Background
Methods
Patients
Healthy | Asthma | |
---|---|---|
Number | 21 | 25 |
Sex (m/f) | 10/11 | 13/12* |
Age | 38.5+/− 13.1 | 43.8 +/−12.0* |
Age of asthma diagnosis | N/A | 16.1 +/−16.0 |
Body Mass Index | 25.7 +/− 3.5 | 27.3 +/− 3.3* |
Atopy (Y/N) | 1/20 | 21/4a
|
ACQ score | N/A | 1.85 +/− 0.79 |
FEV1 % predicted | 103.7+/−17.2 | 72.4 +/− 15.5*** |
FEV1/FVC | 78.8 +/−5.4 | 65.8 +/− 10.4*** |
Reversibility (%) | 3.2 +/− 2.6 | 18.9 +/− 17.4** |
SABA (y/n) | 0/21 | 24/1a
|
LABA (y/n) | 0/21 | 21/4a
|
ICS (y/n) | 0/21 | 25/0** |
Beclomethasone dose (μg/day) | 0 | 1125+/− 558 |
BAL cell yields (×106/ml BAL) | 0.099 +/− 0.038 | 0.107 +/−0.072* |
Cell collection and culture
Cytokine analysis
Flow cytometric analysis of pSTAT5 and PI3Kδ
Immunohistochemistry
Statistical analysis
Results
TCR activation of BAL cells
Effects of inhibition of PI3Kδ and JAK on TCR responses in BAL cells
Compound | Cytokine | IC35 values (nM) | IC50 values (nM) | Mean % inhibition at 10 μM +/− SD | |||
---|---|---|---|---|---|---|---|
Healthy | Asthma | Healthy | Asthma | Healthy | Asthma | ||
Dexamethasone | IFNγ | 2.6 | 3.4 | 7.6 | 28.7 | 75.2 +/− 20.8 | 69.1 +/− 26.7 |
IL-13 | <1.0a
| <1.0a
| 1.1 | 1.2 | 96.6 +/− 6.8 | 77.3 +/− 31.1 | |
IL-17 | 8.7 | 267.8 | 1098 | >10,000b
| 57.6 +/− 15.3 | 45.8 +/− 21.7 | |
Tofacitinib | IFNγ | 56.8 | 56.7 | 135.2 | 141.1 | 96.1 +/− 2.9 | 94.9 +/− 7.2 |
IL-13 | 24.8 | 26.5 | 48.8 | 75.6 | 85.8 +/− 9.4 | 90.0 +/− 11.5 | |
IL-17 | 297 | 1042 | 1321 | 2495 | 80.4 +/− 9.2 | 83.1 +/− 11.0 | |
PIK-294 | IFNγ | 6.8 | 5.3 | 31.7 | 35.8 | 77.5 +/− 17.1 | 84.4 +/− 14.5 |
IL-13 | 1.3 | <1.0a
| 19.0 | 31.2 | 87.4 +/− 9.3 | 93.0 +/− 5.5 | |
IL-17 | 9.6 | 10.1 | 368.4 | 75.9 | 61.3 +/− 14.7 | 70.3 +/− 12.2 |