Follow-Up of Surgical or Nonsurgical Patients with Pulmonary Cryptococcosis: A Real-World Study

Figures & data

Figure 1 Flowchart diagram of eligible study population.

Figure 2 Dynamics of pulmonary cryptococcosis diagnosed in patients from 2009 to 2020.

Table 1 Clinical Features of 163 Patients with PC

Variables	Total (n=163)	Surgical Patients (n=92)	Nonsurgical Patients (n=71)	P value
Age (years)	49 (40–56)	49 (42–56)	48 (40–56)	0.860
Male, n(%)	106 (65.0)	61 (66.3)	45 (63.4)	0.698
Village, n(%)	78 (47.9)	43 (46.7)	35 (49.3)	0.746
History of environmental exposure, n(%)	14 (8.6)	3 (3.3)	11 (15.5)	0.009*
Immunocompromised, n(%)	58 (35.6)	20 (21.7)	38 (53.5)	<0.001*
Diabetes mellitus	19 (11.7)	9 (9.8)	10 (14.1)	0.396
Immunosuppressive drug therapy	16 (9.8)	3 (3.3)	13 (18.3)	0.002*
Malignancy	16 (9.8)	7 (7.6)	9 (12.7)	0.281
Renal transplantation	10 (6.1)	1 (1.1)	9 (12.7)	0.003*
Respiratory system disorders	5 (3.1)	2 (2.2)	3 (4.2)	0.654
Cushing syndrome	2 (1.2)	0 (0.0)	2 (2.8)	0.188
Cirrhosis	2 (1.2)	0 (0.0)	2 (2.8)	0.188
Symptoms
Asymptomatic, n(%)	64 (39.3)	48 (52.2)	16 (22.5)	<0.001*
Cough, n(%)	70 (42.9)	29 (31.5)	41 (57.7)	0.001*
Expectoration, n(%)	55 (33.1)	24 (26.1)	30 (42.3)	0.03*
Chest discomfort, n(%)	45 (27.6)	23 (25.0)	22 (31.0)	0.397
Bloody phlegm, n(%)	15 (9.2)	10 (10.9)	5 (7.0)	0.402
Dyspnea, n(%)	13 (8.0)	3 (3.3)	10 (14.1)	0.011*
Fever, n(%)	10 (6.1)	2 (2.2)	8 (11.3)	0.021*
Laboratory examination
HGB, g/L	138.0 (122.5–149.5)	141.0 (129.3–151.0)	131.0 (120.0–146.0)	0.007*
WBC, 10^9/L	6.2 (5.1–7.7)	5.6 (4.7–6.7)	7.0 (5.6–8.9)	<0.001*
PMN, 10^9/L	3.9 (2.9–5.0)	3.6 (2.4–4.3)	4.5 (3.6–6.3)	<0.001*
LYM, 10^9/L	1.6 (1.2–2.0)	1.6 (1.3–2.1)	1.3 (1.1–1.9)	0.015*
Alb, g/L	40.4 (37.5–42.8)	41.5 (39.1–43.6)	38.7 (33.1–42.0)	<0.001*
ESR, % (Positive/Total)	48.8 (39/80)	30.4 (7/24)	56.1 (32/57)	0.037*
CRP, % (Positive/Total)	28.6 (22/77)	8.7 (2/23)	37.0 (20/54)	0.013*
CrAg, % (Positive/Total)	57.4 (27/47)	12.5 (1/8)	66.7 (26/39)	0.007*
Image findings
Unilateral lesions	136 (83.4)	88 (95.7)	48 (67.6)	<0.001*
Single lobe	129 (79.1)	83 (90.2)	46 (64.8)	<0.001*
Lesions patterns
Nodules/masses	143 (87.7)	90 (97.8)	53 (74.6)	<0.001*
Single	82 (50.3)	64 (69.6)	18 (25.4)
Multi	61 (37.4)	26 (28.3)	35 (49.3)
Pneumonic	11 (6.7)	2 (2.2)	9 (12.7)
Mixed	9 (5.5)	0 (0.0)	9 (12.7)
Largest diameter of lesions(mm)	20.0 (13.0–28.0)	15.0 (12.0–22.0)	26.0 (20.0–38.0)	<0.001*
Accompanying signs
Patchy shadow	55 (33.7)	21 (22.8)	34 (47.9)	0.001*
GGO	30 (18.4)	17 (18.5)	13 (18.3)	0.978
Spiculation	58 (35.6)	41 (44.6)	17 (23.9)	0.006*
Lobulation	42 (25.8)	27 (29.3)	15 (21.1)	0.234
Cavity	33 (20.2)	13 (14.1)	20 (28.2)	0.027*
Air bronchogram	27 (16.6)	14 (15.2)	13 (18.3)	0.598
Pleural involvement	56 (34.4)	28 (30.4)	28 (39.4)	0.230
Pleural effusion	7 (4.3)	2 (2.2)	5 (7.0)	0.241
Hilar lymphadenopathy	38 (23.3)	25 (27.2)	13 (18.3)	0.184
Mediastinal lymphadenopathy	52 (31.9)	31 (33.7)	21 (29.6)	0.576

