Baseline Characteristics (Table 1):
Table 1
Demographics, and Disease Specifics
|
Overall cohort
(n = 84)
|
Non-ICU cohort
(n = 55)
|
ARDS ICU cohort (n = 13)
|
Non-ARDS ICU cohort (n = 16)
|
Age at time of diagnosis (years)
|
49 (6–85)
|
43 (6–82)
|
53 (26–73)
|
63 (27–85)
|
Male sex
|
66.7%
|
65.4%
|
69.2%
|
68.7%
|
Race
• White
• Black
• Other
Place of residence
• Minnesota
• Iowa
• Wisconsin
• Other
|
79.76%
4.76%
15.48%
54.76%
15.5%
11.8%
17.94%
|
78%
4%
18%
60%
16%
4%
20%
|
69%
15%
16%
46%
23%
15%
16%
|
94%
0%
6%
44%
6%
6%
44%
|
Comorbidities
• Hypertension
• Immunosuppression
|
33.3%
29.8%
|
31%
27%
|
23%
31%
|
50%
38%
|
• Diabetes mellitus
|
25%
|
27%
|
19%
|
23%
|
• Malignancy
• ESRD
• COPD
• Organ transplant or HSCT
• Autoimmune disease
• IBD
• Cirrhosis
• ILD
Disease spread
• Local
• Disseminated
|
23.8%
11.9%
11.9%
8.3%
13.1%
1.2%
2.38%
3.5%
77.4%
22.6%
|
22%
9%
11%
9%
12.7%
2%
0%
2%
75%
25%
|
31%
8%
8%
15.4%
15.4%
0%
0%
0%
77%
23%
|
25%
25%
19%
0%
12.5%
0%
13%
6%
87%
13%
|
Systems affected
• Pulmonary
• Skin
• CNS
• Bones
• Kidneys
|
88%
15%
8%
7%
2%
|
89%
18%
9%
9%
2%
|
100%
8%
0%
0%
8%
|
75%
13%
13%
6%
0%
|
A total of 84 patients were identified with 93 unique hospitalizations primarily for blastomycosis. Of all 84 patients, 66.7% (n = 56) were male and 80.0% (n = 67) were white. The median age at diagnosis was 49.0 (IQR 28.1–65.0, range: 6–85) years.
Comorbidities at first admission included hypertension (n = 28, 33.3%); immunosuppressed state (n = 25, 29.8%), diabetes mellitus (n = 21, 25%), malignancy (n = 20, 23.8% including 8 patients with active malignancy at time of diagnosis and 12 with a prior history of malignancy), end stage renal disease (ESRD, n = 10, 11.9%), chronic obstructive pulmonary disease (COPD, n = 10, 11.9%), history of solid organ and/or hematopoietic stem cell transplant (HSCT, n = 7, 8.3%), autoimmune condition (n = 11, 13.1%; rheumatoid arthritis in 3 patients, hypothyroidism in 4 patients and vitiligo in 2 patients, and myositis in 2 patients), interstitial lung disease (ILD, n = 3, 3.5%), liver cirrhosis (n = 2, 2.4%), and inflammatory bowel disease (IBD, n = 1, 1.2%).
Of the 84 patients, blastomycosis affected only one organ in 65 cases (77.4%), and was disseminated in 19 (22.6%). The infection most commonly involved the respiratory system in 74 cases (88%), followed by skin involvement in 13 cases (15%) and the central nervous system (CNS) in 7 cases (8%). Other involved organs included bones (n = 6 (7%)), kidneys (n = 2 (2%)), heart, and spleen.
In those with pulmonary involvement, the disease most commonly affected the right lower lobe (n = 18, 24.3%) followed by the right upper lobe (n = 17, 23.0%), and was bilateral in 15 patients (20.3%).
Diagnosis And Treatment (table 2):
Table 2
Diagnostic method :
|
|
Histopathology
• Positive
• Negative
• Not performed
Culture
• Positive
• Negative
• Not performed
Serology*
• Positive
• Negative
• Not performed
Urinary antigen
• Positive
• Negative
• Not performed
|
70.3%
23.1%
6.6%
75%
14%
11%
48.4%
36.6%
15%
34.8%
27.2%
38%
|
Bronchoalveolar lavage
|
Median (range)
|
Performed
• TNC (range)
• AM
|
51.2%
56.4 (23.8-605.1)
53.5 (17.5-84.75) %
|
• Lymphocyte percentage
• Neutrophil percentage
• Eosinophil percentage
|
2 (1–12) %
40 (9-88.5) %
2 (1–2) %
|
* refers to antibody immunodiffusion assay, antibody enzyme-linked immunoassay, or both. TNC: total nucleated cell count, AM: Alveolar Macrophages. |
The diagnosis of blastomycosis was established with culture in and/or histopathologic examination in 76 (90.5%). In the remaining 8 (9.5%), the diagnosis was established by serologic testing. Bronchoalveolar lavage (BAL) was performed in 43 patients (51.2%); culture was obtained in 39 of those (90.7%) and was positive in 35 patients (90.0%). All cases were reviewed and confirmed by multidisciplinary teams including Infectious Diseases specialists.
