TABLE 1.
Comparisons of Baseline Variables and Clinical Outcomes by Latent Class Analyses Subphenotypes
| Variables | Hypoinflammatory | Hyperinflammatory | p |
|---|---|---|---|
| N | 383 | 115 | |
| Demographics | |||
| Age, median (IQR) | 58.2 (46.0–66.9) | 58.5 (44.0–67.2) | 0.6779 |
| Male gender, n (%) | 200 (52.2) | 68 (59.1) | 0.2313 |
| Body mass index, median (IQR) | 29.0 (25.2–36.1) | 28.3 (24.8–34.2) | 0.2438 |
| Caucasian race, n (%) | 355 (92.7) | 102 (88.7) | 0.2408 |
| History of chronic disease, n (%) | |||
| Diabetes | 127 (33.2) | 39 (33.9) | 0.9700 |
| Chronic obstructive pulmonary disease | 89 (23.2) | 25 (21.7) | 0.8345 |
| Immunosuppression | 78 (20.4) | 25 (21.7) | 0.8511 |
| Chronic kidney disease | 49 (12.8) | 34 (29.6) | < 0.0001 |
| Chronic cardiac failure | 45 (11.7) | 13 (11.3) | 1.0000 |
| Alcohol use | 59 (15.4) | 20 (17.4) | 0.7145 |
| Risk factors for acute respiratory distress syndrome | |||
| Pneumonia, n (%) | 139 (36.3) | 47 (40.9) | 0.4189 |
| Aspiration, n (%) | 63 (16.4) | 20 (17.4) | 0.6406 |
| Sepsis, n (%) | 73 (19.1) | 42 (36.5) | 0.0003 |
| Lung Injury Prediction Score | 5.0 (4.0–6.5) | 6.5 (5.5–8.0) | < 0.0001 |
| Hemodynamic variables, median (IQR) | |||
| Heart rate | 89.0 (76.0–102.0) | 99.0 (83.0–109.5) | 0.0002 |
| Systolic blood pressure | 119.0 (104.0–135.0) | 109.0 (96.0–124.0) | 0.0004 |
| Laboratory variables, median (IQR) | |||
| Arterial pH | 7.4 (7.4–7.4) | 7.3 (7.3–7.4) | < 0.0001 |
| WBC | 11.4 (7.9–16.0) | 15.5 (11.1–23.5) | < 0.0001 |
| Creatinine | 1.0 (0.7–1.6) | 3.2 (1.9–4.7) | < 0.0001 |
| Serum Co2 | 25.0 (22.0–28.0) | 20.0 (18.0–23.0) | < 0.0001 |
| Mechanical ventilation variables, median (IQR) | |||
| Worst Pao2:Fio2 ratio | 164.0 (117.0–208.0) | 163.0 (110.5–221.5) | 0.4363 |
| Peak inspiratory pressure | 25.0 (20.0–31.0) | 26.0 (21.0–32.0) | 0.2508 |
| Tidal volume (per kg of predicted body weight), mL/kg | 6.7 (6.0–7.6) | 6.7 (6.0–7.7) | 0.9442 |
| Saturation, % | 97.0 (95.5–99.0) | 97.0 (95.0–99.0) | 0.2783 |
| Severity of illness and clinical outcomes | |||
| Shock (vasopressor use), n (%) | 178 (46.5) | 89 (77.4) | < 0.0001 |
| Sequential Organ Failure Assessment score, median (IQR) | 6.0 (4.0–8.0) | 10.0 (8.0–11.0) | < 0.0001 |
| Acute kidney injury, n (%) | 219 (57.2) | 106 (92.2) | < 0.0001 |
| 30-d mortality, n (%) | 85 (22.2) | 46 (40.0) | 0.0002 |
| 90-d mortality, n (%) | 94 (24.5) | 50 (43.5) | 0.0001 |
| ICU length of stay, median (IQR) | 9.0 (5.0–15.0) | 9.0 (5.0–14.0) | 0.6497 |
| Ventilator-free days, median (IQR) | 19.0 (0.0–24.0) | 11.0 (0.0–22.0) | 0.0002 |
| Duration of mechanical ventilation, median (IQR), d | 6.5 (4.0–12.0) | 7.0 (4.0–11.0) | 0.6956 |
| Biomarkers, median (IQR) | |||
| IL-6, pg/mL | 43 (20–114) | 207 (50–635) | < 0.0001 |
| IL-8, pg/mL | 14 (7–25) | 37 (22–83) | < 0.0001 |
| IL-10, pg/mL | 0.1 (0.0–4.0) | 8.7 (0.0–21.7) | < 0.0001 |
| Tumor necrosis factor receptor-1, pg/mL | 2,902 (1,801–4,777) | 10,586 (7,652–16,302) | < 0.0001 |
| Angiopoietin-2, pg/mL | 5,446 (3,083–9,896) | 19,054 (13,590–35,875) | < 0.0001 |
| Pentraxin-3, pg/mL | 2,488 (1,098–6,508) | 7,816 (3,406–22,469) | < 0.0001 |
| Fractalkine, pg/mL | 1,271 (528–2,023) | 2,686 (1,902–4,013) | < 0.0001 |
| Suppression of tumorigenicity-2, pg/mL | 132,620 (64,313–328,541) | 622,752 (268,033–1,260,289) | < 0.0001 |
| Procalcitonin, pg/mL | 429 (136–1,404) | 4,191 (2,227–5,029) | < 0.0001 |
| Receptor of advanced glycation end products, pg/mL | 2,533 (1,513–4,258) | 7,491 (5,252–12,803) | < 0.0001 |
| 1-3-beta-D-glucan, pg/mL | 23 (14–39) | 41 (21–73) | < 0.0001 |
IL = interleukin, IQR = interquartile range.
p values for comparisons between hyperinflammatory and hypoinflammatory subphenotypes were obtained from Wilcoxon test for continuous variables and Fisher test for categorical variables. Statistically significant p values (p < 0.05) are highlighted in bold.