Background
Methods
Study design and subjects
Data collection
Treatments of AE-IPF
PMX-DHP therapy
Measurement of cytokine concentrations
Evaluation of HRCT findings
Statistical analysis
Results
Demographic, laboratory, and physiological data
Median (range), n = 31 | |
---|---|
Age, years | 69 (50, 84) |
Sex, male/female | 28/3 |
Smoking, never/ex/current | 4/23/4 |
Pack-year of smoking | 35 (0, 81) |
Diagnosis, surgical lung biopsy/clinical, n | 18/13 |
Period from symptom onset, m | 49 (0, 203) |
Observation period, m | 53 (2, 205) |
%FVC before AE, % | 58.8 (37.5, 89.3) |
FEV1% before AE, % | 87.4 (78.5, 107.0) |
%DLCO before AE, % | 57.1 (33.5, 88.2) |
PaO2 at rest before AE, Torr | 70.5 (49.0, 91.0) |
6MWT distance before AE, m | 360 (160, 507) |
6MWT minSpO2 before AE, % | 82 (60, 87) |
Serum LDH at AE, ng/mL | 344 (220, 602) |
Serum KL-6 at AE, U/mL | 1367 (481, 6404) |
Serum SP-D at AE, ng/mL | 339 (23, 966) |
Extent scores on HRCT before AE (full score: 25) | 12 (7, 19) |
The GAP staging system before AE, I/II/III/unknown | 8/7/10/6 |
Preceding treatments for IPF, +/ - | 18/13 |
Preceding oxygen therapy, +/ - | 9/22 |
Period from admission to commencement of treatments for AE, day | 1 (0, 17) |
Treatment with PMX-DHP, +/- | 14/17 |
Mortality 3 months after AE, n (%) | 12 (38.7) |
Mortality 12 months after AE, n (%) | 23 (74.2) |
Comparisons between patients treated with and without PMX-DHP
PMX-DHP –(median (range), n = 17) | PMX-DHP + (median (range), n = 14) | p value | |
---|---|---|---|
Age, years | 71 (50, 84) | 66.5 (52, 81) | 0.109 |
Sex, male/female | 15/2 | 13/1 | 0.999 |
Smoking, never/ex/current | 3/13/1 | 1/10/3 | 0.346 |
Pack-year of smoking | 25 (0, 80) | 45 (0, 81) | 0.086 |
Period from symptom onset to AE, mo | 72 (0, 203) | 30 (2, 156) | 0.082 |
Observation period, mo | 66 (9, 205) | 50 (2, 162) | 0.463 |
%FVC before AE, % | 46.7 (37.5, 89.3) | 61.9 (40.7, 88.0) | 0.136 |
FEV1% before AE, % | 87.5 (79.7, 100.0) | 87.4 (78.5, 107.0) | 0.769 |
%DLCO before AE, % | 57.1 (33.5, 88.2) | 62.0 ( 44.0, 77.8) | 0.892 |
PaO2 at rest before AE, Torr | 68.5 (53.9, 86.6) | 72.8 (49.0, 91.0) | 0.978 |
6MWT distance before AE, m | 375 (160, 465) | 365 (175, 507) | 0.523 |
6MWT minSpO2 before AE, % | 82 (62, 83) | 82 (60, 87) | 0.721 |
Serum LDH at AE, IU/L | 322 (220, 601) | 347 (277, 602) | 0.409 |
Serum KL-6 at AE, U/mL | 1367 (634, 3160) | 1690 (481, 6404) | 0.174 |
Serum SP-D at AE, ng/mL | 295 (24, 645) | 469 (102, 966) | 0.159 |
Extent scores on HRCT before AE (full score: 25) | 11.5 (7, 19) | 13 (7, 15) | 0.624 |
HRCT-patterns at AE, peripheral/multifocal/diffuse/unknown | 1/2/13/1 | 3/1/10/0 | 0.483 |
The GAP staging system before AE, I/II/III/unknown | 2/3/7/5 | 6/5/3/0 | 0.059 |
Preceding treatment for IPF, +/- | 10/7 | 8/6 | 0.925 |
Preceding oxygen therapy, +/- | 5/12 | 4/10 | 0.999 |
P/F ratio at AE | 162 (44, 316) | 171 (31, 368) | 0.741 |
Extent scores on HRCT at AE (full score: 25) | 20 (13, 25) | 20.5 (14, 25) | 0.915 |
Period from admission to commencement of treatments for AE, day | 1 (0, 6) | 0.5 (0, 17) | 0.755 |
