In contrast to older children and adults there are relatively few studies Tofacitinib Citrate reporting LCI in infants with CF. In infants with CF diagnosed following clinical presentation Lum et al [10] reported 56% with abnormal LCI (LCI>7.8) when compared to healthy infants. Preliminary data from the same group indicate a lower prevalence of abnormal LCI of 25% (5 of 20) in infants diagnosed with CF following NBS suggesting that lower disease severity in young infants compared to older infants [29]. Interestingly the upper limit of normal in the younger infants was ~8.2 compared to 7.8 in older infants aged up to two years of age suggesting a decrease in LCI with age and in agreement with the decline in LCI with age in this study (figure 1). The only other study reporting ventilation distribution in infants diagnosed with CF following NBS is from Belessis [30].

This study reported abnormal LCI in 15 of 47 (32%) infants with CF when compared to local healthy controls studied in the same laboratory with an upper limit of normal of 7.41. Considered together these studies suggest that lung disease in infants with CF is milder than that seen in older children as assessed by LCI. A limitation of the current study is that we do not have local healthy controls and therefore we are unable to make definitive statements regarding the prevalence of abnormal LCI in our study. The methods, equipment and tracer gas used by Belessis [30] are identical to those used in this study. Using an upper limit of normal of 7.41, 10 (20%) of the infants reported in this study have an abnormal LCI.

Infants with an abnormal LCI had an increase in the extent of air trapping (2: 0�C5.9: median: 10�C90th centiles) when compared to infants with a normal LCI (0: 0�C3; Mann-Whitney U test: p=0.03). In contrast there was no different in the extent of bronchiectasis in infants with abnormal LCI (0: 0�C1) when compared to infants with a normal LCI (0:0�C2: p=0.43). Currently no other study in infants with CF has reported moment ratios and the upper limits of normal are unknown. Similarly, the clinically relevant difference in LCI and moment ratios in infants has not been reported and therefore we are unable to speculate on the clinical relevance of the associations between the lung damage and ventilation distribution reported here.

There is an urgent need for multi-centre studies of MBW outcomes in infants from which robust reference equations for ventilation GSK-3 distribution outcomes can be derived. While between centre differences preclude definitive statements on the relationship between abnormal LCI and the presence of lung damage on chest CT in infants with CF, we can clearly state that LCI and moment ratios are not increased with the presence of bronchiectasis in our population of infants and young children diagnosed with CF following NBS.