Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
Abstract
:1. Introduction
2. Methods
2.1. Study Cohort
2.2. Diagnostic Assays
2.3. Statistical Methods
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | % (N) |
---|---|
Male Sex | 71.9 (149/210) |
Race/Ethnicity | |
White | 82.4 (173/210) |
Black | 3.8 (8/210) |
Asian | 3.8 (8/210) |
American Indian | 1.4 (3/210) |
Hispanic | 4.3 (9/210) |
Unknown | 8.6 (18/210) |
State of Residence | |
Minnesota | 43.3 (91/210) |
Wisconsin | 17.6 (37/210) |
Iowa | 13.3 (28/210) |
Illinois | 4.3 (9/210) |
Michigan | 3.8 (8/210) |
North Dakota | 3.8 (8/210) |
Other | 13.8 (29/210) |
Comorbidities | |
Asthma/COPD | 9.0 (19/210) |
Diabetes mellitus | 22.9 (48/210) |
Renal failure 1 | 7.3 (14/193) |
Obesity 2 | 33.9 (65/192) |
Corticosteroid treatment 3 | 7.1 (15/210) |
Pharmacologic immunosuppression 4 | 18.6 (39/210) |
Solid organ transplant | 8.1 (17/210) |
Extrapulmonary Disease | 24.8 (52/210) |
Diagnosis Confirmed by Culture | |
Respiratory secretions/Lung tissue | 60.0 (126/210) |
Skin/soft tissue | 11.0 (23/210) |
Paranasal sinus/Larynx | 1.4 (3/210) |
Bone/Synovial Fluid | 1.4 (3/210) |
Central Nervous System | 0.5 (1/210) |
Bone Marrow | 0.5 (1/210) |
Blood | 0.5 (1/210) |
Urine | 0.5 (1/210) |
Diagnosis confirmed by Histopathology | |
Lung | 62.0 (75/121) |
Skin/soft tissue | 24.8 (30/121) |
Mediastinal lymph node | 6.6 (8/121) |
Pleura | 0.8 (1/121) |
Vocal cord | 1.7 (2/121) |
Mastoid | 0.8 (1/121) |
Bone | 1.7 (2/121) |
Brain | 1.7 (2/121) |
Spleen | 0.8 (1/121) |
Histopathologic Findings | |
Granulomatous Inflammation | 56.7 (68/120) |
Presence of Yeast | 37.1 (78/120) |
Pulmonary Radiographic Findings | |
Consolidation | 46.8 (81/173) |
Nodule/Mass | 69.4 (120/173) |
Cavity | 21.4 (37/173) |
Antifungal Treatment * | |
Liposomal Amphotericin B | 38.9 (81/208) |
Itraconazole | 81.3 (169/208) |
Voriconazole | 14.4 (30/208) |
Fluconazole | 2.8 (7/208) |
Posaconazole | 2.8 (6/208) |
Isavuconazole | 0.5 (1/208) |
No treatment | 2.8 (6/208) |
Mild/Moderate Disease (n = 164) | Severe Disease (n = 46) | Univariate Odds Ratio (95% CI) | p-Value | Multivariate Odds Ratio (95% CI) | p-Value | |
---|---|---|---|---|---|---|
Age in years Mean (SD) | 51.2 (18.13) | 51.3 (18.81) | 1.00 (0.98–1.02) | 0.960 | ||
Male Sex | 70.1 (115/164) | 73.9 (34/46) | 1.21 (0.58–2.53) | 0.617 | ||
Race | ||||||
White | 91.3 (136/149) | 86.1 (37/43) | Reference | |||
Black | 3.4 (5/149) | 7.0 (3/43) | 2.21 (0.50–9.66) | 0.294 | ||
Asian | 4.7 (7/149) | 2.3 (1/43) | 0.53 (0.06–4.40) | 0.553 | ||
American Indian | 0.7 (1/149) | 4.7 (2/43) | 7.35 (0.65–83.32) | 0.107 | ||
Hispanic | 3.7 (5/135) | 0 | - | |||
Asthma/COPD | 9.8 (16/164) | 6.5 (3/46) | 0.65 (0.18–2.32) | 0.502 | ||
Diabetes mellitus | ||||||
