We found that Brody chest CT scan scores were significantly associated with measures of lung disease severity obtained, on average, 5 to 7 years later for subjects followed prospectively in the WI RCT. The strength of this association was generally much stronger than other measures of lung disease severity obtained near the time of the chest CT scan. Previous studies have shown chest CT scans are able to detect early structural abnormalities in children with CF and lung disease progression even in children who have normal PFTs (4
). However, only a few studies have evaluated the association between chest CT scan scores and future lung disease severity. Cademartiri and colleagues (23
) reviewed Bhalla scores of chest CT scans performed at their center between 1991 and 2001 to evaluate the association between chest CT scan scores and future lung disease. There were 57 patients with two to three chest CT scans, performed at a mean age of 15 years (range 9 mo to 38 yr). Bhalla scores did not predict progression of PFTs. However, the strength of their evidence was weakened because the authors did not report actual Bhalla scores or PFT values, and correlations between chest CT scan scores and PFTs were only compared for PFTs expressed in liters, which does not take into account lung growth with age for children.
In a recent study, Loeve and colleagues demonstrated that Brody bronchiectasis subscores predict pulmonary exacerbation frequency over the ensuing 2 years, independent of FEV1
). Subjects with a Brody chest CT scan score worse than the median had more than five times as many pulmonary exacerbations as subjects with a Brody score less than 1. When we examined bronchiectasis subscores, we found that the strength of association with the most recent lung disease measures was even stronger than for the overall Brody chest CT scan score. The long-term significance of bronchiectasis in CF seems clear from Loeve and colleagues’ data and our data reported herein. Although there has been limited research on specific respiratory pathogens and their association with bronchiectasis, observations we published recently (5
) revealed that P. aeruginosa
infections correlated closely with development of this irreversible, structural lesion. The apparent role of mucoid P. aeruginosa
as a determinant of bronchiectasis is consistent with its pathobiology, that is, its protective biofilm resistant to antibiotics (24
) and many toxins and virulence factors (25
Clinically, the implication of our findings, as well as those of Loeve and colleagues, is that chest CT scan scores may be used to identify children with CF who are at significant risk of lung disease progression. These findings are especially helpful because the slow rates of change of traditional spirometry (4
) make using spirometry to monitor progression of lung disease severity in children difficult. Moreover, the patients at most risk of a greater subsequent decline in FEV1
are those with the highest FEV1
). It is unknown what the chest CT scan appearance is in these children with supranormal FEV1
. Patients with high FEV1
and chest CT scan abnormalities may in fact be at greater risk of lung disease progression. Additional studies that use spirometry and chest CT scan scores may be useful to determine if targeting these patients for aggressive treatment decreases the rate of disease progression.
Although chest CT scan scores were more strongly associated with future lung disease severity than spirometry, we found that quantitative chest radiography (Wisconsin and Brasfield chest radiograph scores) were as strongly associated with future lung disease severity as the chest CT scan score. We (28
) and others (29
) have previously demonstrated the sensitivity of quantitative chest imaging in monitoring lung disease progression in children with CF. Although further study is needed, it may be that quantitative chest imaging has a role in detecting bronchiectasis and may provide similar insight into future lung disease progression as chest CT scan, but without exposing patients to larger doses of ionizing radiation with chest CT scan (31
Our study is limited in several ways. First, there was a wide range of follow up times after the chest CT scan: 2 to 10 years. Patients in the study began ageing out of the Wisconsin Neonatal Screening Project in 2005, when the oldest patients turned 21. This raises the possibility that the association we are identifying is between the chest CT scan and the lung disease measures obtained only a short time afterward. However, the strength of association remained when we adjusted for the time between the chest CT scan and the most recent measure of lung disease severity. Also, when we stratified the data by the median follow-up time, the parameter estimates were similar (data not shown). We are unable to make meaningful comparisons between the strengths of association with future lung disease progression between chest CT scan, infection with P. aeruginosa, and pulmonary exacerbation frequency because of the large standard errors for P. aeruginosa and pulmonary exacerbation frequency (). We did take into account the effects of infection with P. aeruginosa by adjusting for the presence of P. aeruginosa in our final model. We had relatively few patients hospitalized for a pulmonary exacerbation (9% of the cohort in 2000 and 24% in the year of the most recent data). Finally, these data were obtained from two CF centers with protocol-managed patients who generally had mild disease and who, before the chest CT scan in 2000, did not receive many of the standard treatments available to patients with CF today. However, given that patients with CF continue to have improvements in PFTs, these data should continue to be applicable.
We have shown that chest CT scan scores are associated with future lung disease severity, and that quantitative chest imaging (chest CT scan and chest radiograph scores) is more strongly associated with future lung disease severity than measures of spirometry. These findings may help clinicians identify patients at risk of future lung disease progression. More studies are needed that include chest imaging and spirometry, and over a longer time frame, to better understand the risk of lung disease progression in children with CF.