Paracoccidioidomycosis: level of pulmonary sequelae in high resolution computed tomography images from patients of two endemic regions of Brazil

Abstract

Background: The purpose of the present study was to evaluate differences in lung damage in patients with paracoccidioidomycosis (PCM) in two endemic regions of Brazil (Botucatu, SP, in the southeastern region and Campo Grande, MS, in the west central region). Methods:The study sought to objectively quantify fibrosis and emphysema treated patients using highresolution computed tomography (HRCT) that was performed according to an established and validated computational method. The analysis was based on clinical data that were associated with objective quantifications of pulmonary sequelae. We performed a retrospective analysis of HRCT exams from 32 successfully treated patients with the chronic form of PCM. The two groups had similar characteristics with regard to age, symptom duration, smoking history, and titers on a diagnostic serologic test. Results:The statistical analysis revealed more severe cases and a higher percentage of emphysema in the Campo Grande group. The mean percentages of emphysema were 40.2% and 13.6% in the Campo Grande and Botucatu groups, respectively. The percentage of fibrosis was significantly higher in the Botucatu group (11.3%) than in the Campo Grande group (2.3%). Conclusions:The present results may reflect differences in cryptic species of P. brasiliensis in these two geographic regions of Brazil. Further studies should be done to clarify the differences observed herein. Such findings may help unveil differences among cryptic species in terms of the pulmonary consequences that are caused by this disease, which would be highly beneficial to PCM patients.

Chronic exposure to cigarette smoke transiently worsens the disease course in a mouse model of pulmonary paracoccidioidomycosis

“…Although the epidemiological evidence strongly supports the hypothesis that smoking may lead to the development of the pulmonary CF of PCM [1][2][3][4][5] , no study to date has demonstrated the possible mechanism for this association. In our study, we evaluated for the first time the influence of smoking in a murine experimental model of CF pulmonary PCM.…”

“…Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most often, as an asymptomatic or subclinical infection that may manifest later on in an individual's life, the chronic form. Epidemiological studies of PCM aiming to identify factors that lead the infected individual to manifest the disease have shown a strong association between smoking and the development of the chronic form of PCM [1][2][3][4] . The epidemiological link between PCM and smoking is reinforced by a case-control study in which the authors demonstrated that smokers were 14 times more likely to develop the disease among patients from an endemic area in Brazil.…”

The Therapy of Pulmonary Fibrosis in Paracoccidioidomycosis: What Are the New Experimental Approaches?

“…Thus, several compounds with anti-fibrotic or anti-inflammatory properties have been employed to treat IPF or bleomycin-induced PF at an experimental level; these compounds include pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal), among others. PTX is characterized by its immunomodulatory properties; this compound has been shown to reduce the production of pro-inflammatory cytokines including TNF-α, IL-1-α, IL-6, and IL-8 [27], as well as to have exerted an anti-fibrotic effect through the inhibition of both fibroblast proliferation and ECM synthesis [28,29]. AZT, an antibiotic belonging to the macrolide group, has also been shown to exert an antifibrotic effect; thus, in a model of bleomycin-induced pulmonary fibrosis, AZT treatment reduces the production of both the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and the chemokines MCP-1 and keratinocyte chemoattractant in the lungs [30].…”

“…Noteworthy, there were not differences in the interstitial fibrotic tomographic abnormalities [ 27 ]; interestingly, those patients were treated with different antifungal drugs including itraconazole, sulfamethoxazole-trimethoprim, sulfadiazine, ketaconazole or a combination of two or more of these antifungals for treatment [ 27 ]. Furthermore, comparison of patients from two different geographic regions of Brazil, which were treated exclusively with cotrimoxazole, showed that the percentage of fibrosis was significantly higher in those evaluated patients from Botucatu (11.3%) than those from Campo Grande (2.3%); on the other hand, patients from Campo Grande presented more emphysema [ 28 ]. The above studies indicate that the presence of fibrosis not necessarily translate into severe functional deficits, a fact that could be related to the antifungal drug employed; additionally, the differences on clinical presentation, especially in the development of fibrosis or emphysema could be related to different causal cryptic species of the Paracoccidioides genus present in the geographic regions.…”

Efeito da exposição crônica à fumaça de cigarro em modelo experimental murino na reativação da paracoccidioidomicose

“…Em uma série de vinte casos com a forma crônica, todos os pacientes eram fumantes (41). Outros autores também relatam a presença do tabagismo entre os pacientes com a forma crônica da doença (42)(43)(44). Essa alta frequência de tabagismo entre pacientes com PCM, ultrapassa 93%, e parece ser um fator de risco para o desenvolvimento da micose (8).…”