Background
Patients and methods
Patients
Data collection
Statistical analysis
Results
Study population and clinical manifestations
Missing data | All patients N = 47 | aMDA-5 ARF N = 19 | AS ARF N = 28 |
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Age, years median [IQR] | 0 | 60 [52–69] | 60 [51–67] | 63 [54–73] | 0.51 |
Male, n (%) | 0 | 23 (49) | 8 (42) | 15 (54) | 0.64 |
SOFA score median [IQR] | 0 | 5 [3–8] | 4 [2–8] | 5 [3–8] | 0.77 |
SAPSII median [IQR] | 0 | 35 [27–53] | 34 [27–53] | 38 [27–50] | 0.94 |
Comorbidities, n (%) | |||||
Chronic respiratory failure | 0 | 1 (2) | 0 (0) | 1 (4) | 1.00 |
Congestive heart failure | 0 | 0 (0) | 0 (0) | 0 (0) | 1.00 |
Cirrhosis | 0 | 1 (2) | 0 (0) | 1 (4) | 1.00 |
Chronic kidney failure | 0 | 0 (0) | 0 (0) | 0 (0) | 1.00 |
Active solid cancer or malignant hemopathy | 0 | 0 (0) | 0 (0) | 0 (0) | 1.00 |
HIV | 0 | 0 (0) | 0 (0) | 0 (0) | 1.00 |
Diabetes mellitus | 0 | 5 (11) | 1 (5) | 4 (14) | 0.64 |
Obesity (body mass index ≥ 30 kg/m2) | 0 | 1 (2) | 0 (0) | 1 (4) | 1.00 |
No comorbidities | 0 | 40 (85) | 18 (95) | 22 (79) | 0.60 |
Active or former tobacco use, n (%) | 0 | 20 (43) | 7 (37) | 13 (46) | 0.73 |
Respiratory manifestations, n (%) | |||||
Delay first respiratory sign—ICU admission, days | 2 | 21 [10–41] | 21 [11–43] | 21 [10–41] | 0.73 |
Dry cough | 0 | 23 (49) | 8 (42) | 15 (54) | 0.64 |
Chest pain | 0 | 0 (0) | 0 (0) | 0 (0) | 1.00 |
Hemoptysis | 0 | 1 (2) | 0 (0) | 1 (4) | 1.00 |
Bilateral crackles | 5 | 34 (81) | 13 (77) | 21 (84) | 0.69 |
Fever (> 38 °C) | 0 | 27 (57) | 9 (47) | 18 (64) | 0.40 |
Extra-respiratory manifestations, n (%) | |||||
Myalgia | 0 | 11 (23) | 2 (11) | 9 (32) | 0.16 |
Muscles weakness | 0 | 6 (13) | 1 (5) | 5 (18) | 0.38 |
Arthralgia/arthritis | 0 | 14 (30) | 6 (32) | 8 (29) | 1.00 |
Cutaneous manifestations | 0 | 20 (43) | 13 (68) | 7 (25) | 0.008 |
Mechanic’s hand | 0 | 8 (17) | 3 (15) | 5 (19) | 1.00 |
Raynaud’s phenomenon | 0 | 3 (6) | 1 (5) | 2 (7) | 1.00 |
Facial erythema | 0 | 12 (26) | 9 (47) | 3 (11) | 0.007 |
Gottron’s papules | 0 | 5 (11) | 5 (26) | 0 (0) | 0.008 |
Ulcerations | 0 | 3 (6) | 3 (16) | 0 (0) | 0.06 |
Trunk rash | 0 | 7 (15) | 5 (26) | 2 (7) | 0.10 |
No extra-respiratory manifestations | 0 | 17 (36) | 6 (31) | 11 (39) | 0.81 |
Laboratory and radiological findings
Missing data | All patients N = 47 | aMDA-5 ARF N = 19 | AS ARF N = 28 |
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Biological data at ICU admission, median [IQR] | |||||
Leukocytes count (103/mm3) | 1 | 11.5 [8.5–17] | 8.4 [6.7–9.8] | 16.0 [12.1–21.1] | < 0.001 |
