Published online January 2, 2007
PEDIATRICS
Vol. 119
No. 1
January 2007, pp.
156-157
(doi:10.1542/peds.2006-3074)
The Meaning of "Early" Diagnosis in a New Era of Cystic Fibrosis Care
Philip M. Farrell, MD, PhD
Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Abbreviations: CF, cystic fibrosis
In 1970, a great pioneer clinical researcher in cystic fibrosis (CF), Dr Harry Shwachman, identified a very significant survival advantage for patients with CF who were given their diagnosis before 3 months of age if they were well enough to avoid initial hospitalization.1 His article in Pediatrics was provocative and uniquely impressive at the time, because he showed dramatically better outcomes in the early-diagnosis group without even publishing statistical analyses. Accordingly, Shwachman asserted that "early" diagnosis meant that patients with CF would be identified by 3 months of age. On the other hand, he recognized that this would be impossible without newborn screening. I remember vividly sitting next to Harry in 1975 at a National Academy of Sciences workshop on CF diagnosis2 while he argued forcefully for newborn screening as the method of identifying potential patients with CF for confirmatory sweat tests, rather than the traditional method of reacting to signs/symptoms of the disease. Now, 3 decades later, Sims et al3 (in this issue of Pediatrics) have redefined the meaning of early diagnosis for children with CF. Their well-designed study, which took advantage of the United Kingdom Cystic Fibrosis Database (registry) and focused on matched F508del homozygotes, demonstrated convincingly that clinical diagnoses after 2 months of age are associated with worse outcomes (evidence of more severe malnutrition) and a greater treatment burden; the latter is likely to be associated with a lower quality of life, particularly because the treatment for CF can become worse than the disease per se. This research adds to the excellent discoveries of Dr Anil Mehta's team3 and builds on earlier observations from many regions that demonstrated both gastrointestinal/nutritional and pulmonary signs/symptoms of CF develop much earlier than originally expected (ie, by 2 months of age).4–7
The article by Sims et al3 has also demonstrated that we have clearly entered a new era of CF care, made possible by routine early diagnosis through newborn screening. This new era is characterized by a better strategy of clinical management in which prevention in presymptomatic populations has become the dominant feature rather than the traditional approach of interventions after illnesses develop. As Sims et al point out, the new approach is proactive, rather than reactive, and results in more individualized care. In connection with this, it seems surprising that treatment in the United Kingdom continues to incorporate daily anti–Staphylococcus aureus therapy (oral flucloxacillin),8 particularly when so many studies have shown that this treatment increases the risk of patients acquiring Pseudomonas aeruginosa.9,10
This new era is also characterized by predominately ambulatory care, rather than recurrent hospitalizations, and a fundamentally preemptive philosophy in which we strive to prevent both malnutrition and chronic P aeruginosa infections through routine clinical management. I want to emphasize that this does not necessarily mean more treatment but, rather, more appropriate treatment and potentially less of a therapeutic burden for children and their parents. The new era should also be associated with economic benefits that are related to fewer hospitalizations and less of the relatively expensive therapies such as intravenous antibiotics. Eventually, we all hope that a molecular therapeutic strategy aimed at enhancing chloride-channel function will be preemptive for CF lung disease per se.
Finally, one might ask why more regions of the Western world are not screening newborns routinely for CF with the excellent tests available and following Centers for Disease Control and Prevention recommendations.11 Sims et al3 mention that "policy makers have widely used the reasoning that CF screening is of no benefit because lung function is no better for patients with CF whether they have been screened at birth or not." In fact, they are correct that this is one of the remaining issues, but unfortunately, those who wish to see better pulmonary function in children with CF diagnosed through screening have failed to recognize 2 important considerations: (1) pulmonary function tests are not as sensitive and reliable in young children with CF,12 and (2) the course of lung disease in CF is greatly influenced by numerous postnatal factors/exposures that seem to be much stronger determinants than the age at diagnosis.13
Because even the very best general pediatricians find it impossible to diagnose CF routinely before 2 months of age without newborn screening, it is imperative for all regions with a substantial incidence of CF to proceed with implementation of screening programs as recommended by the recent Maternal and Child Health Bureau report.14 As emphasized elsewhere, however, "excellent implementation is the key to ensuring more good than harm"15 for all newborn screening and especially for CF. Frankly, every child with CF deserves the opportunity for early diagnosis (ie, it is clearly in their best interests), and Sims et al3 have conclusively demonstrated that "early" means <2 months of age. Dr Harry Shwachman would be delighted with this confirmation of his convictions and the great advantages of the new era for children with CF.
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FOOTNOTES
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Accepted Oct 26, 2006.
Address correspondence to Philip M. Farrell, MD, PhD, Department of Pediatrics, University of Wisconsin, 610 Walnut St, Madison, WI 53726. E-mail: pmfarrell{at}wisc.edu
The author has indicated he has no financial relationships relevant to this article to disclose.
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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