Table 3.
Demographics, Clinical, and Inflammatory Characteristics of Asthma SCs
| SC1 | SC2 | SC3 | SC4 | SC5 | P Value | Significant Intergroup Differences (Bonferroni Corrected)* | |
|---|---|---|---|---|---|---|---|
| Totals | 37 | 14 | 18 | 18 | 13 | NA | NA |
| Asthma, n (%) | 22 (59) | 13 (93) | 18 (100) | 15 (83) | 13 (100) | 0.0006 | SC3 > SC1, SC5 > SC1† |
| Severe asthma, n (%) | 5 (13.5) | 4 (29) | 11 (61) | 2 (11) | 9 (69) | <0.0001 | SC3 > SC1, SC3 > SC4, SC5 > SC1, SC5 > SC4 |
| Severity (HC/mild–mod no ICS/mild + ICS/mod + ICS/severe) | 16/9/7/0/5 | 1/6/1/2/4 | 0/1/1/5/11 | 3/8/2/3/2 | 0/1/2/1/9 | <0.0001 | SC3 > SC1 (severity), SC3 > SC4, SC5 > SC1 |
| Age, mean ± SE | 34.7 ± 2.0 | 29.6 ± 3.3 | 40.3 ± 2.9 | 29.3 ± 2.9 | 41.5 ± 3.4 | 0.011 | SC5 > SC4†, SC3 > SC4† |
| Duration, mean ± SE | 20.4 ± 2.6 | 20.8 ± 3.3 | 28.8 ± 2.9 | 19.3 ± 3.0 | 32.9 ± 3.4 | 0.008 | SC5 > SC4, SC5 > SC1 |
| Sex, M/F | 14/23 | 8/6 | 6/12 | 4/14 | 5/8 | 0.37 | NS |
| Race, W/AA/O | 26/4/2 | 7/6/0 | 10/4/3 | 6/5/1 | 7/3/2 | 0.19 | NS |
| BMI, mean ± SE | 28.0 ± 1.1 | 29.6 ± 1.7 | 32.0 ± 1.5 | 27.6 ± 1.5 | 32.3 ± 1.8 | 0.08 | NS |
| Atopy, Y/N | 24/11 | 13/1 | 14/4 | 16/1 | 10/1 | 0.11 | NS |
| Positive allergy skin tests, n (mean ± SE) | 2.6 ± 0.5 | 4.6 ± 0.9 | 4.9 ± 0.8 | 5.1 ± 0.8 | 3.7 ± 1.0 | 0.039 | NS |
| Diagnosis of CRS, n (%) | 10/34 (29) | 3/14 (21) | 10/17 (59) | 5/18 (28) | 5/12 (42) | 0.16 | NS |
| Pneumonia history, n (%) | 10/34 (29) | 2/14 (14) | 11/17 (65) | 8/18 (44) | 8/12 (67) | 0.008 | SC3 > SC2, SC5 > SC2† |
| Juniper AQLQ, mean ± SE | 5.9 ± 0.2 | 4.8 ± 0.4 | 3.5 ± 0.3 | 5.4 ± 0.3 | 4.1 ± 0.4 | <0.0001 | SC1 > SC3, SC4 > SC3, SC1 > SC5, SC4 > SC5 |
| FEV1% pred, mean ± SE | 88.7 | 76.4 | 61.6 | 83.9 | 69.5 | <0.0001 | SC1 > SC3, SC4 > SC5, SC1 > SC5 |
| FVC% pred, mean ± SE | 93.7 ± 2.8 | 86.6 ± 4.5 | 78.2 ± 4.0 | 91.7 ± 4.0 | 78.0 ± 4.7 | 0.005 | SC5 > SC1, SC3 > SC1 |
| BDR %, mean ± SE | 13.7 ± 4.2 | 20.2 ± 6.9 | 49.2 ± 6.0 | 14.5 ± 5.9 | 27.7 ± 7.2 | <0.0001 | SC3 > SC1, SC3 > SC4, SC3 > SC2 |
| ED/Hosp in past 1 yr, n (%) | 3/34 (9) | 6/14 (43) | 12/17 (71) | 4/18 (22) | 8/12 (67) | <0.0001 | SC2 > SC1†, SC3 > SC1, SC3 > SC4 |
| IgE, IU/ml, median 25th–75th percentiles | 59 (16–110) | 279 (146–852) | 141 (47–731) | 154 (69–414) | 409 (36–632) | 0.005 | SC2 > SC1, SC4 > SC1, SC5 > SC1 |
| Blood eos, mean ± SE (med %) | 158 ± 24 (2) | 354 ± 39 (4) | 336 ± 34 (5) | 250 ± 33 (5) | 175 ± 41 (2.5) | <0.0001 | SC2 > SC1, SC2 > SC5, SC3 > SC1, SC3 > SC5 |
| BAL mac, mean ± SE (med %) | 6,294 ± 1,080 (86.7) | 8,727 ± 1,707 (91.4) | 5,865 ± 1,505 (89.4) | 7,534 ± 1,549 (87.3) | 8,839 ± 1,843 (85.2) | 0.52 | NS |
| BAL lymph, mean ± SE (med %) | 778 ± 128 (9) | 517 ± 202 (5.8) | 413 ± 179 (6.3) | 1,080 ± 184 (10.6) | 593 ± 219 (7.9) | 0.09 | NS |
| BAL neu, mean ± SE (med %) | 149 ± 51 (1.7) | 179 ± 82 (1.6) | 180 ± 72 (1.9) | 203 ± 74 (1.7) | 497 ± 89 (2.7) | 0.02 | SC5 > SC1, SC5 > SC3 |