C-reactive protein (mg/L) | 9 | 139 [40–208] | 38 [22–99] | 187 [128–262] | 0.30 |
Procalcitonine (ng/mL) | 9 | 0.30 [0.12–0.56] | 0.32 [0.11–0.48] | 0.30 [0.13–1.42] | < 0.001 |
Creatininemia (µmol/L) | 14 | 63 [51–78] | 59 [51–73] | 64 [51–80] | 0.04 |
Creatine kinase (UI/L) | 3 | 157 [69–256] | 127 [75–186] | 192 [69–932] | 0.76 |
Creatine kinase ≥ 2N | 3 | 9 (20) | 1 (6) | 8 (31) | 0.02 |
PaCO2 (mmHg) | 1 | 34 [31–41] | 34 [32–42] | 33 [31–41] | 0.06 |
PaO2/FiO2 (mmHg) | 3 | 123 [83–147] | 139 [91–174] | 117 [78–144] | 0.82 |
Chest X-ray, n (%) | |||||
Bilateral opacities | 0 | 45 (96) | 19 (100) | 26 (93) | 0.51 |
Lower lobe location | 0 | 46 (98) | 19 (100) | 27 (96) | 1.00 |
Number of quadrants on chest X-ray, n | |||||
1 | 0 | 1 (3) | 0 (0) | 1 (4) | 0.30 |
2 | 27 (68) | 10 (59) | 17 (74) | ||
4 | 12 (30) | 7 (41) | 5 (22) | ||
Chest CT scan, n (%) | |||||
Performed | 0 | 47 (100) | 19 (100) | 28 (100) | 1.00 |
Ground-glass attenuation | 0 | 37 (78) | 18 (96) | 19 (68) | 0.03 |
Alveolar consolidations | 0 | 35 (75) | 13 (68) | 22 (79) | 0.51 |
Septal thickening | 0 | 12 (26) | 8 (42) | 4 (14) | 0.05 |
Pleural effusion | 0 | 13 (28) | 3 (16) | 10 (36) | 0.24 |
Pneumothorax | 0 | 4 (9) | 3 (16) | 1 (3.6) | 0.29 |
Pneumomediastinum | 0 | 1 (2) | 1 (5) | 0 (0) | 0.40 |
Mediastinal lymphadenopathy | 0 | 18 (38) | 7 (37) | 11 (39) | 1.00 |
Signs of lung fibrosis | 0 | 17 (36) | 6 (32) | 11 (39) | 0.82 |
Traction bronchiectasis | 0 | 17 (36) | 6 (32) | 11 (39) | 0.82 |
Reticulations | 0 | 12 (26) | 4 (21) | 8 (29) | 0.78 |
Honeycombing | 0 | 5 (10) | 1 (5) | 4 (14) | 0.64 |
Broncho-alveolar lavage (BAL), n (%) or median [IQR] | |||||
Performed | 0 | 42 (89) | 16 (84) | 26 (93) | 0.38 |
Delay ICU admission—BAL | 0 | 1 [0–3] | 0 [− 1.5–1.0] | 2 [1–4] | 0.08 |
Total cell count (103/mL) | 8 | 250 [140–330] | 250 [128–390] | 250 [160–290] | 0.42 |
Lymphocytes (%) | 1 | 11 [4–30] | 22 [8–34] | 5 [3–17] | 0.06 |
Neutrophils (%) | 2 | 38 [13–65] | 15 [6–36] | 51 [20–80] | 0.001 |
Macrophages (%) | 2 | 40 [20–60] | 53 [39–73] | 29 [15–83] | 0.009 |
Eosinophils (%) | 6 | 0 [0–2] | 0 [0–1] | 0 [0–2] | 0.154 |
Presence of siderophages | 5 | 2 (4) | 1 (6) | 1 (4) | 1.00 |
Lung biopsy, n (%) | 0 | 4 (9) | 1 (5) | 3 (11) | – |
Diffuse alveolar damage | 1 | 0 | 1 | ||
Usual interstitial pneumonitis | 1 | 0 | 1 | ||
Organizing pneumonia | 2 | 1 | 1 | ||
Skin biopsy, n (%) | 0 | 6 (13) | 5 (26) | 1 (4) | – |
Normal | 1 | 0 | 1 | ||
Lichenoïd dermatitis | 3 | 3 | 0 | ||
Dermatomyositis | 2 | 2 | 0 | ||
