Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa

Abstract

Introduction: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. 
 
 Purpose: Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods.
 
 Materials and methods: A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle).
 
 Results: Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase].
 
 Conclusions: The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

Blood mRNA biomarkers distinguish variable systemic and sputum inflammation at treatment initiation of inhaled antibiotics in cystic fibrosis: A prospective non-randomized trial

“…Given that treatment is localized to the airways and not systemic, changes in circulating leukocyte gene expression is a relatively novel finding. In particular, changes in blood or sputum inflammatory markers are usually non-significant in clinical trials of inhaled antibiotics [ 22 ]. Consistent with prior studies, single genes do not change significantly following treatment.…”

Utilizing centralized biorepository samples for biomarkers of cystic fibrosis lung disease severity

“…The differences observed could reflect influences of these unmatched variables. While a higher prevalence of MRSA infection could contribute to increased circulating inflammatory protein concentrations in the severe cohort, azithromycin and inhaled antibiotics conversely reduce systemic inflammatory markers [24,43] . Also, it is important to note that individuals with known CF-related liver disease or diabetes were excluded from these analyses.…”

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association)

“…Using the methodology described, we selected 25 studies carried out between 1995 and 2008. 94 - 118 Five were observational studies 101 - 103 , 109 , 117 and the others were classified as RCTs. Samples sizes were over 200 in 9 of the studies, of which 2 included more than 500 individuals ( and ).…”