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Pulmonary abnormalities in mice with paracoccidioidomycosis: a sequential study comparing high resolution computed tomography and pathologic findings.

ABSTRACT: BACKGROUND: Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters. METHODOLOGY: Male BALB/c mice were intranasally inoculated with 3 x 10(6) Paracoccidioides brasiliensis (Pb) conidia (n = 50) or PBS (n = 50). HRCT was done every four weeks to determine pulmonary lesions, quantify lung density, reconstruct and quantify lung air structure. Lungs were also analyzed by histopathology and histomorphometry. RESULTS: Three different patterns of lesions were evidenced by hrct and histopathology, as follows: nodular-diffuse, confluent and pseudo-tumoral. The lesions were mainly located around the hilus and affected more frequently the left lung. At the 4th week post-challenge HRCT showed that 80% of the Pb-infected mice had peri-bronchial consolidations associated with a significant increase in upper lung density when compared with controls, (-263+/-25 vs. -422+/-10 HU, p<0.001). After the 8th and 12th weeks, consolidation had progressed involving also the middle regions. Histopathology revealed that consolidation as assessed by HRCT was equivalent histologically to a confluent granulomatous reaction, while nodules corresponded to individual compact granulomas. At the 16th week of infection, confluent granulomas formed pseudotumoral masses that obstructed large bronchi. Discrete focal fibrosis was visible gradually around granulomas, but this finding was only evident by histopathology. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that conventional HRCT is a useful tool for evaluation and quantification of pulmonary damage occurring in experimental mouse PCM. The experimental design used decreases the need to sacrifice a large number of animals, and serves to monitor treatment efficacy by means of a more rational approach to the study of human lung disease.

SUBMITTER: Lopera D

PROVIDER: S-EPMC2894136 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Pulmonary abnormalities in mice with paracoccidioidomycosis: a sequential study comparing high resolution computed tomography and pathologic findings.

Lopera Damaris D Naranjo Tonny T Hidalgo José Miguel JM de Oliveira Pascarelli Bernardo Miguel BM Patiño Jairo Hernando JH Lenzi Henrique Leonel HL Restrepo Angela A Cano Luz Elena LE

PLoS neglected tropical diseases 20100629 6

<h4>Background</h4>Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters.<h4>Methodology</h4>Male BALB/c mice were intr ...[more]

PMID: 20614019

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Project description:OBJECTIVE:To characterize the high-resolution computed tomography (HRCT) pulmonary abnormalities in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS:Pulmonary HRCT images were reconstructed from whole-spine computed tomography (CT) images of 67 patients with SAPHO syndrome. HRCT images of 58 healthy controls were also obtained and reviewed. Patients with pneumonia and tuberculosis were excluded. Demographic and clinical data such as gender, age, onset age, disease duration, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hs-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were collected from the SAPHO syndrome patients. Demographic characteristics, ESR and hs-CRP data from the healthy controls were also recorded. Student's t test, Mann-Whitney U test, chi-squared test and logistic regression were employed to compare the HRCT findings of the two groups of patients. RESULTS:The median age of the SAPHO syndrome patients was 47.0 years, interquartile range [38.0-53.0]; that of the healthy controls was 37.0[30.8-53.8]. From the detailed HRCT evaluations, abnormalities were identified in 45 patients. We found irregular linear opacities in 29 (43.3%) patients, opacities in 22 (32.8%), ground-glass opacity in 11 (16.4%), pleural thickening in 9 (13.4%), solitary nodules in 6 (9%), bronchiectasis in 3 (4.5%), pulmonary bulla in 2 (3%), multiple nodules in 1 (1.5%), and reticular patterns in 1 (1.5%). Compared to the healthy controls, the SAPHO syndrome patients had a significantly higher rate of opacities but a significantly lower percentage of nodules (especially multiple nodules), although the overall rates of abnormal HRCT findings were similar in the two groups. According to the multivariate logistic regression analysis, increased age and BASDAI < 4 were significant predictors of abnormal HRCT findings. CONCLUSION:Our study is the first to address HRCT pulmonary abnormalities in SAPHO syndrome patients. SAPHO syndrome patients have a significantly higher percentage of opacities and a significantly lower rate of pulmonary nodules than healthy controls. BASDAI and age are possible good predictors of abnormal HRCT pulmonary findings.

Dataset Information

Pulmonary abnormalities in mice with paracoccidioidomycosis: a sequential study comparing high resolution computed tomography and pathologic findings.

Publications

Pulmonary abnormalities in mice with paracoccidioidomycosis: a sequential study comparing high resolution computed tomography and pathologic findings.

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