Background
Methods
Study population
Microbiological analyses
Clinical data and classification of patients
Statistical analysis
Results
Study population
All patients | FEV1 at serum sampling | Persistent A. fumigatus detection | |||||
---|---|---|---|---|---|---|---|
(n = 104) | (< 80% pred.) (n = 55) | (≥80% pred.) (n = 42) | P value | No (n = 82) | Yes (n = 22) | P value | |
Age [years (min-max)] | 19.3 (4–51) | 24.0 (6–51) | 15.7 (7–31) | < 0.001 | 17.9 (4–51) | 24.8 (10–51) | 0.001 |
Sex [female/male] | 43/61 | 22/33 | 17/25 | 0.962 | 32/50 | 11/11 | 0.353 |
BMI [kg/m2 (± STD)] | 19.7 (± 3.9) | 20.4 (± 3.6) | 19.2 (± 3.6) | 0.114 | 19.2 (± 3.7) | 21.6 (± 3.8) | 0.006 |
Mean BDG [pg/ml (± STD)] | 50 (± 84) | 68 (± 100) | 32 (± 57) | 0.003 | 40 (± 63) | 89 (± 131) | 0.022 |
Median BDG [pg/ml (IQR)] | 22 (3–62) | 37 (12–82) | 11 (0–42) | 18 (2–48) | 50 (14–115) | ||
BDG [normal/elevated, (% elevated)] | 77/27 (26.0%) | 36/19 (34.5%) | 36/6 (14.3%) | 0.024 | 66/16 (19.5%) | 11/11 (50.0%) | 0.004 |
Mean GM [ODI (± STD)] | 0.18 (± 0.22) | 0.22 (± 0.28) | 0.14 (± 0.10) | 0.150 | 0.15 (± 0.12) | 0.30 (± 0.40) | 0.013 |
Median GM [ODI (IQR)] | 0.10 (0.1–0.2) | 0.10 (0.1–0.2) | 0.10 (0.1–0.1) | 0.10 (0.1–0.1) | 0.10 (0.1–0.3) | ||
GM [normal/elevated, (% elevated)] | 97/7 (6.7%) | 49/6 (10.9%) | 41/1 (2.4%) | 0.108 | 78/4 (4.9%) | 19/3 (13.6%) | 0.145 |
Persistent A. fumigatus detection [no. of patients (%)] | 22 (21.2%) | 16 (29.1%) | 6 (14.3%) | 0.084 | – | – | – |
A. fumigatus-specific antibodies [normal/elevated, (% elevated)] | 100/4 (3.8%) | 52/3 (5.5%) | 41/1 (2.4%) | 0.451 | 78/4 (4.9%) | 22/0 (0%) | 0.291 |
A. fumigatus-specific IgE level [kU/l, (± STD)] | 3.8 (± 9.9) | 5.2 (± 11.3) | 2.3 (± 8.2) | 0.004 | 4.5 (± 10.9) | 1.1 (± 2.0) | 0.687 |
rAsp f4-IgE level [kUA/l, (± STD)] | 0.5 (± 2.5) | 0.7 (± 3.1) | 0.3 (± 1.5) | 0.073 | 0.6 (± 2.7) | 0.1 (± 0.2) | 0.879 |
rAsp f6-IgE level [kUA/l (± STD)] | 0.5 (± 2.3) | 0.7 (± 3.0) | 0.1 (± 0.7) | 0.245 | 0.6 (± 2.5) | 0.0 (± 0.0) | 0.118 |
S. aureus detection [no. of patients (%)] | 11 (10.6%) | 2 (3.6%) | 7 (16.7%) | 0.028 | 10 (12.2%) | 1 (4.5%) | 0.300 |
P. aeruginosa detection [no. of patients (%)] | 35 (33.7%) | 31 (56.4%) | 4 (9.5%) | < 0.001 | 22 (26.8%) | 13 (59.1%) | 0.004 |
P. aeruginosa-specific antibodies [normal/elevated, (% elevated)] | |||||||
against alkaline protease | 70/14 (16.7%) | 26/12 (31.6%) | 38/1 (2.6%) | 0.001 | 62/10 (13.9%) | 8/4 (33.3%) | 0.094 |
