A 10-year study reveals clinical and laboratory evidence for the ‘semi-invasive’ properties of chronic pulmonary aspergillosis

Figures & data

Table 1 Diagnostic criteria of pulmonary aspergilloma, chronic pulmonary aspergillosis and invasive pulmonary aspergillosis in this study

Category	Diagnostic criteria
Chronic pulmonary aspergillosis^a	All of the following:
	1. Chronic pulmonary or systemic symptoms (duration, three months) compatible with chronic pulmonary aspergillosis, including at least one of the following symptoms: weight loss, productive cough or hemoptysis.
	2. Cavitary pulmonary lesion with evidence of paracavitary infiltrates, new cavity formation or expansion of cavity size over time.
	3. Either positive result of serum Aspergillus precipitins test or isolation of Aspergillus sp. from pulmonary or pleural cavity.
	4. Elevated levels of inflammatory markers (C-reactive protein, plasma viscosity or erythrocyte sedimentation rate).
	5. Exclusion of other pulmonary pathogens, by results of appropriate cultures and serological tests, that are associated with similar disease presentation, including mycobacteria and endemic fungi (especially Coccidioides immitis and Histoplasma capsulatum).
	6. No overt immunocompromising conditions (for example, HIV infection, leukemia and chronic granulomatous disease).
Invasive pulmonary aspergillosis^b
Proven	Microscopic analysis (sterile material): histologic, cytologic or direct microscopic examination of a specimen obtained by needle aspiration or biopsy in which hyphae are seen accompanied by evidence of associated tissue damage.
	Culture (sterile material): recovery of Aspergillus sp. by culture of a specimen obtained by a sterile procedure from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process, excluding bronchoalveolar lavage fluid.
Probable	Host factors (any one):
	1. Recent history of neutropenia (<0.5x10^9 neutrophils/L for >ten days) temporally related to the onset of fungal disease.
	2. Receipt of an allogeneic stem cell transplant.
	3. Prolonged use of corticosteroids at a mean minimum dose of 3 mg/kg/day of prednisone equivalent for >three weeks.
	4. Treatment with other recognized T-cell immunosuppressants, such as cyclosporine, TNF-α blockers, specific monoclonal antibodies (such as alemtuzumab) or nucleoside analogues during the past 90 days.
	5. Inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency).
	Clinical criteria: The presence of one of the following three signs on CT: (1) dense, well-circumscribed lesion(s) with or without a halo sign; (2) air-crescent sign; or cavity.
	Mycological criteria (any one):
	1. Direct test (cytology, direct microscopy, or culture): Aspergillus sp. in sputum, tracheal aspirate, bronchoalveolar lavage fluid, bronchial brush, indicated by either the presence of fungal elements denoting a mold or recovery by culture of Aspergillus sp.
	2. Indirect tests (detection of antigen or cell–wall constituents): galactomannan antigen detected in plasma or serum.
Probable without prespecified radiologic findings	Same as for ‘probable’ invasive pulmonary aspergillosis except that a positive serum galactomannan antigen result was required, and the abnormal pulmonary infiltrates findings did not fulfill the prespecified radiological criteria.
Pulmonary aspergilloma^c	The presence of a single mobile mass within an existing cavity on chest radiograph or thoracic CT scan, with or without culture of Aspergillus sp. from respiratory tract specimens.

Abbreviations: computerized tomography, CT; human immunodeficiency virus, HIV.

a Adopted from Denning et al.⁵

b Adopted from De Pauw et al.⁶ and Nucci et al.⁷ Possible IPA was not included in this study.

c Adopted from Tam et al.⁸

Table 2 Comparative demographics, mycological investigation results, hospitalization and treatment of patients with chronic pulmonary aspergillosis, invasive pulmonary aspergillosis and pulmonary aspergilloma

Parameter	CPA (n=29)	IPA (n=51)	P (CPA versus IPA)	PA (n=31)	P (CPA versus PA)
Age (years)	64 (7–83)	51 (7–82)	<0.001	66 (40–87)	NS
Sex (male)	25 (86.2)	34 (66.7)	NS	28 (90.3)	NS
Mycological investigations
Serum galactomannan antigen^a	10 (35.7)	28 (54.9)	NS	7 (24.1)	NS
Serum anti-Aspergillus antibody^b	11 (45.8)	3 (7.1)	<0.001	22 (71.0)	NS
Culture
Positive culture from any respiratory tract specimen^c	25 (86.2)	28 (63.6)	NS	20 (64.5)	NS
Aspergillus species isolated from culture
Aspergillus fumigatus	17 (68.0)	18 (64.3)	NS	10 (50.0)	NS
Aspergillus flavus	2 (8.0)	3 (10.7)	NS	0 (0.0)	NS
Aspergillus niger	0 (0.0)	0 (0.0)	NS	3 (15.0)	NS
Aspergillus terreus	0 (0.0)	1 (3.6)	NS	1 (5.0)	NS
Aspergillus sp.	4 (16.0)	6 (21.4)	NS	6 (30.0)	NS
>1 species	2 (8.0)	0 (0.0)	NS	0 (0.0)	NS
Duration of hospitalization (days)	19.0 (1.0–150.0)	38.0 (1.0–177.0)	0.031	12.0 (1.0–137.0)	NS
Antifungal treatment
Use of antifungal drugs	29 (100.0)	41 (80.4)	0.011	15 (48.4)	<0.001
Itraconazole	25	17	<0.001	13	<0.001
Voriconazole	10	19	NS	3	0.028
Posaconazole	0	4	NS	0	NS
Amphotericin B	2	17	0.012	0	NS
Echinocandins	0	15	0.002	1	NS
Duration of antifungal drugs (days)	176.5 (8.0–539.0)	42.5 (1.0–502.0)	NS	106.0 (7.0–411.0)	NS

