1. Baseline Demographics and Characteristics
Summaries of baseline demographics and patient characteristics are presented in Table 1. 108 adult Cystic Fibrosis patients seen at the University of Virginia Adult Cystic Fibrosis Clinic were screened for eligibility, but only 85 unique patients with adequate AEC data, IgE data, or both after exclusion were included in the final analysis. All but five patients with complete AEC data also had complete IgE data. The characteristics of the sample of patients in the IgE analysis were highly similar to the characteristics of the sample of patients in the AEC analysis.
Table 1
Characteristics
|
All Patients
(n = 85)
|
IgE Analysis
(n = 80)
|
AEC Analysis
(n = 54)
|
Gender
Male: n (%)
Female: n (%)
|
41 (48.2%)
44 (51.8%)
|
38 (47.5%)
42 (52.5%)
|
27 (50.0%)
27 (50.0%)
|
Age
Between 18–30 years
Between 30–50 years
Above 50 years
Mean (SD)
Median (IQR)
|
38 (44.7%)
36 (42.4%)
11 (12.9%)
34.2 (10.7)
31.8 (12.8)
|
37 (46.3%)
33 (41.2%)
10 (12.5%)
33.7 (10.3)
30.9 (13.0)
|
23 (42.6%)
24 (44.4%)
7 (13.0%)
34.7 (11.0)
32.6 (13.2)
|
CFTR Mutation Information
delF508 Homozygous
delF508 Heterozygous
Other Mutation
|
49 (57.7%)
34 (40.0%)
2 (2.4%)
|
48 (60.0%)
30 (37.5%)
2 (2.5%)
|
32 (59.3%)
22 (40.7%)
0 (0.0%)
|
Initial Disease Severity
Normal (ppFEV1 > 90%)
Mild (70% <ppFEV1 ≤ 90%),
Moderate (40% <ppFEV1 ≤ 70%)
Severe (ppFEV1 ≤ 40%)
Not Available
|
23 (27.1%)
26 (30.6%)
25 (29.4%)
10 (11.8%)
1(1.2%)
|
22 (27.5%)
25 (31.2%)
23 (28.7%)
10 (12.5%)
0 (0.0%)
|
13 (24.1%)
19 (35.2%)
17 (31.5%)
4 (7.4%)
1 (1.9%)
|
Pre-ETI Inhaled Steroids
Yes
No
Not Available
|
51 (60.0%)
33 (38.8%)
1 (1.2%)
|
49 (61.3%)
30 (37.5%)
1 (1.3%)
|
30 (55.6%)
24 (44.4%)
0 (0.0%)
|
Colonization
MRSA
Pseudomonas
Other Bacteria
Fungus
Not Available
|
25 (29.4%)
50 (58.8%)
32 (37.6%)
36 (42.4%)
1 (1.2%)
|
21 (26.3%)
48 (60.0%)
31 (38.8%)
36 (45.0%)
1 (1.3%)
|
17 (31.5%)
29 (53.7%)
21 (38.9%)
25 (46.3%)
0 (0.0%)
|
Note: “All patients” refers to all patients included either the IgE analysis, AEC analysis, or both.
|
Table 1. IgE = Immunoglobulin E, ETI = Elexacaftor/Tezacaftor/Ivacaftor, ppFEV1 = percent predicted Forced Expiratory Volume in 1 second, MRSA = Methicillin Resistant Staphylococcus Aureus, AEC = Absolute Eosinophil Count
2. IgE and ETI Therapy
IgE data were log-transformed to induce normality prior to analysis. The estimated change in IgE after ETI initiation is plotted in Fig. 1. After adjusting for covariates, patients’ log-transformed 12-month mean IgE decreased by 0.224 (t = -3.838, P < 0.001, 95% CI: [0.108, 0.341]), corresponding to a reduction of 20.10% (95% CI: [10.23%, 28.89%]), following ETI initiation.
3. Post-ETI Initiation Change in IgE and Lung Function
After determining that ETI initiation was associated with a change in 12-month mean IgE, we investigated whether initial lung function impacted the magnitude of the change in IgE after ETI. In this mixed model, the reduction of IgE following ETI initiation remained statistically significant (t = 4.060, P < 0.001). However, IgE at baseline did not significantly differ by initial disease severity (F = 1.559, P = 0.206), and the reduction in IgE following ETI therapy did not significantly differ by initial disease severity (F = 0.208, P = 0.890). These results show that in our patients, initial lung function is not associated with the magnitude of change in mean IgE after ETI initiation.
4. Post-ETI Change in IgE and Microbiological Colonization
We also investigated whether fungus colonization, Pseudomonas colonization, or MRSA colonization alone modified the magnitude of the change in IgE after ETI using subgroup analysis through univariate and multivariable models. Univariate and multivariable models produced similar results, so all values reported below are adjusted estimates.
As shown in Fig. 2A, after starting ETI, patients with at least one positive fungal culture prior to ETI experienced a significant percent reduction in mean IgE (-28.91%, t = -4.021, P < 0.001, 95% CI: [-39.89%, -15.93%]), but patients with no history of fungal colonization did not (-11.68%, t = -1.622, P = 0.109, 95% CI: [-24.17%, + 2.87%]). The difference in the average magnitude of IgE change between patients with and without at least one positive fungal culture was not significant (t = -1.899, P = 0.061). Figure 2B displays our results for MRSA. The percent reductions in mean IgE following ETI initiation were significant in both patients with (-36.26%, t = -4.176, p < 0.001, 95% CI: [-48.49%, -21.12%]) and without MRSA colonization (-12.83%, t = -2.098, P = 0.039, 95% CI: [-23.48%, -0.69%]). The magnitude of reduction was significantly larger in patients with MRSA colonization (t = 2.481, P = 0.015). Finally, a significant percent reduction in mean IgE was observed both in patients with (-19.32%, t = -2.849, P = 0.005, 95% CI: [-30.48%, -6.36%]) and without (-21.33%, t = -2.544, P = 0.013, 95% CI: [-34.80%, -5.07%]) Pseudomonas colonization after starting ETI (Fig. 2C). There was no significant difference in the average magnitude of IgE change between patients with and without Pseudomonas colonization (t = 0.209, P = 0.835).
In summary, these results indicate that without considering the effects of the presence of other microorganisms, a reduction in mean IgE was only observed in the presence and not absence of a positive fungal culture and the magnitude of reduction in mean IgE after ETI initiation was only impacted by prior MRSA colonization.
5. AEC and ETI
AEC data were log-transformed to induce normality prior to analysis. The estimated change in log AEC after ETI initiation is plotted in Fig. 3. Without controlling for any covariates, ETI initiation was not associated with a significant change in log-transformed AEC (t = -0.112, P = 0.911, 95% CI: [-0.144, 0.128]). The multivariable model demonstrated that over the course of the entire study, men have statistically significantly lower AEC than women. On average, men had 37.71% lower AEC than women (t = -2.756, P = 0.009, 95% CI: [12.18%, 55.81%]). However, even after adjusting for covariates, ETI initiation still had no association with a change in log-transformed AEC (t = -0.187, P = 0.851, 95% CI: [-0.149, 0.124]).