against elastase | 69/15 (17.9%) | 25/13 (34.2%) | 38/1 (2.6%) | < 0.001 | 60/12 (16.7%) | 9/3 (25.0%) | 0.485 |
against exotoxin A | 65/19 (22.6%) | 24/14 (36.8%) | 34/5 (12.8%) | 0.015 | 58/14 (19.4%) | 7/5 (41.7%) | 0.088 |
WBC [× 103/μl (± STD)] | 9.1 (± 4.3) | 10.1 (± 5.2) | 7.5 (± 2.4) | 0.002 | 8.8 (± 3.3) | 10.1 (± 7.0) | 0.891 |
CRP [mg/l (± STD)] | 6.5 (± 19.1) | 11.6 (± 25.1) | 0.7 (± 1.0) | < 0.001 | 4.6 (± 12.2) | 13.6 (± 33.6) | 0.114 |
Total IgG [lowered/normal/elevated] | 12/62/25 | 3/26/21 | 7/31/4 | 0.002 | 12/49/19 | 0/13/6 | 0.187 |
Total IgE level [normal/elevated, (% elevated)] | 65/37 (36.3%) | 27/26 (49.1%) | 33/9 (21.4%) | 0.006 | 54/27 | 11/10 | 0.225 |
Fatty acid-binding protein 2 [pg/ml (± STD)] | 2407 (± 1471) | 2279 (± 1429) | 2565 (± 1524) | 0.248 | 2540 (± 1574) | 1889 (± 871) | 0.115 |
FEV1 at serum sampling [% predicted (± STD)] | 73.1 (± 24.1) | 55.8 (± 15.9) | 95.8 (± 9.9) | – | 75.7 (± 23.9) | 64.2 (± 23.1) | 0.057 |
Cough frequency [none/temporarily/permanently/at night] | 11/64/19/6 | 1/33/14/4 | 8/28/4/1 | 0.007 | 11/50/16/4 | 0/14/3/2 | 0.278 |
Number of pulmonary exacerbations within the last 12 months | 0.56 (± 0.77) | 0.76 (± 0.90) | 0.40 (± 0.55) | 0.044 | 0.52 (± 0.72) | 0.74 (± 0.93) | 0.293 |
Systemic antibiotic therapy at serum sampling [no. of patients (%)] | 30 (28.8%) | 19 (34.5%) | 10 (23.8%) | 0.252 | 23 (28.0%) | 7 (31.8%) | 0.729 |
Systemic antibiotic therapy courses (no. (± STD) | |||||||
12 month before serum sampling | 1.6 (± 2.0) | 2.2 (± 2.3) | 0.9 (± 1.1) | < 0.001 | 1.4 (± 1.6) | 2.2 (± 3.0) | 0.477 |
6 month after serum sampling | 1.0 (± 1.4) | 1.3 (± 1.7) | 0.5 (± 0.8) | 0.008 | 0.8 (± 1.1) | 1.5 (± 2.4) | 0.314 |
Nebulized antibiotic [none/temporarily/permanently] | |||||||
12 month before serum sampling | 58/16/30 | 18/9/28 | 33/7/2 | < 0.001 | 54/11/17 | 4/5/13 | < 0.001 |
at serum sampling | 51/38 | 14/34 | 30/4 | < 0.001 | 48/23 | 3/15 | < 0.001 |
6 month after serum sampling | 57/21/26 | 17/14/24 | 33/7/2 | < 0.001 | 52/16/14 | 5/5/15 | 0.001 |
Inhaled corticosteroids [no. of patients (%)] | 14 (14.6%) | 9 (18.4%) | 5 (12.5%) | 0.449 | 9 (11.7%) | 5 (26.3%) | 0.106 |
Exocrine pancreatic insufficiency [no. of patients (%)] | 93 (89.4%) | 50 (90.9%) | 39 (92.9%) | 0.730 | 72 (87.8%) | 21 (95.5%) | 0.300 |
CF-related diabetes mellitus [no. of patients (%)] | 11 (10.6%) | 8 (14.5%) | 3 (7.1%) | 0.255 | 9 (11.0%) | 2 (9.1%) | 0.799 |