Abbreviations: bronchoalveolar lavage, BAL; chronic pulmonary aspergillosis, CPA; computerized tomography, CT; chest radiograph, CXR; invasive pulmonary aspergillosis, IPA; left lower lobe, LLL; left upper lobe, LUL; not significant, NS; pulmonary aspergilloma, PA; right lower lobe, RLL; right middle lobe, RML; right upper lobe, RUL.

The data are the number or proportion (%) of patients.

a Serum galactomannan antigen was obtained in 28 (96.6%), 51 (100.0%) and 29 (93.5%) patients with CPA, IPA and PA, respectively.

b Serum anti-Aspergillus antibody was obtained in 24 (82.8%), 42 (82.4%) and 31 (100.0%) patients with CPA, IPA and PA, respectively.

c At least one respiratory tract specimen was collected for fungal culture in 29 (100.0%), 44 (86.3%) and 31 (100.0%) patients with CPA, IPA and PA, respectively.

Table 3 Comparative radiological investigation results of patients with chronic pulmonary aspergillosis, invasive pulmonary aspergillosis and pulmonary aspergilloma

Investigation	CPA (n=29)	IPA (n=51)	P (CPA versus IPA)	PA (n=31)	P (CPA versus PA)
Radiological studies^a
Site of CXR abnormality
RUL	7 (24.1)	5 (9.8)	NS	16 (51.6)	0.036
RML	3 (10.3)	4 (7.8)	NS	0 (0.0)	NS
RLL	1 (3.4)	3 (5.9)	NS	1 (3.2)	NS
LUL	5 (17.2)	5 (9.8)	NS	14 (45.2)	0.027
LLL	0 (0.0)	1 (2.0)	NS	0 (0.0)	NS
Multilobar	13 (44.8)	30 (58.8)	NS	0 (0.0)	<0.001
CXR features
Normal	0 (0.0)	3 (5.9)	NS	0 (0.0)	NS
Cavitary lesion(s)	19 (65.5)	8 (15.7)	<0.001	31 (100.0)	<0.001
Consolidation or collapse	10 (34.5)	31 (60.8)	0.036	2 (6.5)	0.009
Nodule(s)	2 (6.9)	8 (15.7)	NS	5 (16.1)	NS
Pleural effusion	2 (6.9)	9 (17.6)	NS	0 (0)	NS
Fibrosis	13 (44.8)	7 (13.7)	<0.001	19 (61.3)	NS
Site of thoracic CT scan abnormality
RUL	4 (15.4)	3 (9.4)	NS	16 (53.3)	0.005
RML	3 (11.5)	2 (6.3)	NS	0 (0.0)	NS
RLL	1 (3.8)	0 (0.0)	NS	0 (0.0)	NS
LUL	5 (19.2)	3 (9.4)	NS	14 (46.7)	0.047
LLL	0 (0.0)	1 (3.1)	NS	0 (0.0)	NS
Multilobar	13 (50.0)	22 (68.8)	NS	0 (0.0)	<0.001
Thoracic CT scan features
Normal	0 (0.0)	1 (3.1)	NS	0 (0.0)	NS
Cavitary lesion(s), halo or air-crescent sign	26 (100.0)	12 (37.5)	<0.001	30 (100.0)	NS
Consolidation or collapse	12 (46.2)	14 (43.8)	NS	2 (6.7)	0.002
Nodule(s)	6 (23.1)	13 (40.6)	NS	8 (26.7)	NS
Pleural effusion	4 (15.4)	8 (25.0)	NS	2 (6.7)	NS
Fibrosis	14 (53.8)	6 (18.8)	<0.001	23 (76.7)	NS

Abbreviations: bronchoalveolar lavage, BAL; chronic pulmonary aspergillosis, CPA; computerized tomography, CT; chest radiograph, CXR; invasive pulmonary aspergillosis, IPA; left lower lobe, LLL; left upper lobe, LUL; not significant, NS; pulmonary aspergilloma, PA; right lower lobe, RLL; right middle lobe, RML; right upper lobe, RUL.

The data are the number or proportion (%) of patients.

a CXR was performed in all 111 patients. Thoracic CT scan was performed in 26 (89.7%), 30 (96.7%) and 32 (62.7%) patients with CPA, PA and IPA, respectively.

Figure 1 The total number of patients with CPA, IPA and PA, and the reasons for exclusion are shown. chronic pulmonary aspergillosis, CPA; invasive pulmonary aspergillosis, IPA; pulmonary aspergilloma, PA.

Figure 2 Kaplan–Meier survival curves for CPA, IPA and PA through two years after admission are shown. The values in percentage represent survival rates at 2 years after admission. CPA, chronic pulmonary aspergillosis; IPA, invasive pulmonary aspergillosis; PA, pulmonary aspergilloma.

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