Background
Materials and methods
Study population and study design
Population
Diagnosis and measurements
Radiological evaluation
Patient stratification
Follow-up
Chitotriosidase assay
Statistical analysis
Results
Clinical, radiological and functional parameters
Sarcoidosis population | Controls | p-value | |
---|---|---|---|
N° | 694 | 101 | |
Male (%) | 270 (39) | 34 (33) | 0.1310 |
Age (years) | 55.8 ± 12.8 | 52.2 ± 17.2 | 0.2065 |
Smoking history (pack/year) | 4.4 ± 9.7 | 5.1 ± 11.6 | 0.3457 |
• Current (%) | 49 (7) | 10 (10) | 0.1199 |
• Former (%) | 225 (32.4) | 25 (25) | 0.1199 |
• Never (%) | 420 (60.5) | 66 (66) | 0.1199 |
Biomarkers determination (basal sampling) | |||
• Chitotriosidase nmol/ml/h | 175.4 ± 89.4 | 34.2 ± 13.8 | < 0.0001 |
• ACE UI/ml | 48.5 ± 26.7 | 34.3 ± 21.8 | 0.0014 |
• Lysozyme mg/dl | 5.4 ± 2.3 | 4.6 ± 2.1 | 0.0524 |
Sarcoidosis steroid-free | Sarcoidosis on therapy | p-value | |
---|---|---|---|
N° | 370 | 324 | |
Male (%) | 160 (43) | 128 (39.5) | 0.4012 |
Age (years) | 55.6 ± 14.9 | 54.2 ± 13.4 | 0.5978 |
Smoking history (pack/year) | 4.8 ± 10 | 5.1 ± 10.4 | 0.1849 |
• Current (%) | 18 (4.8) | 19 (5.8) | 0.4012 |
• Former (%) | 117 (31.6) | 79 (24.3) | 0.4012 |
• Never (%) | 235 (63.5) | 226 (69.7) | 0.4012 |
Biomarkers determination (basal sampling) | |||
• Chitotriosidase nmol/ml/h | 180.1 ± 99.2 | 168.2 ± 118.2 | 0.3210 |
• ACE UI/ml | 49.3 ± 24.2 | 48.5 ± 24.8 | 0.5031 |
• Lysozyme mg/dl | 5.8 ± 1.8 | 5.4 ± 2.4 | 0.8265 |
Comorbidities | 228 (61.2%) | 199 (61.4%) | 0.7887 |
• Arterial Hypertension (%) | 93 (25.1) | 67 (20.4) | 0.1624 |
• Diabetes Mellitus (%) | 21 (5.6) | 27 (8.3) | 0.0578 |
• Osteopenia/Osteoporosis (%) | 112 (30.2) | 110 (33.9) | 0.1875 |
• Thyroid disorder (%) | 29 (7.8) | 25 (7.7) | 0.9410 |
• Psychiatric disorder (%) | 14 (3.7) | 18 (5.5) | 0.2178 |
• GERD/Hiatal ernia (%) | 32 (8.6) | 31 (9.5) | 0.5264 |
• Other (%) | 29 (7.8) | 33 (10.1) | 0.1765 |
PFTs | |||
• FVC l (%) | 3.6 ± 1.1 (105.7 ± 18.2) | 3.5 ± 1.1 (104.2 ± 18.4) | 0.2455 |
• FEV1 l (%) | 2.8 ± 0.9 (98.5 ± 19) | 2.7 ± 1 (95.8 ± 19) | 0.0945 |
• FEV1/FVC | 76.1 ± 7.8 | 75.8 ± 8.7 | 0.6210 |
• TLC l (%) | 6.3 ± 1.6 (110.8 ± 18.8) | 6.1 ± 1.4 (109.1 ± 16.9) | 0.3401 |
• DLCO % | 83.1 ± 15.6 | 77.7 ± 16.9 | 0.002 |
• KCO % | 92.7 ± 15.8 | 89.6 ± 15.8 | 0.0089 |
Radiological assessment (Scadding) | |||
• Stage 0 (%) | 177 (47.8) | 116 (35) | <0.0001 |
