Definition
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) protein (chromosome 7). Mutations in the CFTR gene result in defective chloride transport in epithelial cells resulting in many clinical manifestations: pancreatic insufficiency, diabetes mellitus, obstructive biliary disease and cryptogenic cirrhosis, malabsorption, azoospermia, and sinopulmonary disease including bronchiectasis and obstructive pulmonary disease.
CFTR Modulators
Modulators that help increase CFTR function are now changing the landscape of CF. Combination pills appear to be more effective, and based on their mutation profile patients may be on triple, double, or single therapy. The main adverse effect for the 4 medications currently on the market are LFT elevations.
Evaluation for CF Exacerbation
- Pulmonary disease represents the primary cause of morbidity and mortality in CF patients and is the most common reason for hospital admission.
- Symptoms: increased cough and sputum production, shortness of breath, fatigue.
- Signs: increased work of breathing and respiratory rate, increased crackles of exam.
- Studies: airflow obstruction with >10% decrease in FEV1, new infiltrate on chest imaging.
Microbiology
- Pseudomonas aeruginosa (PA) is usually the most significant pathogen in adulthood, often multi-drug resistant.
- Staph. aureus (and MRSA) has become more prevalent in recent years.
- Other pathogens: Burkholderia cenocepacia, Haemophilus influenza, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Aspergillus (evaluate for ABPA), and nontuberculous mycobacteria.
- Obtain CF specific sputum cultures (bacterial, fungal and AFB) and sensitivities on each admission unless obtained the previous week (requisitions must indicate the patient has CF).
Management
- When hospitalized it is typically for IV antibiotics, ongoing trials re: optimal duration of therapy.
- Place in a single room and on contact precautions (for patient safety).
- Two IV antibiotics for PA and coverage for MRSA based upon review of most recent cultures. 14 days of antibiotics (21 days if sinus disease). Most common regimen includes an aminoglycoside and a b-lactam active against P. aeruginosa. Patients with CF have larger volume of distribution and rapid renal clearance requiring higher doses of antibiotics. Monitor aminoglycoside and vancomycin levels.
- Mucus clearance:
- Increase frequency of therapy Vest, and Acapella (IPV also available).
- Inhaled therapies include DNAse, hypertonic saline, and bronchodilators.
- GI/nutrition: order unrestricted, general diet with regular snacks and nutritional supplements. Recommend Nutrition consult. If patient has diabetes, manage with insulin, not caloric restriction. Supplemental enzymes for ADEK vitamins. Pancreatic enzymes with snacks and meals.
- Bowel regimen to prevent DIOS (distal intestinal obstruction syndrome).
- Complications: monitor for hemoptysis and bowel obstruction.
Cystic Fibrosis Pulmonary Guidelines Treatment of Pulmonary Exacerbations. Am J Respir Crit Care Med 2009;180:802-808.
Halfhide, C, Evans, HJ, Couriel, J. Inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2005.
Mogayzel PJ, Naureckas ET, Robinson KA et al. Cystic fibrosis pulmonary guidelines. chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2013;187:680-689.
Ren CL, Morgan RL, Oermann C, et al. Cystic Fibrosis Pulmonary Guidelines: Use of CFTR Modulator Therapy in Patients with Cystic Fibrosis. Ann Am Thorac Soc. 2018 Mar. https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Medications/CFTR-Modulator-Therapies/