Cystic Fibrosis Critical Care
No Longer an Oxymoron

Kristin Wallick, Jerry A. Nick, and David M. Rodman

University of Colorado Cystic Fibrosis Center, University of Colorado Health Sciences Center, National Jewish Medical and Research Center, Denver, Colorado

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In this month's issue of the Journal (pp. 335-338), Sood and colleagues (Sood) report on outcomes of intensive care unit (ICU) admission for patients with cystic fibrosis (CF) (1). Unique to this study was the relatively advanced age of the patient population studied: 35 yr for male and 26 yr for female patients. In many ways this report exemplifies the remarkable changes in the demographics and treatment of CF over the past two decades. Although a "cure" for CF remains elusive, steady improvement has been made in methods of airway clearance, antibiotic usage, and nutritional support. When combined with more sophisticated methods of diagnosis, the mean age of patients with CF in the United States has increased from 12 yr in 1982 to 16 yr in 1999, with median survival increasing from 14 to 32 yr (2). The entire community of CF caregivers deserves recognition for this remarkable achievement.

Attendant with this improvement in outcome has been a shift in patients with advanced lung disease from the pediatric to the adult age range. This change occurred so rapidly that it took many CF caregivers by surprise. In 1990 there were only five established, fully functional adult CF programs in the United States. In response to this challenge, the CF community, led by a mandate from the Cystic Fibrosis Foundation (CFF), set out to train adult pulmonologists in CF care. That initiative has been quite successful, as 68 of the 117 U.S. CF centers now have accredited adult programs.

The decision to develop adult CF programs did not come without intensive debate. There are cogent arguments both for and against the separation of CF care into age-specific programs. Arguments in favor of keeping adult patients with CF in the pediatric CF center include continuity of care, lack of adult pulmonologists' expertise and interest in CF, patient preference, and the obvious financial and educational ramifications of transitioning a significant number of patients to an adult CF program. Arguments supporting transitioning adult patients with CF to an adult CF program include the need for age-specific care for problems unique to or more prevalent in adults, sensitivity to the psychosocial needs of adults with chronic illness, preference of many older patients to be cared for in an adult setting, coordination with lung transplantation programs, and the need to develop adult pulmonology expertise in CF both to improve care and ensure accurate diagnosis of atypical presentations of CF.

Reports in more recent issues of the Journal have highlighted medical complications of CF that are more prevalent in adults. The September issue included four reports of adult complications of CF, two related to metabolic bone disease, one describing CF-related diabetes mellitus (CFRD), and one relating the outcome of patients awaiting lung transplantation (3). The report by Sood and coworkers in this issue adds to this spectrum by addressing outcome of ICU hospitalization (1). These five reports highlight some of the medical problems that are becoming increasingly important in the care of adults with CF. Other important adult CF issues not directly addressed include reproduction and pregnancy, end-of-life decision making, increased prevalence of drug-resistant infections with advanced age, increased risk of gastrointestinal malignancy, and diagnosis of atypical presentations of CF.

CFRD is a complication of pancreatic destruction, and requirement for insulin therapy is seen in upward of 15% of adults with CF. As the mean age of patients with CF rises, the prevalence of CFRD will likely increase concomitantly. The presence of CFRD is an independent risk factor for accelerated deterioration in lung function and premature mortality (5). The report of Mila and coworkers in the September issue of the Journal demonstrated that decline in pulmonary function was directly related to reduced insulin production, which suggests the possibility of a causal relationship. Diagnosis and treatment of CFRD are significantly different from diagnosis and treatment of either type 1 or type 2 diabetes mellitus, and these differences have become an important component of comprehensive care administered in adult CF programs (7). Why CFRD is associated with a poorer prognosis, and whether earlier diagnosis and insulin therapy will correct the accelerated decline in pulmonary function in CF, remain to be tested.

Metabolic bone disease is much more prevalent in CF than in most other chronic lung diseases. This is due to the complex digestive system abnormalities seen in most patients with CF, as well as to the use of oral and inhaled corticosteroids as a component of therapy and the chronic inflammatory state present in CF (3). Aris and colleagues reported in the September issue of the Journal that bisphosphonate therapy was superior to vitamin D and calcium alone in patients who had metabolic bone disease and had received lung transplantation (4). The role of bone densitometry and bisphosphonate therapy in the adult CF population is not certain, and will require further investigation.

The report by Vizza and coworkers in the September issue of the Journal analyzed outcome of patients with CF with severe lung disease awaiting lung transplantation. The authors report that nearly one-quarter of patients died before transplantation could be performed. Although the presence of CFRD and decreased exercise capacity were associated with the deaths, an accurate predictive model for mortality in this group of patients with CF could not be defined (6). Clearly our understanding of the events that affect mortality in patients with CF with advanced lung disease will need to be expanded before we can determine more accurately which patients should be transplanted and when should they be listed.

