Lessons Learned from Cystic Fibrosis

Vol. 14 •Issue 2 • Page 43
Lessons Learned from Cystic Fibrosis

Clinicians and Researchers Can Benefit From the Advances Made in Improving Patients’ Survival

The care of patients with cystic fibrosis offers many valuable lessons in the treatment of other life-threatening acute and chronic respiratory diseases.

Cystic fibrosis is the most common lethal inherited disorder in Caucasians, occurring in about one out of every 3,400 live births in the United States.1 Life expectancy has increased from a median survival age of 10 in the 1960s to 34 in 2003.2

The key to improvement in survival in CF has been using multiple strategies. These include multidisciplinary care based in centers of excellence, epidemiologic evaluation of risk factors and current therapeutic strategies, and well-designed, adequately powered clinical trials of new therapies.


Comprehensive, multidisciplinary care benefits patients with complex respiratory disease.

Shortly after the Cystic Fibrosis Foundation was established in 1955, a network of accredited CF Care Centers was formed. These centers are required to have qualified physicians, nurses, dieticians, respiratory or physical therapists, and social workers. Many facilities also have genetic counselors, psychologists and pharmacists as active members of the multidisciplinary care team.

Quarterly visits with the CF care team are recommended. Each team member completes a comprehensive patient evaluation at least once annually. CF team members meet regularly to coordinate care. This multidisciplinary approach promotes health maintenance, proactive screening, and early intervention for complications.

Many pediatric pulmonary centers now use a multidisciplinary approach in the treatment of other populations, including ventilator-dependent children and those who have bronchopulmonary dysplasia and other chronic respiratory disease.

The success of the CF Care Centers network is increasingly being applied to other populations outside the United States. The Australian Working Group on Indigenous Pediatric Respiratory Health has published guidelines for evaluation and treatment of children with non-CF bronchiectasis.3

These recommendations include a multidisciplinary approach, quarterly review by a physician, and aggressive treatment of pulmonary exacerbations with two to six weeks of antibiotic therapy based on sputum microbiology.


Use of patient registries can improve understanding of disease and promote best practices.

The CF Foundation patient data registry continuously collects data on the health of people with CF enrolled at accredited CF centers. These data have provided practitioners with important information on trends in health and treatment, and on risk factors for worse outcomes.

Recent examples include reports of the effects of air pollution, socioeconomic status, and female gender on CF outcomes. Results of registry analyses also have supported the importance of good nutrition and have described the effect of specific bacteria in CF lung disease.

Researchers increasingly are interested in using patient registries to learn more about rare lung diseases. Efforts are under way to develop specialty evaluation and treatment centers and disease registries for a variety of respiratory disorders, including pediatric interstitial lung disease and primary ciliary dyskinesia.


An aggressive approach to nutrition improves outcomes in patients with lung disease.

A sentinel paper published in 1988 described outcomes in large CF programs in Toronto and Boston.4 Subjects at these programs had no difference in age-adjusted pulmonary function; however, patients in Toronto had a median survival of 30 years, while those in Boston had a median survival of only 21 years. Nutritional parameters, including height, were better in the Toronto subjects.

These findings led to widespread adoption of a high-calorie, unrestricted fat diet. Nutritional status has improved in U.S. children with CF between 1990 and 2003, a likely contributor to increasing survival in this population.2

Nutritional management in critically ill patients is being studied actively. Malnutrition is common in patients hospitalized in intensive care units and results in increased morbidity and mortality.5

Better evaluation of resting energy expenditure and improved understanding of appropriate parenteral and enteral nutrition support is likely to further improve outcomes of patients with critical illness. Nutrition support also is considered to be essential in support of patients with bronchiectasis and chronic obstructive pulmonary disease.


Airway clearance and mucolytic therapy are important tools in managing purulent lung disease.

Airway clearance techniques have been a mainstay of CF therapy for decades. These include chest physiotherapy with percussion and postural drainage, and newer techniques such as high frequency chest wall oscillation using a compressor and vest, positive expiratory pressure techniques, and intrapulmonary percussive ventilation.

Many authors suggest the use of airway clearance techniques in patients with non-CF bronchiectasis, although a review in 2000 concluded that there’s inadequate evidence to either support or refute their use.6

A crossover study of a vibratory positive expiratory pressure therapy device compared to the active cycle of breathing technique showed no significant difference in ventilatory function or symptoms between the techniques, but patients preferred the device.7

Recombinant human dornase alfa inhalation solution (Pulmozyme®, Genentech) is frequently prescribed for prevention and treatment of CF lung disease. In a multicenter clinical trial, rh-DNase was found to modestly increase FEV1 and significantly reduce frequency of pulmonary exacerbation in patients with CF and FEV1 between 25 percent and 75 percent of predicted for age.8 A subsequent study found similar results in a younger cohort with higher baseline pulmonary function.9

There’s little information about the use of rh-DNase in patients with non-CF bronchiectasis. A study of rh-DNase in COPD showed no reduction in mortality. A case report described improvement in pulmonary function and a reduction in cough in a teenage girl with Kartagerner’s syndrome.10 Such “n of 1” trials of therapy may be useful in assessing effectiveness of this drug in individual patients.


