakes whole body)<br />(adc.com)<br />
Enzyme Therapy<br />Treatment with enzyme extracts of porcine origin<br />Contain amylase, protease, and lipase<br />Enteric-coated microspheres or microtablets<br />proton pump inhibitor may be used to increase effectiveness<br />