Muscle biopsy, n (%) | 0 | 7 (15) | 4 (21) | 3 (11) | – |
Inflammatory myositis | 7 | 4 | 3 |
Broncho-alveolar fluid analysis and histological data
ICU management and outcome
Missing data | All patients N = 47 | aMDA-5 ARF N = 19 | AS ARF N = 28 |
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Treatment, n (%) or median [IQR] | |||||
Antibiotics therapy at ICU admission | 0 | 41 (89) | 15 (79) | 26 (96) | 0.14 |
Immunosuppressive treatment | 0 | 47 (100) | 19 (100) | 28 (100) | 1.00 |
Delay ICU-IS treatment (days) | 0 | 6 [3–12] | 4 [1.5–11] | 6 [4–16] | 0.25 |
Corticosteroids pulses | 0 | 47 (100) | 19 (100) | 28 (100) | 1.00 |
Cyclophosphamide | 0 | 34 (72) | 16 (84) | 18 (64) | 0.24 |
Rituximab | 0 | 7 (15) | 6 (32) | 1 (4) | 0.01 |
Cyclosporine | 0 | 2 (4) | 2 (10) | 0 (0) | 0.16 |
Tacrolimus | 0 | 2 (4) | 2 (11) | 0 (0) | 0.16 |
Basiliximab | 0 | 2 (4) | 2 (11) | 0 (0) | 0.16 |
Intravenous immunoglobulins | 0 | 10 (21) | 5 (26) | 5 (18) | 0.50 |
Plasma exchange | 0 | 8 (17) | 7 (37) | 1 (4) | 0.005 |
Number of immunosuppressive treatments | 0 | 2 [2, 3] | 3 [2–4] | 2 [1, 2] | < 0.001 |
Ventilatory support, n (%) | |||||
Noninvasive ventilation before intubation | 0 | 14 (30) | 4 (21) | 10 (36) | 0.45 |
High-flow nasal cannula oxygen before intubation | 0 | 21 (45) | 11 (58) | 10 (36) | 0.23 |
Tracheal intubation | 0 | 43 (92) | 18 (95) | 25 (89) | 0.64 |
ARDS | 0 | 42 (89) | 18 (95) | 24 (86) | 0.64 |
Mild (200 < PaO2/FiO2 ≤ 300 mmHg) | 0 | 1 (2) | 1 (6) | 0 (0) | 0.43 |
Moderate (100 < PaO2/FiO2 ≤ 200 mmHg) | 0 | 5 (12) | 0 (0) | 5 (21) | 0.06 |
Severe (PaO2/FiO2 ≤ 100 mmHg) | 0 | 36 (86) | 17 (94) | 19 (79) | 0.21 |
Nitric oxide inhalation | 0 | 23 (50) | 14 (74) | 9 (33) | 0.02 |
Neuromuscular blocking agents | 0 | 36 (78) | 17 (90) | 19 (70) | 0.16 |
Prone position | 0 | 26 (57) | 12 (63) | 14 (52) | 0.64 |
Veno-venous ECMO | 0 | 8 (17) | 6 (32) | 2 (7) | 0.05 |
Extra-ventilatory support, n (%) | |||||
Renal replacement therapy | 0 | 8 (17) | 4 (21) | 4 (14) | 0.70 |
Vasopressors | 0 | 37 (79) | 17 (90) | 20 (71) | 0.17 |
Outcome, n (%) or median [IQR] | |||||
Duration of invasive mechanical ventilation (days) | 0 | 21 [14–35] | 19 [9–26] | 23 [17–37] | 0.34 |
Length of ICU stay (days) | 0 | 26 [19–38] | 22 [17–36] | 28 [21–38] | 0.20 |
Length of hospital stay (days) | 0 | 38 [22–67] | 22 [19–44] | 44 [33–70] | 0.015 |
ICU mortality | 0 | 21 (45) | 16 (84) | 5 (18) | < 0.001 |
Hospital mortality | 0 | 24 (51) | 16 (84) | 8 (29) | 0.001 |
Comparison between hospital survivors and non-survivors