• Stage 1 (%) | 45 (12.1) | 28 (9) | <0.0001 |
• Stage 2 (%) | 56 (15.1) | 67 (21) | < 0.0001 |
• Stage 3 (%) | 81 (21.8) | 83 (24) | <0.0001 |
• Stage 4 (%) | 11 (2.9) | 30 (10) | <0.0001 |
Clinical assessment | |||
• No symptoms (%) | 145 (39.1) | 98 (30.2) | 0.0123 |
• Cough (%) | 132 (35.6) | 110 (33.9) | 0.8812 |
• Dyspnea (%) | 155 (41.8) | 133 (41) | 0.8120 |
• Asthenia (%) | 118 (31.8) | 119 (36.7) | 0.1125 |
• Arthtralgia (%) | 71 (19.1) | 76 (23.4) | 0.1198 |
Localizations of disease | |||
• Isolated pulmonary | 284 (76.7) | 143 (44.1%) | <0.0001 |
• Lung + extrapulmonary | 55 (14.8%) | 111 (34.2%) | <0.0001 |
• Extrapulmonary only | 31 (8.3%) | 70 (21.6%) | <0.0001 |
Clinical phenotypes | |||
• Abdominal (%) | 14 (3.7) | 16 (4.9) | <0.0001 |
• OCCC (%) | 12 (3.2) | 20 (6.1) | <0.0001 |
• Muscoloskeletal-cutaneous (%) | 35 (9.4) | 78 (24) | <0.0001 |
• Isolated pulmonary (%) | 284 (76.7) | 143 (44.1) | <0.0001 |
• Extrapulmonary (%) | 25 (6.7) | 67 (20.6) | <0.0001 |
Lab parameters | |||
• 24 h urine calcium mg/dl | 177.1 ± 136.8 | 222.6 ± 139.9 | 0.0289 |
COS classification | 247 | 309 | |
• 1 (%) | 49 (19.8) | 0 | <0.0001 |
• 2 (%) | 50 (20.2) | 0 | <0.0001 |
• 3 (%) | 33 (13.3) | 0 | <0.0001 |
• 4 (%) | 29 (11.7) | 0 | <0.0001 |
• 5 (%) | 31 (12.5) | 0 | <0.0001 |
• 6 (%) | 55 (22.2) | 10 (3.2) | <0.0001 |
• 7 (%) | 0 | 112 (36.2) | <0.0001 |
• 8 (%) | 0 | 151 (48.8) | <0.0001 |
• 9 (%) | 0 | 36 (11.6) | <0.0001 |
Chitotriosidase assay
Chitotriosidase and radiological features
No lung involvement | Lymph node + micronodular | Macronodular and consolidation | Lung fibrosis | P-value | |
---|---|---|---|---|---|
N° (%) | 27 (11.8) | 127 (55.9) | 62 (27.1) | 12 (5.6) | |
Male (%) | 10 (39) | 59 (46) | 26 (42) | 2 (16) | 0.2063 |
Age yrs | 57.6 ± 10.1 | 55.1 ± 12.7 | 57.3 ± 12.2 | 53.2 ± 12.7 | 0.5185 |
Smoking history (pack/year) | 7.2 ± 11.7 | 3.8 ± 9 | 3.7 ± 9.1 | 8.2 ± 13.4 | 0.4052 |
• Current (%) | 3 (11) | 7 (5) | 3 (5) | 0 | 0.5357 |
• Former (%) | 8 (29) | 37 (29) | 24 (38) | 3 (25) | 0.5357 |
• Never (%) | 16 (59) | 82 (65) | 35 (56) | 9 (75) | 0.5357 |
Biomarkers determination (basal sampling) | |||||
• Chitotriosidase nmol/ml/h | 196.7 ± 150.9 | 284.2 ± 355.2 | 132.3 ± 119.7 | 666.3 ± 311 | 0.0005 |
• ACE UI/ml | 51.4 ± 22.3 | 63.7 ± 31.3 | 50.1 ± 17.9 | 61.6 ± 26.1 | 0.0047 |
• Lysozyme mg/dl | 4.5 ± 1.7 | 5.9 ± 2.2 | 5.1 ± 1.8 | 6.5 ± 2.4 | 0.0033 |