Notes: Data are presented as Median (IQR), n (%) or n. *P < 0.05.

Abbreviations: HGB, hemoglobin; WBC, white blood cell; PMN, polymorphonuclear; LYM, lymphocyte; Alb, albumin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; CrAg, cryptococcal antigen; GGO, ground glass opacities.

Table 2 Diagnosis and Treatment Outcomes of 163 Patients with PC

Variables	Total (n=163)	Surgical Patients (n=92)	Nonsurgical Patients (n=71)	P value
Illness course	30 (15–60)	30 (15–60)	30 (12–90)	0.788
Primary Diagnosis
Uncertainty	70 (42.9)	43 (46.7)	27 (38.0)	<0.001*
Cancer	46 (28.2)	46 (50.0)	0 (0.0)
Pneumonia	42 (25.8)	0 (0.0)	42 (59.2)
Metastasis	2 (1.2)	1 (1.1)	1 (1.4)
Pulmonary abscess	1 (0.6)	1 (1.1)	0 (0.0)
Connective tissue diseases	1 (0.6)	0 (0.0)	1 (1.4)
Lymphomatoid granulomatosis	1 (0.6)	1 (1.1)	0 (0.0)
Therapy
Antifungal drugs only	71 (43.6)	—	71 (100.0)	<0.001*
Simple surgery	24 (14.7)	24 (26.1)	—
Surgery + antifungal drugs	68 (41.7)	68 (73.9)	—
Fluconazole	135 (97.1)	64 (94.1)	71 (100.0)
Itraconazole	4 (2.9)	4 (5.9)	—
Dosage(mg/d)	300 (200–433)	300 (150–300)	375 (300–450)	<0.001*
Course(M)	3 (1–6)	2 (1–3)	6 (3–8)	<0.001*
Treatment effects
Treatment response	142 (87.1)	84 (91.3)	58 (81.7)	0.069
Recovery	83 (50.9)	68 (73.9)	15 (21.1)
Improvement	59 (36.2)	16 (17.4)	43 (60.6)
Treatment failure	21 (12.9)	8 (8.7)	13 (18.3)
Persistence	6 (3.7)	0 (0.0)	6 (8.5)
Progression	15 (9.2)	8 (8.7)	7 (9.9)

Notes: Data are presented as Median (IQR), n (%) or n. *P < 0.05.

Figure 3 Treatment and follow-up outcomes among different populations. (A) Treatment and follow-up outcomes of asymptomatic and symptomatic patients with different antifungal regimen. (B) Treatment and follow-up outcomes of immunocompetent and immunocompromised patients with different antifungal regimen.

Table 3 Univariate and Multivariate Analysis of Factors Associated with Treatment Failure in 163 Patients with PC

