Table 1.
Demographic and Clinical Characteristics of the YKL-40 Clusters in the YCAAD, SARP and NYUBAR Cohorts
| Total cohort | Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | p value | |
|
| ||||||
| Discovery Cohort: YCAAD Subjects | 156 | 76 (49%) | 30 (19%) | 20 (13%) | 30 (19%) | |
|
| ||||||
| Age (years) | 49 (37–58) | 42 (17–52) | 49 (37–56) | 52 (44–57) | 60 (52–65) | <0.01 |
|
| ||||||
| Female gender | 117 (75%) | 70 (92%) | 7 (23%) | 13 (65%) | 27 (90%) | <0.01 |
|
| ||||||
| Race | ||||||
| White | 114 (73%) | 60 (79%) | 24 (80%) | 11 (55%) | 19 (63%) | 0.2 |
| African-American | 29 (19%) | 10 (13%) | 6 (20%) | 5 (25%) | 8 (27%) | |
| Other | 13 (8%) | 6 (8%) | 4 (20%) | 3 (10%) | ||
|
| ||||||
| Hispanic | 18 (12%) | 6 (8%) | 3 (10%) | 3 (15%) | 6 (20%) | 0.36 |
|
| ||||||
| BMI (kg/m2) | 28.9 (23.8–35.7) | 25.1 (22.2–32.0) | 30.0 (25.7–32.4) | 31.2 (27.1–37.1) | 32.9 (29.0–39.7) | <0.01 |
|
| ||||||
| Age of onset (years) | 21 (5–39) | 16 (5–31) | 30 (10–40) | 5 (3–14) | 42 (25–54) | <0.01 |
|
| ||||||
| Asthma duration (years) | 21 (10–33) | 18 (12–32) | 20 (6–29) | 40 (32–50) | 16 (7–30) | <0.01 |
|
| ||||||
| Severe by EPR-3 | 63 (40%) | 16 (21%) | 13 (43%) | 16 (80%) | 18 (60%) | <0.01 |
|
| ||||||
| Lifetime hospitalizations for asthma | 65 (42%) | 22 (29%) | 12 (40%) | 15 (75%) | 16 (53%) | <0.01 |
|
| ||||||
| Hospitalizations for asthma in the past year | 35 (22%) | 11 (15%) | 6 (20%) | 7 (35%) | 11 (37%) | 0.04 |
|
| ||||||
| ACT score | 17 (11–21) | 20 (17–23) | 13 (10–19) | 15 (9–20) | 10 (9–17) | <0.01 |
|
| ||||||
| FEV1 Pre-BD* | 82 (60–94) | 91 (85–103) | 72 (62–85) | 43 (34–53) | 72 (53–81) | <0.01 |
|
| ||||||
| FEV1 Post-BD* | 86 (71–98) | 96 (86–108) | 86 (76–98) | 51 (39–56) | 75 (61–86) | <0.01 |
|
| ||||||
| FEV1/FVC Post-BD | 74 (65–81) | 79 (73–85) | 70 (64–75) | 53 (41–66) | 71 (64–83) | <0.01 |
|
| ||||||
| Bronchodilator Response* | 5 (2–9) | 4 (2–7) | 12 (4–20) | 6 (4–8) | 5 (1–10) | <0.01 |
|
| ||||||
| ICS use | 127 (81%) | 55 (72%) | 25 (83%) | 20 (100%) | 27 (90%) | 0.02 |
|
| ||||||
| ICS dose (mcg/day) | 500 (0–675) | 320 (0–640) | 410 (0–830) | 640 (500–1000) | 640 (500–1000) | <0.01 |
|
| ||||||
| Oral or systemic CS | 18 (12%) | 3 (4%) | 3 (10%) | 3 (15%) | 9 (30%) | <0.01 |
|
| ||||||
| LABA use | 103 (66%) | 40 (53%) | 18 (60%) | 19 (95%) | 26 (87%) | <0.01 |
|
| ||||||
| Serum YKL-40 (ng/mL) | 63 (35–108) | 48 (32–71) | 50 (33–88) | 74 (46–108) | 206 (110–311) | <0.01 |
|
| ||||||
| Total cohort | Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | p value | |
|
| ||||||
| Validation Cohort 1 | ||||||
|
| ||||||
| SARP Subjects | 167 | 84 (50%) | 57 (34%) | 14 (8%) | 12 (7%) | |
|
| ||||||
| Age (years) | 36 (26–47) | 33 (25–44) | 35 (25–43) | 51 (38–59) | 48 (46–54) | <0.01 |
|
| ||||||
| Female gender | 115 (68%) | 84 (100%) | 19 (33%) | 6 (43%) | 4 (33%) | <0.01 |
|
| ||||||
| Race | ||||||
| White | 119 (71%) | 60 (71%) | 41 (72%) | 11 (79%) | 7 (58%) | 0.56 |
| African-American | 41 (25%) | 19 (23%) | 15 (26%) | 2 (14%) | 5 (42%) | |
| Other | 7 (4%) | 5 (6%) | 1 (2%) | 1 (7%) | ||
|
| ||||||
| BMI (kg/m2) | 26.8 (23.5–32.4) | 26.1 (23.0–29.8) | 27.0 (24.0–32.8) | 28.6 (24.4–32.4) | 31.1 (27.1–33.3) | 0.17 |
|
| ||||||
| Age of onset (years) | 10 (4–26) | 11 (4–22) | 6 (2–22) | 5 (1–28) | 40 (38–46) | <0.01 |
|
| ||||||