PFTs | |||||
• FVC l (%) | 3.6 ± 0.9 (107 ± 18) | 3.4 ± 1.1 (100 ± 19) | 3.5 ± 1.1 (108 ± 15.3) | 2.7 ± 1.1 (79.3 ± 15.8) | <0.0001 |
• FEV1 l (%) | 2.8 ± 0.8 (100.7 ± 18.7) | 2.6 ± 0.9 (93.3 ± 19.8) | 2.6 ± 0.9 (94 ± 15.6) | 2.1 ± 0.8 (74.5 ± 17.3) | 0.0013 |
• FEV1/FVC | 77.2 ± 5.8 | 76.2 ± 8.6 | 75.1 ± 5 | 78.1 ± 8.2 | 0.3125 |
• TLC l (%) | 6.2 ± 1.3 (109 ± 15.8) | 6 ± 1.5 (105 ± 16.7) | 6.2 ± 1.4 (115.4 ± 18.5) | 4.6 ± 1.6 (91.5 ± 17.2) | 0.0575 |
• DLCO % | 85.3 ± 16.1 | 77.5 ± 14.9 | 79.5 ± 17.6 | 50.4 ± 16.2 | <0.0001 |
• KCO % | 96.3 ± 13.5 | 91.6 ± 19.3 | 89.2 ± 15.6 | 74.7 ± 17.8 | 0.0026 |
Clinical assessment | |||||
• No symptoms (%) | 18 (66) | 44 (35) | 17 (27) | 2 (16) | 0.0018 |
• Cough (%) | 3 (11) | 36 (28) | 16 (26) | 4 (33) | 0.2981 |
• Dyspnea (%) | 4 (15) | 54 (43) | 21 (34) | 8 (66) | 0.0074 |
• Asthenia (%) | 4 (15) | 39 (31) | 16 (26) | 5 (41) | 0.2497 |
• Arthtralgia (%) | 2 (7) | 32 (25) | 25 (40) | 4 (33) | 0.0118 |
Clinical onset | |||||
• Asymptomatic (%) | 24 (89) | 72 (57) | 47 (76) | 10 (83) | 0.0017 |
• Lofgren syndrome (%) | 1 (3) | 8 (6) | 4 (6) | 0 | 0.7808 |
Clinical phenotypes | |||||
• Abdominal (%) | 1 (3) | 14 (11) | 1 (1.6) | 2 (16) | 0.5170 |
• OCCC (%) | 2 (7) | 7 (5) | 3 (5) | 0 | 0.5170 |
• Muscoloskeletal-cutaneous (%) | 3 (11) | 16 (12.6) | 9 (14) | 1 (8) | 0.5170 |
• Isolated pulmonary (%) | 21 (77) | 88 (69.2) | 48 (77) | 9 (75) | 0.5170 |
• Extrapulmonary (%) | 0 | 2 (1.5) | 1 (1.6) | 0 | |
COS classification | 19 | 95 | 51 | 10 | |
• 1 (%) | 4 (21) | 1 (1) | 0 | 0 | 0.0002 |
• 2 (%) | 3 (16) | 3 (3) | 0 | 0 | 0.0002 |
• 3 (%) | 2 (10) | 3 (3) | 0 | 0 | 0.0002 |
• 4 (%) | 2 (10) | 3 (3) | 3 (6) | 0 | 0.0002 |
• 5 (%) | 1 (5) | 4 (4) | 3 (6) | 0 | 0.0002 |
• 6 (%) | 1 (5) | 9 (9) | 9 (17) | 2 (20) | 0.0002 |
• 7 (%) | 4 (21) | 26 (21) | 10 (19) | 1 (10) | 0.0002 |
• 8 (%) | 2 (10) | 36 (36) | 22 (43) | 5 (50) | 0.0002 |
• 9 (%) | 0 | 11 (11) | 4 (8) | 2 (20) | 0.0002 |
Chitotriosidase activity in relation to extrapulmonary localizations and GenPhenResA phenotypes
Chitotriosidase activity in relation to COS classification
Chitotriosidase activity at follow-up
Δ Chitotriosidase (nmol/ml/h) | p-value | |
---|---|---|
Therapy modification | ||
• Improved (n = 47) | −64.5 ± 118.1 | 0.2045 |
• Stable (n = 164) | −1.3 ± 214.4 | 0.9389 |
• Worsened (n = 215) | 44.1 ± 131.4 | 0.0012 |