CF-related liver disease [no. of patients (%)] | 30 (28.8%) | 16 (29.1%) | 14 (33.3%) | 0.654 | 22 (27.8%) | 8 (32.0%) | 0.729 |
All patients | Serum BDG level | Serum GM level | |||||
---|---|---|---|---|---|---|---|
(n = 104) | Normal (< 60) (n = 77) | Elevated (≥60) (n = 27) | P value | Normal (< 0.5) (n = 97) | Elevated (≥0.5) (n = 7) | P value | |
Age [years (min-max)] | 19.3 (4–51) | 18.1 (4–48) | 22.7 (4–51) | 0.079 | 18.6 (4–51) | 29.6 (14–51) | 0.047 |
Sex [female/male] | 43/61 | 31/46 | 12/15 | 0.704 | 40/57 | 3/4 | 0.933 |
BMI [kg/m2 (± STD)] | 19.7 (± 3.9) | 19.8 (± 3.9) | 19.4 (± 3.9) | 0.739 | 19.8 (± 3.9) | 19.3 (± 2.7) | 0.897 |
Mean BDG [pg/ml (± STD)] | 50 (± 84) | 16 (± 17) | 148 (± 116) | – | 50 (± 86) | 57 (± 26) | 0.044 |
Median BDG [pg/ml (IQR)] | 22 (3–62) | 11 (0–28) | 108 (69–179) | 20 (3–56) | 59 (48–68) | ||
BDG [normal/elevated, (% elevated)] | 77/27 (26.0%) | – | – | – | 73/24 (24.7%) | 4/3 (42.9%) | 0.291 |
Mean GM [ODI (± STD)] | 0.18 (± 0.22) | 0.15 (± 0.17) | 0.24 (± 0.32) | 0.013 | 0.13 (± 0.1) | 0.89 (± 0.4) | – |
Median GM [ODI (IQR)] | 0.10 (0.1–0.2) | 0.10 (0.10) | 0.10 (0.10) | 0.10 (0.10) | 0.70 (0.6–1.2) | ||
GM [normal/elevated, (% elevated)] | 97/7 (6.7%) | 73/4 (5.2%) | 24/3 (11.1%) | 0.291 | – | – | – |
Persistent A. fumigatus detection [no. of patients (%)] | 22 (21.2%) | 11 (14.3%) | 11 (40.7%) | 0.004 | 19 (19.6%) | 3 (42.9%) | 0.145 |
S. aureus colonization/infection [no. of patients (%)] | 11 (10.6%) | 10 (13.0%) | 1 (3.7%) | 0.177 | 11 (11.3%) | 0 (0.0%) | 0.346 |
P. aeruginosa colonization/infection [no. of patients (%)] | 35 (33.7%) | 23 (29.9%) | 12 (44.4%) | 0.168 | 30 (30.9%) | 5 (71.4%) | 0.029 |
P. aeruginosa-specific antibodies [normal/elevated, (% elevated)] | |||||||
against alkaline protease | 70/14 (16.7%) | 52/11 (17.5%) | 18/3 (14.3%) | 0.735 | 67/12 (15.2%) | 3/2 (40.0%) | 0.149 |
against elastase | 69/15 (17.9%) | 52/11 (17.5%) | 17/4 (19.0%) | 0.869 | 67/12 (15.2%) | 2/3 (60.0%) | 0.011 |
against exotoxin A | 65/19 (22.6%) | 48/15 (23.8%) | 17/4 (19.0%) | 0.651 | 65/14 (17.7%) | 0/5 (100.0%) | < 0.001 |
A. fumigatus-specific antibodies [normal/elevated, (% elevated)] | 100/4 (3.8%) | 74/3 (3.9%) | 26/1 (3.7%) | 0.964 | 93/4 (4.1%) | 7/0 (0.0%) | 0.584 |
A. fumigatus-specific IgE level [kU/l, (± STD)] | 3.8 (± 9.9) | 3.6 (± 9.5) | 4.4 (± 11.2) | 0.777 | 4.0 (± 10.2) | 1.8 (± 1.7) | 0.051 |