All | 23.2 (38/164) | 21.7 (10/46) | 0.92 (0.42–2.03) | 0.838 | ||
Insulin-Dependent | 7.9 (13/164) | 13.0 (6/46) | 1.74 (0.62–4.87) | 0.290 | ||
Renal Failure | 5.4 (8/149) | 15.6 (7/45) | 3.25 (1.11–9.52) | 0.032 | 2.43 (0.79–7.46) | 0.119 |
Obesity | 31.5 (47/149) | 41.9 (18/43) | 1.56 (0.78–3.14) | 0.210 | ||
Extrapulmonary Disease | 26.2 (43/164) | 19.6 (9/46) | 0.68 (0.31–1.53) | 0.357 | ||
Corticosteroid Treatment | 7.9 (13/164) | 4.4 (2/46) | 0.53 (0.11–2.43) | 0.412 | ||
Pharmacologic Immunosuppression | 19.5 (32/164) | 15.2 (7/46) | 0.74 (0.30–1.81) | 0.509 | ||
Solid Organ Transplant | 6.7 (11/164) | 10.9 (5/46) | 1.70 (0.56–5.16) | 0.352 | ||
Neutrophilia1 | 43.1 (59/137) | 72.7 (32/44) | 3.52 (1.67–7.42) | 0.001 | 3.35 (1.53–7.35) | 0.002 |
Lymphopenia2 | 27.7 (38/137) | 59.1 (26/44) | 3.76 (1.85–7.64) | <0.001 | 3.34 (1.59–7.03) | 0.001 |
Survivors (n = 185) | Non-Survivors (n = 25) | Univariate Hazards Ratio (95% CI) | p-Value | Multivariate Hazards Ratio (95% CI) | p-Value | |
---|---|---|---|---|---|---|
Age in years mean (SD) | 49.9 (1.33) | 60.8 (3.37) | 1.04 (1.01–1.07) | 0.007 | 1.04 (1.01–1.08) | 0.009 |
Male Sex | 71.4 (132/185) | 68.0 (17/25) | 0.85 (0.35–2.10) | 0.729 | ||
Race/Ethnicity | ||||||
White | 90.6 (154/170) | 86.4 (19/22) | Reference | |||
Black | 3.5 (6/170) | 9.1 (2/22) | 2.71 (0.63–11.62) | 0.181 | ||
Asian | 4.7 (8/170) | 0 | - | |||
American Indian | 1.2 (2/170) | 4.6 (1/22) | 3.19 (0.43–23.83) | 0.259 | ||
Hispanic | 2.6 (4/156) | 5.9 (1/17) | 2.26 (0.29–16.53) | 0.447 | ||
Asthma/COPD | 9.7 (18/185) | 4.0 (1/25) | 0.39 (0.49–3.03) | 0.366 | ||
Diabetes mellitus | ||||||
All | 23.2 (43/185) | 20.0 (5/25) | 0.83 (0.29–2.33) | 0.717 | ||
Insulin-Dependent | 8.7 (16/185) | 12.0 (3/25) | 1.44 (0.39–5.34) | 0.585 | ||
Renal Failure | 5.9 (10/169) | 20.0 (5/25) | 3.98 (1.23–12.81) | 0.021 | 2.51 (0.70–8.92) | 0.156 |
Obesity | 33.7 (57/169) | 34.8 (8/23) | 1.05 (0.42–2.63) | 0.920 | ||
Extrapulmonary Disease | 26.5 (49/185) | 12.0 (3/25) | 0.38 (0.11–1.32) | 0.128 | ||
Corticosteroid Treatment | 7.0 (13/185) | 8.0 (2/25) | 1.15 (0.24–5.43) | 0.859 | ||
Pharmacologic Immunosuppression | 17.8 (33/185) | 24.0 (6/25) | 1.45 (0.54–3.92) | 0.459 | ||
Solid Organ Transplant | 7.0 (13/185) | 12.0 (3/25) | 1.80 (0.48–6.83) | 0.385 | ||
Neutrophilia1 | 47.8 (75/157) | 66.7 (16/24) | 2.19 (0.88–5.40) | 0.090 | 2.84 (1.04–7.76) | 0.041 |
Lymphopenia2 | 29.9 (47/157) | 70.8 (17/24) | 5.68 (2.21–14.61) | <0.001 | 4.50 (1.67–12.11) | 0.003 |
All Respiratory Specimens | Sputum | Lower Respiratory Tract Specimens | p-Value * | |
---|---|---|---|---|
KOH/Calcofluor White Smear | 46.7 | 39.1 | 49.3 | 0.47 |
(36.2–57.4) | (20.5–61.2) | (37.0–61.6) | ||
42/90 | 9/23 | 33/67 | ||
PCR | 67.6 | 45.5 | 76.9 | 0.12 |
(50.1–81.5) | (18.1–75.4) | (55.9–90.3) | ||
