Table 1.
Analytes according to FeNO and Blood Eos–based Stratification Strategies
| Analyte (LLOD)* | FeNO (ppb) |
Blood Eos (×109/L) |
Healthy Control Subjects (n = 10) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| <25 (n = 17) | 25 to <50 (n = 30) | ⩾50 (n = 27) | r (P Value) | <0.15 (n = 21) | 0.15 to <0.30 (n = 22) | ⩾0.30 (n = 31) | r (P Value) | ||
| Biomarker | |||||||||
| FeNO, ppb | 16 (13–20) | 39 (32–42) | 83 (60–123)† | — | 38 (23–55) | 38 (26–74)† | 45 (25–89)† | 0.24 (0.04) | 19 (11–28) |
| Blood Eos, ×109/L | 0.17 (0.1–0.54) | 0.24 (0.1–0.35) | 0.26 (0.19–0.55)† | 0.24 (0.04) | 0.09 (0.05–0.12) | 0.23 (0.19–0.25) | 0.54 (0.36–0.66)† | — | 0.14 (0.09–0.18) |
| Sputum | |||||||||
| Eos, % | 0.8 (0.4–5.3) | 2.7 (1.1–17.8)† | 12.8 (3.3–35.5)† | 0.51 (0.0002) | 2.7 (0.7–6.1) | 5.1 (0.5–30.5)† | 4.3 (1–21)† | NS | 0.3 (0.3–0.4) |
| IL-4 (0.2) | 0.1 (0.1–0.3) | 0.4 (0.1–1.1)† | 0.8 (0.2–1.2)† | 0.48 (<0.0001) | 0.3 (0.1–1)† | 0.4 (0.1–0.9) | 0.3 (0.1–1)† | NS | 0.1 (0.1–0.1) |
| IL-5 (0.5) | 1.2 (0.4–4.6) | 4.6 (1.9–7.8) | 10.9 (2.9–29.8)† | 0.47 (0.0002) | 2.3 (1.1–9.7) | 5.3 (1.5–15.1)† | 4.7 (1.8–10.8)† | NS | 0.3 (0.2–2.7) |
| IL-13 (4.2) | 6.4 (2.1–8.8) | 7 (5.8–14.2)† | 8.4 (6.4–13.9)† | 0.26 (0.04) | 7 (5.1–11.5)† | 8.3 (4–12.5)† | 7.6 (6–12.2)† | NS | 2.1 (2.1–2.1) |
| IL-33 (0.6) | 0.9 (0.3–1.3) | 0.9 (0.3–2.1)† | 1.7 (0.7–2.9)† | 0.35 (0.006) | 0.9 (0.3–1.9) | 1.4 (0.5–2.6)† | 1 (0.3–2.3)† | NS | 0.3 (0.3–0.3) |
| TSLP (0.9) | 2.4 (1–9.3) | 6.4 (2.3–10.7)† | 11.9 (5–20.7)† | 0.41 (0.001) | 4.9 (1.5–16.9) | 9.1 (1.9–2.6) | 7.1 (2.5–15)† | NS | 0.9 (0.5–1.8) |
| Eotaxin-3 (4.2) | 34 (2–71) | 133 (23–369)† | 353 (245–804)† | 0.55 (<0.0001) | 76 (23–264) | 215 (9–418)† | 191 (29–390)† | NS | 2 (2–26) |
| TARC (0.4) | 17 (9–89) | 27 (18–77) | 58 (38–301)† | 0.32 (0.02) | 35 (19–107)† | 41 (9–101) | 36 (17–88) | NS | 6 (2–21) |
| LTE4 (7.8) | 59 (23–114) | 138 (42–465)† | 133 (42–730)† | NS | 64 (23–139) | 94 (48–343) | 163 (49–676)† | NS | 7 (4–70) |
| PGD2 (19.5) | 241 (173–384) | 217 (119–354) | 209 (135–439) | NS | 213 (133–505) | 219 (183–389) | 222 (117–439) | NS | 89 (43–200) |
| IFN-γ (0.3) | 0.3 (0.2–0.5) | 0.4 (0.2–1.8) | 0.6 (0.2–1.5) | NS | 0.5 (0.2–1.7) | 0.4 (0.2–2.6) | 0.3 (0.2–0.8) | NS | 0.2 (0.2–2.1) |
| TNF (0.4) | 1.5 (0.4–10.2) | 2 (0.8–7.5) | 3.3 (1.5–6.7) | NS | 2.5 (1–6.7) | 3.2 (0.5–8.5) | 2 (0.7–8.6) | NS | 2.9 (0.4–16.7) |
| Serum | |||||||||
| IL-4 (0.1) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | NS | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | NS | 0.1 (0.1–0.1) |