rAsp f4-IgE level | 0.5 (± 2.5) | 0.2 (± 1.1) | 1.3 (± 4.5) | 0.768 | 0.5 (± 2.5) | 0.3 (± 0.4) | 0.048 |
rAsp f6-IgE level | 0.5 (± 2.3) | 0.2 (± 0.8) | 1.2 (± 4.3) | 0.930 | 0.5 (± 2.4) | 0.0 (± 0.0) | 0.391 |
WBC [×103/μl (± STD)] | 9.1 (± 4.3) | 8.6 (± 3.3) | 10.3 (± 6.3) | 0.183 | 9.0 (± 4.5) | 9.2 (± 2.3) | 0.529 |
CRP [mg/l (± STD)] | 6.5 (± 19.1) | 4.5 (± 12.2) | 12.1 (± 30.9) | 0.125 | 6.5 (± 19.6) | 6.6 (± 9.0) | 0.506 |
Total IgG [lowered/normal/elevated] | 12/62/25 | 9/49/17 | 3/13/8 | 0.553 | 12/58/22 | 0/4/3 | 0.392 |
Total IgE level [normal/elevated] | 65/37 | 53/24 | 12/13 | 0.060 | 61/34 | 4/3 | 0.707 |
Fatty acid-binding protein 2 [pg/ml (± STD)] | 2411 (± 1481) | 2468 (± 1588) | 2236 (± 1105) | 0.712 | 2373 (± 1469) | 2917 (± 1673) | 0.392 |
FEV1 at serum sampling [% predicted (± STD)] | 73.1 (± 24.1) | 77.1 (±22.8) | 61.6 (±25.5) | 0.007 | 73.6 (± 24.7) | 66.1 (± 14.1) | 0.407 |
Cough frequency [none/temporarily/permanently/at night] | 11/64/19/6 | 11/49/11/3 | 0/15/8/3 | 0.038 | 11/58/18/6 | 0/6/1/0 | 0.589 |
Number of pulmonary exacerbations within the last 12 months | 0.56 (± 0.77) | 0.46 (± 0.72) | 0.85 (± 0.83) | 0.008 | 0.57 (± 0.78) | 0.43 (± 0.54) | 0.762 |
Systemic antibiotic therapy at serum sampling [no. of patients (%)] | 30 (28.8%) | 18 (23.4%) | 12 (44.4%) | 0.038 | 28 (28.9%) | 2 (28.6%) | 0.987 |
Systemic antibiotic therapy courses (no. (± STD) | |||||||
12 month before serum sampling | 1.6 (± 2.0) | 1.4 (± 1.8) | 2.0 (± 2.4) | 0.415 | 1.5 (± 2.0) | 2.1 (± 1.6) | 0.120 |
6 month after serum sampling | 1.0 (± 1.4) | 0.8 (± 1.1) | 1.5 (± 2.1) | 0.047 | 1.0 (± 1.5) | 1.0 (± 1.0) | 0.619 |
Nebulized antibiotic [none/temporarily/permanently] | |||||||
12 month before serum sampling | 58/16/30 | 49/10/18 | 9/6/12 | 0.024 | 56/16/25 | 2/0/5 | 0.032 |
at serum sampling | 51/38 | 43/25 | 8/13 | 0.042 | 49/33 | 2/5 | 0.109 |
6 month after serum sampling | 57/21/26 | 46/15/16 | 11/6/10 | 0.173 | 55/20/22 | 2/1/4 | 0.124 |
Inhaled corticosteroids [no. of patients (%)] | 14 (14.6%) | 10 (13.0%) | 4 (14.8%) | 0.662 | 13 (13.4%) | 1 (14.3%) | 0.982 |
Exocrine pancreatic insufficiency [no. of patients (%)] | 93 (89.4%) | 67 (87.0%) | 26 (96.3%) | 0.177 | 86 (88.7%) | 7 (100%) | 0.346 |
CF-related diabetes mellitus [no. of patients (%)] | 11 (10.6%) | 7 (9.1%) | 4 (14.8%) | 0.405 | 9 (9.3%) | 2 (28.6%) | 0.109 |