Factors	Univariate Analysis				Multivariate Analysis
	Treatment Response (n=142)	Treatment Failure (n=21)	OR (95% CI)	P value	OR (95% CI)	P value
Age (years)	49 (40–55)	48 (42–61)	1.020 (0.979–1.063)	0.348
Male, n (%)	96 (67.6)	10 (47.6)	0.436 (0.173–1.099)	0.078
Village, n (%)	63 (44.4)	15 (71.4)	3.135 (1.150–8.547)	0.026*
History of environmental exposure, n (%)	12 (8.5)	2 (9.5)	1.140 (0.237–5.495)	0.870
Immunocompromised, n (%)	47 (33.1)	11 (52.3)	2.223 (0.882–5.607)	0.090
Illness course (d)	30 (15–60)	20 (10–105)	0.999 (0.994–1.003)	0.560
HGB<130g/L	43 (30.3)	12 (57.1)	3.070 (1.205–7.823)	0.019*
WBC>9.50*10^9/L	8 (5.6)	7 (33.3)	8.375 (2.641–26.559)	<0.001*
PMN>6.30*10^9/L	12 (8.5)	8 (38.1)	6.667 (2.308–19.258)	<0.001*	18.079 (3.539–92.352)	0.001*
Alb<40g/L	61 (43.0)	18 (85.7)	7.967 (2.245–28.274)	0.001*	7.781 (1.947–31.089)	0.004*
Bilateral lesions	22 (15.5)	5 (23.8)	1.705 (0.566–5.132)	0.343
Multiple lobes	29 (20.4)	5 (23.8)	0.821 (0.278–2.428)	0.722
Lesions patterns
Single nodule/mass	76 (53.5)	6 (28.6)	Reference	0.033*
Multi nodules/masses	52 (36.6)	9 (42.9)	2.192 (0.736–6.531)	0.159
Pneumonic	9 (6.3)	2 (9.5)	2.815 (0.493–16.087)	0.245
Mixed	5 (3.5)	4 (19.0)	10.133 (2.139–48.004)	0.004*
Largest diameter of lesions(mm)	19.0 (12.7–28.0)	20.0 (14.0–29.0)	1.009 (0.982–1.037)	0.528
Only antifungal drug	58 (40.8)	13 (61.9)	2.353 (0.917–6.038)	0.075
Simple surgery	22 (15.5)	2 (9.5)	0.574 (0.125–2.642)	0.476
Postoperative antifungal treatment	62 (43.7)	6 (28.6)	0.516 (0.189–1.407)	0.196
Antifungal dosage (mg/d)
<200	25 (17.6)	6 (28.6)	5.160 (0.967–27.535)	0.055	19.317 (2.067–180.524)	0.009*
200–400	52 (36.6)	11 (52.4)	4.548 (0.956–21.640)	0.057	13.141 (1.777–97.196)	0.012*
≥400	43 (30.3)	2 (9.5)	Reference	0.176	Reference	0.064
Antifungal course (M)
<2	33 (23.2)	8 (38.1)	2.036 (0.609–6.807)	0.248
2—6	45 (31.7)	6 (28.6)	1.120 (0.318–3.945)	0.860
≥6	42 (29.6)	5 (23.8)	Reference	0.524

Notes: Data are presented as median (IQR), n (%) or n. *P < 0.05.

Abbreviations: HGB, hemoglobin; WBC, white blood cell; PMN, polymorphonuclear; Alb, albumin; CI, confidence interval; OR, odds ratio.

Table 4 Univariate and Multivariate Analysis of Factors Associated with Treatment Failure in 71 Nonsurgical Patients with PC

Factors	Univariate Analysis				Multivariate Analysis
	Treatment Response (n=58)	Treatment Failure(n=13)	OR (95% CI)	P value	HR (95% CI)	P value
Age (years)	48 (39–55)	48 (41–64)	1.023 (0.972–1.076)	0.397
Male, n (%)	40 (69.0)	5 (38.5)	0.281 (0.081–0.980)	0.046*
Village, n (%)	27 (46.6)	8 (61.5)	0.544 (0.159–1.864)	0.333
History of environmental exposure, n (%)	10 (17.2)	1 (7.7)	0.400 (0.047–3.437)	0.404
Immunocompromised, n (%)	30 (51.7)	8 (61.5)	1.493 (0.436–5.111)	0.532
Illness course (d)	30 (15–90)	30 (3–120)	0.999 (0.994–1.004)	0.706
HGB<130g/L	24 (41.4)	8 (61.5)	2.267 (0.660–7.782)	0.194
WBC>9.50*109/L	7 (12.1)	6 (46.2)	6.245 (1.625–24.006)	0.008*
PMN>6.30*109/L	9 (15.5)	7 (53.8)	6.352 (1.728–23.345)	0.005*	11.663 (2.272–59.879)	0.003*
Alb<40g/L	36 (62.1)	11 (84.6)	3.361 (0.680–16.602)	0.137
Bilateral lesions	18 (31.0)	5 (38.5)	1.389 (0.399–4.839)	0.606
Multiple lobes	20 (34.5)	5 (38.5)	1.187 (0.343–4.110)	0.786
Lesions patterns
Single nodule/mass	16 (27.6)	2 (15.4)	Reference	0.216
Multi nodules/masses	29 (50.0)	6 (46.2)	1.655 (0.299–9.177)	0.564
Pneumonic	8 (13.8)	1 (7.7)	1.000 (0.078–12.757)	1.000
Mixed	5 (8.6)	5 (30.8)	6.400 (0.891–45.992)	0.065
Largest diameter of lesions(mm)	23.5 (20.0–33.0)	23.5 (22.8–27.5)	0.977 (0.922–1.036)	0.444
Antifungal dosage (mg/d)	400 (300–450)	300 (250–300)	0.992 (0.986–0.998)	0.013*
<200	5 (8.6)	2 (15.4)	6.400 (0.727–56.323)	0.094	20.268 (1.651–248.895)	0.019*
200–400	21 (36.2)	9 (69.2)	6.857 (1.346–34.930)	0.020*	9.576 (1.521–60.290)	0.016*
≥400	32 (55.2)	2 (15.4)	Reference	0.063	Reference	0.031*
Antifungal course (M)	6 (3–8)	3 (1–6)	0.791 (0.635–0.985)	0.036*
<2	7 (12.1)	4 (30.8)	4.229 (0.904–19.786)	0.067
2—6	14 (24.1)	4 (30.8)	2.114 (0.495–9.027)	0.312
≥6	37 (63.8)	5 (38.5)	Reference	0.177