The study by Sood and colleagues illustrates several important issues in adult CF care. Not surprisingly, they found that patients with clearly reversible indications for ICU admission, such as massive hemoptysis, pneumothorax, and need for antibiotic desensitization, did extremely well. The outcome for patients admitted with acute respiratory failure was less favorable, with nearly half dying in the ICU. Of the survivors, the vast majority received lung transplantation within 12 mo of the event (1). Interpreting the data differently, the immediate response to ventilatory support was actually surprisingly good. More than half of patients who required intubation and mechanical ventilation were discharged from the ICU. Of that subset, about half required lung transplantation while still ventilated and half were ultimately extubated. Thus, in this group of severely ill CF patients with respiratory failure, nearly one-quarter were successfully weaned from mechanical ventilation.

Although this report suggests that intubation and mechanical ventilation for respiratory failure are not uniformly associated with imminent death, the options remain quite limited. In the unique environment of the University of North Carolina, 8 of 14 patients in this situation were able to receive lung transplantation in a relatively short amount of time. The worldwide shortage of donor organs for lung transplantation makes this option increasingly difficult to offer on an emergent basis. While living lung donation is a potential option, and was used in three of the reported cases, it is appropriate only for a highly selected subset of patients (8).

The report by Sood and colleagues provides excellent guidelines for the care of patients with CF who require ICU hospitalization. It also raises some important issues that will require additional study. Using lung function alone, they were unable to predict which individuals would survive mechanical ventilation and which would succumb or require transplantation. Analysis of other variables will need to be performed in future studies to determine if a predictive algorithm can be developed to help in the triage decision. This is particularly important when lung transplantation is not a viable option. This study also provides applicable information concerning advance directives and mechanical ventilation usage in CF patients with advanced lung disease. In patients who are not transplantation candidates, the decision to institute mechanical ventilation should still be undertaken with the understanding that there is a limited chance for a good outcome. End-of-life decision making becomes a critical component of comprehensive care for these individuals, and remains an important area for research.

CF care has entered a new era, and the day will soon come when more than 50% of patients with CF are over age 18 yr. This demographic shift has brought new challenges to CF programs and mandates reassessment of the role of intensive medical therapy in advanced disease. The report on ICU outcome in this issue is an important step in the direction of understanding the needs of, and optimizing care for this important and steadily growing patient population.

Acknowledgments: Supported by grants from the Department of Veterans Affairs (Merit Review), the National Institute of Environmental Health Sciences (ES07498 and ES09607), and the National Heart, Lung, and Blood Institute (HL62628 and HL64855).

Supported by the National Institutes of Health (RO1-HL64937, RO1-HL 58115, and P6-HL58418; to B.A.F.), the American Heart Association (J.P.E.), and the Deutsche Herzstiftung (S.B).

	References

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1. Sood N, Paradowski L, Yankaskas J. Outcomes of intensive care unit care in adults with cystic fibrosis. Am J Respir Crit Care Med 2001; 163: 335-338 [Abstract/Free Full Text].

2. Cystic Fibrosis Foundation. Patient Registry 1999: Annual data report. Besthesda, MD: Cystic Fibrosis Foundation; 1999.

3. Ionescu A, Nixon L, Evans W, Stone M, Lewis-Jenkins V, Chatam K, Shale D. Bone density, body composition, and inflammatory status in cystic fibrosis. Am J Respir Crit Care Med 2000; 162: 789-794 [Abstract/Free Full Text].

4. Aris R, Lester G, Renner R, Winders A, Blackwood A, Lark R, Ontjes D. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 2000; 162: 941-846 [Abstract/Free Full Text].

5. Milla C, Warwick J, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance. Am J Respir Crit Care Med 2000; 162: 891-895 [Abstract/Free Full Text].

6. Vizza C, Yusen R, Lynch P, Fedele F, Patterson A, Trulock E. Outcome of patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2000; 162: 819-825 [Abstract/Free Full Text].

7. Moran A, Hardin D, Rodman D, Allen H, Beall R, Borowitz D, Brunzell C, Campbell P, Chesrown S, Duchow C, Fink R, Fitzsimmons S, Hamilton N, Hirsch I, Howenstine M, Klein D, Madhun Z, Penscharz P, Quittner A, Robbins M, Schindler T, Schissel K, Schwarzenberg S, Stallings V, Tullis D, Zipf W. Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res Clin Pract 1999; 45: 61-73 [Medline].

8. Barbers R. Cystic fibrosis: bilateral living lobar versus cadaveric lung transplantation. Am J Med Sci 1998; 315: 155-160 [Medline].