Helping patients with cystic fibrosis live longer

Mechanical therapies are often preceded by airway dilation with short- and long-acting bronchodilators and inhaled steroids that open airways for optimal airway clearance.⁴ Thick secretions can be treated directly and enzymatically with nebulized dornase alpha,^4,8 which is also best administered before mechanical clearance therapy. Finally, viscosity of airway secretions can be decreased by improving the hydration of the ASL with nebulized 7% hypertonic saline.^4,8

Infection suppression. Thickened pulmonary secretions create a fertile environment for the development of chronic infection. By the time most CF patients reach adulthood, many are colonized with mucoid producing strains of Pseudomonas aeruginosa.^4,8-10 Many may also have chronic infection with Staphylococcus aureus, some strains of which may be methicillin-resistant. Quarterly culture and sensitivity results can be essential in directing acute antibiotic therapy, both in the hospital and ambulatory settings. In addition, in the case of Pseudomonas, inhaled antibiotics suppress chronic infection, improve lung function, decrease pulmonary secretions, and reduce inflammation.

Formulations are available for tobramycin and aztreonam, both of which are administered every other month to reduce toxicities and to deter antibiotic resistance. Some patients may use a single agent or may alternate agents every month. When acute antibiotic therapy is necessary for a pulmonary exacerbation, the inhaled agent is generally withheld. If outpatient treatment is warranted, the only available oral antibiotics with anti-pseudomonal activity are ciprofloxacin and levofloxacin.^4,8-10S aureus can be treated with trimethoprim/sulfamethoxazole or doxycycline.^4,8-10

Inflammation reduction is addressed with high-dose ibuprofen twice daily, azithromycin daily or 3 times weekly, or both. Children up to age 18 benefit from ibuprofen, which also improves forced expiratory volume in one second (FEV₁) to a greater extent than azithromycin.⁸ Adults, however, face the risk of gastrointestinal bleeding and renal dysfunction with ibuprofen, which must be weighed against its potential anti-inflammatory benefit. Both populations, however, benefit from chronic azithromycin, whose mechanism of action in this setting is believed to be more anti-inflammatory than bacterial suppression, since it has no direct bactericidal effect on the primary colonizing microbe, P aeruginosa.^4,11

Gastrointestinal system: Pancreas

Cystic fibrosis was first comprehensively described in 1938 and was named for the diseased appearance of the pancreas.¹² As happens in the lungs, thick pancreatic duct secretions create a cycle of tissue destruction, inflammation, and dysfunction.² CF patients lack adequate secretion of pancreatic enzymes and bicarbonate into the small bowel, which progressively leads to pancreatic dysfunction in most patients.

As malabsorption of nutrients advances, patients suffer varying degrees of malnutrition and vitamin deficiency, especially of the fat-soluble vitamins A, D, E, and K. Over 85% of CF patients have deficient pancreatic function, requiring pancreatic enzyme supplementation with all food intake and daily vitamin supplementation.²

Because exercise has yielded comparable results to mechanical or airflow clearance devices, CF patients should engage in regular, vigorous exercise.

Ensuring adequate nutrition. Most CF patients experience a chronic mismatch of dietary intake against caloric expenditure and benefit from aggressive nutritional management featuring a high-calorie diet with supplementation in the form of nutrition shakes or bars.² There is a well-documented linear relationship between BMI and FEV₁. Lung function declines in CF when a man’s body mass index (BMI) falls below 23 kg/m² and a woman’s BMI drops below 22 kg/m².² For this reason, the goal for caloric intake can be as high as 200% of the customary recommended daily allowance.²

Watch for CF-related diabetes. Since the pancreas is also the major source of endogenous insulin, nearly half of adults with CF will develop cystic fibrosis-related diabetes (CFRD) as pancreatic deficiency progresses.¹³ Similar to the relationship between BMI and FEV₁, there is a relationship between glucose intolerance and FEV₁. For this reason, annual diabetes screening is recommended for all CF patients ages 10 years and older.¹³ Because glycated hemoglobin (HbA1c) may not accurately reflect low levels of glucose intolerance, screen for CFRD with a 2-hour 75-g oral glucose tolerance test.¹³ Early insulin therapy can help maintain BMI and lower average blood sugar in support of FEV₁. Once CFRD is diagnosed, the goals and recommendations for control are largely the same as those recommended by the American Diabetes Association for other forms of diabetes.¹³

Gastrointestinal system: Alimentary canal

CF is often mistakenly believed to be primarily a pulmonary disease since 85% of the mortality is due to lung dysfunction,⁷ but intermittent abdominal pain is a common experience for most patients, and disorders can range from gastroesophageal reflux disease (GERD) to small bowel bacterial overgrowth (SBBO) to constipation. Up to 85% of adult patients experience symptoms of reflux, with as many as 40% of cases occurring silently.² Proton pump inhibitors are a first-line treatment, but they can also contribute to intestinal bacterial overgrowth and pulmonary infections.