| BAL eos, mean ± SE (med %) | 52 ± 23 (0.3) | 74 ± 37 (0.5) | 84 ± 33 (0.7) | 88 ± 33 (0.5) | 44 ± 39 (0.2) | 0.84 | NS |
| FeNO, ppb, mean ± SE | 23.0 ± 4.0 | 52.9 ± 6.9 | 71.5 ± 5.6 | 52.3 ± 6.0 | 22.9 ± 6.3 | <0.0001 | SC3 > SC5, SC3 > SC1, SC2 > SC5, SC2 > SC1, SC4 > SC1, SC4 > SC5 |
| BA use, n (%)‡ | 13/29 (45) | 10/10 (100) | 11/12 (92) | 14/17 (82) | 9/9 (100) | <0.0001 | SC2 > SC1, SC3 > SC1, SC5 > SC1 |
| Daily BA use, n (%)‡ | 7/29 (24) | 7/10 (70) | 11/12 (92) | 4/17 (24) | 6/9 (67) | <0.0001 | SC2 > SC1†, SC3 > SC1, SC3 > SC4 |
| LABA use, n (%)‡ | 6/29 (21) | 6/10 (60) | 12/12 (100) | 4/17 (24) | 8/9 (89) | <0.0001 | SC3 > SC1, SC5 > SC1, SC3 > SC4, SC5 > SC4 |
| ICS high dose, n (%) | 5/37 (13.5) | 3/14 (21) | 11/18 (61) | 2/18 (11) | 9/13 (69) | <0.0001 | SC3 > SC1, SC3 > SC4, SC5 > SC1, SC5 > SC4 |
| OCS, n (%)‡ | 3/36 (8) | 2/14 (14) | 8/18 (44) | 1/18 (6) | 5/13 (39) | 0.035 | NS |
| Omalizumab treatment, n (%) | 1/36 (3) | 0 | 3/18 (17) | 0 | 3/13 (23) | 0.026 | NS |
| AEC T2 expression, geomean ± SE | 1,563 ± 562 | 4,150 ± 715 | 5,402 ± 608 | 5,934 ± 666 | 1,793 ± 715 | <0.0001 | SC4 > SC1, SC4 > SC5, SC3 > SC1, SC3 > SC5, SC2 > SC1† |
| AEC EGR expression, geomean ± SE | 896 ± 45 | 555 ± 57 | 275 ± 49 | 448 ± 53 | 479 ± 57 | <0.0001 | SC1 > SC3, SC1 > SC4, SC1 > SC5, SC1 > SC2, SC2 > SC3, SC5 > SC3† |
| BALcAMP expression, geomean ± SE | 1,929 ± 106 | 1,397 ± 134 | 1,230 ± 114 | 2,120 ± 125 | 1,288 ± 134 | <0.0001 | SC4 > SC3, SC4 > SC5, SC4 > SC2, SC1 > SC3, SC1 > SC5, SC1 > SC2 |
| BAL lymphocyte module, geomean ± SE | 762 ± 140 | 438 ± 178 | 543 ± 151 | 1,183 ± 165 | 1,080 ± 178 | 0.008 | SC4 > SC2, SC4 > SC3† |
Definition of abbreviations: AA = African American; AEC = airway epithelial cell; AQLQ = asthma quality-of-life questionnaire; BA = β-agonist; BDR = bronchodilator response; BMI = body mass index; CRS = chronic rhinosinusitis; ED/Hosp = emergency department visits or hospitalizations; EGR = epithelial growth and repair; eos = eosinophils; FeNO = fractional exhaled nitric oxide; HCs = healthy control subjects; ICS = inhaled corticosteroids; LABA = long-acting β-agonist; lymph = lymphocytes; mac = macrophages/monocytes; med = median; mod = moderate; mod + ICS = moderate asthma on inhaled corticosteroids; NA = not applicable; neu = neutrophils; NS = not significant; O = other; OCS = oral corticosteroid; SC = subcluster; W = white.
SCs were determined by K means clustering of BAL and AEC gene expression. Differences in clinical characteristics were determined and reported here.
Significant intergroup differences listed achieved a Bonferroni-corrected P value of P ≤ 0.005.
Highly significant P values, although not reaching stringent Bonferroni correction (i.e., P ≤ 0.009).
23% of participants were missing BA and LABA use data.