© 2003 American Thoracic Society
Mutations of CFTR gene and intermediate sweat chloride levelsTo the Editor:The paper by Lebecque and colleagues (1) highlights again the inadequacy of considering cystic fibrosis (CF) as an "all-or-none" disease, as well as highlighting important failings in the interpretation of laboratory tests. We have recently proposed the concept of "pre-CF" (2), and this allows characterization of their 10 patients. Thus, by our classification patients 1, 7, 9, and 10 clearly have CF, and should be treated as such. Patients 2, 3, and 8 have pre-CF (i.e., they have the genetic predisposition to CF) with a low (but not zero) risk of disease progression. The treatment and follow up issues for these patients have been discussed (2). Critical to classifying patients 4–6 is knowing whether the cultures positive for Staphylococcus aureus were sputum or throat swab; positive throat swabs are notorious for having a low positive predictive value for lower airway cultures (3, 4), but a positive sputum would be a phenotypic feature of CF. Another fundamental point is how to interpret equivocal tests. Clearly, whatever the sweat test results, patients 1, 7, 9, and 10 should have been treated for CF. It is essential that clinicians should not be deterred from treating phenotypic CF by equivocal laboratory tests. CF is a clinical diagnosis, which may be supported by laboratory tests; but a firm clinical diagnosis should not be overturned because the current "gold standard" test is negative. After all, we now have recognized cases of clinical CF, with a completely normal CF gene sequence (5, 6).
a Royal Brompton Hospital London, United Kingdom REFERENCES
From the Authors:We thank Dr. Bush and Dr. Wallis for their comments.Our study illustrates that in a tiny minority of borderline and atypical cases even sophisticated investigations may still leave the clinician puzzled as to the diagnosis of CF (1). Specifically, current limitations of exhaustive genetic testing have been well recognized and the interpretation of carefully performed nasal potential difference measurements may be difficult in such cases.
Bush and Wallis state that patient 7 clearly has CF. Is it so evident? This 7-year-old boy had intermediate sweat chloride values (48 mmol/L), normal nasal potential studies and a Nevertheless, we certainly agree that diagnostic systems are not a substitute for clinical judgement. We also obvioulsy would treat phenotypic CF, realizing however that the management of respiratory symptoms of this disease remains to some extent aspecific and thus independent from a firm diagnosis. Classifying patients who do not have "classical CF" remains a controversial area and a difficult task with numerous and important implications, including the issues of health insurance and genetic counselling (2–5).
a Cliniques Universitaires Saint-Luc Brussels, Belgium REFERENCES
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508/R117H (7T) CFTR genotype. He presented with a major complex congenital cardiac malformation and had a history of recurrent respiratory infections, at times associated with wheeze. Pseudomonas aeruginosa and Staphylococcus aureus were occasionnally cultured from pharyngeal aspirates but his frequent hospital admissions could play a role. Cardiac surgery was successfully performed 30 months ago. The child was not admitted to hospital since. Inhaled steroids are prescribed as well as ampicillin prophylaxis for asplenia. Respiratory symptoms have disappeared. The chest X-ray is not suggestive of CF and no CF pathogen was isolated from respiratory secretions during the past 24 months (8 cultures). Should he now be labeled as a pre-CF patient, according to Bush and Wallis (