Inhaled antibiotics are promising agents for purulent lung disease. Most people with CF develop chronic airways infection with Pseudomonas aeruginosa, which is associated with pulmonary exacerbations and declining lung function.

In a large multicenter clinical trial, chronic, intermittent administration of tobramycin inhalation solution (TOBI®, Chiron) improved FEV1 and reduced pulmonary exacerbation frequency in patients with CF, P. aeruginosa, and FEV1 between 25 percent and 75 percent of predicted for age.11

A subsequent study of patients with milder pulmonary function abnormalities was terminated early because of the marked reduction in pulmonary exacerbations in tobramycin-treated patients.

Patients with other forms of purulent lung di-sease also are frequently infected with P. aeruginosa. A multicenter trial of tobramycin in patients with non-CF bronchiectasis showed a reduction in P. aeruginosa sputum density and improvement in general health status, as assessed by a physician, in patients receiving tobra-mycin compared to those receiving a placebo.12

The role of inhaled antibiotics in other acute and chronic infections hasn’t been established.


Aggressive treatment of hyperglycemia improves outcomes in serious lung disease.

CF-related diabetes mellitus (CFRDM) occurs in a significant proportion of individuals with CF. When oral glucose tolerance tests are routinely performed, up to 26 percent of teenagers and 43 percent of adults older than 30 years are found to have CFRDM.13

CFRDM is associated with an increased rate of nutritional failure, increased pulmonary morbidity and earlier death. Furthermore, impaired glucose tolerance without diabetes is associated with a more rapid decline in pulmonary function in people with CF.14 Increasing evidence suggests that optimizing glycemic control in CFRDM is associated with improved outcomes.

The role of glycemic control in critically ill patients has become the focus of recent trials; tighter glycemic control, maintaining serum glucose levels between 80 and 100 mg/dL, improves survival compared to looser glycemic control, maintaining serum glucose between 180 and 200 mg/dL. The patients studied primarily have been adults in surgical ICUs. Further evidence is needed before the effect of rigorous control of serum glucose can be fully evaluated.15 n


1. Kosorok MR, Wei WH, Farrell PM. The incidence of cystic fibrosis. Stat Med. 1996;15(5):449-62.

2. Cystic Fibrosis Foundation. Patient Registry. Annual Data Report to the Center Directors. 2003 Bethesda, Md.

3. Chang AB, Grimwood K, Mulholland EK, Torzillo PJ; Working Group on Indigenous Paediatric Respiratory Health. Bronchiectasis in indigenous children in remote Australian communities. Med J Aust. 2002;177(4):200-4.

4. Corey M, McLaughlin FJ, Williams M, Levison H. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol. 1988;41(6):583-91.

5. Giner M, Laviano A, Meguid MM, Gleason JR. In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition. 1996;12(1):23-9.

6. Jones AP, Rowe BH. Bronchopulmonary hygiene physical therapy for chronic obstructive pulmonary disease and bronchiectasis. Cochrane Database of Systematic Reviews 2000; CD000045.

7. Thompson CS, Harrison S, Ashley J, Day K, Smith DL. Randomized crossover study of the Flutter device and the active cycle of breathing technique in non-cystic fibrosis bronchiectasis. Thorax. 2002;57(5):446-8.

8. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med. 1994;331(10):637-42.

9. Quan JM, Tiddens HA, Sy JP, et al. A two-year, randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis and mild lung function abnormalities. J Pediatr. 2001;139(6):813-20.

10. Desai M, Weller PH, Spencer DA. Clinical benefit from nebulized human recombinant DNase in Kartagener’s syndrome. Pediatr Pulmon. 1995;20(5):307-8.

11. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999;340(1):23-30.

12. Barker AL, Couch L, Fiel SB, et al. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med. 2000;162(2 Pt 1):481-5.

13. Moran A, Doherty L, Wang X, Thomas W. Abnormal glucose tolerance in cystic fibrosis. J Pediatr. 1998;133(1):10-6.

14. Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000;162(3 Pt 1):891-5.

15. Gropper MA. Evidence-based management of critically ill patients: analysis and implementation. Anesth Analg. 2004;99(2):566-72.

Dr. McColley is the division head of pulmonary medicine and the director of the Cystic Fibrosis Center at Children’s Memorial Hospital in Chicago. She’s also associate professor of pediatrics at Feinberg School of Medicine, Northwestern University, Chicago, a member of the Cystic Fibrosis Foundation Center Committee, and on the board of directors of the American Thoracic Society.