Systemic biomarkers of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis.

Research Institute for Internal Medicine, University of Oslo, Oslo, Norway. .
BMC Infectious Diseases (Impact Factor: 3.03). 06/2012; 12:144. DOI: 10.1186/1471-2334-12-144
Source: PubMed

ABSTRACT The purpose of this study was to investigate mediators of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis (CNPA), a locally, destructive process of the lung due to invasion by Aspergillus species.
Measurements of selected biomarkers in 10 patients with CNPA and 19 healthy, matched controls were performed with enzyme-linked immunosorbent assay (ELISA) and multiplex methodology. The gene expressions of relevant biomarkers were analyzed with real-time quantitative RT-PCR.
Increased concentrations of circulating mediators of inflammation interleukin (IL)-6, IL-8, RANTES, TNF-α, ICAM-1 and mediators involved in endothelial activation and thrombosis (vWF, TF and PAI-1) were observed in patients with CNPA. The concentration of the anti-inflammatory cytokine IL-10 was increased both in plasma and in PBMC in the patient population. The gene expression of CD40L was decreased in PBMC from the patient group, accompanied by decreased concentrations of soluble (s) CD40L in the circulation.
The proinflammatory response against Aspergillus may be counteracted by reduced CD40L and sCD40L, as well as increased IL-10, which may compromise the immune response against Aspergillus in patients with CNPA.

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    ABSTRACT: Chronic pulmonary aspergillosis (CPA) is a group of consuming diseases usually presenting with prolonged and relapsing cough, dyspnoea and weight loss. Acute symptoms such as haemoptysis and bronchial or pulmonary haemorrhage may occasionally occur. CPA affects patients with underlying pulmonary conditions, for example, chronic obstructive pulmonary disease or mycobacteriosis or common immunosuppressive conditions such as diabetes. Precise epidemiology is unknown, and while prevalence is considered low the chronic and relapsing nature of the disease challenges the treating physician. Diagnostics largely rely on serologic Aspergillus precipitins and findings on thoracic computed tomography. The latter are manifold comprising cavity formation, pleural involvement and sometimes aspergilloma. Other markers for aspergillosis are less helpful, in part due to the non- or semi-invasive nature of these forms of Aspergillus infection. Various antifungals were shown to be effective in CPA treatment. Azoles are the most frequently applied antifungals in the outpatient setting, but are now compromised by findings of Aspergillus resistance. Long-term prognosis is not fully elucidated and may be driven by the underlying morbidities. Prospective registry-type studies may be suitable to systematically broaden our CPA knowledge base. This article gives an overview of the available literature and proposes a clinical working algorithm for CPA management.
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