© 2005 American Thoracic Society
Ventilation Inhomogeneities in Patients with Cystic FibrosisInappropriate Reference Data and Errors?To the Editor:We wish to seek clarification of data published recently in the Journal in which Kraemer and coworkers demonstrate the role of the lung clearance index (LCI) measured by multiple breath washout in the longitudinal assessment of children with cystic fibrosis (1). To facilitate interpretation of the data, it is important to know the number of subjects at each age in which LCI measurements were performed. No information is given regarding this in either the manuscript or the online supplement. Although it is stated that 50% of subjects had abnormal LCI at 6.3 years, we are unaware of how many children this actually refers to, and whether analysis was restricted to those subjects performing all the lung function tests. It is also unclear whether the median onset of abnormal LCI is due entirely to cystic fibrosis (CF) pulmonary disease or due to comparison with inappropriate reference data. Inspection of Figure 1 of the paper shows that the mean z-scores for FEV1, maximal expiratory flow (MEF50) and LCI are approximately –2, –2, and +10, respectively, at six years of age. While other investigators report relatively normal parameters of forced expiration at this age, a mean z-score of such magnitude for LCI raises questions about the calculation of the z-scores. LCI z-scores as high as +22 were identified in some subjects (as evident in Figure 3). Clarification is therefore required regarding the suitability of comparing LCI of the current cohort of CF subjects with that of the reference population. LCI as an index of breathing inefficiency is calculated as the ratio of the cumulative expired volume required to decrease the concentration of expired gas by a predetermined amount to functional residual capacity. The authors identified sex differences, with LCI higher in females, that were not evident in their original healthy population (2). However, as cumulative expired volume was smaller and functional residual capacity greater in females than males, LCI must in fact be smaller in females with CF. Therefore, Figure 2 and the explanation provided for elevated LCI in females by the authors are erroneous. As demonstrated recently (3, 4), the measurement of LCI is an exciting method for assessing early lung disease in those with CF. Our prejudice is that LCI may also be useful to track lung function of individuals longitudinally. Unfortunately, we must ask the authors to clarify some of the issues raised before we can rely on such evidence to replace our prejudice.
Royal Children's Hospital, Melbourne, Australia FOOTNOTES Conflict of Interest Statement: S.C.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.F.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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