Thymus and Activation Regulated Chemokine Clinical Trial
Official title:
Role of Thymus-And Activation-Regulated Chemokine (TARC) In Diagnosis Of Allergic Bronchopulmonary Aspergillosis
This study aims to assess the value of TARC in diagnosis of allergic Bronchopulmonary Aspergillosis.
Allergic bronchopulmonary Aspergillosis (ABPA) is a pulmonary hypersensitivity disease
mediated by an allergic response to Aspergillus fumigates. ABPA occurs in, 10% of cystic
fibrosis (CF) patients and may lead to acute worsening of respiratory status and ongoing
decline in lung function, ultimately progressing to a chronic state and lung fibrosis without
adequate treatment. Despite the existence of the gold-standard Nelson criteria, diagnosis of
ABPA in CF patients remains difficult. The wide variation in diagnostic practices between
clinics, different estimates of prevalence and a delay in recognition lead to under treatment
(Virnig and Bush 2007).
The main reason for the difficulties in diagnosis of ABPA and ABPA exacerbations in CF
patients is the overlap of diagnostic criteria for ABPA with common manifestations of CF.
Pulmonary infiltrates, obstructive lung disease and bronchiectasis occur regularly in CF
patients, due to the underlying disease with bacterial colonisation, and thus are not
specific to ABPA. Furthermore lung colonisation with A. fumigatus occurs in 20-25% of CF
patients. Therefore, as stated in the most recent consensus document on diagnosis and therapy
of ABPA in CF patients, serological findings should contribute strongly to the confirmation
or exclusion of clinically suspected ABPA (Stevens, Moss et al. 2003).
The diagnosis of allergic bronchopulmonary Aspergillosis (ABPA) in cystic fibrosis (CF) is a
challenge. Thymus- and activation-regulated chemokine (TARC) has recently been reported to
play a role in ABPA (Latzin, Hartl et al. 2008).
TARC levels (analyzed by sandwich ELISA) increased early in the course of ABPA, before total
IgE elevation, with an inverse correlation between TARC levels and spirometric parameters
(FEV 1) identified in CF patient with ABPA. Elevated TARC level was strongly correlated with
the level of rAsp f4 in ABPA patients, while no association was found with the other
recombinants (rAsp f1, f2, f3 and f6). This biomarker showed a greater test accuracy for ABPA
diagnosis than all other biological markers tested (total IgE, specific c IgG and antibodies
against recombinants allergens rAsp f1, rAsp f3, rAsp f4 and rAsp f6). It seems to be able to
differentiate CF patients with ABPA from those colonized or sensitized to A. fumigatus.
Furthermore, corticotherapy decreases the TARC secretion, producing a rapid decrease of serum
TARC level that can be used to follow patient evolution as well as the effect of
corticosteroid therapy in ABPA (Delhaes, Frealle et al. 2010).
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