Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Abstract

Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ₁ concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.

Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

“…Although prednisolone has been shown to downregulate GR production in HeLa cells (Shimojo et al, 1995) here we saw no effect on GR production in non-decidualized or decidualized hESF. Our data suggests that prednisolone suppresses hESF pro-inflammatory cytokine production as has previously been shown in other cell types (Karagiannidis et al, 2004;Andersson et al, 2005;Shmarina et al, 2017). It is interesting that prednisolone suppressed hESF production of IL11, LIF, and LIFR which we previously showed enhanced progesterone-induced decidualization (Dimitriadis et al, 2003;Shyua et al, 2011).…”

Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis

“…A cross-sectional study was unable to show anti-inflammatory effects of azithromycin ( Shmarina et al, 2017 ). Plasma tumor necrosis factor-α concentrations were higher, whereas plasma concentrations of IL-10, which inhibits synthesis of pro-inflammatory cytokines, were lower in CF patients who received basic therapy along with azithromycin ( n = 59) compared with CF patients who received basic therapy only ( n = 102) ( Shmarina et al, 2017 ).…”