| Asthma duration (years) | 19 (9–32) | 17 (9–29) | 20 (15–33) | 33 (29–45) | 7 (4–11) | <0.01 |
|
| ||||||
| Lifetime hospitalizations for asthma | 71 (43%) | 30 (36%) | 24 (42%) | 12 (86%) | 5 (42%) | 0.01 |
|
| ||||||
| FEV1 Pre-BD* | 80 (62–92) | 88 (80–98) | 73 (59–88) | 32 (28–41) | 58 (49–70) | <0.01 |
|
| ||||||
| FEV1 Post-BD* | 92 (79–102) | 96 (88–106) | 89 (79–100) | 44 (40–49) | 79 (71–98) | <0.01 |
|
| ||||||
| Bronchodilator Response* | 10 (5–16) | 7 (4–10) | 15 (12–22) | 10 (6–14) | 12 (10–22) | <0.01 |
|
| ||||||
| ICS use | 73 (44%) | 35 (42%) | 22 (39%) | 7 (50%) | 9 (75%) | <0.01 |
|
| ||||||
| Oral or systemic CS | 19 (12%) | 5 (6%) | 5 (9%) | 5 (36%) | 3 (25%) | <0.01 |
|
| ||||||
| LABA use | 83 (50%) | 37 (44%) | 25 (44%) | 10 (71%) | 11 (92%) | <0.01 |
|
| ||||||
| Serum YKL-40 (ng/mL) | 49 (34–68) | 43 (33–61) | 54 (28–69) | 70 (42–101) | 67 (50–165) | <0.01 |
|
| ||||||
| Total cohort | Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | p value | |
|
| ||||||
| Validation Cohort 2 | ||||||
|
| ||||||
| NYUBAR Subjects | 341 | 205 (60%) | 97 (28%) | 15 (4%) | 24 (7%) | |
|
| ||||||
| Age (years) | 37 (25–50) | 34 (24–49) | 34 (26–43) | 46 (42–62) | 54 (48–62) | <0.01 |
|
| ||||||
| Female gender | 242 (71%) | 205 (100%) | 11 (11%) | 9 (60%) | 17 (71%) | <0.01 |
|
| ||||||
| Race | ||||||
| White | 75% (255) | 76% (159) | 68% (66) | 67% (10) | 83% (20) | 0.06 |
| African-American | 19% (66) | 20% (40) | 19% (19) | 27% (4) | 13% (3) | |
| Other | 6% (21) | 3% (6) | 13% (13) | 6% (1) | 4% (1) | |
|
| ||||||
| Hispanic | 188 (55%) | 119 (58%) | 47 (49%) | 9 (60%) | 13 (54%) | 0.46 |
|
| ||||||
| BMI (kg/m2) | 28.0 (24.0–33.0) | 28.0 (23.0–33.0) | 27.0 (24.0–32.0) | 32.0 (27.5–40.0) | 28.5 (24.0–33.5) | 0.09 |
|
| ||||||
| Age of onset (years) | 16 (8–28) | 18 (10–27) | 12 (6–22) | 9 (5–21) | 45 (39–53) | <0.01 |
|
| ||||||
| Asthma duration (years) | 16 (7–28) | 15 (6–25) | 18 (12–29) | 36 (32–42) | 8 (3–16) | <0.01 |
|
| ||||||
| Severe by EPR-3 | 209 (61%) | 121 (59%) | 50 (52%) | 15 (100%) | 23 (96%) | 0.01 |
|
| ||||||
| Hospitalizations for asthma in the past year | 36 (11%) | 14 (7%) | 11 (11%) | 7 (47%) | 4 (17%) | <0.01 |
|
| ||||||
| FEV1 Pre-BD* | 82 (71–93) | 86 (76–95) | 79 (68–89) | 40 (33–48) | 67 (55–72) | <0.01 |
|
| ||||||
| FEV1 Post-BD* | 87 (76–96) | 89 (80–99) | 86 (77–95) | 48 (45–51) | 73 (60–76) | <0.01 |
|
| ||||||
| Bronchodilator Response* | 4 (1–7) | 3 (1–6) | 5 (2–10) | 4 (1–9) | 6 (2–8) | 0.001 |
|
| ||||||
| ICS use | 191 (56%) | 109 (53%) | 45 (46%) | 15 (100%) | 22 (92%) | <0.01 |
|
| ||||||
| Oral or systemic CS | 199 (58%) | 115 (56%) | 51 (53%) | 15 (100%) | 18 (75%) | <0.01 |
|
| ||||||
| LABA use | 141 (41%) | 85 (42%) | 29 (30%) | 12 (80%) | 15 (63%) | <0.01 |
|
| ||||||
| Serum YKL-40 (ng/mL) | 56 (42–87) | 52 (40–80) | 57 (39–86) | 99 (60–177) | 103 (61–156) | <0.01 |
Data are n (%) or median (interquartile range) unless otherwise specified.
*
Percent of predicted
Definition of abbreviations: YCAAD: Yale Center for Asthma and Airways Disease; SARP: Severe Asthma Research Program; NYUBAR: New York University/Bellevue Asthma Registry; BMI: Body Mass Index; EPR-3: Expert Panel Report-3; ACT: Asthma Control Test; FEV1: Forced Expiratory Volume 1 Second; BD: Bronchodilator; FVC: Forced Vital Capacity; ICS: Inhaled Corticosteroids; CS: Corticosteroids; LABA: Long-Acting Beta Agonist.