Notes: Data are presented as median (IQR), n (%) or n. *P < 0.05.

Abbreviations: HGB, hemoglobin; WBC, white blood cell; PMN, polymorphonuclear; Alb, albumin; CI, confidence interval; OR, odds ratio.

Table 5 Univariate and Multivariate Analysis of Factors Associated with Treatment Failure in 92 Surgical Patients with PC

Factors	Univariate Analysis				Multivariate Analysis
	Treatment Response (n=84)	Treatment Failure(n=8)	OR (95% CI)	P value	OR (95% CI)	P value
Age (years)	49 (41–56)	49 (46–54)	1.015 (0.948–1.087)	0.673
Male, n (%)	56 (66.7)	5 (62.5)	0.833 (0.186–3.740)	0.812
Village, n (%)	36 (42.9)	7 (87.5)	9.333 (1.099–79.279)	0.041*	12.067 (1.306–111.517)	0.028*
History of environmental exposure, n (%)	2 (2.4)	1 (12.5)	5.857 (0.471–72.903)	0.169
Immunocompromised, n (%)	17 (20.2)	3 (35.7)	2.365 (0.514–10.889)	0.269
Illness course(d)	30 (15–60)	18 (13–75)	0.997 (0.987–1.007)	0.542
HGB<130g/L	19 (22.6)	4 (50.0)	3.421 (0.781–14.986)	0.103
WBC>9.50*10^9/L	1 (1.2)	1 (12.5)	11.857 (0.667–210.625)	0.092
PMN>6.30*10^9/L	3 (3.6)	1 (12.5)	3.857 (0.353–42.148)	0.269
Alb<40g/L	25 (29.8)	7 (87.5)	16.520 (1.930–141.377)	0.010*	20.317 (2.237–184.525)	0.007*
Lesions patterns
Single nodule/mass	60 (71.4)	4 (50.0)	Reference	0.179
Multi nodules/masses	23 (27.4)	3 (37.5)	1.957 (0.406–9.425)	0.403
Pneumonic	1 (1.2)	1 (12.5)	15.000 (0.784–286.823)	0.072
Largest diameter of lesions(mm)	15.5 (11.3–22.0)	14.5 (13.3–38.8)	1.029 (0.989–1.069)	0.157
Hilar lymphadenopathy	20 (23.8)	5 (62.5)	5.333 (1.170–24.309)	0.031*
Mediastinal lymphadenopathy	26 (31.0)	5 (62.5)	3.718 (0.826–16.734)	0.087
Antifungal dosage (mg/d)
<200	20 (23.8)	4 (50.0)	4.200 (0.709–24.879)	0.114
≥200	42 (50.0)	2 (25.0)	Reference
Antifungal course (M)
<2	26 (31.0)	4 (50.0)	2.769 (0.471–16.270)	0.260
≥2	36 (42.9)	2 (25.0)	Reference

Notes: Data are presented as median (IQR), n (%) or n. *P < 0.05.

Abbreviations: HGB, hemoglobin; WBC, white blood cell; PMN, polymorphonuclear; Alb, albumin; CI, confidence interval; OR, odds ratio.