CF-related liver disease [no. of patients (%)] | 30 (28.8%) | 25 (32.5%) | 5 (18.5%) | 0.169 | 28 (28.9%) | 2 (28.6%) | 0.987 |
FEV1 at serum sampling | BDG | GM | |||||||
---|---|---|---|---|---|---|---|---|---|
Correlation Coefficient r | Significance level p-value | Coefficient of determination r2 | Correlation Coefficient r | Significance level p-value | Coefficient of determination r2 | Correlation Coefficient r | Significance level p-value | Coefficient of determination r2 | |
Age | −0.382 | < 0.001 | 0.146 | 0.187 | 0.057 | 0.035 | 0.186 | 0.058 | 0.035 |
BMI | −0.028 | 0.787 | 0.001 | - 0.075 | 0.452 | 0.006 | −0.041 | 0.682 | 0.002 |
FEV1 at serum sampling | – | – | – | - 0.460 | < 0.001 | 0.212 | −0.213 | 0.037 | 0.045 |
No. of pulmonary exacerbations (last 12 month) | −0.301 | 0.004 | 0.091 | 0.266 | 0.009 | 0.071 | 0.024 | 0.818 | 0.001 |
Systemic antibiotic therapy courses | |||||||||
12 month before serum sampling | −0.438 | < 0.001 | 0.192 | 0.281 | 0.004 | 0.079 | 0.186 | 0.059 | 0.035 |
6 month after serum sampling | −0.338 | 0.001 | 0.114 | 0.277 | 0.005 | 0.077 | 0.232 | 0.019 | 0.054 |
WBC | −0.450 | < 0.001 | 0.203 | 0.246 | 0.012 | 0.061 | 0.168 | 0.091 | 0.028 |
CRP | −0.621 | < 0.001 | 0.386 | 0.267 | 0.006 | 0.071 | 0.131 | 0.188 | 0.017 |
BDG | −0.460 | < 0.001 | 0.212 | – | – | – | 0.281 | 0.004 | 0.079 |
GM | − 0.213 | 0.037 | 0.045 | 0.281 | 0.004 | 0.079 | – | – | – |
A. fumigatus-specific IgE level | −0.311 | 0.002 | 0.097 | 0.181 | 0.070 | 0.033 | 0.062 | 0.154 | 0.004 |
rAsp f4-IgE level | −0.203 | 0.051 | 0.041 | 0.151 | 0.134 | 0.023 | 0.041 | 0.688 | 0.002 |
rAsp f6-IgE level | −0.066 | 0.532 | 0.004 | 0.051 | 0.613 | 0.003 | −0.179 | 0.074 | 0.032 |
Fatty acid-binding protein 2 | 0.159 | 0.125 | 0.025 | 0.044 | 0.666 | 0.002 | 0.072 | 0.475 | 0.005 |
Microbiological predictors of an impaired FEV1predicted value
Independent variables | Regression coefficient | p-value | R2 corr. | Effect size f |
---|---|---|---|---|
Age | −0.073 | 0.772 | 52.6% | 1.05 (strong effect) |
BDG | −0.098 | 0.002 | ||
Persistent A. fumigatus detection | −2.951 | 0.562 | ||
A. fumigatus-specific IgE level | 0.045 | 0.810 | ||
S. aureus detection | 16.337 | 0.011 | ||
P. aeruginosa detection | −13.628 | 0.023 | ||
WBC | −2.911 | < 0.001 | ||
CRP | −0.015 | 0.933 | ||
Systemic antibiotic therapy within the last 12 month | − 1.939 | 0.115 | ||
Nebulized antibiotic within the last 12 month | 0.890 | 0.832 |