Administration of steroid-pulse therapy for AE, +/- | 17/0 | 14/0 | NS. |
Administration of Immunosuppresants for AE, +/- | 12/5 | 9/5 | 0.709 |
Administration of Sivelestat sodium hydrate for AE, +/- | 3/14 | 5/9 | 0.413 |
Intubation at AE, +/- | 3/14 | 5/9 | 0.413 |
PMX-DHP
PMX-DHP (n = 14, 20 episodes) | |
---|---|
Perfusion duration, 6h/12h | 2/18 |
Cycles of perfusion, 2 times/3 times | 19/1 |
Interval of each perfusion, 12h/18h | 18/2 |
Period from admission to commencement of PMX-DHP, day | 1 (0, 17) |
Adverse events | Pulmonary thromboembolism: 1 |
Effects of treatment with PMX-DHP on acute phase of AE-IPF
Effects of treatment with PMX-DHP on survival
Variable | Hazard ratio | 95% CI | p value | |
---|---|---|---|---|
Lower | Upper | |||
Age at biopsy, yr | 1.040 | 0.977 | 1.108 | 0.220 |
Sex, female | 0.432 | 0.122 | 1.526 | 0.193 |
Pack-year of smoking | 0.993 | 0.978 | 1.008 | 0.367 |
Symptom onset, mo | 1.001 | 0.994 | 1.009 | 0.737 |
Extent score on HRCT before AE | 1.127 | 0.970 | 1.311 | 0.119 |
FVC before AE, % pred | 0.989 | 0.956 | 1.023 | 0.514 |
FEV1/FVC, % | 0.953 | 0.877 | 1.035 | 0.249 |
DLCO before AE, % pred | 0.987 | 0.958 | 1.018 | 0.416 |
Resting PaO2, mmHg | 0.999 | 0.961 | 1.039 | 0.961 |
Distance in six-minute walk test | 0.998 | 0.992 | 1.005 | 0.609 |
Minimum SpO2 in six-minute walk test | 0.960 | 0.884 | 1.043 | 0.338 |
Serum LDH, IU/L | 1.003 | 0.997 | 1.008 | 0.305 |
Serum KL-6, U/mL | 1.000 | 1.000 | 1.000 | 0.447 |
Serum SP-D, ng/mL | 0.999 | 0.997 | 1.001 | 0.256 |
The GAP staging system before AE | 1.089 | 0.639 | 1.854 | 0.754 |
Preceding treatments for IPF, + | 0.913 | 0.399 | 2.088 | 0.829 |
Preceding oxygen therapy, + | 1.662 | 0.678 | 4.074 | 0.267 |
P/F ratio at AE | 0.999 | 0.994 | 1.003 | 0.565 |
Extent score on HRCT at AE | 1.077 | 0.954 | 1.215 | 0.231 |
Period from admission to commencement of treatments for AE, day | 1.104 | 0.985 | 1.237 | 0.090 |
Administration of Immunosuppressant for AE, + | 1.403 | 0.548 | 3.593 | 0.481 |
Administration of Sivelestat sodium hydrate for AE, + | 0.787 | 0.290 | 2.131 | 0.637 |
PMX-DHP, + | 0.399 | 0.161 | 0.988 | 0.047 |
ΔWBC 2 days after commencement of treatments for AE, /μL | 1.000 | 1.000 | 1.000 | 0.423 |
ΔNeutrophil 2 days after commencement of treatments for AE, /μL | 1.000 | 1.000 | 1.000 | 0.607 |
ΔP/F ratio 2 days after commencement of treatments for AE | 0.990 | 0.983 | 0.997 | 0.008 |
ΔLDH 2 days after commencement of treatments for AE, IU/L | 1.006 | 1.002 | 1.011 | 0.009 |
ΔAngiopoietin-2 2 days after commencement of treatments for AE, pg/mL | 1.000 | 1.000 | 1.001 | 0.307 |
Variable | Hazard ratio | 95% CI | p value | |
---|---|---|---|---|
Lower | Upper | |||
Extent score on HRCT before AE | 1.177 | 0.982 | 1.409 | 0.078 |
Period from admission to commencement of treatments for AE, day | 1.092 | 0.974 | 1.224 | 0.132 |
PMX-DHP, + | 0.345 | 0.127 | 0.936 | 0.037 |
ΔP/F ratio 2 days after commencement of treatments for AE | 0.989 | 0.982 | 0.997 | 0.004 |
ΔLDH 2 days after commencement of treatments for AE, IU/L | 1.007 | 1.002 | 1.013 | 0.007 |