Results
Of the 247 patients followed at the two centers, 89 patients (36%) had FEV1 ≥80% predicted measured at 147 different time points and data was available for all the study parameters. Table 1 summarizes the CFTR mutation classes of the participating patients, showing that most of them have 2 mutations from class I, II and/or III mutations, which are associated with the classical more severe phenotype and PI, and 11 patients (12%) have CFRD.
Almost all the patients with normal pulmonary function demonstrated the presence of lung disease: 86% had elevated LCI, 92% had structural abnormalities measured by CT-Brody score, 21% have chronic PA infections, 19% had at least one major PEx requiring IV antibiotic treatment during the year previous to the assesment.
As shown in Figure 1, 86% of patients have abnormal LCI (LCI >7.5) values, some of which were even substantially increased. A correlation between LCI and FEV1 could be observed even in the normal range, though the correlation was not strong (Figure 1). Analyzing the different ages of the patients, we noticed that FEV1 as well as LCI were found to be weakly correlated to the patient age (r=-0.18; p=0.03 and r=0.33; p<0.001, respectively).
Most of the patients had significant structural abnormalities in their lungs as seen on HRCT, and as can be seen in Figure 2, it had weak correlation with FEV1 (r=-0.32; p=0.008).
The most common structural abnormalities observed were air trapping, increased peribronchial thickening, and bronchiectasis (in 83%, 78%, and 54% of the patients respectively) (Table 1). These three parameters were found to be strongly correlated with LCI (air trapping r=0.49; p<0.001; peribronchial thickening r=0.74; p<0.001, and bronchiectasis r=0.68; p<0.001). Furthermore, a high correlation between TBS and LCI was observed (r=0.77; p<0.001) (Figure 3). Patients with normal or slightly increased LCI were found to have minimal structural changes, whereas patients with high LCI had significant structural changes as expressed by high TBS.
Chronic PA infection was found in 19 patients (21%), and was significantly associated with older age (mean age 26.8±12.1 yrs of PA positive vs 14.5±5.5 yrs of PA negative, p<0.001). Patients with chronic PA infection had significantly higher LCI values compared with those with no PA (11.9 ± 3.1 vs. 9.7 ± 2.3 respectively, p=0.01) and significant higher TBS (38.3 ±25.0 vs. 20.2 ± 19.4 respectively, p=0.01). Furthermore, as shown in Table 2, the 28 patients who had at least one major PEx during the year previous to the study had significant higher LCI (p=0.04) and TBS (p<0.001) values. There were 13 patients who received more than 14 days of IV Abx treatment in the year prior to the study. These patients had significant higher LCI (p=0.03) and TBS values (p=0.002). No significant differences were found for FEV1, LCI and/or TBS for the other variables analyzed, including gender, CFTR mutation classes, pancreatic status, BMI, CFRD, 6MWD test, number of minor PEx and/or number of PO Abx treatment days in the previous year.