Icu Admission, Management And Outcomes:
The median hospital stay was 8 (IQR 4–17) days for the study cohort. A total of 29 (34.5%) admissions were managed in the ICU with a median ICU stay of 6 (IQR 1–21) days.
A seasonal variation in the rate of admission to the ICU were noted; patients who presented in winter were six-times more likely to be admitted to the ICU when compared to those presented in spring P = 0.028.
Among those admitted to the ICU (n = 29); 13 (44.8%) had ARDS. A total of 14 (48.3%) patients required non-invasive mechanical ventilation and 20 (69%) required invasive mechanical ventilation (7 (35%) initiated on admission and 13 (65%) failed non-invasive mechanical ventilation). Tracheostomy was performed in 9 patients (33.3%) after a median of 7.5 days (4–28) days of invasive mechanical ventilation. Further details regarding respiratory support are summarized in Table 3.
Table 3
ICU interventions and respiratory support
|
Overall
(N = 29)
|
ARDS ICU cohort (n = 13)
|
Non-ARDS ICU cohort (n = 16)
|
Median ICU stay period
• Vasopressors
• Number of vasopressors
• Patients required one vasopressors
• Patients required two or more vasopressors
• Glucocorticoids
• ARDS
• Renal replacement therapy
• Tracheostomy
• ECMO
o Median duration of use (range)
Mortality Rate
|
6 days
75.9%
2 (1–4)
7 (31.8%)
15(68.2%)
62%
44.8%%
41.4%%
33.3%%
14.8%
21 (11–183) days
41.4%
|
8 days
100%
3 (1–4)
3 (23%)
10 (77%)
92.3%
100%
53.8%
46.1%
33.3%
21 (11–183)
46.1%
|
2.5 days
56.2%
2 (1–4)
4 (44.4%)
5 (55.6%)
62.5%
0%
31.2%
21.4%
0%
-
37.5%
|
Respiratory support in ICU:
• Nasal cannula or face mask
• Non-invasive mechanical ventilation*
• Invasive mechanical ventilation
o Median duration of use (range)
• PF ratio: median (range)
o Lowest within first 24 hours of ventilation
o Lowest during ventilation
• FiO2: median (range)
o Highest within first 24 hours of ventilation
o Highest during ventilation
• PEEP: median (range)
o Highest during ventilation
|
79.3%
48.3%
69%
7.5 (1.5–57) days
93.3 (34–325)
83.7 (30–194)
0.875 (0.24-1)
0.95 (0.4-1)
10 (5–20)
|
92.3%
76.9%
100%
8 (1.5–57)
83.7 (34–325)
81 (30–176)
1 (0.24-1)
1 (0.5-1)
14 (10–20)
|
68.7%
25%
43.7%
7 (4–41)
130.8 (74–230)
104.2 (74–194)
0.6 (0.4-1)
0.6 (0.4-1)
6 (5–12)
|
* refers to continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or both. # Data was found for 9 patients only. |
Vasopressor support was required for 22 (75.9%) patients, of which, 15 (68.2%) required multiple vasopressors. Four (14.8%) patients required initiation of ECMO for refractory hypoxemic respiratory failure. Of those, 3 (75%) required veno-venous ECMO and 1 (25%) required veno-arterial ECMO for concurrent heart failure. The median duration ECMO was required was 21 (11–183) days. Only 1 patient was successfully weaned from ECMO support while the remaining 3 patients died because of (fulminant pulmonary blastomycosis, disseminated blastomycosis complications, and acute hypoxemic respiratory failure).
Renal replacement therapy (RRT) was required for 12 (41.4%) patients; of whom, 4 patients were receiving RRT prior to the admission due to ESRD while 8 patients required new initiation of RRT for acute kidney injury. Of the 8 patients who required initiation of RRT, 3 developed chronic kidney disease after discharge and remained on dialysis until the last follow-up.
In addition to antifungal therapy, glucocorticoids were administered in 18 (62%) cases with a median dose of 46 (8-1250) mg prednisone-equivalent per day, for a median duration of use of 6 (1-106) days.
Mortality In Blastomycosis Patients:
A total of 25 (29.8%) patients died at the end of follow-up with a total of 12 hospital deaths (14.3%) directly related to blastomycosis. The overall in-hospital, ICU and ARDS mortality rates were 14.3%, 41.4% and 46.1%, respectively.
Using univariate analysis, a positive correlation was observed between in-hospital mortality and age > 65 years at the time of diagnosis (P = 0.04), and renal replacement therapy (P = 0.03), and invasive mechanical ventilation use (P = 0.048). However; no correlation was found between steroid use, chronic lung disease, chronic heart disease, number of lobes involved, and ARDS. Multivariable logistic regression could not be done due to the small sample size. For 1-month mortality, a positive correlation was observed between mortality and ICU admission (P = 0.0007), age more than 65 at time of diagnosis (P = 0.01), Renal replacement therapy (P = 0.03), and invasive mechanical ventilation use (P = 0.048). Multivariable logistic regression could not be done due to small sample size.