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Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa
Yazeed Toukan1, Michal Gur, Fahed H Hakim
1Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology. email@email.com.
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.
Insights
Cystic fibrosis patients on inhaled tobramycin powder therapy showed stable lung function during the off-treatment month. However, Interleukin-6 (IL-6) levels were higher off therapy, suggesting increased inflammation.
Area of Science:
- Pulmonology
- Infectious Diseases
- Pharmacology
Background:
- Cystic Fibrosis (CF) management includes inhaled tobramycin for chronic Pseudomonas aeruginosa colonization.
- Alternate monthly on/off therapy with inhaled tobramycin is recommended.
- Tobramycin inhaled powder (TIP™) is replacing nebulizer treatments, but on/off cycle effects are unclear.
Purpose of the Study:
- To evaluate changes in spirometry, lung clearance index, and inflammatory markers during on/off TIP therapy cycles in CF patients.
Main Methods:
- Prospective pilot study in 19 CF patients using TIP for two consecutive months (on/off).
- Evaluations conducted at the end of the off-treatment month and after 28 days of TIP treatment.
Main Results:
- Spirometry and lung clearance index remained stable during the off-treatment period.
- Serum Interleukin-6 (IL-6) levels significantly increased (p=0.022) during the off-treatment month.
- Other inflammatory markers (hs-CRP, IL-8, TNF-α, α1AT, neutrophilic elastase) showed non-significant changes off therapy.
Conclusions:
- Lung function appears stable in CF patients during the off-month of TIP therapy.
- Elevated IL-6 off therapy suggests potential for increased inflammation.
- Larger multicenter studies are needed to confirm the efficacy and safety of the on/off TIP treatment strategy.
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