Non-survivors N = 24 | Survivors N = 23 |
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Clinical, biological and immunological characteristics, n (%) or median [IQR] | |||
Age | 65 [59–70] | 55 [50–64] | 0.062 |
Male | 9 (38) | 14 (61) | 0.19 |
SOFA | 5 [2–8] | 5 [3–8] | 0.73 |
SAPSII | 32 [28–53] | 41 [27–54] | 0.82 |
Type of autoantibodies | |||
Anti-MDA-5 | 16 (67) | 3 (13) | 0.001 |
Anti-synthetase antibody | 8 (33) | 20 (87) | 0.001 |
JO-1 | 3 (13) | 10 (44) | 0.04 |
PL7 | 3 (13) | 6 (26) | 0.28 |
PL12 | 1 (4) | 3 (13) | 0.35 |
EJ | 1 (4) | 1 (4) | 1 |
Delay first respiratory sign—ICU admission, days | 21 [10–43] | 20 [10–39] | 0.31 |
Creatine kinase ≥ 2N | 3 (13) | 6 (29) | 0.27 |
PaO2/FiO2 upon ICU admission | 126 [90–149] | 117 [82–147] | 0.65 |
Chest X-ray and CT scan, n (%) | |||
Number of quadrants on chest X-ray | |||
1 | 1 (5) | 0 (0) | 0.74 |
2 | 13 (62) | 14 (74) | |
4 | 7 (33) | 5 (26) | |
Ground-glass attenuation on chest CT scan | 22 (92) | 15 (65) | 0.04 |
Alveolar consolidations on chest CT scan | 14 (58) | 21 (91) | 0.02 |
Signs of lung fibrosis on chest CT scan | 9 (38) | 8 (35) | 1.00 |
Broncho-alveolar lavage (BAL), n (%) or median [IQR] | |||
Total cell count (103/mL) | 250 [80–370] | 260 [189–293] | 0.36 |
Lymphocytes percentage | 17 [5–31] | 7 [3–18] | 0.33 |
Lymphocytes > 10% | 12 (55) | 9 (45) | 0.76 |
Lymphocytes > 25% | 8 (36) | 4 (20) | 0.41 |
Neutrophils percentage | 20 [10–52] | 49 [18–73] | 0.12 |
Neutrophils > 40% | 8 (38) | 11 (55) | 0.44 |
Neutrophils > 65% | 3 (14) | 7 (35) | 0.16 |
Management in ICU, n (%) or median [IQR] | |||
Immunosuppressive (IS) treatment | |||
Delay ICU admission—IS treatment | 4 [3–12] | 6 [3–16] | 0.63 |
Number of IS treatments | 3 [2, 3] | 2 [1, 2] | 0.002 |
Corticosteroids | 24 (100) | 23 (100) | 1.00 |
Cyclophosphamide | 20 (83) | 14 (61) | 0.16 |
Rituximab | 6 (25) | 1 (4) | 0.10 |
Basiliximab | 2 (8) | 0 (0) | 0.49 |
Cyclosporine | 1 (4) | 1 (4) | 1.00 |
Tacrolimus | 2 (8) | 0 (0) | 0.19 |
Intravenous immunoglobulins | 7 (29) | 3 (13) | 0.29 |
Plasma exchange | 6 (25) | 2 (9) | 0.25 |
Tracheal intubation | 24 (100) | 19 (83) | 0.05 |
ARDS | 23 (96) | 19 (83) | 0.19 |
Severe (PaO2/FiO2 ≤ 100 mmHg) | 22 (96) | 14 (74) | 0.07 |
Moderate (100 < PaO2/FiO2 ≤ 200 mmHg) | 1 (4) | 4 (21) | 0.16 |
Mild (200 < PaO2/FiO2 ≤ 300 mmHg) | 0 (0) | 1 (5) | 0.45 |
Nitric oxide inhalation | 18 (78) | 5 (22) | < 0.001 |
Veno-venous ECMO | 6 (25) | 2 (9) | 0.25 |
Vasopressors | 21 (88) | 16 (70) | 0.17 |
Renal replacement therapy | 5 (21) | 3 (13) | 0.70 |