25/37 | 5/11 | 20/26 |
All | Pulmonary Disease | Extrapulmonary Disease | p-Value * | |
---|---|---|---|---|
BlastomycesEIA | 52.1 | 47.3 | 68.8 | 0.13 |
(40.7–63.3) | (34.7–60.2) | (44.4–85.8) | ||
37/71 | 26/55 | 11/16 | ||
BlastomycesImmunodiffusion | 39.6 | 36.1 | 52.6 | 0.19 |
(30.1–49.8) | (26.0–47.7) | (31.7–72.7) | ||
36/91 | 26/72 | 10/19 | ||
BlastomycesComplement Fixation | 22.9 | 17.9 | 42.9 | 0.31 |
(12.1–39.0) | (7.9–35.6) | (15.8–75.0) | ||
8/35 | 5/28 | 3/7 | ||
Urine Blastomyces Antigen | 80.8 | 87.8 | 54.6 | 0.03 |
(68.1–89.2) | (74.5–94.7) | (28.0–78.7) | ||
42/52 | 36/41 | 6/11 | ||
Serum Blastomyces Antigen | 64.3 | 66.7 | 60.0 | 1.00 |
(38.8–83.7) | (35.4–87.9) | (23.1–88.2) | ||
9/14 | 6/9 | 3/5 | ||
Histoplasma Complement Fixation | 17.9 | 17.9 | None | - |
(7.9–35.6) | (7.9–35.6) | |||
5/28 | 5/28 | |||
HistoplasmaImmunodiffusion | 0/7 | 0/7 | None | - |
Urine Histoplasma Antigen | 58.8 | 58.6 | 60.0 | 1.00 |
(42.2–73.6) | (40.7–74.5) | (23.1–88.2) | ||
20/34 | 17/29 | 3/5 |
Age/Sex | Radiographic Findings | Diagnosis | Treatment/Relapse |
---|---|---|---|
62 M | Dense left lower lobe consolidation | Culture of bronchial washings | Itraconazole for 7 months Recurrence after 12 months |
Dense right lower lobe consolidation | BAL culture | Itraconazole for 6 months | |
54 F | Right apical lung cavity and irregular nodules | BAL DNA probe | Itraconazole for 15 months Relapse after 23 months |
Thickening of the cavity wall and cavitating nodules | Urine Antigen (2.73 ng/mL) | Itraconazole for 24 months Relapse after 8 months | |
Masslike consolidation in the inferior margins of the cavity | Urine Antigen (2.43 ng/mL) | Itraconazole for 14 months Voriconazole for 25 months | |
31 M | Right upper lobe mass with rib invasion | Chest wall soft tissue biopsy: granulomatous inflammation | Itraconazole for 9 months Relapse after 9 months |
New T12 vertebral body lesion | Vertebral body biopsy negative for microorganisms, negative culture | Posaconazole for 12 months |
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O’Dowd, T.R.; Mc Hugh, J.W.; Theel, E.S.; Wengenack, N.L.; O’Horo, J.C.; Enzler, M.J.; Vergidis, P. Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study. J. Fungi 2021, 7, 888. https://doi.org/10.3390/jof7110888
O’Dowd TR, Mc Hugh JW, Theel ES, Wengenack NL, O’Horo JC, Enzler MJ, Vergidis P. Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study. Journal of Fungi. 2021; 7(11):888. https://doi.org/10.3390/jof7110888
Chicago/Turabian StyleO’Dowd, Timothy R., Jack W. Mc Hugh, Elitza S. Theel, Nancy L. Wengenack, John C. O’Horo, Mark J. Enzler, and Paschalis Vergidis. 2021. "Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study" Journal of Fungi 7, no. 11: 888. https://doi.org/10.3390/jof7110888