| IL-5 (0.4) | 1.1 (1–1.2)† | 0.6 (0.5–0.9)† | 0.6 (0.4–1.6)† | NS | 0.4 (0.4–0.6) | 0.6 (0.6–1.6)† | 0.8 (0.6–1.5)† | 0.41 (0.03) | 0.2 (0.2–0.4) |
| IL-13 (6.7) | 3.3 (3.3–3.3) | 3.3 (3.3–9.9) | 3.3 (3.3–14.1) | NS | 3.3 (3.3–3.3) | 8.8 (3.3–13.3) | 3.3 (3.3–10) | NS | 9.2 (7.8–9.8) |
| IL-33 (0.4) | 0.2 (0.2–0.3) | 0.8 (0.2–0.8) | 0.2 (0.2–0.8) | NS | 0.2 (0.2–0.8) | 0.4 (0.2–0.8) | 0.2 (0.2–0.8) | NS | 0.4 (0.4–0.4) |
| TSLP (0.5) | 1.3 (1–2.1) | 1.8 (0.6–2.5) | 2.7 (1.8–4.5)† | NS | 1.7 (1.2–3.6) | 2.3 (1.9–4.4)† | 1.8 (0.8–2.7) | NS | 1.4 (0.9–1.5) |
| Eotaxin-3 (4.2) | 9 (6–30) | 18 (7–32) | 16 (13–29) | NS | 18 (14–31) | 29 (12–34)† | 13 (7–18) | NS | 8 (4–13) |
| TARC (0.2) | 427 (108–571) | 252 (147–463) | 226 (89–430 | NS | 314 (195–664) | 190 (92–252) | 344 (146–480) | NS | 206 (124–285) |
| IFN-γ (0.3) | 0.4 (0.4–0.5) | 0.5 (0.2–0.7) | 0.3 (0.2–1.2) | NS | 0.3 (0.2–0.6) | 0.7 (0.2–2.3) | 0.2 (0.2–0.6) | NS | 0.4 (0.2–0.7) |
| TNF (0.4) | 1.8 (0.9–3.8)† | 0.6 (0.2–2) | 1.2 (0.2–4.2)† | NS | 1.7 (0.2–2.3)† | 0.6 (0.2–2) | 0.9 (0.3–1.9)† | NS | 0.2 (0.2–0.3) |
| Clinical | |||||||||
| ACQ-5 score | 1.2 (0.5–1.8) | 1.6 (0.2–2.2) | 2 (0.8–3) | NS | 1.6 (0.5–2.1) | 1.7 (0.7–2.9) | 1.2 (0.6–2.2) | NS | — |
| FEV1, % predicted | 88 (78–103) | 85 (75–98) | 81 (72–96) | NS | 81 (77–94) | 83 (74–97) | 85 (76–99) | NS | — |
| FEV1/FVC, % | 72 (64–82) | 68 (61–79) | 72 (60–77) | NS | 71 (62–82) | 68 (61–77) | 72 (61–80) | NS | — |
| Asthma attacks in the past year | 1 (0–3) | 1 (0–4) | 3 (0–5) | 0.25 (0.03) | 1 (0–5) | 1.5 (0–4) | 1 (0–4) | NS | — |
Definition of abbreviations: ACQ-5 = five-item Asthma Control Questionnaire; Eos = eosinophils; FeNO = fractional exhaled nitric oxide; LLOD = lower limit of detection; LTE4 = leukotriene E4; NS = not significant; PGD2 = prostaglandin D2; TARC = thymus activation–regulated cytokine (CCL17); TNF = tumor necrosis factor; TSLP = thymic stromal lymphopoietin.
P values ⩾0.05 are not significant.
Data are presented as median (interquartile range) in pg/ml unless stated otherwise.
Spearman correlation coefficients (r) and associated P values are in bold if retained after controlling for a false discovery rate <0.05 across the 52 computed correlations.
Cytokine levels that were not quantified were assigned the arbitrary value of 0.5 × the lower limit of detection to allow analysis.
Adjusted P value <0.05 compared with healthy control subjects on Kruskal-Wallis test adjusted for six comparisons.